Epidemiological Data Research Articles

Epidemiologic trends and survival outcomes in patients with primary digestive system lymphoma in the United States.

Primary digestive system lymphoma (PDSL) is an important entity of extranodal lymphoma, yet updated epidemiologic and survival data are lacking. Patients diagnosed with PDSL between 1975 and 2020 were identified from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier analysis estimated survival outcomes. Multivariable Cox regression identified independent risk factors, and nomograms were developed to predict 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS). A total of 30,568 patients with PDSL were identified, with 57.9% being male and 80.4% white. The most frequent tumor site was the stomach (48.7%) and diffuse large B-cell lymphoma (DLBCL) was the predominant histologic subtype (45.0%). The overall incidence from 2016 to 2020 was 11.11 per 1,000,000 persons, with a decrease observed in lymphoma rates for the stomach, small intestine, large intestine, and pancreas. Long-term trends showed an initial rise in PDSL incidence, followed by a decline since the 1990s. The median OS across all patients was 103months, with appendiceal lymphoma showing the highest median OS of 253months. Factors including diagnosis year, age, sex, race, primary tumor site, histologic subtype, stage, and treatment modalities were significantly associated with OS and CSS. Nomograms achieved C-indices of 0.720 for OS and 0.723 for CSS in the training cohort. The incidence of PDSL initially increased but has recently declined. Survival for all PDSL patients has improved over time. Nomograms to predict survival for patients with DLBCL exhibited good predictive and discriminating abilities.

Design characteristics of integrated surveillance of antimicrobial resistance at the human, animal, and environment interfaces

Abstract Efforts have been made to strengthen national and global antimicrobial resistance (AMR) surveillance programs by integrating data collection across the human, animal, and environmental sectors. We searched the literature to review published studies reporting the implementation of integrated AMR surveillance approaches, and we identified a total of 96 articles from 36 countries published from 2000 to 2022, which met our inclusion criteria. Standard review protocols were applied in our study. Out of 96 studies, 47 (49%) articles integrated AMR analysis from human and animal (HA) populations, 24 (25%) considered human, animal, and environmental (HAE) samples together, 11 (12%) studies included animal and environment (AE) samples, and 12 (13%) integrated human and environmental (HE) surveillance. Human isolate-based and animal isolate-based surveillance were the most common study designs (38, 52.8%), with the remainder applying human case-based and isolate-based for animal populations (32, 44.4%). Finally, our results demonstrate that AMR studies on E. coli revealed a lower correlation between human and animal AMR prevalence compared to Salmonella spp. and Campylobacter spp. studies. Different aspects of surveillance design were associated with the level of correlation of AMR prevalence between sectors. Our study found that while global efforts for integrated AMR surveillance have increased in the past 10 years, significant variation exists between studies with regard to the epidemiological and laboratory aspects of their surveillance designs. Our findings indicate that to enable the generation of comparable epidemiological data across countries and sectors, there is a need for the development of a global protocol to support the design of surveillance programs that aim to conduct integrated surveillance of AMR.

Integrating contact tracing data to enhance outbreak phylodynamic inference: a deep learning approach.

Phylodynamics is central to understanding infectious disease dynamics through the integration of genomic and epidemiological data. Despite advancements, including the application of deep learning to overcome computational limitations, significant challenges persist due to data inadequacies and statistical unidentifiability of key parameters. These issues are particularly pronounced in poorly resolved phylogenies, commonly observed in outbreaks such as SARS-CoV-2. In this study, we conducted a thorough evaluation of PhyloDeep, a deep learning inference tool for phylodynamics, assessing its performance on poorly resolved phylogenies. Our findings reveal the limited predictive accuracy of PhyloDeep (and other state-of-the-art approaches) in these scenarios. However, models trained on poorly resolved, realistically simulated trees demonstrate improved predictive power, despite not being infallible, especially in scenarios with superspreading dynamics, whose parameters are challenging to capture accurately. Notably, we observe markedly improved performance through the integration of minimal contact tracing data, which refines poorly resolved trees. Applying this approach to a sample of SARS-CoV-2 sequences partially matched to contact tracing from Hong Kong yields informative estimates of superspreading potential, extending beyond the scope of contact tracing data alone. Our findings demonstrate the potential for enhancing phylodynamic analysis through complementary data integration, ultimately increasing the precision of epidemiological predictions crucial for public health decision making and outbreak control.

SMART DENGUE CONTROL

This research presents a novel approach to combating dengue by integrating Biological Control methods with Artificial Intelligence (AI). The objective of the study is to reduce the Aedes aegypti mosquito population and decrease dengue transmission through sustainable strategies. A comprehensive research methodology was used, involving extensive literature review, case studies, and data analysis to identify the main factors driving the high incidence of dengue in Brazil. The research applied AI tools to analyze epidemiological, meteorological, and environmental data, allowing for early outbreak predictions and targeted interventions. AI-enhanced surveillance systems were also employed to monitor mosquito populations and identify breeding sites more accurately. These strategies were combined with biological control methods, such as using natural predators and genetically modified mosquitoes, to manage mosquito populations effectively. The study demonstrate that the integration of AI and biological control can significantly improve the efficiency, accuracy, and sustainability of dengue control measures. The study concludes that this data-driven approach, when adapted to local contexts, can reduce reliance on chemical pesticides and offer a more resilient framework for long-term dengue management.

The Changing Face of Hepatitis Delta Virus Associated Hepatocellular Carcinoma

Hepatitis delta virus (HDV) infection requires the presence of hepatitis B virus (HBV), and chronic HBV–HDV coinfection is considered the most severe form of viral hepatitis. When compared with HBV mono-infection, HBV–HDV coinfection is associated with higher rates of liver cirrhosis and hepatocellular carcinoma (HCC). In this review, we aim to elucidate the complex relationship between HDV infection and the development of HCC. The exact mechanisms underlying the carcinogenic potential of HDV remain to be fully elucidated. Evidence suggests that HDV has both indirect and direct oncogenic effects. Indirect effects promote accelerated progression to liver cirrhosis, which results in a different tumor microenvironment. Direct oncogenic effects are suggested by a distinct molecular signature. The recent epidemiological data regarding HBV–HDV coinfection should make us reconsider the HCC screening strategy, with special focus in younger non-cirrhotic patients. Finally, treating HCC in patients with chronic HDV poses unique challenges due to the complex interplay between HBV and HDV and the severity of liver disease. An in-depth understanding of the epidemiology and pathophysiology of HDV infection and carcinogenesis is essential to improve disease management in this high-risk population.

Comprehensive newborn screening for severe combined immunodeficiency, X-linked agammaglobulinemia, and spinal muscular atrophy: the Chinese experience.

Newborn screening (NBS) for severe combined immunodeficiency (SCID), X-linked agammaglobulinemia (XLA), and spinal muscular atrophy (SMA) enables early diagnosis and intervention, significantly improving patient outcomes. Advances in real-time polymerase chain reaction (PCR) technology have been instrumental in facilitating their inclusion in NBS programs. We employed multiplex real-time PCR to simultaneously detect T-cell receptor excision circles (TRECs), kappa-deleting recombination excision circles (KRECs), and the absence of the survival motor neuron (SMN) 1 gene in dried blood spots from 103,240 newborns in Zhejiang Province, China, between July 2021 and December 2022. Of all the samples, 122 were requested further evaluation. After flow cytometry evaluation and/or genetic diagnostics, we identified one patient with SCID, two patients with XLA, nine patients with SMA [one of whom also had Wiskott-Aldrich Syndrome (WAS)], and eight patients with other medical conditions. The positive predictive values (PPVs) of NBS for SCID, XLA, and SMA were 2.44%, 2.78%, and 100%, respectively. The estimated prevalence rates in the Chinese population were 1 in 103,240 for SCID, 1 in 51,620 for XLA, and 1 in 11,471 for SMA. This study represents the first large-scale screening in mainland China using a TREC/KREC/SMN1 multiplex assay, providing valuable epidemiological data. Our findings suggest that this multiplex assay is an effective screening method for SCID, XLA, and SMA, potentially supporting the universal implementation of NBS programs across China.

Genomic diversity of Campylobacter jejuni and Campylobacter coli isolates recovered from human and poultry in Australia and New Zealand, 2017 to 2019.

We used genomic and epidemiological data to assess and compare the population structure and origins of Campylobacter, a major foodborne pathogen, in two neighbouring countries with strong trade and cultural links, similar poultry production systems and frequent movement of people and food products. The most common sequence types (STs) differed between Australia and New Zealand, with many unique to each country. Over half of all STs were represented by a single isolate. Multidrug-resistant (MDR) genotypes were detected in 0.8% of all samples, with no MDR isolates detected in poultry. Quinolone and tetracycline resistant ST6964 was prevalent in New Zealand (10.6% of C. jejuni). Closely related isolates suggested some similar food sources or contacts. We have shown that there is little genetic overlap in human and poultry STs of Campylobacter between the countries, which highlights that this common foodborne pathogen has domestic origins in Australia and New Zealand.

Monkeypox 2024 outbreak: Fifty essential questions and answers.

As the world still vividly recalls the previous monkeypox (mpox) outbreak that impacted over 120 countries worldwide with more than 99,000 cases in 2022, we are now facing a second wave of infections from the monkeypox virus (MPXV), characterized by an exponential increase in cases. The current 2024 outbreak has already recorded more than 20,000 cases in Africa, marking a dramatic escalation compared to previous outbreaks. The predominance of the newly identified clade Ib variant, first detected in the Democratic Republic of the Congo (DRC) and now identified across multiple African nations and beyond, underscores its enhanced transmissibility and potential for international spread, evidenced by cases in Sweden and Thailand. The World Health Organization (WHO) declared on August 14, 2024, the current mpox outbreak a Public Health Emergency of International Concern (PHEIC), calling for heightened global public health measures. The ongoing pattern of unusual, frequent, and extensive outbreaks of mpox with potential global implications poses significant questions. This review addresses, in the format of 50 questions and answers, the 2024 mpox outbreak, detailing its characteristics, epidemiological data, and impact compared to previous outbreaks. It comprehensively explores critical questions related to MPXV virological characteristics, immunological response, clinical manifestations, epidemiology, diagnostics, and available treatments. The review also documents the significant and evolving challenges posed by the current mpox outbreak, highlighting its scale, spread, and public health response.

Injuries Following COVID-19 Infection in Academy-level Male Youth Soccer Players.

Injury epidemiology data are key to injury prevention strategy development. Most such data surrounding the COVID-19 pandemic compare team injury data during the pandemic to that before the pandemic; few investigate injuries by infection status and even less involve academy-level organizations. We hypothesized that in male youth developmental academy-level soccer players, the rate of injury would be higher following COVID-19 infection than in the uninfected. Retrospective cohort study involving 141 male youth athletes from a single midwestern US developmental soccer academy during the spring 2022 soccer season. Injury data was gathered prospectively and analyzed retrospectively. Injury rate (incidence per 1000 playing hours), type, location, severity, mechanism, and mode of play were compared between COVID-19-positive and -negative athletes. Thirty-four (24.11%) of 141 athletes tested positive for COVID-19. Of those 34, 20 (58.8%) sustained at least 1 injury, totaling 30 injuries. Of the 107 (75.89%) uninfected athletes, 30 (28.04%) sustained at least 1 injury, totaling 37 injuries. COVID-19-positive athletes sustained injuries at higher rates (7.10, 95% CI: 4.79-10.14) than uninfected athletes (2.71, 95% CI: 1.91-3.74), with an infected to uninfected adjusted injury rate ratio of 2.08 (95% CI: 1.20-3.59, P=0.008). COVID-19 positive players were 2.78 times more likely to sustain an injury following their infection than uninfected players (95% CI: 1.14-6.96, P=0.026). There were no significant differences in injury type (P=0.515), location (P=0.319), severity (P=0.679), mechanism (P=0.225), or mode of play (P=0.557) between groups. Among academy-level youth soccer athletes, injury rate increased significantly after COVID-19 infection; injury patterns were similar. II - Retrospective cohort study.

CLINICAL FEATURES OF COVID-19 INFECTION IN NEWBORNS: A RETROSPECTIVE ANALYSIS

Background. The COVID-19 pandemic has significantly impacted all age groups, including newborns. During the fifth surge, the prevalence of the Omicron variant among infants increased dramatically. While SARS-CoV-2 is generally milder in children than adults, newborns are vulnerable due to their immature immune systems. Clinical manifestations in newborns can range from asymptomatic to severe cases with respiratory distress or multi-organ dysfunction. Purpose of study. Description of clinical manifestations, course and outcomes of coronavirus infection in newborns. Materials and methods of study. A retrospective analysis was conducted on 110 newborns with COVID-19 admitted to the Children’s Clinical Infectious Diseases Hospital of Almaty between 2021 and early 2022. The study used electronic medical records as the source of research data. Demographic data such as age and sex were collected, along with epidemiological data including international or domestic travel within two weeks prior to the onset of the disease, known exposure to a person with positive SARS-CoV-2 infection, and a history of pregnancy. Results. The infants’ mean age was 17 days, with 44 boys (40%) and 66 girls (60%). Four newborns were admitted to the hospital at less than seven days of life. When analyzing the severity of the cases, the following proportions of newborns were observed: (3/110, 2.7%) were asymptomatic, (44/110, 40%) had mild symptoms, (57/110, 51.8%) were moderately severe, (4/110, 3.6%) severe, and (2/110, 1.8%) had very severe illness. The majority (68.4%) were hospitalized within three days of symptom onset. Fever was common, and all infants underwent chest CTs. Despite some severe cases, 99% had favorable outcomes, with only one fatality. Conclusion. This study indicates that most COVID-19 infections in newborns were contracted from household contacts. Clinical symptoms in infants included fever, catarrhal symptoms, and signs of intoxication, with some showing normal temperatures. Laboratory findings varied, with common changes including monocytosis and neutrophilia. Respiratory complications, such as bronchitis and pneumonia, were prevalent. Comorbidities, particularly congenital disorders, increased the risk of severe outcomes and mortality. Most newborns recovered within 1-2 weeks, though viral carriage persisted in many.

Managing Amitraz Poisoning: Epidemiological Data and Clinical Insights From a Tertiary Care Hospital in Southern India

Managing Amitraz Poisoning: Epidemiological Data and Clinical Insights From a Tertiary Care Hospital in Southern India

The Use of Ceftazidime–Avibactam in a Pediatric Intensive Care Unit—An Observational Prospective Study

Background/objectives: Infections caused by carbapenem-resistant Enterobacterales (CRE) are progressively increasing in Pediatric Intensive Care Units (PICUs). Its treatment is challenging due to the lack of pediatric trials. CRE infections are associated with significantly poor outcomes, but ceftazidime–avibactam (CAZ-AVI) has been reported to be successful in their treatment. This study aimed to describe the use and outcome of CAZ-AVI in a PICU. Results: Ten patients were included, with 12 episodes of clinical suspicion or confirmed multidrug-resistant (MDR) bacterial infections treated with CAZ-AVI for surgical prophylaxis, suspicion of sepsis, pneumonia, and surgical wound infection. Of these patients, 80% received empirical treatment because of previous MDR bacterial colonization, and 60% were administrated combination therapy with aztreonam for Metallo-β-Lactamases (MBL)strains. No bacteria were resistant to CAZ-AVI. The average duration of the treatment was 3 days when cultures turned negative and 7 days when MDR bacteria were isolated. Methods: This was an observational prospective study of children treated with CAZ-AVI in the PICU of a tertiary hospital in 2022. Epidemiological, clinical, microbiological, and outcome data were collected. Conclusions: The most frequent use of CAZ-AVI in our PICU was the short-term empirical treatment for patients with previous MDR bacterial colonization and clinical suspicion of bacteremia or sepsis. Furthermore, the combination of CAZ-AVI plus aztreonam could be more effective for CRE infections, especially type Ambler class B as MBL strains.

Real-World Effectiveness of All-Oral Direct-Acting Antivirals in Patients With Hepatitis C Virus-Related HCC.

The association between direct-acting antiviral (DAA) treatment and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is currently unclear. Hence, we aim to assess the association between DAA treatment and mortality rate among Medicare beneficiaries with HCV-related HCC. This retrospective cohort study screened 19,813 adults in 2013-2019 Surveillance, Epidemiology, and End Results data linked with Medicare data. Patients with HCV-related HCC initiating DAA therapy after their first HCC diagnosis were compared with patients with HCV-related HCC who received no HCV treatment. After inverse probability treatment weighting, multivariable Cox proportional hazards models compared mortality rates between the groups. Subgroup and sensitivity analyses were based on HCC stage (early vs. advanced), type of HCC treatment (curative, palliative, none), and DAA treatment duration. In total 3,777 patients with HCV-related HCC were identified (mean age: 68.2 years, 75.2% male, 61.8% White), of whom 19% initiated DAA therapy. Crude incidence mortality rates were 17.9 and 90.7 deaths per 100 person-years in the DAA and HCV-untreated groups, respectively. Cox regression models indicated that DAA therapy was associated with decreased risk of all-cause mortality (adjusted hazard ratio, 0.33; 95% CI 0.31-0.36). Median survival time was 45.7 (95% CI 40.9-57.9) months in the DAA group and 7.7 (95% CI 7.3-8.2) months in the HCV-untreated group (P < 0.001). All subgroup and sensitivity analyses were consistent with the main analyses. DAA therapy was associated with survival benefits for patients with HCV-related HCC regardless of the stage or type of HCC treatment and should not be withheld from this population of Medicare beneficiaries.

Benchmark dose modeling for epidemiological dose-response assessment using case-control studies.

Following a previous article that focused on integrating epidemiological data from prospective cohort studies into toxicological risk assessment, this paper shifts the focus to case-control studies. Specifically, it utilizes the odds ratio (OR) as the main epidemiological measure, aligning it with the benchmark dose (BMD) methodology as the standard dose-response modeling approach to determine chemical toxicity values for regulatory risk assessment. A standardized BMD analysis framework has been established for toxicological data, including input data requirements, dose-response models, definitions of benchmark response, and consideration of model uncertainty. This framework has been enhanced by recent methods capable of handling both cohort and case-control studies using summary data that have been adjusted for confounders. The present study aims to investigate and compare the "effective count" based BMD modeling approach, merged with an algorithm used for converting odds ratio to relative risk in cohort studies with partial data information (i.e., the Wang algorithm), with the adjusted OR-based BMD analysis approach. The goal is to develop an adequate BMD modeling framework that can be generalized for analyzing published case-control study data. As in the previous study, these methods were applied to a database examining the association between bladder and lung cancer and inorganic arsenic exposure. The results indicate that estimated BMDs and BMDLs are relatively consistent across both methods. However, modeling adjusted OR values as continuous data for BMD estimation aligns better with established practices in toxicological BMD analysis, making it a more generalizable approach.

Epidemiological surveillance of Neospora caninum in sheep (Ovis aries) and European mouflon (Ovis aries musimon) in southern Spain.

Neospora caninum is a protozoan with a facultative heteroxenous life cycle, with canids as the definitive hosts and other mammals, mainly ruminants, acting as intermediate hosts. This parasite is recognized as one of the major abortifacient pathogens in cattle. Although reproductive disorders have also been reported in other domestic and wild ruminants, epidemiological data on N. caninum in ruminant species other than cattle is still limited. Here, we evaluate the seroprevalence and risk factors associated with N. caninum exposure in sheep (Ovis aries) and European mouflon (Ovis aries musimon) in southern Spain. Serum samples from 390 sheep and 387 free-ranging mouflons were tested for antibodies against N. caninum using in-house time-resolved fluorescence immunoassay based on NcGRA7 as a recombinant antigen. The individual seroprevalence was 26.2% (95%CI: 22.0-30.7) in sheep and 5.7% (95%CI: 3.8-8.5) in mouflons. At least one seropositive animal was detected in all the 26 sheep farms (100%) and in eight of the 18 (44.4%) hunting estates sampled. The presence of dogs on the farm (≥3) and the sheep breed (purebred) were potential risk factors associated with exposure to N. caninum in sheep. Our results indicate a high circulation of N. caninum in sheep farms in southern Spain. Control measures should be implemented to limit the exposure to this protozoan in sheep flocks. Although we have confirmed for the first time the presence of anti- N. caninum antibodies in European mouflon in Spain, and, despite the relatively low seroprevalence found, the impact of this parasite on mouflon populations should be further studied.

Role of Vitamin D in Gynecological Cancer: State of the Art

: Vitamin D and Vitamin D Receptors have gained more importance beyond their roles in bone metabolism and calcium homeostasis. Several epidemiological studies have confirmed that vitamin D has a specific function in a wide variety of gynecological cancers, such as ovarian cancer, endometrial cancer, cervical cancer, uterine fibroid, and vulvar cancer. The different anti-cancer mechanisms exerted by vitamin D on tumor cells are cell proliferation, cancer progression, angiogenesis, cell cycle arrest, and inflammation. The role of vitamin D is well emphasized in ovarian cancer and uterine fibroids, with limited studies available on cervical cancer and other types of gynecological cancers. Overall, most epidemiological data support that inadequate or low levels of vitamin D in the circulation are associated with risk and poor prognosis in several types of gynecological cancer. It is evident that vitamin D plays a prominent role as an anticancer agent against numerous types of cancer. This review focuses on the etiology and role of vitamin D and the Vitamin D Receptor in various types of gynecological cancer, as well as the mechanism of Vitamin D and its metabolites in the management of gynecological cancer.

Non-AIDS defining cancers in HIV-infected individuals: a concise review

Non-acquired immunodeficiency syndrome (AIDS)-defining cancers (NADCs) present a growing concern in human immunodeficiency virus (HIV)-infected individuals, impacting morbidity and mortality rates. This paper synthesizes current epidemiological data and explores the multifaceted relationship between HIV infection and NADC risk. Epidemiological studies indicate a shifting landscape of cancer incidence among HIV-infected populations, with a notable rise in NADCs over recent decades. Factors such as prolonged life expectancy due to effective antiretroviral therapy (ART) and aging of the HIV-infected population contribute to this trend. Despite the overall decline in AIDS-defining cancers, NADCs have emerged as a significant cause of morbidity and mortality in HIV-infected individuals. Immunodeficiency, chronic inflammation, and oncogenic viral co-infections, such as human papillomavirus and hepatitis C virus, compound the risk of developing NADCs. Diagnostic challenges persist, with delayed detection and suboptimal management contributing to poor outcomes. Treatment modalities for NADCs in HIV-infected individuals require careful consideration, balancing cancer-directed therapy with potential interactions with ART and immune reconstitution. Prevention strategies, including cancer screening and lifestyle modifications, are crucial in mitigating the burden of NADCs in this population. As the landscape of HIV care continues to evolve, understanding the epidemiology and clinical characteristics of NADCs is imperative for optimizing clinical management and improving outcomes in HIV-infected individuals.

Prevalence of inhaled allergen sensitization among patients with suspected allergic diseases in Sichuan province: 3-year data from a single center

Allergic diseases are becoming increasingly common, and they are a threat to people’s health. Exploring the distribution characteristics of allergen-specific immunoglobulin E (sIgE) in people from Sichuan province, southwest China, can provide clinical epidemiological data. This study enrolled 12,204 consecutive patients with suspected allergies from May 2018 to May 2021. Among the patients, 4206 were diagnosed with allergic rhinitis or asthma. The Rayto Lumiray 1600 detection system and sIgE and total IgE (tIgE) detection kits were used to measure the levels of nine common sIgE and tIgE. sIgE ≥ 0.35 IU/mL was considered positive. The sensitization rate of D1 (Dermatophagoides pteronyssinus) is the highest (22.97%), followed by D2 (Dermatophagoides farinae) (23.33%); M3 (Aspergillus fumigatus) has the lowest positive rate (1.5%). E5 (Canis familiaris) and I6 (Blatella germanica) exhibited relatively high sensitization rates (8.64% and 12.35%, respectively). Allergen sensitization was significantly higher in men than in women. Moreover, 90.3% of sensitization samples from D1 were combined with at least one of the other eight allergens. Similarly, a positive correlation was demonstrated between D1, D2, and E1 (Felis domesticus). In addition, patients with allergic rhinitis (91.88% and 91.54%, respectively), allergic asthma (72.44% and 74.01%, respectively), and allergic rhinitis with asthma (92.12% and 93.22%, respectively) were mainly sensitized to D1 and D2. D1, D2, I6, and E5 are the main allergens. Moreover, D1 and D2 are the main allergens in patients with respiratory allergic diseases. Research focusing on the distribution of allergens and the characteristics of hypersensitivity in different people helps prevent, diagnose, and treat allergic diseases.

Female sex hormones inversely regulate acute kidney disease susceptibility throughout life.

While epidemiological and experimental studies have demonstrated kidney-protective effects of estrogen and female sex in adulthood, some epidemiological data showed deterioration of kidney function during puberty when estrogen production increases. However, molecular mechanisms explaining these conflicting phenomena remain unknown. Here, we showed that the pubertal sex hormone surge in female mice increases susceptibility to kidney ischemia reperfusion injury partly via downregulation of insulin-like growth factor 1 receptor (IGF-1R) expression in proximal tubules. Adult mice ovariectomized pre-pubertally (at postnatal day 21) showed strong tolerance to kidney ischemia, which was partly reversed by the administration of 17β-estradiol, while adult mice ovariectomized post-pubertally (at 8 weeks of age) were vulnerable to kidney ischemia. Kidney tubular IGF-1R protein expression decreased during postnatal growth but was highly expressed in adult mice ovariectomized pre-pubertally and in infant mice, which might be partly explained by different expression of an E3 ligase (MDM2) of IGF-1R. Mice deficient of Igf-1r in proximal tubules (iIGF-1RKO mice) during postnatal kidney growth showed increased susceptibility to ischemic injury. RNA-seq and western blotting analysis using proximal tubular cells from pre-pubertally ovariectomized iIGF-1RKO and control mice revealed altered expression of cell cycle-associated molecules such as cyclin D1. These results suggest that Igf-1r deletion during postnatal growth renders proximal tubular cells susceptible to ischemia possibly via altered cell cycle regulation. Thus, our findings provide evidence that exposure to pubertal sex hormones leads to increased susceptibility to kidney ischemia, which is partly mediated by modulation of IGF-1R signaling.

Congenital Epidermolysis Bullosa Epidemiology among Children of Russian Federation

Background. The prevalence of all types of congenital epidermolysis bullosa (СEB) worldwide is approximately 11 cases per 1 million according to the latest data from the American Epidermolysis Bullosa Registry. Data on the prevalence of СEB in Russian Federation is scattered, while data on life expectancy and mortality for this this disease is absent. This article presents medical and epidemiological data on children with СEB in Russian Federation. Objective. The aim of the study is to analyze clinical and epidemiological features of children with СEB in Russian Federation. Methods. We have performed analysis of the clinical and epidemiological features among pediatric population of Russian Federation with СEB using the “Registers of Genetic and Other Rare Diseases” of the “Butterfly Children” charitable foundation. Results. There are 491 children with СEB in Russian Federation as of 2024 according to the national registry data from “Registers of Genetic and Other Rare Diseases” of the “Butterfly Children” charitable foundation. The ratio of boys and girls was 1.08:1, that is relevant to the global data. The prevalence of CEB in children aged from 0 to 17 years in Russian Federation is 15.48 cases per 1,000,000 children as of January 1, 2024. The highest number of children with CEB were revealed in the Republic of Dagestan — 54 (11%) children, which is apparently due to the high rate of consanguineous marriages (50%). Other regions with high prevalence are Moscow Region (n = 28, 5.7%), Moscow (n = 25, 5.1%), Saint Petersburg (n = 26, 5.2%) and Krasnodar Territory (n = 23, 4.6%). Largest age group of children (from 12 to 18 years) includes 146 patients with mean age of 14.32 ± 1.72 years. The most common form of CEB is dystrophic one — 261 patients, the next one is simplex — 191 patients, then junctional form — 31 patient, and Kindler syndrome — 8 patients. The birth rate of children with CEB by year during the period from 2019 to 2023 (per 100,000 children born): 2019 — 1.42, 2020 — 2.09, 2021 — 2.65, 2022 — 2.76 and 2023 — 1.74. The arithmetic mean birth rate of children with CEB over a five-year period was 2.13 cases per 100,000 children born. The registry contains information on 22 deceased patients, average age was 3.06 ± 4.66 (from 0 to 15 years, median 0.54 years). The highest number of fatal outcomes was observed in the Republic of Dagestan (n = 3). Junctional CBE dominates in fatal outcomes among all the CEB types — 59.1% (n = 13 cases, 0.40 ± 0.22 years). The highest mortality was observed in I age group (from 0 to 1 year), which is 65.2% (15 fatal outcomes). Multisystem organ failure resulting from sepsis was the most common cause of death in both types of CEB (junctional and dystrophic). The mortality trend in the junctional form of CEB shows a decline in mortality, while the dystrophic type shows a stable situation during 2021–2023 years — 2 fatal outcomes per year. Junctional CEB has higher mortality rate at early age: survival curve shows sharp decline in the first months of life indicating high mortality in early life. The probability of survival drops to almost 0% in the first 100 days. Higher survival rate is more specific for the dystrophic type of CEB. Conclusion. This study demonstrates the significance and necessity to create and maintain registers for rare (orphan) diseases. Registry maintenance is an effective model for real understanding of the number of patients and value of needed assistance from the government to this category of patients.