Peak Incidence Research Articles

Effects of Shoulder Exercises with and Without Cervical Exercises on Pain and Function in the Patients with Cervical Spondylosis: Randomized Controlled Trial

Background: Cervical spondylosis is a chronic, degenerative, progressive disease of osteocartilagenous component of cervical spine that is usually age related and more common in men than in women, with a peak incidence between the ages of 40 and 60 years for both men and women.Objective: The aim of the study is to determine effects of shoulder exercises with and without cervical exercises on pain and function in patients with cervical spondylosis.Methods: Sixty eight diagnosed cervical spondylosis patients with 30-60 years of age were selected and randomly allocated in experimental and control groups, 34 in each group. The study was conducted in the physical therapy department of WAPDA hospital, Lahore. All participants were following the 6 weeks supervised exercise program, 4 sessions per week. Experimental group received shoulder exercises with cervical exercises while the control group received cervical exercises. Clinical outcomes were measured with visual analog scale for pain and neck disability index for function.Results: Analysis of final 61 patients were included, 31 in experimental and 30 in control (3 and 4 patients did not follow the study completely). Mean aged for experimental and control group was 49.39 ±7.022 and 49.23 ±6.704 respectively. Results showed that there was statically and clinically significance difference that as observed in from of reduction of pain P=0.001 and improvement of function P= 0.01Conclusion: Overall improvement was observed in both groups, results of study shows that shoulder exercises with cervical isometric exercises were more beneficial for outcomes of pain and function in experimental group. So we can conclude that shoulder exercise should be an integral part of treatment for cervical spondylosis patients.

EPIDEMIOLOGICAL ANALYSIS OF MORBIDITY AND MORTALITY FROM CANCER
 OF THE UTERINE BODY OF THE POPULATION OF ALMATY IN 2012-2022

Relevance: Cancer of the uterine body (CUB) is one of the most common types of malignant neoplasms and ranks 6th among the most
 frequently diagnosed cancers in women in the world. Despite the improvement of treatment methods, the incidence and mortality from CUB
 remain high. According to forecasts by the International Agency for Research on Cancer, by 2040, the incidence of CUB is expected to increase
 by more than 50%. Therefore, studying the epidemiological features of CUB is important for developing prevention and treatment strategies.
 The study aimed to analyze the morbidity and mortality from CUB in the female population of Almaty in 2012-2022.
 Methods: The material for the study was data from the information system «Electronic Register of Inpatient Patients» on newly
 identified cases and those registered at the dispensary with a histologically confirmed diagnosis of CUB «Malignant neoplasm of the
 uterine body» (From 54 to ICD-10) of the population of Almaty for the period from 2012 to 2022. Epidemiological indicators were calculated
 per 100,000 female population. The absolute growth, growth rate, and visibility indicators were calculated to analyze changes in intensive
 indicators over time. The database was formed, and the results were statistically processed using Microsoft Excel and the SPSS Statistics
 26 statistical package.Results: There was an increase in the crude incidence of CUB in the female population of Almaty in 2012-2022 by 3.14 times. The incidence
 of CUB increased with age, where the peak incidence was noted in the age group of 60-64 years (58.9±8.68 cases per 100,000 female population
 95% CI = 39.5-78.2). Mortality from CUB decreased from 13.5 cases in 2012 to 1.3 cases per 100,000 female population in 2022 (10.4 times).
 Conclusion: The conducted epidemiological analysis showed the need for further detailed study of the risk factors contributing to the
 occurrence of CUB and improvement of the activities of health services, starting from the primary health care level.

EPIDEMIOLOGICAL SITUATION OF SKIN CANCER AND MELANOMIA
 IN THE REPUBLIC OF KAZAKHSTAN IN 2012-2022

Relevance: Skin cancer, including melanoma, is a major health problem and one of the most common cancers in the world.
 The study aimed to obtain a complete epidemiological picture of skin cancer and melanoma in the Republic of Kazakhstan for 11 years,
 including analysis of data for 2022, considering various parameters such as age, sex, ethnicity, region, and tumor type.
 Methods: The study used data from patients registered in the national cancer registry of the Republic of Kazakhstan from 2012 to 2022,
 diagnosed with skin carcinoma and skin melanoma (ICD-10 code: C44-C43). The number of skin carcinomas and melanoma cases is presented as absolute and crude rates per 100,000 population. Absolute standardized morbidity and mortality rates were calculated using the world
 standard (World).
 Results: At the end of 2022, 19,714 and 2,689 patients were diagnosed with “Skin Cancer” or “Skin Melanoma” in the Republic of Kazakhstan, respectively. From 2012 to 2022, the incidence of skin cancer increased by 24% and melanoma by 15%. In 2022, the incidence of skin
 cancer and melanoma was higher among women by 24% and 26%, respectively. Mortality from skin cancer is in 23rd place, from melanoma in
 21st place. Mortality rates from skin cancer and melanoma were 0.5 and 0.7 per 100 thousand population, respectively. The peak incidence of skin cancer in 2022 was observed in the age group 65-74 years (36%), and mortality in the age groups 65-74 and 75-84 years (17% each). The
 peak incidence of skin melanoma in 2022 was observed in the age groups 55-64 years and 65-74 years (24% and 25%), and mortality in the
 groups 45-54 years and 35-44 years (14% and 10%).
 Conclusion: There has been a steady increase in the incidence of skin cancer and melanoma, which indicates the seriousness of this problem in the country and underlines the need for further measures to prevent, diagnose and treat skin cancer and melanoma in the Republic of
 Kazakhstan. It should be remembered that many cases of skin cancer can be prevented with simple precautions.

SEASONAL INCIDENCE OF Rhopalosiphum maidis (Fitch) ON MAIZE CROP IN GUNTUR AND KRISHNA DISTRICTS OF ANDHRA PRADESH

The seasonal occurrence of Rhopalosiphum maidis (Fitch) on maize was carried out in the Guntur and Krishna districts of Andhra Pradesh during rabi, 2021-2022 and rabi, 2022-2023. A total of 30 farmer fields were selected from six mandals of maize growing areas viz., Bapatla, Tsunduru, Ponnur, Karlapalem in Guntur district and two mandals viz., Mopidevi and Avanigadda in Krishna district.The population of aphids was recorded at weekly intervals on randomly selected 25 plants of each farmer field from germination to harvesting stage of the crop. The aphids were counted as number of aphids on 1 cm2 leaf area from three leaves (top, middle, lower) of eachplant. The data was statistically analyzed using SPSS for Windows (version 20.0) and Microsoft Excel 2016. In rabi 2021-22 the initial incidence of aphids was commenced from SMW5 (0.21 aphids sq. cm-1) and the highest mean population was recorded in SMW 9 (3.64 aphids sq. cm-1). In rabi 2022-23 the initial incidence was first noticed during SMW4 (1.71 aphids sq. cm-1) and the peak incidence was noticed during SMW 6(4.96 aphids sq. cm-1).The population of aphids showed a positive significant correlation with maximum temperature in both the seasons i.e., rabi, 2021- 22 (r=0.685**) and rabi, 2022-23 (r=0.612*).

SARS-CoV-2, influenza A/B and respiratory syncytial virus positivity and association with influenza-like illness and self-reported symptoms, over the 2022/23 winter season in the UK: a longitudinal surveillance cohort

BackgroundSyndromic surveillance often relies on patients presenting to healthcare. Community cohorts, although more challenging to recruit, could provide additional population-wide insights, particularly with SARS-CoV-2 co-circulating with other respiratory viruses.MethodsWe estimated the positivity and incidence of SARS-CoV-2, influenza A/B, and RSV, and trends in self-reported symptoms including influenza-like illness (ILI), over the 2022/23 winter season in a broadly representative UK community cohort (COVID-19 Infection Survey), using negative-binomial generalised additive models. We estimated associations between test positivity and each of the symptoms and influenza vaccination, using adjusted logistic and multinomial models.ResultsSwabs taken at 32,937/1,352,979 (2.4%) assessments tested positive for SARS-CoV-2, 181/14,939 (1.2%) for RSV and 130/14,939 (0.9%) for influenza A/B, varying by age over time. Positivity and incidence peaks were earliest for RSV, then influenza A/B, then SARS-CoV-2, and were highest for RSV in the youngest and for SARS-CoV-2 in the oldest age groups. Many test positives did not report key symptoms: middle-aged participants were generally more symptomatic than older or younger participants, but still, only ~ 25% reported ILI-WHO and ~ 60% ILI-ECDC. Most symptomatic participants did not test positive for any of the three viruses. Influenza A/B-positivity was lower in participants reporting influenza vaccination in the current and previous seasons (odds ratio = 0.55 (95% CI 0.32, 0.95)) versus neither season.ConclusionsSymptom profiles varied little by aetiology, making distinguishing SARS-CoV-2, influenza and RSV using symptoms challenging. Most symptoms were not explained by these viruses, indicating the importance of other pathogens in syndromic surveillance. Influenza vaccination was associated with lower rates of community influenza test positivity.

Abstract 3905: Targeting RNA demethylase ALKBH5 blocks growth and improves therapy response in osteosarcoma

Abstract Background: Osteosarcoma (OS) arises primarily in children and adolescents, with a second peak in incidence in those over the age of 50. Unfortunately, outcomes of patients with metastatic or relapsed osteosarcoma have remained abysmal. Moreover, patients who survive have a highly compromised quality of life due to debilitating side effects associated with chemotherapy drugs. Virtually no new drug has been approved for treating OS in the last three decades. Recently our group showed that ALKBH5 is critical for promoting OS growth and metastasis and may thus serve as a unique driver of OS. We therefore hypothesized that epigenetic changes, specifically mRNA demethylation mediated by the RNA demethylase ALKBH5, play a pivotal role in OS growth and metastasis, and hence approaches aimed at inhibiting ALKBH5 activity could prove clinical utility for patients with OS. Methods: shRNA and CRISPR-Cas9-based knockout were used to study the effect of depleting ALKBH5 in osteosarcoma and the effect it has on growth and metastasis. Fluorescence-based high-throughput screening (HTS) assay was used to identify targets of ALKBH5. FDA-approved and LOPAC compound libraries were used. SPR analysis was used to determine the Mefloquine-ALKBH5 interaction. In vitro and In vivo intratibial orthotopic models were used to test the efficacy of Mefloquine for blocking OS growth. Experiments are currently underway to test the effect of combining Mefloquine and doxorubicin in inhibiting OS growth and metastasis. Results: We showed that upregulation of the ALKBH5 attenuates histone H2A monoubiquitination to result in the induction of key pro-tumorigenic genes and consequently unchecked cell cycle progression, incessant DNA replication, and upregulation of DSB repair. Unbiased high throughput screening using a LOPAC library identified mefloquine as a potential ALKBH5 inhibitor. SPR analysis showed the interaction of Mefloquine with ALKBH5 catalytic domain. M6A dot blot confirmed that mefloquine inhibits the catalytic activity of ALKBH5. Cell-based assays showed reduced short-term and long-term growth with the treatment of mefloquine. In vivo models showed a reduction in tumor volume upon mefloquine oral treatment. Conclusion: Our results establish RNA demethylase ALKBH5 as a novel driver of OS. This project has a direct translational relevance as an FDA-approved drug can be repurposed for treating OS patients as a monotherapy or in combination with doxorubicin and be formally tested in the clinic without much delay. Citation Format: Daisy Medina, Santosh Timilsina, Panneerdoss Subbarayalu, Prabhakar Pitta Venkata, Deepika Singh, Trong Phat Do, Shuo Zhou, Yogesh K. Gupta, Daohong Zhou, Manjeet K. Rao. Targeting RNA demethylase ALKBH5 blocks growth and improves therapy response in osteosarcoma [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 3905.

Abstract 3832: Fluid-overload associated large B-cell lymphoma and determinants of outcomes: Analysis of a pooled database

Abstract Background: Fluid overload-associated large B-cell lymphoma (FOLBCL) is a new WHO lymphoma entity previously known as PEL-like lymphoma or HHV8-unrelated PEL-like lymphoma. It is a rare lymphoma that arises within fluid-filled body cavities without a solid component. FOLBCL occurs in the absence of immunodeficiency and is commonly associated with conditions associated with fluid overload. It expresses mature B-cell phenotype and occasional EBV infection markers. We conducted this study to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect outcomes in this rare and newly defined lymphoma subtype. Materials & Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 115 cases that fit the diagnostic criteria for FOLBCL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 115 patients with confirmed FOLBCL were identified. The median age was 74, with a peak incidence between 72 and 82 years. There was a male preponderance with M:F of 2. The pleural, pericardial, and peritoneal cavities were involved in 75%, 34, and 27%. The median duration of symptoms before diagnosis was 1 month. Patients presented with constitutional symptoms and hepatosplenomegaly in 13% and 1%, respectively—no patients presented with lymph node and bone marrow involvement. The median OS of the whole group was 16 months. Patients younger than 70 had better median OS than 70 and older (24 vs. 10 months, p=0.008). The presence of any malignant peritoneal effusion was associated with worse OS when compared to effusion limited to the thoracic cavity (7 vs. 24 months, p=0.005). LDH>500 was also associated with worse OS (p=0.02). Sex, the presence of fluid overload-causing conditions, and serum IL2R levels did not seem to impact OS. MYC re-arrangement had numerically worse OS when present but did not reach statistical significance. Chemotherapy demonstrated superior OS compared to no treatment (24 vs. 7 months, p=0.009). Patients who attained CR as their best response had a superior median OS (p<0.0001). Conclusion: This study presents updated clinicopathologic data from a pooled cohort of patients with FOLBCL. It identifies the age, the primary location of cavitary disease, LDH, active therapy, and quality of response to treatment as key determinants of OS. Citation Format: Philip A. Haddad, Supriya Gupta, Christopher Graham. Fluid-overload associated large B-cell lymphoma and determinants of outcomes: Analysis of a pooled database [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 3832.

Abstract 6148: Multiple new Ewing sarcoma susceptibility loci expand knowledge of germline genetic etiology and nominate mechanisms of risk

Abstract Ewing sarcoma (EwS) is a rare and aggressive pediatric cancer with peak incidence in the second decade of life. EwS occurs primarily in children of European ancestry suggesting a genetic component to susceptibility. Prior investigations identified six susceptibility loci associated with EwS, with evidence for additional signals not reaching the commonly accepted threshold for genome-wide significance (i.e., p<5×10−8). At least two of these loci demonstrate evidence of tagging variation in length of nearby GGAA microsatellites, which alter binding of the pathognomonic EWSR1::FLI1 fusion resulting in downstream dysregulation of target genes promoting sarcomagenesis. To identify additional susceptibility loci, we performed the largest genome-wide association study (GWAS) to date consisting of 1,640 EwS cases and 8,457 cancer-free individuals of European ancestry from 8 studies and matched by principal components. Genotype imputation was carried out by study/array using TOPMed data as the reference and each set was analyzed using PLINK 1.9 adjusting for significant principal components. Variants were included in each study if minor allele count was greater than five in each set of cases. Individual study results were combined using fixed effects meta-analysis in Metasoft with variants demonstrating evidence for heterogeneity excluded.For previously reported EwS loci (i.e., 1p36.22, 6p25.1, 10q21.3, 15q15.1, 20p11.22 and 20p11.23), odds ratios (OR) remained high for GWAS (OR=1.5-2.4) and the -log10 p-values grew by several orders of magnitude, providing strong evidence for replication in the additional 907 EwS cases and 7,111 cancer-free controls. Our analysis identified five novel loci reaching genome-wide significance (P-valuemeta< 5×10−8) at 5q32, 7q32.3, 8q24.2, 13q32.3, and 17q23.2. Risk allele frequency of newly identified loci ranged from 0.001 to 0.75with estimated ORs ranging from 1.31-4.30. eQTL analyses nominated nearby biologically plausible candidate genes for future functional investigation including LARS1, a gene implicated in osteosarcoma and skeletal muscle dysgenesis, at the 5q32 locus and COX5BP6, a gene implicated in age at menarche and testosterone levels, at 13q32.3.Our results add to evidence supporting a strong inherited genetic component to EwS risk and particularly a genetic architecture harboring a substantial number of common variants with moderate effect. Ongoing work is focusing on enrichment analyses of GGAA microsatellite repeat sequences in identified risk loci to search for evidence for germline-somatic interactions with EWSR1::FLI1. Citation Format: Aubrey K. Hubbard, Weiyin Zhou, Carrie Boyce, Javed Khan, Melissa M. Hudson, Kirsten K. Ness, Zhaoming Wang, Katherine A. Janeway, Philip J. Lupo, Lindsay M. Morton, Stephen J. Chanock, Thomas G. Grünewald, Olivier Delattre, Mitchell J. Machiela, Ewing Sarcoma Germline Genetics Group. Multiple new Ewing sarcoma susceptibility loci expand knowledge of germline genetic etiology and nominate mechanisms of risk [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 6148.

Abstract 4808: Small intestinal leiomyosarcoma in a young adult

Abstract Objectives: • Outline the epidemiology of leiomyosarcoma•Identify the immunohistochemistry of a leiomyosarcoma Introduction: Primary small intestinal malignancies are rare malignancies as compared with other malignancies of the gastrointestinal tract. Here, we present a case of a jejunal leiomyosarcoma in a young adult. Case Presentation: A 23-year-old Caucasian male with GERD presented with five months of abdominal pain, intermittent nausea with non-bloody emesis, and a 20-pound weight loss. Presenting vital signs were within normal limits. Physical exam revealed conjunctival pallor with epigastric tenderness to palpation. Serology demonstrated iron deficiency anemia, hemoccult positive stool, negative CEA, CA19-9, and AFP tumor markers. HIV antigen antibody and EBV-PCR were non-reactive. CT of the abdomen and pelvis revealed markedly thickened heterogenous jejunal loop in the left hemiabdomen with associated mesenteric adenopathy and small volume pelvic ascites. EGD with push enteroscopy revealed a single, malignant appearing and ulcerated mass in the proximal jejunum. PET-CT showed a hypermetabolic, multilobulated, ill-defined mass involving multiple loops of jejunum. He underwent exploratory laparotomy with resection of a proximal jejunal mass (10x8 x7 cm), mesenteric lymphadenectomy, and a jejunojejunostomy creation. Pathology demonstrated leiomyosarcoma (pT2aN0MoG3), and he was initiated on cyclophosphamide and doxorubicin. Discussion: Primary small intestinal malignancies are rare malignancies with an incidence of less than 5% of all GI malignancies. 56 cases of GI leiomyosarcoma in adults were identified between 2000-2012 with a peak incidence between 55-59 years of age (Aggarrwal 2012). Leiomyosarcomas are soft tissue sarcomas arising from bones, tendons, blood vessels, or muscles with a spectrum of disease ranging from low-grade cutaneous lesions to aggressive lesions of internal organs with significant potential for metastasis (Pipe 2002). Diagnosis is based on immunohistochemical positivity for SMA, desmin, and h-caldesmon, and negativity for CD117, CD34, and DOG1.1, notably lacking KIT and PDGFRA mutations (Aggarwal 2012). Treatment involves surgical resection and a cost benefit analysis of adjuvant chemotherapy with (Reynolds, 2014). This case of a 23 year old, without significant risk factors, diagnosed with a jejunal leiomyosarcoma presents as one of the youngest cases ever to be reported and emphasizes the importance of recognizing the cancer in a broader range of the adult population. Citation Format: Alyssa A. Guo, Blake H. Bentley, Abigail L. Ellington, Haiyan Lu, William C. Lippert. Small intestinal leiomyosarcoma in a young adult [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 4808.

Incidence rates of retinal vascular occlusive diseases from 2011 to 2020 in South Korea: a nationwide cohort study

BackgroundRetinal vascular occlusions, including retinal vein occlusion and retinal artery occlusion, are common causes of visual impairment. In order to evaluate the national medical burden and help improve ophthalmic health care policy planning, we investigated the incidence of retinal vascular occlusive diseases from 2011 to 2020 in Korea.MethodsThis study is a nationwide population-based retrospective study using data from the Korea national health claim database of the Health Insurance Review and Assessment (HIRA) service. We identified retinal vascular occlusive diseases registered from January 1, 2009, to December 31, 2020, according to the retinal vascular occlusion code (H34) and its sub-codes from international classification of disease, tenth revision diagnosis code. We used data from the entire Korean population based on the 2015 census of the population in Korea to calculate standardized incidence rates.ResultsWe identified 348,775 individuals (male, 161,673 [46.4%]; female, 187,102 [53.6%]) with incident retinal vascular occlusion (H34), 10,451 individuals (males, 6,329 [60.6%]; females, 4,122 [39.4%]) with incident central retinal artery occlusion (H34.1), and 252,810 individuals (males, 114,717 [45.4%]; females, 138,093 [54.6%]) with incident retinal vein occlusion (H34.8) during the 10-year study period. The weighted mean incidence rate of retinal vascular occlusion was 70.41 (95% CI, 70.18–70.65) cases/100,000 person-years. The weighted mean incidence rate of central retinal artery occlusion was 2.10 (95% CI, 2.06–2.14) cases/100,000 person-years. The weighted mean incidence rate of retinal vein occlusion was 50.99 (95% CI, 50.79–51.19) cases/100,000 person-years.ConclusionThe total retinal vascular occlusion and retinal vein occlusion showed a decreasing trend until 2020. However, the central retinal artery occlusion decreased until 2014 and remained stable without a significant further decline until 2020. The incidence of total retinal vascular occlusion and retinal vein occlusion was higher in females than in males, while the incidence of central retinal artery occlusion was higher in males. All retinal vascular occlusive diseases showed an increasing incidence with older age; the peak age incidence was 75–79 years for total retinal vascular occlusion and retinal vein occlusion, and 80–85 years for central retinal artery occlusion.

Characteristics of infections with ancestral, Beta and Delta variants of SARS-CoV-2 in the PHIRST-C community cohort study, South Africa, 2020-2021

BackgroundData on the characteristics of individuals with mild and asymptomatic infections with different SARS-CoV-2 variants are limited. We therefore compared the characteristics of individuals infected with ancestral, Beta and Delta SARS-CoV-2 variants in South Africa.MethodsWe conducted a prospective cohort study in a rural and an urban site during July 2020-August 2021. Mid-turbinate nasal swabs were collected twice-weekly from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time reverse transcription polymerase chain reaction (rRT-PCR). Differences in demographic and clinical characteristics, shedding and cycle threshold (Ct) value of infection episodes by variant were evaluated using multinomial regression. Overall and age-specific incidence rates of infection were compared by variant.ResultsWe included 1200 individuals from 222 households and 648 rRT-PCR-confirmed infection episodes (66, 10% ancestral, 260, 40% Beta, 322, 50% Delta). Symptomatic proportion was similar for ancestral (7, 11%), Beta (44, 17%), and Delta (46, 14%) infections (p=0.4). After accounting for previous infection, peak incidence shifted to younger age groups in successive waves (40-59 years ancestral, 19-39 years Beta, 13-18 years Delta). On multivariable analysis, compared to ancestral, Beta infection was more common in individuals aged 5-12 years (vs 19-39)(adjusted odds ratio (aOR) 2.6, 95% confidence interval (CI)1.1-6.6) and PCR cycle threshold (Ct) value <30 (vs >35)(aOR 3.2, 95%CI 1.3-7.9), while Delta was more common in individuals aged <5 (aOR 6.7, 95%CI1.4-31.2) and 5-12 years (aOR 6.6 95%CI2.6-16.7)(vs 19-39) and Ct value <30 (aOR 4.5, 95%CI 1.3-15.5) and 30-35 (aOR 6.0, 95%CI 2.3-15.7)(vs >35).ConclusionsConsecutive SARS-CoV-2 waves with Beta and Delta variants were associated with a shift to younger individuals. Beta and Delta infections were associated with higher peak viral loads, potentially increasing infectiousness.

Abstract P100: Global Burden of Atrial Fibrillation and Atrial Flutter and Its Trend From 1990-2019 in G20 Countries: Results From the GBD 2019

Background: Atrial Fibrillation and Atrial Flutter (Afib) ranks 6th in mortality and 7th in disability amongst all cardiovascular disease the G20 nations. Method: We employed 2019 Global Burden of Disease methodology. Afib and Flutter, non-fatal health outcomes, such as incidence and prevalence, were estimated using the Bayesian meta-regression tool (DisMod MR 2.1). Fatal health outcomes were assessed using the Cause of Death Ensemble Model (CODEm), considering factors like age, gender, year, and location throughout the G20 from 1990 to 2019. Results: From 1990 to 2019, prevalence rose from 23.2 million (95%UI: 17.6-29.7) to 48.9 million (37.5-61.6). The annual percentage change (APC) in incidence surged by 102% (1.8-3.8 million), DALYs by 119% (3-6 million), and deaths by 168% (93,864-251,272). Despite these increases, the age-standardized rate per 100,000 person-years declined over the past three decades. In 2019, the U.S. reported the highest age-standardized incidence rate at 109.52 (88.97-131.92) per 100,000, while Sweden had the top mortality rate of 8.63 (4-10.32) per 100,000. The age group 65-69 had the peak incidence count of 700,768 (362,032-1,158,177). Meanwhile, the highest death count was in the 85-89 age bracket with 59,325 (48,618-70,077), and the most DALYs were in the 80-84 age group with 1,083,488 (882,995-1,323,533) in 2019. Males consistently faced a higher burden than females over this period. Conclusion: AFib and AF accounted for 1.88% deaths amongst all cardiovascular casualties in 2019. Clinicians in the G20 countries must prioritize early detection and intervention for Afib and flutter, especially in males and the elderly, given its escalating prevalence and its ranking as a major cause of death and disability. Public health strategies in the G20 nations should focus on targeted awareness and interventions to combat the rising burden of atrial fibrillation, with countries like the United States and Sweden requiring heightened attention due to their notably high incidence and mortality rates.

Therapeutic Potential of Natural Flavonoids: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective on Parkinson's Disease

Abstract: Parkinson’s disease (PD) is a prominent area of study within the field of neurology, particularly neurodegenerative disease (ND). The peak incidence of PD occurs in those over the age of 45, and the disease’s prevalence rises continuously with age, the incidence of PD has skyrocketed over the world. A slow decline in neural function characterizes NDs, but the pathophysiological mechanisms behind this decline remain elusive. Because the pathophysiological mechanisms behind neurodegeneration are intricate, the clinical issue of finding efficient, multi-target treatments still exists. Furthermore, adequate neuroprotective medicines are currently scarce, necessitating the development of new therapeutic agents. There is currently no medicine for PD that is without side effects. The ability of natural flavonoids to lower the risk of PD has contributed to an increase in their popularity in recent years, models both in vivo and in vitro. Flavonoids are multi-target natural substances that affect distinct pathogenic pathways in neurodegeneration. As a result, the emphasis has turned to discovering natural product inhibitors for the treatment of PD. The majority of the results pointed to flavonoids' beneficial role in the treatment of PD and no adverse events were reported. This review offered scientific data on the protective and preventative functions of flavonoids. It has been demonstrated that flavonoids have a neuroprotective effect by activating anti-apoptotic mechanisms that target mitochondrial dysfunction and produce neurotrophic factors. In addition to having antioxidant, anti-inflammatory, and protective dopaminergic neurons. Even though no evidence using flavonoids as a treatment might reverse the abnormal phenotypes of PD patients, it was also indicated that flavonoids might be promising natural remedies for PD prevention and could be used as therapeutic agents against PD.

Epidemiological characteristics of diarrheagenic Escherichia coli infection in infectious diarrhea outpatients aged 15 years and older in Shanghai, 2014-2021

Objective: To understand the epidemiological characteristics of diarrheagenic Escherichia (E. ) coli infection in infectious diarrhea outpatients aged 15 years and older in Shanghai and provide evidence for the development of disease control strategies. Methods: Based on multistage systematic sampling, diarrhea surveillance was conducted in 22 sentinel hospitals in Shanghai, the information about cases' demographic, clinical, and epidemiological characteristics were collected. Stool samples were collected for the detection and typing of diarrheagenic E. coli by local centers for disease control and prevention. The positive rate of diarrheagenic E. coli in different populations and seasons from 2014 to 2021 were analyzed. Statistical analysis was conducted by using χ2 test. Results: In 15 185 diarrhea cases, 8.05% (1 222/15 185) were positive for diarrheagenic E. coli. The positive rate was higher in men (8.74%, 684/7 824) than in women (7.31%, 538/7 361). The positive rate was highest in age group 15-29 years (9.14%, 335/3 665) and the annual positive rate was highest in 2021 (10.21%, 83/813), the differences were all significant (P<0.05). In the 1 264 strains of diarrheagenic E. coli analyzed through PCR, enterotoxingenic E. coli was the most frequently identified pathogen (50.24%, 635/1 264), followed by enteroadhesive E. coli (27.93%, 353/1 264), and enteropathogenic E. coli (21.36%, 270/1 264). The positive rate of diarrheagenic E. coli showed obvious seasonality with peak in summer (13.92%, 774/5 562) (χ2=495.73, P<0.001). Conclusions: Diarrheagenic E. coli has become a prominent pathogen in infectious diarrhea cases in Shanghai, the disease can occur all the year round with incidence peak during summer and autumn. Predominant subtypes included enterotoxingenic E. coli, enteroadhesive E. coli and enteropathogenic E. coli. Targeted prevention and control strategies are needed for diarrheagenic E. coli-induced infectious diarrhea in different age groups, seasons and for different types of infections.

Long-term Ocular Outcomes in Congenital Toxoplasmosis Treated Perinatally.

Congenital toxoplasmosis (CT) can be accompanied by serious organ manifestations, particularly retinochoroiditis, and may occur throughout life. We aimed to monitor long-term ocular prognosis in a large French cohort of patients with CT and its changes over time in the context of mandatory prenatal screening (since 1992) and incidence decrease since 2008. Patients with CT diagnosed between 1987 and 2021 were prospectively included and followed for up to 35 years. The effect of the period of conception on the risk of first retinochoroiditis has been tested using a flexible extension of the Cox model. Incidence rates of retinochoroiditis were estimated. A total of 646 infected live born children were followed for a median of 12 years (range, 0.5-35); 187 patients (29%) had at least 1 ocular lesion (first at a median age of 5 years; range, 0-26 years) with peaks at 7 and 12 years. Early maternal infection and the presence of nonocular signs at birth were associated with a higher risk of retinochoroiditis, whereas delayed diagnosis of CT (after birth versus before or at birth) was associated with a lower risk (13% decrease for each additional month after birth; P = .01). A period effect for the risk of developing retinochoroiditis in patients born after 2008 was not detected. Despite prenatal screening and prolonged perinatal treatment, retinochoroiditis is not a rare event in French patients with CT and can occur well into adulthood, with peak incidences at 7 and 12 years of age. It rarely causes severe damage but warrants regular follow-up into adulthood.

Recent trends in the epidemiology and clinical outcomes of inflammatory bowel disease in South Korea, 2010-2018.

Inflammatory bowel disease (IBD) was previously regarded as a Western disease; however, its incidence is increasing in the East. The epidemiology of IBD in Asia differs significantly from the patterns in the West. To comprehensively investigate the epidemiology of IBD in South Korea, including its incidence, prevalence, medication trends, and outcomes. We analyzed claims data from the Health Insurance Review and Assessment Service and Rare and Intractable Diseases (RIDs), operated by the National Health Insurance Service of South Korea. Patients with IBD were identified based on the International Classification of Diseases, Tenth Revision, and RID diagnostic codes for Crohn's disease (CD) and ulcerative colitis (UC) from 2010 to 2018. In total, 14498 and 31409 patients were newly diagnosed with CD and UC, respectively, between 2010 and 2018. The annual average incidence of CD was 3.11 cases per 105 person-years, and that of UC was 6.74 cases per 105 person-years. Since 2014, the incidence rate of CD has been stable, while that of UC has steadily increased, shifting the peak age group from 50-year-olds in 2010 to 20-year-olds in 2018. The CD and UC prevalence increased consistently over the study period; the use of 5-aminosalicylates and corticosteroids gradually decreased, while that of immunomodulators and biologics steadily increased in both CD and UC. The clinical outcomes of IBD, such as hospitalization and surgery, decreased during the study period. The CD incidence has been stable since 2014, but that of UC has increased with a shift to a younger age at peak incidence between 2010 and 2018. IBD clinical outcomes improved over time, with increased use of immunomodulators and biologics.

Enhancing seasonal influenza projections: A mechanistic metapopulation model for long-term scenario planning

In temperate regions, annual preparation by public health officials for seasonal influenza requires early-season long-term projections. These projections are different from short-term (e.g., 1–4 weeks ahead) forecasts that are typically updated weekly. Whereas short-term forecasts estimate what “will” likely happen in the near term, the goal of scenario projections is to guide long-term decision-making using “what if” scenarios. We developed a mechanistic metapopulation model and used it to provide long-term influenza projections to the Flu Scenario Modeling Hub. The scenarios differed in their assumptions about influenza vaccine effectiveness and prior immunity. The parameters of the model were inferred from early season hospitalization data and then simulated forward in time until June 3, 2023. We submitted two rounds of projections (mid-November and early December), with the second round being a repeat of the first with three more weeks of data (and consequently different model parameters). In this study, we describe the model, its calibration, and projections targets. The scenario projection outcomes for two rounds are compared with each other at state and national level reported daily hospitalizations. We show that although Rounds 2 and 3 were identical in definition, the addition of three weeks of data produced an improvement to model fits. These changes resulted in earlier projections for peak incidence, lower projections for peak magnitude and relatively small changes to cumulative projections. In both rounds, all four scenarios presented conceivable outcomes, with some scenarios agreeing well with observations. We discuss how to interpret this agreement, emphasizing that this does not imply that one scenario or another provides the ground truth. Our model's performance suggests that its underlying assumptions provided plausible bounds for what could happen during an influenza season following two seasons of low circulation. We suggest that such projections would provide actionable estimates for public health officials.

Could Microbiota Edit Oxalate Nephrolithiasis’ Story?

Abstract: Nephrolithiasis is a complex multifactorial pathology which contributes to the onset of genetics factors, environmental factors, diet and lifestyle, in addition this pathology has recently been associated with an increased risk of developing cardiovascular diseases increasing the burden of health care costs1. Nephrolithiasis is characterized by a complex of manifestations resulting from the formation and transit along the urinary tract of crystalline agglomerates stones, composed of poorly soluble substances. Kidney stones are elements of hard consistency, consisting of a solid component mixed with an organic matrix, i.e. proteins normally present in the urine. Most stones are calcium based, it is estimated that those of calcium oxalate (CaOx) and calcium phosphate (CaP) correspond to 80% of all calculations. In 9% of cases they are of uric acid, in 10% struvite (magnesium ammonium phosphate hexahydrate) and in 1% are other type (cystine, ammonium urate acid)2. Nephrolithiasis is a common cause of morbidity in the United States, responsible for hospitalization in 1 per 1000 of the population every year3-4, while in Asia the probability of forming kidney stones is very low (1-5%). The peak incidence was observed in subjects between 18 and 45 years, with a prevalence greater than 5-10 times in males. Was estimated that 5% of American women and 12% of men will develop an episode of calculating at some point in life5. 40% of patients with a first episode of nephrolithiasis have a second episode within 2-3 years and 75% relapse within 7-10 years. After 20 years, it is estimated that in less than 10% of patients do not develop stones again6

Association between patient ethnicity and prostate cancer diagnosis following a prostate-specific antigen test: a cohort study of 730,000 men in primary care in the UK

BackgroundBlack men have higher prostate-specific antigen (PSA) levels and higher prostate cancer incidence and mortality than White men, while Asian men tend to have lower prostate cancer incidence and mortality than White men. Much of the evidence comes from the USA, and information from UK populations is limited.MethodsThis retrospective cohort study used data on patients registered at general practices in England contributing to the Clinical Practice Research Datalink (CPRD) Aurum dataset. Those eligible were men aged 40 and over with a record of ethnicity and a PSA test result recorded between 2010 and 2017 with no prior cancer diagnosis.The aim was to assess the incidence of prostate cancer following a raised PSA test result in men from different ethnic groups. Additionally, incidence of advanced prostate cancer was investigated. Cancer incidence was estimated from multi-level logistic regression models adjusting for potential confounding factors.Results730,515 men with a PSA test were included (88.9% White). Black men and men with mixed ethnicity had higher PSA values, particularly for those aged above 60 years. In the year following a raised PSA result (using age-specific thresholds), Black men had the highest prostate cancer incidence at 24.7% (95% CI 23.3%, 26.2%); Asian men had the lowest at 13.4% (12.2%, 14.7%); incidence for White men was 19.8% (19.4%, 20.2%). The peak incidence of prostate cancer for all groups was in men aged 70–79. Incidence of prostate cancer diagnosed at an advanced stage was similar between Black and White men.ConclusionsMore prostate cancer was diagnosed in Black men with a raised PSA result, but rates of advanced prostate cancer were not higher in this group. In this large primary care-based cohort, the incidence of prostate cancer in men with elevated PSA levels increases with increasing age, even when using age-adjusted thresholds, with Black men significantly more likely to be diagnosed compared to White or Asian men. The incidence of advanced stage prostate cancer at diagnosis was similar for Black and White men with a raised PSA result, but lower for Asian men.

SARS-CoV-2 and influenza virus coinfections in the Tuscan population during the 2021/2022 influenza season.

The 2021/2022 influenza season was not characterised by a well-defined incidence peak. As reported by the Italian National Institute of Health, a high value of incidence of influenza cases was recorded in week 13, but it was still lower than in other influenza seasons. This abnormal circulation was probably due to relaxation of the COVID-19 pandemic restriction measures, such as social distancing, smart-working, home leaning and the use of masks, which greatly reduced the circulation of respiratory-transmitted viruses, including human respiratory syncytial virus (HRSV). The symptoms of SARS-CoV-2 and influenza are quite similar, sharing the human-to-human transmission route via respiratory droplets. The aim of this study was to estimate the rate of coinfection with influenza viruses and/or HRSV in SARS-CoV-2-positive subjects (N = 940) in a population of central Italy during the 2021/2022 season. A total of 54 cases of coinfection were detected during the study period, 51 cases (5.4%) of SARS-CoV-2 and influenza virus and three cases (0.3%) of SARS-CoV-2 and HRSV coinfection. These results highlight the importance of continuous monitoring of the circulation of influenza virus and other respiratory viruses in the context of the COVID-19 pandemic.