Common Cause Research Articles

Updates on pharmacological treatment for Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia, and its rising prevalence is constantly increasing the global health burden. There are currently no curative therapies for AD, and current treatment options provide only modest clinical benefit. Despite numerous clinical trials, there have been no major additions to the AD treatment armamentarium this century. The prevailing pathomechanistic hypothesis for AD begins with abnormal accumulation of amyloid β (Aβ) leading to plaque development, and disease-modifying candidate therapies have largely aimed to disrupt this process. Numerous clinical trials of monoclonal antibodies directed at various stages of Aβ plaque development have yielded mostly negative results; however, recent results suggest that a breakthrough may be on the horizon. The past two years have yielded positive results for three monoclonal antibodies (aducanumab, lecanemab, and donanemab) although questions remain regarding their clinical effectiveness. Additional clarity is needed to determine whether the clinical benefits are great enough to offset the treatment risks and the resource implications for healthcare systems. This review provides a foundational context and update on recent disease-modifying therapies for AD that have reached Phase III clinical trials. Up-to-date information on these therapies will help clinicians better inform their clinical decision-making and the counselling they can offer patients and their carers.

Intelligence model for Alzheimer’s disease detection with optimal trained deep hybrid model

Alzheimer’s disease (AD), a neurodegenerative disorder, is the most common cause of dementia and continuing cognitive deficits. Since there are more cases each year, AD has grown to be a serious social and public health issue. Early detection of the diagnosis of Alzheimer’s and dementia disease is crucial, as is giving them the right care. The importance of early AD diagnosis has recently received a lot of attention. The patient cannot receive a timely diagnosis since the present methods of diagnosing AD take so long and are so expensive. That’s why we created a brand-new AD detection method that has four steps of operation: pre-processing, feature extraction, feature selection, and AD detection. During the pre-processing stage, the input data is pre-processed using an improved data normalization method. Following the pre-processing, these pre-processed data will go through a feature extraction procedure where features including statistical, enhanced entropy-based and mutual information-based features will be extracted. The appropriate features will be chosen from these extracted characteristics using the enhanced Chi-square technique. Based on the selected features, a hybrid model will be used in this study to detect AD. This hybrid model combines classifiers like Long Short Term Memory (LSTM) and Deep Maxout neural networks, and the weight parameters of LSTM and Deep Maxout will be optimized by the Self Updated Shuffled Shepherd Optimization Algorithm (SUSSOA). Our Proposed SUSSOA-based method’s statistical analysis of best values such as 57%, 53%, 28%, 25%, and 21% is higher than the other models like SSO, BMO, HGS, BRO, BES, and ISSO respectively.

Optimizing feature selection and parameter tuning for breast cancer detection using hybrid GAHBA-DNN framework

Breast cancer has been life-threatening for many years as it is the common cause of fatality among women. The challenges of screening such tumors through manual approaches can be overcome by computer-aided diagnosis, which aids radiologists in making precise decisions. The selection of significant features is crucial for the estimation of prediction accuracy. This work proposes a hybrid Genetic Algorithm (GA) and Honey Badger Algorithm (HBA) based Deep Neural Network (DNN), HGAHBA-DNN for the concurrent optimal features selection and parameter optimization; further, the optimal features and parameters extracted are fed into the DNN for the prediction of the breast cancer. It fuses the benefits of HBA with parallel processing and efficient feedback with GA’s excellent global convergent rate during the processing stages. The aforementioned method is evaluated on the Wisconsin Original Breast Cancer (WOBC), Wisconsin Diagnostic Breast Cancer (WDBC), and the Surveillance, Epidemiology, and End Results (SEER) datasets. Subsequently, the performance is validated using several metrics like accuracy, precision, Recall, and F1-score. The experimental result shows that HGAHBA-DNN obtains accuracy of 99.42%, 99.84%, and 92.44% for the WOBC, WDBC, and SEER datasets respectively, which is much superior to the other state-of-the-art methods.

Clinical Characteristics and Compliance of Diabetic Macular Edema Patients to Intravitreal Anti-VEGF Injection Loading Dose at Cipto Mangunkusumo Hospital

Introduction & ObjectivesDiabetic retinopathy is the fifth most common cause of preventable blindness. In cases of diabeticmacular edema (DME), loading dose is a critical phase to achieve a stable concentration ofintravitreal vascular endothelial growth factor (VEGF) in order to prevent progressivity. This studyaims to determine the demographic and clinical characteristics, waiting time, compliance, as well asthe relationship between education, domicile and clinical outcomes to compliance during loadingdose in DME patients. MethodsIn this retrospective descriptive study, we reviewed medical records of DME patients who receivedanti-VEGF intravitreal injection between 1 January 2019 and 31 December 2020, while alsocomparing records in 2019 (pre-Covid-19) and 2020 (during Covid-19). ResultsThere were 160 patients (207 eyeballs) in 2019 and 83 patients (114 eyeballs) in 2020 who receivedloading dose with similar profiles of sex, age, education, initial visual acuity and central macularthickness (CMT). Median waiting times in 2019 and 2020 were 19 days and 23.5 days, respectively(p=0.016). Only 25 (30.5%) and 15 (35.7%) patients were punctual in 2019 and 2020, respectively.There was no significant relationship between education and domicile with compliance (p= 0.45, p=0.51). Furthermore, there were visual acuity improvements of -0.18 logMAR and -0.0 logMAR in thepunctual and unpunctual group, respectively, as well as CMT decrease of -181 ?m and -156 ?m,respectively. ConclusionMost patients who received loading dose were unpunctual. There was no significant relationshipbetween education and domicile with compliance. Furthermore, there were more significantimprovements in clinical outcomes among the punctual patients.

Leveraging Directed Causal Discovery to Detect Latent Common Causes in Cause-Effect Pairs.

The discovery of causal relationships is a fundamental problem in science and medicine. In recent years, many elegant approaches to discovering causal relationships between two variables from observational data have been proposed. However, most of these deal only with purely directed causal relationships and cannot detect latent common causes. Here, we devise a general heuristic which takes a causal discovery algorithm that can only distinguish purely directed causal relations and modifies it to also detect latent common causes. We apply our method to two directed causal discovery algorithms, the information geometric causal inference (IGCI) of (Daniusis et al., 2010) and the kernel conditional deviance for causal inference of (Mitrovic et al., 2018), and extensively test on synthetic data-detecting latent common causes in additive, multiplicative and complex noise regimes-and on real data, where we are able to detect known common causes. In addition to detecting latent common causes, our experiments demonstrate that both the modified algorithms preserve the performance of the original in distinguishing directed causal relations.

Airway management during a respiratory arrest in a clinical simulation scenario. Experience at a pediatric residency program.

Introduction. Respiratory failure is the most common cause of cardiac arrest in pediatrics. Recognizing and managing it adequately is critical. Simulation is used to improve medical skills. The objective of this study was to establish the proportion of pediatric residents who recognized a respiratory arrest in a child at a simulation center. Methods. This was an observational study in 77 residents. A simulation of a patient with respiratory distress that progressed to respiratory arrest was used. Results. Among the 77 participants, 48 recognized respiratory arrest (62.3%). The mean time to recognize respiratory arrest was 38.16 seconds. Conclusion. Respiratory arrest was recognized by 62.3% of participants. Among those who did so, the average time was 38.16 seconds. Severe failures were noted in some of the expected interventions.

الكشف عن بعض عوامل الضراوة بين المبيضات المعزولة من المرضى وانتشار جين candidalysin ECE1

المبيضات البيضاء هي مسبب شائع لعدوى الجهاز التنفسي وداء المبيضات الفموي لدى الناس ، ومسببات أمراض الخميرة الانتهازية والأسباب الرئيسية للمرض والوفيات لدى الأشخاص الذين يعانون من نقص المناعة وتسبب التهابات سطحية على الأسطح المخاطية التي تصيب ملايين الأشخاص في جميع أنحاء العالم. كان الهدف الرئيسي من هذه الدراسة هو التحقق من انتشار بعض عوامل الضراوة التي لها القدرة على تكوين الأغشية الحيوية (Biofilm)، والبروتينيز (Proteinase)، وإنتاج الهيمولايسين( Hymolysine) بين عزلات C. albicans التي تشمل انتشار جين Candidalysin (ECE1). تم جمع العينات خلال الفترة من ايار 2022 الى اب 2022 من 280 عينة (مسحة) لمرضى عراقيين من مختلف الاعمار والاجناس غير مكررين كانوا يعانون من داء المبيضات الفموي وامراض الجهاز التنفسي في مستشفيات بغداد (مستشفى مدينه الطب و مستشفى اليرموك التعليمي ومستشفى مدينه الامامين الطبية التعليمية). تم زراعة العينات التي تم جمعها على وسط اكار السابرويد دكستروز (SDA) مضاف اليه كلورامفينيكول كمضاد للبكتيريا بتركيز 10 ميكجم / مل ، وتم حضن الاطباق الملقحة على وسط SDA عند 37 درجة مئوية لمدة تتراوح بين 24-48 ساعة.أظهرت نتائج الاستنبات أن 102 عينة كانت موجبه، منها58 (56.86%) من تجويف الفم و 44 (43.14%) من الجهاز التنفسي، بينما 178 منها كانت سالبة , تم الكشف عن عزلات المبيضات باستخدام الطرق التقليدية والتي تشمل (النمو على وسط HiCrome Candida ، إنتاج الأنبوب الجرثومي Germ tube ، تكوين الابواغ الكلاميديه Clamydospore وتم تأكيد نتئج التعريف باستخدام نضام VITEK-2 بينت النتائج ان من بين 102 عزلة C. albicans هي الاكثر شيوعا بين الانواع بنسبة 68.63 % ثم تلتها C. tropicalis بنسبة %10.78 ثم C. kruzei %5.88 وC. kefyr %5.88 C. parapsilosis % 4.9 بينما كانت C. glabrata % 3.9 وتمثل النسبة الاقل بين الانواع . تم فحص حساسية عزلات المبيضات للأدوية المضادة للفطريات بطريقة انتشار القرص ، والتي أجريت على النحو الموصى به بواسطة(CLSI) M44-A -وثيقة . أظهرت العزلات درجة عالية من الحساسية للأمفوتريسين-ب 93.14% وكلوتريمازول 90.20% ونسياتين 85.92% ،تم التحقق من انتشار جينCandidalysin (ECE1) بين 70 عزلة من C. albicans باستخدام تقنية تفاعل البلمرة المتسلسل PCR ، وأظهرت النتائج أن 41 58.57% تحتوي على جين Ece1 في تجويف الفم والجهاز التنفسي. و 34 عزلة 48.57% من C. albicans كانت منتجة قوية للغشاء الحيوي, بينما 30 عزلة 42.86% عزلة انتجت بروتيناز و 20 عزلة 28.57% عزلة لديها القدرة على تحلل الدم.

Diagnostic Imaging for Retinoblastoma Cancer Staging: Guide for Providing Essential Insights for Ophthalmologists and Oncologists.

Retinoblastoma is the most common cause of all intraocular pediatric malignancies. It is caused by the loss of RB1 tumor suppressor gene function, although some tumors occur due to MYCN oncogene amplification with normal RB1 genes. Nearly half of all retinoblastomas occur due to a hereditary germline RB1 pathogenic variant, most of which manifest with bilateral tumors. This germline RB1 mutation also predisposes to intracranial midline embryonal tumors. Accurate staging of retinoblastoma is crucial in providing optimal vision-, eye-, and life-saving treatment. The AJCC Cancer Staging Manual has undergone significant changes, resulting in a universally accepted system with a multidisciplinary approach for managing retinoblastoma. The authors discuss the role of MRI and other diagnostic imaging techniques in the pretreatment assessment and staging of retinoblastoma. A thorough overview of the prevailing imaging standards and evidence-based perspectives on the benefits and drawbacks of these techniques is provided. Published under a CC BY 4.0 license. Test Your Knowledge questions for this article are available in the supplemental material.

Risk Factors and Frequency of Foot Ulceration in Patients Receiving Chronic Hemodialysis Treatment.

To determine the prevalence and risk factors of foot ulceration in patients receiving hemodialysis treatment. A total of 180 patients who received hemodialysis treatment in two state hospitals and a private health center between April 2017 and September 2017 were included in the study. The researchers collected data using a patient information form and by conducting physical evaluation of the lower extremities. They used the diabetic foot risk assessment algorithm to classify risk according to the data obtained. Of the patients receiving hemodialysis treatment, 6.7% had foot ulceration, 19.4% had a history of foot ulceration, and 8.3% had a history of hospitalization associated with ulceration in a lower extremity. Infected foot ulceration was the most common (6.1%) cause of hospitalizations. In the group with current or past foot ulceration, diabetic nephropathy was the most common etiologic factor of end-stage kidney disease (48.6%); there was a significant between-group difference in diabetic nephropathy (P < .05). Etiologic factors had a significant effect on foot ulcerations: As determined by univariate logistic regression, diabetes (odds ratio [OR], 2.727; P < .05), presence of neuropathy (OR, 4.208; P < .05), low-density lipoprotein cholesterol (OR, 1.013; P < .05), and serum albumin (OR, 0.302; P < .036) all had a statistically significant effect on the presence of foot ulcerations. Patients receiving hemodialysis treatment are at high risk for foot ulceration. Therefore, patient awareness strategies should be expanded to include individuals with end-stage renal disease regardless of diabetes status. Clinical and dialysis nurses should educate these patients about foot ulcerations and foot health to prevent ulcer development.

Torsion and clinical features in patients with acquired fourth cranial nerve palsy

This retrospective study aimed to compare objective/subjective torsion and other clinical characteristics of patients with acquired trochlear nerve palsy. This study included 82 consecutive patients who were diagnosed with acquired fourth cranial nerve palsy between 2014 and 2021 and who were followed up for ≥ 6 months. The etiologies, ocular deviation, objective and subjective torsions were reviewed. The etiologies were classified as ischemic, traumatic, brain lesion, idiopathic, or other. The patients were classified into two groups according to the recovery state: full recovery and partial/no-recovery. We compared the torsion and clinical features based on the etiology and recovery state. The average age was 59.1 ± 11.1 years, and 58 (71.0%) of the patients were male. The most common cause was ischemic (n = 49, 59.7%) and other common causes included traumatic (n = 16, 19.5%), brain lesion (n = 8, 9.8%), idiopathic (n = 5, 6.1%) and others (n = 4, 4.9%). Of the 82 patients, 56 (68.3%) were assigned to the full recovery group, and 26 (31.7%) were assigned to the partial/no-recovery group. The average age and number of patients with ischemic causes of palsy were greater in the full recovery group (p = 0.026 and p < 0.000, respectively). The vertical deviation angle, tilted angle on the Lancaster red-green test (LRGT), proportion of patients who experienced subjective torsion on the LRGT, and head tilt were smaller in the full recovery group (p = 0.037, 0.042, 0.045, and 0.006, respectively). Ischemic trochlear nerve palsy, advanced age, a small deviation angle at the primary position, and few cases of excyclotorsion on LRGT were characteristic of the full recovery group of acquired unilateral trochlear nerve palsy patients.

Profile of Blood Donors and Reasons for Deferral at a District Hospital in North Goa

Introduction: A blood transfusion is a life-sustaining procedure in several medical and surgical conditions. It isvital that an adequate inventory of safe blood is established by implementing stringent donor selection criteria andscreening for transfusion transmitted infections by ultrasensitive methods of detection. Despite a huge population,scarcity of blood lingers nationwide and it is important to analyse the varied reasons of deferrals in order to lessenthe deferrals in the future.The aim of this paper is to scrutinise the demographic profile of blood donors and evaluate the patterns andreasons for donor deferral at North Goa District hospital, India.Materials and Methods: This is a retrospective study carried out at the Blood Centre , North Goa Districthospital,India,. All those who registered for donation between June 2022 till May 2023 were included in the study.The donors were screened by a questionnaire followed by medical examination and were selected or deferredbased on the guidelines laid down by Drugs and Cosmetics Act,1940 and Directorate General of Health Services,MoHFW,Govt of India1.2 .Data was collected using a proforma and analysed by SPSS software wherever indicated.Results: During this time period, 2611 donors registered for blood donation, out of which 425 donors were deferreddue to diverse reasons. Most of the donors were voluntary donors(98.3%) of which majority were males(86.4%).The commonest cause of deferral in males was high BP(24%) and high Hb(11.3%) whereas the commonest cause ofdeferrals in females was low Hb (46.9%). Most of the donors were rejected due to temporary reasons(97.1%). Thecommonest reason of permanent deferrals was a medical history of uncontrolled DM.

A study to untangle the puzzle of urinary incontinence and frailty co-occurrence among older adults: The roles of depression and activity engagement.

To explore the co-occurrence of urinary incontinence and frailty by testing the roles of depression and activity engagement guided by the mechanisms of common cause and interaction pathways. A secondary analysis of a 1-year three-wave panel data collected from older nursing home residents in China. Changes in depression and activity engagement were regressed on urinary incontinence and frailty incidence underpinned by the common cause mechanism of chronic conditions co-occurrence, and these changes were also taken as mediators linking from frailty to urinary incontinence incidence supported by the interaction pathways' mechanism. A total of 348 older adults were included in this study, and 55.7% were women. The co-occurrence of urinary incontinence and frailty was found in 16.7% of the participants at baseline. Older adults with sole frailty at baseline had almost twice the rate of incident urinary incontinence (32.7%) compared with those without (16.7%) over a 1-year period. The subsample analyses showed that changes in depression and activity engagement failed to significantly predict the incidence of urinary incontinence and frailty. The mediating roles of these changes linking frailty to urinary incontinence incidence were also not statistically significant. The co-occurrence of urinary incontinence and frailty is prevalent in older nursing home residents. Older adults with frailty at baseline are more likely to develop urinary incontinence a year later. The common cause and interaction pathways mechanisms for the co-occurrence of urinary incontinence and frailty were not verified with changes in depression and activity engagement. The phenomenon of urinary incontinence and frailty co-occurrence should be given extreme emphasis. Although statistically significant findings on the roles of depression and activity engagement were not inferred, this study provides multiple possibilities for future studies to test and depict a clear picture of this co-occurrence. What problem did the study address? This study was designed to test the roles of depression and activity engagement in predicting the incidence of urinary incontinence and frailty, and the mediating roles in linking frailty to urinary incontinence incidence. What were the main findings? Despite the methodological pitfalls in literature have been addressed, neither depression nor activity engagement would significantly predict the incidence of urinary incontinence and frailty in older adults. Their mediating roles in linking frailty to urinary incontinence incidence were also not significant. Where and on whom will the research have an impact? Our findings add important pieces of evidence to promote researchers' understanding and provide an important basis for untangling the puzzle of urinary incontinence and frailty co-occurrence. The report of this study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement guidelines. No patient or public contribution.

Abstract 6145: A trans-ethnic meta-analysis identified additional novel genomic loci associated with cervical cancer

Abstract Introduction: Cervical cancer is the second most common cause of cancer-related deaths among women worldwide. Genome-wide association studies (GWAS) have identified genetic variants associated with cervical cancer. However, these discoveries have been limited by the small sample sizes of the individual cohorts. To identify additional novel loci associated with cervical cancer, we performed a trans-ethnic meta-analysis. Methods: GWAS summary data for trans-ethic meta-analysis were identified in women of European ancestry from the UK Biobank, East Asian ancestry from Biobank Japan, and African ancestries from the pan-UK Biobank and Johannesburg cancer study. Meta-analyses were performed using fixed effect inverse variance weighted method implemented in GWAMA. To localize putative genomic loci associated with cervical cancer, we performed fine mapping using the Bayesian approach by calculating the marginal posterior probability of causality for each single nucleotide polymorphisms (SNPs) and 99% credible set size. Results: Our meta-analysis identified four additional novel genomic loci associated with cervical cancer. These loci include: rs147778467 (odds ratio [OR] = 1.12, 95% confidence interval [CI] = 1.08-1.16, P-value = 3.12 x 10-08) in RGS21, rs53150478 (OR =1.03, 95%CI = 1.01-1.05, P-value = 4.48 x 10-08) in MAN1C1, rs113842373 (OR = 0.68, 95%CI = 0.56-0.81, P-value = 2.31 x 10-09) in LINCO1850 and rs75372437 (OR = 0.80, 95%CI = 0.72-0.88, P-value = 3.32 x 10-08) in RNU6-356P. These loci are implicated in carcinogenic pathways. Moreover, our Bayesian fine mapping identified five loci with a marginal posterior probability of causality &amp;gt; 1 and reduced the 99% credible set sizes. Conclusion: We identified additional novel loci associated with cervical cancer and our fine mapping identified loci with a high posterior probability of being causal. Citation Format: Abram Bunya Kamiza, Jean-Tristan Brandenburg, Michele Ramsay, Christopher Mathew. A trans-ethnic meta-analysis identified additional novel genomic loci associated with cervical cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6145.

Neoplasia detection in FIT positive screening colonoscopies compared with an age-controlled symptomatic cohort: a retrospective review

Colonoscopy following a positive FIT test in an average risk population is effective in reducing CRC incidence and mortality. While lower gastrointestinal symptoms remain a common cause for referral for colonoscopy, symptoms are poor predictors of clinically significant disease. The study was performed to compare neoplasia detection FIT +ve individuals and age-matched symptomatic cohorts. A single centre retrospective observational study was performed including all index colonoscopies performed on patients aged 60-70 from January 2015 to September 2021. Diagnostic yield was reported as adenoma detection rate, SSL detection rate, detection of high risk finding or adenocarcinoma. 8,106 colonoscopies were performed on patients aged 60-70 years. 3,695 (45.6%) originated from screening (FIT +ve). With exclusion criteria applied, 2,640 (59.9%) for screening and 1,767 (40.1%) for symptomatic patients were included. Median age in screening was 65 years (IQR 62-67) and 64 years in the symptomatic group (IQR 62-68), with male predominance in both groups (n=1,536, 58.1%, n=944, 53.4%). There were significant differences in both the ADR (56% vs 26.3%, p&amp;lt;0.01) and the SSLDR (10.4% vs. 8.1%, p=0.05) in the screening cohort compared to the symptomatic group. High risk findings (21.3% vs. 7.5%, p&amp;lt;0.01) were significantly more prevalent in the screening group with a considerably higher colorectal cancer (4.7% vs. 0.9%, p=&amp;lt;0.001) detection rate. FIT based triage significantly outperforms symptom based investigation for individuals in the 60-70 age group. Patients should be preferentially referred to organised colorectal cancer screening. FIT can be performed on symptomatic patients, to identify low risk individuals.

Abstract 3211: Development of first in class zip code drug conjugate in pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PC) is the fourth most common cancer-related cause of death in Western countries. It is projected that PC will become the second most prevalent cause of cancer-related mortality by the year 2030. Although chemotherapy may offer certain advantages to those who have been diagnosed with pancreatic cancer, its effectiveness is notably constrained by the emergence of chemoresistance and excessive toxicity. In recent studies, it has been established that circulating tumor DNA (ctDNA) serves as a mechanism for cell-specific genetic transfer. We discovered that transposon sequences (known as Zip Codes, ZC) were responsible for ctDNA cell targeting. Therefore, we investigated the possibility of hijacking these ZC to deliver drugs specifically. We began by determining whether PDCA ZC synthesized chemically could target PDCA cells selectively. To achieve this, ZC sequences were labeled with CY5 for high-throughput microscopy. Results show that numerous PDCA-ZC were specific and efficient at targeting PC cell lines while sparing other cancer cell lines. The AluSc8 (PCZC) sequence was chosen for further investigation. The specificity of PCZC for targeting cells was validated using pancreatic islet cells. Based on these findings, we developed a technique for conjugating PCZC with SN38 via a CL2A linker. The results indicated that PCZC-SN38 was a very effective agent at killing PC cells (IC50: 1 μg), but not other cancer cell lines. The therapeutic efficacy of PCZC-N38 was evaluated in vivo using PDX (patient-derived xenografts, Garcia et al Plos One 2013). Maximum tolerated dose testing (MTD) (dosing from 1 to 21 mg of PCZC-SN38/Kg) failed to reach an MTD. Subsequently, we evaluated the efficacy signal of PCZC-SN38 by administering PCZC-SN38 to animals three times per week for three weeks at concentrations of 3 and 30 mg/kg of DNA (equivalent to 0.05 and 0.5 SN38 mg/kg). We used animals treated with vehicle, PCZC alone, and irinotecan (either once per week (50 mg/kg) or three times per week (0.5 mg/Kg) as a comparison. PCZC-SN38 decreased tumor growth by 41% and 70%, respectively, when compared to the vehicle or PCZC alone. The observed efficacy did not result in a change in body weight. In contrast, every animal administered irinotecan at a dosage of 50 mg/kg died within a week. On the contrary, animals that were given irinotecan at a dosage of 0.5 mg/kg demonstrated a growth inhibition of 60% and exhibited remarkable tolerability. Currently, research is being undertaken to determine the therapeutic efficacy of PCZC-SN38 at higher doses. The results outlined in this study illustrate the preliminary application of PC targeted drug delivery using a PC zip code drug conjugate. The results of our study demonstrate an innovative methodology for targeting PC cells specifically with therapeutic cargo material and supports further preclinical development of PCZC-SN38 for PC. Citation Format: Munnever Cinar, Purnachandra Ganji, Andrey Pisarev, Lourdes Martinez-Medina, Dhana S. Bandi, Pavan K. Puvvula, Steven Chang, Daniel Maneval, Bassel El-Rayes, Leon Bernal-Mizrachi. Development of first in class zip code drug conjugate in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3211.

Breastfeeding and fatty liver - is there any association?

The campaign to promote the natural feeding of infants, at least for the first six months of life, conducted over recent years has deep justification from a medical point of view. Numerous gynecological and pediatric societies around the world recommend breastfeeding as the most appropriate way of feeding infants. It has been proven that the benefits of this type of nutrition go beyond nutritional aspects, proper growth and development. The list of long-term metabolic benefits, which include reducing the incidence of obesity, allergies, infections and diabetes, is constantly growing. It has been shown that the method of feeding infants using various mechanisms may influence the tendency of the liver to accumulate fatty compounds and develop fatty liver disease with its metabolic consequences leading to liver failure, cirrhosis and hepatocellular carcinoma. This is an important discovery due to the growing obesity epidemic in adults and children. Metabolic dysfunction - associated fatty liver disease (MAFLD) has become the most common cause of chronic liver disease, affecting 25% of the global population. The results of studies conducted in recent years have shown the protective effect of breastfeeding on the risk of developing MAFLD later in life in both children and breastfeeding women. New scientific reports provide the basis for qualifying breastfeeding as a modifiable risk factor for MAFLD.

The Effect of Apathy and Depressive Syndromes on Functional Outcomes in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia. Its initially characterized by progressive short-term memory loss followed by cross-domain cognitive decline in later stages resulting in significant functional deficits and loss of activities of daily living (ADLs) independence. Apathy and depression are frequent neuropsychiatric sequelae in AD, but their contribution to functional deficits is poorly understood. We aimed to quantitatively investigate if apathy and depressive symptoms predict ADLs in AD. We also wanted to fractionate apathy dimensions by factor-analyzing the apathy evaluation scale (AES) and then investigate the dimensions' relation to ADLs. We recruited a sample of 115 patients with probable or possible AD and assessed them for depression, apathy, and ADLs alongside other measures. We hypothesized that apathy and depressive symptoms would predict ADLs and that AES items will load into cognitive, behavioral, and affective factors that would differentially relate to ADLs. Our results indicated that apathy symptoms predict ADLs deficits. The AES items resolved into a three-factor solution but the manner of clustering diverged from that proposed by AES authors. When these factors were regressed simultaneously, only behavioral apathy predicted global ADLs. Distinguishing basic from instrumental ADLs showed that behavioral and cognitive apathy symptoms associate with ADLs deficits while affective symptoms do not. Our results highlight the influence of apathy on ADLs in AD. This has important implications for patient care considering the high prevalence of apathy in AD and other dementing illnesses.

Pediatric Cases Diagnosed with Drug-Related Acute Tubulointerstitial Nephritis: A Single-Center Experience

Aim: Acute tubulointerstitial nephritis (TIN) is inflammation of the renal interstitium. It is also a common cause of acute kidney injury (AKI). The aim is to contribute to the literature by evaluating patients diagnosed with drug-induced TIN.&#x0D; Material methods: 29 Turkish children aged between 3 and 217 months, 5 of whom had undergone a biopsy, were retrospectively analyzed in terms of clinical and laboratory findings.&#x0D; Results: 29 patients, 19 of whom were girls, were evaluated. The mean age at diagnosis was 138.6(3-217) ± 67.4 months. Nausea-vomiting complaint of 12 cases, 6 under treatment during hospitalization, 4 with headache, 2 with isolated fatigue, and the remaining 5 patients with incidentally detected renal function test disorder, oligo-anuria, urinary incontinence, red urination, and uveitis. At the time of diagnosis, 4 patients had hypertension and 26 patients had AKI. Two of these cases were anuric. The low eGFR values at the time of diagnosis were observed to improve at the end of the follow-up. Hematuria was detected in 18 cases and of them were macroscopic hematuria. 4 patients had pyuria, 19 patients had proteinuria, and 2 of them were nephrotic. FeNa was the most common abnormality of the tubular tests with 4.5%. Biopsy was performed in 5 cases. While one of the patients presented with uveitis, uveitis developed in 1 patient during the 3rd month of follow-up.&#x0D; Conclusion: Consequently, although TIN is a reversible disease, its recognition is important in terms of treatment and follow-up.

Community Preferences for the Care of Older People at the End of Life: How Important is the Disease Context?

Population preferences for care at the end of life can inform palliative care policy and direction. Research investigating preferences for care at the end of life has focused predominantly on the context of advanced cancer, with relatively little attention to other life-limiting illnesses that are common causes of death. We aimed to investigate preferences for the care of older people at the end of life in three different disease contexts. The purpose was to understand if population preferences for care in the last 3 weeks of life would differ for patients dying from cancer, heart failure or dementia. Three discrete choice experiments were conducted in Australia with a general population sample using similar methods but different end-of-life disease contexts. Some attributes were common across the three experiments and others differed to accommodate the specific disease context. Each survey was completed by a different panel sample aged ≥45years (cancer, n=1548; dementia, n=1549; heart failure, n=1003). Analysis was by separate mixed logit models. The most important attributes across all three surveys were costs to the patient and family, patient symptoms and informal carer stress. The probability of choosing an alternative was lowest (0.18-0.29) when any one of these attributes was at the least favourable level, holding other attributes constant across alternatives. The cancer survey explored symptoms more specifically and found patient anxiety with a higher relative importance score than the symptom attribute of pain. Dementia was the only context where most respondents preferred to not have a medical intervention to prolong life; the probability of choosing an alternative with a feeding tube was 0.40 (95% confidence interval 0.36-0.43). This study suggests a need for affordable services that focus on improving patient and carer well-being irrespective of the location of care, and this message is consistent across different disease contexts, including cancer, heart failure and dementia. It also suggests some different considerations in the context of people dying from dementia where medical intervention to prolong life was less desirable.

Incidental but Not Insignificant: Thyroid Cancer in Patients with Graves Disease.

Graves disease is the most common cause of hyperthyroidism in the US. Treatment with antithyroid drugs and radioactive iodine is more commonly used than surgical management with total thyroidectomy (TTx). However, incidentally discovered thyroid cancer (TC) has been described on surgical pathology from patients who underwent surgical treatment of Graves disease, which would be missed with these other treatment strategies. We sought to determine the incidence rate of TC among patients with surgically treated Graves disease. We retrospectively reviewed patients with Graves disease who underwent TTx at a single institution from 2011 to 2023. Pathology reports were reviewed for TC. Patient demographics, preoperative laboratory and radiological evaluations, preoperative medical management, and surgical outcomes were compared between patients with and without incidental TC. There were 934 patients, of whom 60 (6.4%) patients had incidentally discovered TC on pathology. The majority (58.3%) of patients had papillary thyroid carcinoma, followed by 33.3% with papillary microcarcinoma. Preoperative ultrasound (US) was obtained in 564 (60.4%) of patients, with 44.3% with nodules, but only 34 (13.7%) of those with nodules had TC on final pathology. Preoperative fine needle aspiration was obtained in 15 patients with TC, and 8 patients (53.3%) were reported as benign lesions, which ultimately had TC on final pathology. There was no difference in sex, race or ethnicity, preoperative medical management, and postoperative outcomes between the 2 groups. Incidental TC was found on surgical pathology in 6.4% of patients undergoing TTx for Graves disease. Preoperative imaging with US and fine needle aspiration were often unreliable at predicting TC. The incidence of TC should not be underestimated when counseling patients on definitive management for Graves disease.