Multiple Etiologies Research Articles

CERVICAL DEGENERATIVE MYELOPATHY, PANORAMIC REVIEW

Introduction: cervical degenerative myelopathy (DCM) is a general term that entails multiple etiologies. DCM is a group of pathological entities that originate compression of the cervical spinal cord, where spasticity, hyperreflexia, pathological reflexes, loss of manual dexterity, among others, are found. Objective: to detail the current information related to cervical degenerative myelopathy, epidemiology, clinical presentation, role of complementary examinations, pathophysiology, pathogenesis and treatment. Methodology: a total of 32 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 21 bibliographies were used because the other articles were not relevant to this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: cervical degenerative myelopathy, cervical spondylotic myelopathy, cervical pain, ossification of the yellow ligament and degenerative disc disease. Results: cervical myelopathy occurs in almost all individuals with canal stenosis greater than 60%. Spinal cord injury (SCI) is a devastating disorder that influences remarkable neurological morbidity and significant wear and tear on quality of life. The incidence and prevalence of SCI in North America is between 4.1 and 60.5 per 100,000, robust epidemiological data is difficult to obtain because of the multifactorial etiology of the disease process. Conclusions: cervical degenerative myelopathy involves multiple etiologies, all these entities together represent the most common reason for degenerative and non-traumatic alteration of the spinal cord in adult individuals. Degenerative disorders are more common at C5 and C6 or C6 and C7, because of the increased mobility in these sections. It is difficult to obtain solid epidemiological data because of the multifactorial etiology of the disease process. The symptoms and signs presented by the pathology are varied, so an adequate physical examination and a good clinical history should be taken. The pathology can significantly alter neurological function and lead to disability, so early recognition and treatment can prevent further deterioration of affected individuals. Surgical decompression is almost universally indicated with the intention of preventing progression and achieving maximum recovery potential. KEY WORDS: myelopathy, cervical, degenerative, pain, spinal, neuralgia.

A rare case report of bilateral vestibulopathy due to otosyphilis.

Bilateral vestibulopathy is an important cause of imbalance. There are multiple etiologies of bilateral vestibulopathy (BVP), but reports of BVP due to otosyphilis are rare. A 39-year-old male was referred to our medical center due to vertigo, persistent dizziness and gait disturbance for 2 months. Bilateral vestibulopathy due to otosyphilis was considered in this case, as confirmed through analyses of vestibular function, laboratory tests, and penicillin treatment. The patient was was treated with a high dose of penicillin G (24 × 106 IU/d) for 14 days. The patient's symptoms had improved greatly following treatment, with dizziness and gait disturbance having completely resolved at 3 months following hospital discharge. Bilateral vestibulopathy should be considered when evaluating patients with acute or subacute persistent dizziness. Clinicians should also be aware of the potential for otosyphilis among patients who report BVP.

Artificial Intelligence and Its Role in Diagnosing Heart Failure: A Narrative Review.

Heart failure (HF) is prevalent globally. It is a dynamic disease with varying definitions and classifications due to multiple pathophysiologies and etiologies. The diagnosis, clinical staging, and treatment of HF become complex and subjective, impacting patient prognosis and mortality. Technological advancements, like artificial intelligence (AI), have been significant roleplays in medicine and are increasingly used in cardiovascular medicine to transform drug discovery, clinical care, risk prediction, diagnosis, and treatment. Medical and surgical interventions specific to HF patients rely significantly on early identification of HF. Hospitalization and treatment costs for HF are high, with readmissions increasing the burden. AI can help improve diagnostic accuracy by recognizing patterns and using them in multiple areas of HF management. AIhas shown promise in offering early detection and precise diagnoses with the help of ECG analysis, advanced cardiac imaging, leveraging biomarkers, and cardiopulmonary stress testing. However, its challenges include data access, model interpretability, ethical concerns, and generalizability across diverse populations. Despite these ongoing efforts to refine AI models, it suggests a promising future for HF diagnosis. After applying exclusion and inclusion criteria, we searched for data available on PubMed, Google Scholar, and the Cochrane Library and found 150 relevant papers. This review focuses on AI's significant contribution to HF diagnosis in recent years, drastically altering HF treatment and outcomes.

18F-Fluorodeoxyglucose-Avid Benign Anthracotic Mediastinal Lymphadenitis Mimicking Metastatic Lymphadenopathy.

The staging of malignancy is critical for its effective management. 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) imaging is a common modality for malignancy staging, which identifies areas of FDG avidity. However, multiple benign etiologies can cause false-positive 18F FDG-avid nodes. Among these, extrapulmonary involvement of anthracosis in the form of lymphadenopathy is a rare entity. In patients with concomitant malignancies, the presence of 18F FDG-avid anthracotic lymph nodal enlargement may mimic nodal metastasis. Endosonography-guided tissue acquisition may help differentiate between the two. Herein, we describe six cases of FDG-avid benign anthracotic lymphadenitis detected during staging workups for patients with malignancies who later underwent curative resection.

Neuronal autoantibodies in the cerebrospinal fluid of 148 patients with schizophrenia and 151 healthy controls

Schizophrenia is a syndrome with multiple etiologies, one of which is the potential for an autoimmune disease of the brain such as N-methyl-d-aspartate receptor (NMDAR) encephalitis, which can induce psychosis resembling schizophrenia. Here, we examined anti-neuronal autoantibodies related to psychosis using both cell- (CBA) and tissue-based assays (TBA) in the cerebrospinal fluid (CSF) of patients with chronic schizophrenia and control participants. First, we screened for the antibodies against leucine-rich glioma-inactivated 1 (LGI1), γ-aminobutyric acid B receptor (GABABR), dipeptidyl aminopeptidase-like protein 6 (DPPX), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR1/R2), and contactin-associated protein-like 2 (CASPR2) in 148 patients with schizophrenia. No antibodies were detected. Next, we performed CBA for NMDAR antibodies in 148 patients with schizophrenia and 151 age- and sex-matched controls. Although we detected relatively weak immunoreactivity for NMDAR in the CSFs of two patients with schizophrenia and three controls, no samples were positive when strict criteria were applied. For TBA in the rat hippocampus and cerebellum, we detected positive signals in the CSFs of 13 patients with schizophrenia and eight controls. Positive samples were analyzed for paraneoplastic syndrome and antinuclear antibodies using immunoblotting. The CSFs of nine patients and six controls were positive for dense fine speckle 70 (DFS70) antibodies. Additionally, antibodies against centromere protein (CENP)-A and CENP-B were detected in patients with schizophrenia. Our results suggest that autoantibodies against NMDAR, LG1, GABABR, DPPX, AMPAR1/R2, and CASPR2 are not associated with the pathogenesis of chronic schizophrenia. Moreover, we emphasize the importance of considering the effect of anti-DFS70 antibodies when analyzing autoantibodies in CSF samples. Conclusively, we obtained no evidence suggesting that the most frequent neuronal autoantibodies in the CSF play a role in the pathogenesis of schizophrenia, even in our sample.

Screening for dilated cardiomyopathy in immediate family members: to whom, how, when (and where).

Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular dilation and systolic dysfunction in the absence of coronary artery disease, valvular disease, congenital heart disease, or altered haemodynamic conditions. Dilated cardiomyopathy can recognize multiple aetiologies, including infectious processes, effect of toxic substances, immunological mechanisms, and genetic causes. In recent years, many genes coding for proteins involved in the structure and function of the cardiomyocytes have been associated with the development of DCM, making the identification of familial forms increasingly frequent. At the same time, an ever-increasing use of cardiac magnetic resonance imaging has made it possible to identify early morpho-functional alterations in subjects with initial forms of the disease, or carriers of pathogenic genetic variants. The increasingly in-depth understanding of the genetic and molecular mechanisms operating in DCM has also favoured the development of new therapeutic strategies including drugs with molecular targets and gene therapies. In this panorama, screening of family members of patients affected by DCM represents an important tool for early diagnosis, treatment, and prognostic stratification. In relation to its clinical relevance and its complexity, it is important that family screening and follow-up of identified patients are carried out in units dedicated to the treatment and study of cardiomyopathies.

The genetic association between hyperthyroidism and heart failure: a Mendelian randomization study.

Hyperthyroidism is an endocrine disease with multiple etiologies and manifestations. Heart failure (HF) is a common, costly, and deadly medical condition in clinical practice. Numerous studies have suggested that abnormal thyroid function can induce or aggravate the development of heart disease. However, no study has demonstrated a causal relationship between hyperthyroidism and heart failure. Therefore, the purpose of this study was to explore the causal link between hyperthyroidism and HF. Summary data for genetically predicted hyperthyroidism were obtained from a genetic association study. The data examined for genetically determined all-cause heart failure came from 218,208 individuals from the FinnGen Consortium. Two-sample Mendelian randomization (MR) analysis was used to estimate the causal link between hyperthyroidism and heart failure. Statistical analyses were conducted using the inverse variance-weighted, weighted median, simple median, weighted mode, MR-PRESSO (number of distribution = 5000), MR-Egger, and leave-one-out. The results of the inverse-variance weighted analysis indicated a causal association between hyperthyroidism and an increased risk of all-cause heart failure (IVW: β=0.048, OR=1.049, 95%CI: [1.013 to 1.087], P=0.007). Similarly, the weighted median approach demonstrated a positive correlation between hyperthyroidism and all-cause heart failure (OR=1.049, [95% CI, 1.001-1.100]; P=0.044). Additionally, no horizontal pleiotropy or heterogeneity was observed. The leave-one-out analysis revealed that the majority of the SNP-driven associations were not influenced by a single genetic marker. Our study observed a causal relationship between hyperthyroidism and all-cause heart failure. Hyperthyroidism may associate with heart failure genetically.

Udder thermogram-based deep learning approach for mastitis detection in Murrah buffaloes

Mastitis, a production disease with multiple etiologies, inflicts significant economic losses among dairy farmers around the globe. In this study, an attempt has been made to detect mastitis through a Convolutional Neural Networks (CNN)-based deep learning model using 7615 udder thermograms of 40 Murrah buffaloes. The thermograms were grouped separately as healthy, sub-clinical (SCM), and clinical mastitis (CM) affected udder quarters based on California Mastitis Test (CMT) scores, Somatic Cell Count (SCC) values and thermal image analysis. Results of thermogram analysis revealed a significant increase (p < 0.01) in the mean values of udder skin surface temperature (USST) among SCM and CM-affected quarters compared to healthy quarters to the tune of 1.32 and 2.61 °C, respectively. The USST showed a strong positive correlation with the CMT score (r = 0.87, p < 0.01) and log10SCC value (r = 0.88, p < 0.01). The sequential (Normal vs. Clinical and Normal vs. Sub-clinical) models had training accuracy and validation accuracy of 0.999 and 0.988, 0.991 and 0.978, respectively. The confusion matrix for Normal vs. Clinical and Normal vs. Sub-clinical models reflected a loss of 0.009 and 0.029, precision of 0.947 and 0.980, and recall of 0.996 and 0.904, respectively. Consequently, the sequential (Normal vs. Clinical and Normal vs. Sub-clinical) models achieved a testing accuracy of 0.970 and 0.943, respectively. Thus, the improved deep-learning CNN models efficiently predicted SCM and CM cases in Murrah buffaloes.

Case Series of Multicontact Peripheral Nerve Stimulation in the Transversus Abdominis Plane for Chronic Abdominal Wall Pain

ObjectivesManaging abdominal pain can be difficult. This is due to the nonspecific nature of the pain, the multiple etiologies, and the different mechanisms underlying this type of pain. Abdominal wall pain in particular poses its own challenges. Traditionally, chronic abdominal wall pain has been managed with nonopioid analgesics, and in severe cases, opioid therapy has been considered. For patients with chronic abdominal wall pain refractory to medication management, peripheral nerve blocks and spinal cord stimulation also have been trialed with some success. In this study, we present a case series in patients with chronic abdominal wall pain who were treated with a multicontact peripheral nerve stimulation (PNS) system in the transversus abdominis plane (TAP). Materials and MethodsThis was a single-center, retrospective case series. Data were included from adults with chronic abdominal wall pain whose symptoms were refractory to standard medical management and who underwent a multicontact PNS system placement in the TAP. ResultsFour patients met the inclusion criteria. All four patients underwent a multicontact PNS trial lead placement in the TAP. One patient reported no benefit from the trial. The remaining three patients underwent a permanent multicontact PNS system placement in the TAP. ConclusionsIn patients with chronic abdominal wall pain whose symptoms are refractory to conservative medical management, PNS may be an alternative treatment option. As the use of PNS for chronic abdominal wall pain and other fascial planes continues to develop, additional research is necessary to determine optimal placements and specific stimulation parameters.

Environmental and behavioral variables associated with lower urinary tract diseases in domestic cats

Objectives: Feline lower urinary tract disease (LUTD) is a frequently seen disease with multiple etiologies. Since it is a complex condition, the aim of this study is to evaluate the factors that may affect the development of the disease.&#x0D; Materials and Methods: Demographic, clinical, behavioral and environmental parameters of 30 cats diagnosed with lower urinary tract disease and 15 aged-matched healthy cats presented to Ankara University Small Animal Hospital were evaluated. &#x0D; Results: In the diseased group, the male population was higher and the cats were overweight. The number of food, water and litter boxes and litter material were found to differ significantly between groups. Daily habits such as playing with a scratching board and self-grooming differed between the groups. Inappropriate behaviors observed by the owners of the cats in the first group were listed as urinating/defecating outside the litter box and showing aggression towards the owner, guests, and/or other animals. &#x0D; Conclusions: The results of this study show that the detailed evaluation and regulation of the daily needs of cats is important for the emergence or recurrence of the disease and therefore may contribute to the correct management of the treatment process in cats with lower urinary tract disease.

ADHD: Development of a printable poster for parents, teachers and healthcare professionals

IntroductionADHD is a very frequent reason for consultation in child psychiatry. It affects 2.5% of children and 5% of adults. Diagnosis is clinical. Treatment is based on medication combined with psychosocial interventions.ObjectivesDevelop an ADHD guide for caregivers.MethodsWe carried out a literature review covering the last 5 years using the google scholar and pubmed search engines, including the key words ADHD, in order to produce a printable guide for caregivers working with children, in particular school teachers and healthcare personnel.ResultsAttention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting 5% of school-age children.It is characterized by abnormally high levels of developmental inattention, hyperactivity and impulsivity, leading to impaired personal, social, academic or occupational functioning. Because of its pervasiveness, ADHD can interfere negatively with general well-being, as well as with social life, academic performance and the development of social skills, which can lead to low self-esteem.ADHD has multiple etiologies. It is thought to be due to a complex interaction between genes and environment. In fact, genetic vulnerability predisposes to the disorder which, under the influence of an unfavorable environment, expresses itself in clinical symptoms represented by 2 dimensions: inattention, hyperactivity and impulsivity.Diagnosis is essentially clinical, and treatment is based on medication combined with psychosocial interventions.ConclusionsADHD is one of the most frequently encountered disorders in general practice, pediatrics and child psychiatry. Early recognition of the disorder enables appropriate management, while limiting the impact of the disease on the functioning of the young person and his or her family.Disclosure of InterestNone Declared

A case of diabetic striatopathy due to uncontrolled type 2 diabetes.

Hemichorea-hemiballismus (HCHB) syndrome is a syndrome characterized by choreic movements which are irregular, nonrepetitive, and random movements, and ballismus which are spontaneous and violent movements. HCHB syndrome with a metabolic cause is a rare presentation that can be precipitated by uncontrolled diabetes. Presented here is a case of HCHB syndrome with right-sided neuroimaging findings and contralateral chorea due to uncontrolled type 2 diabetes mellitus. This patient was found to be obtunded with a blood glucose of greater than 500 mg/dL by EMS. After the administration of insulin, she was able to answer clarifying questions of noncompliance with her antihyperglycemic medications. She had a computed tomography without contrast of the head which showed hyperdense lesions in the right caudate nucleus and putamen consistent with HCHB syndrome. She was started on treatment for nonketotic hyperglycemia with insulin. As her mentation improved, she was able to cooperate with physical examination, which revealed irregular and violent movements in the left upper and lower extremities. Her hemichorea and hemiballismus improved with strict glycemic control, and she was able to be discharged to a skilled nursing facility for further rehabilitation. She would later have repeated hospitalizations for poor glycemic control, and repeat neuroimaging would reveal the resolution of hyperdensities after 4 months. HCHB syndrome due to uncontrolled diabetes has been termed diabetic striatopathy and is characterized by poor glycemic control, unilateral striatal hyperdensity on CT imaging, and contralateral choreic movements. Diabetic striatopathy remains a poorly understood disease, and the exact pathophysiologic mechanism has not been definitively elucidated. Diabetic striatopathy is a relatively new term for metabolic etiology of hemichorea-hemiballismus syndrome and was coined in 2009. The triad for diabetic striatopathy is poor glycemic control, unilateral striatal hyperdensity on CT imaging, and contralateral choreic movements. Multiple etiologies have been suggested for the cause of diabetic striatopathy including petechial hemorrhage, mineral deposition, myelin destruction, and infarction with reactive astrocytosis; however, the exact mechanism has yet to be determined. Antidopaminergic medications may be used to control the choreic movements of diabetic striatopathy; however, the mainstay of treatment is glycemic control, often with insulin therapy.

A challenging case of a pituitary macroadenoma and toxic thyroid adenoma with inappropriate TSH secretion.

Thyroid-stimulating hormone-secreting pituitary adenomas (TSHomas) are rare, accounting for less than 1% of all pituitary adenomas. We present a case of hyperthyroidism secondary to a likely TSHoma and coexisting functional thyroid adenoma. Laboratory errors and familial abnormalities in thyroid function tests were ruled out, and a diagnosis of the toxic thyroid adenoma was confirmed on a thyroid uptake scan. However, the triiodothyronine suppression test was contraindicated due to the patient's cardiovascular disease, and the thyrotropin-releasing hormone stimulation test, measurement of glycoprotein hormone alpha-subunit, and genetic testing were unavailable. Magnetic resonance imaging of the brain revealed a suprasellar pituitary macroadenoma measuring 40 mm × 20.3 mm × 17 mm. The patient was initiated on carbimazole; however, thyroid stimulating hormone and thyroxine levels remained elevated. The patient declined trans-sphenoidal surgery and was treated with radioactive iodine to manage the toxic thyroid adenoma, leading to reduced thyroxine levels and symptom improvement. Unfortunately, the patient passed away before long-acting somatostatin analogs became available. This case highlights the diagnostic and therapeutic challenges involved in managing thyrotoxicosis with dual etiology. Hyperthyroidism can have multiple etiologies, which can coexist in the same patient. Persistent discordant thyroid function tests warrant further investigation. The gold standard for diagnosis of TSHomas remains immunohistochemical analysis of the tumor tissue.

New Daily Persistent Headache.

This article describes the clinical features, etiology, differential diagnosis, management, and prognosis of new daily persistent headache. New daily persistent headache has attracted renewed attention as it may arise in the setting of a COVID-19 infection. Spontaneous intracranial hypotension, particularly from CSF-venous fistulas, remains an important secondary headache disorder to consider before diagnosing new daily persistent headache. Symptomatic treatment for new daily persistent headache may include acute and preventive therapies used for migraine and tension-type headache, such as triptans, oral preventive agents, onabotulinumtoxinA, and agents that target calcitonin gene-related peptide. New daily persistent headache is a daily headache syndrome that starts acutely and can only be diagnosed after 3 months have elapsed and other secondary and primary headache diagnoses have been excluded. The clinical manifestations largely resemble either chronic migraine or chronic tension-type headache. The underlying cause is unknown, but it is plausible that multiple etiologies exist and that it is not a single disease entity. The prognosis is variable but often poor, and the treatment approach is largely extrapolated from the management of chronic migraine and chronic tension-type headache.

Healthcare Utilization (HCU) Reduction with High-Frequency (10 kHz) Spinal Cord Stimulation (SCS) Therapy.

Spinal cord stimulation (SCS) is a well-established treatment for patients with chronic pain. With increasing healthcare costs, it is important to determine the benefits of SCS in healthcare utilization (HCU). This retrospective, single-center observational study involved 160 subjects who underwent implantation of a high-frequency (10 kHz) SCS device. We focused on assessing trends in HCU by measuring opioid consumption in morphine milligram equivalents (MME), as well as monitoring emergency department (ED) and office visits for interventional pain procedures during the 12-month period preceding and following the SCS implant. Our results revealed a statistically significant reduction in HCU in all domains assessed. The mean MME was 51.05 and 26.52 pre- and post-implant, respectively. There was a 24.53 MME overall decrease and a mean of 78.2% statistically significant dose reduction (p < 0.0001). Of these, 91.5% reached a minimally clinically important difference (MCID) in opioid reduction. Similarly, we found a statistically significant (p < 0.01) decrease in ED visits, with a mean of 0.12 pre- and 0.03 post-implant, and a decrease in office visits for interventional pain procedures from a 1.39 pre- to 0.28 post-10 kHz SCS implant, representing a 1.11 statistically significant (p < 0.0001) mean reduction. Our study reports the largest cohort of real-world data published to date analyzing HCU trends with 10 kHz SCS for multiple pain etiologies. Furthermore, this is the first and only study evaluating HCU trends with 10 kHz SCS by assessing opioid use, ED visits, and outpatient visits for interventional pain procedures collectively. Preceding studies have individually investigated these outcomes, consistently yielding positive results comparable to our findings.

Diabetes mellitus is a risk factor for incident chronic kidney disease: A nationwide cohort study

ObjectiveDiabetes mellitus and chronic kidney disease are multifactorial conditions with multiple etiologies that share similar pathophysiologies. This nationwide cohort study examined the impact of diabetes mellitus on the follow-up development of chronic kidney disease. MethodsBy retrieving the Longitudinal Health Insurance Database 2005, 5121 patients with diabetes mellitus were included in this study and 5121 patients without diabetes mellitus, who were matched according to sex, age, and Charlson comorbidity index made up the control group. The adjusted hazard ratios for chronic kidney disease were calculated using Cox proportional hazards regression analysis. Kaplan–Meier analysis was used to estimate the cumulative incidence of chronic kidney disease rate in the diabetes mellitus and control groups. ResultsAfter adjusting for sex, age, and Charlson comorbidity index score, the diabetes mellitus group had a 1.380 times higher (95% CI: 1.277–1.492) risk of developing chronic kidney disease than the control group. Further stratified analysis showed that patients with diabetes mellitus had a significantly higher risk of developing chronic kidney disease regardless of their sex, age, and Charlson comorbidity index score, compared to those without diabetes mellitus. ConclusionsThere is a possibility that diabetes mellitus serves as an independent risk factor for chronic kidney disease development. Early screening and monitoring of diabetes mellitus appear to be of great importance in the prevention of chronic kidney disease.

Role of liver sinusoidal endothelial cell damage in the developmental process of hepatic sinusoidal obstruction syndrome: a focus on the research progress of immune inflammatory mechanisms

Hepatic sinusoidal obstruction syndrome (HSOS) is a type of secondary vascular disease of the liver that is mainly associated with the ingestion of pyrrole alkaloids (PAs) and hematopoietic stem cell transplantation (HSCT) treatment, resulting in severe liver dysfunction, multiple organ failure, and even death. Hepatic sinusoidal dilatation and obstruction, hepatocyte coagulative necrosis, and hepatic lobular inflammation are the main pathological manifestations of HSOS. The key initiating process for the pathogenesis of HSOS is damage to liver sinusoidal endothelial cells (LSECs). Currently, it is believed that LSECs are damaged by the involvement of multiple etiologies and mechanisms, and secondary coagulation and fibrinolysis disorders, oxidative stress, and inflammatory responses are the occurrence contributors to HSOS; however, the mechanism has not been fully elucidated. Therefore, the role of immune-inflammatory mechanisms has received increasing attention in LSEC damage. This article provides an overview of the epidemiology, etiology, and pathological changes of HSOS and reviews the physiological functions, common etiological damage mechanisms, and the key role of LSEC damage in the pathogenesis of HSOS, with a special focus on the role and research progress of immune-inflammatory mechanisms for LSEC damage in recent years. Furthermore, we believe that in-depth study and elucidation of the role of immune-inflammatory mechanisms in LSEC damage and the pathogenesis of HSOS and diagnosis will provide feasible research and development ideas for the screening and identification of new markers and drug treatment targets for HSOS.

Hepatitis B virus-related hepatocellular carcinoma has superior overall survival compared with other etiologies.

Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue. Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder. Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745-0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0-A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B-D (p = 0.973); or who underwent non-curative treatments (p = 0.1). Patients with HBV-related HCC had superior OS than patients with other HCC etiologies.

Mathematical modeling in autoimmune diseases: from theory to clinical application.

The research & development (R&D) of novel therapeutic agents for the treatment of autoimmune diseases is challenged by highly complex pathogenesis and multiple etiologies of these conditions. The number of targeted therapies available on the market is limited, whereas the prevalence of autoimmune conditions in the global population continues to rise. Mathematical modeling of biological systems is an essential tool which may be applied in support of decision-making across R&D drug programs to improve the probability of success in the development of novel medicines. Over the past decades, multiple models of autoimmune diseases have been developed. Models differ in the spectra of quantitative data used in their development and mathematical methods, as well as in the level of "mechanistic granularity" chosen to describe the underlying biology. Yet, all models strive towards the same goal: to quantitatively describe various aspects of the immune response. The aim of this review was to conduct a systematic review and analysis of mathematical models of autoimmune diseases focused on the mechanistic description of the immune system, to consolidate existing quantitative knowledge on autoimmune processes, and to outline potential directions of interest for future model-based analyses. Following a systematic literature review, 38 models describing the onset, progression, and/or the effect of treatment in 13 systemic and organ-specific autoimmune conditions were identified, most models developed for inflammatory bowel disease, multiple sclerosis, and lupus (5 models each). ≥70% of the models were developed as nonlinear systems of ordinary differential equations, others - as partial differential equations, integro-differential equations, Boolean networks, or probabilistic models. Despite covering a relatively wide range of diseases, most models described the same components of the immune system, such as T-cell response, cytokine influence, or the involvement of macrophages in autoimmune processes. All models were thoroughly analyzed with an emphasis on assumptions, limitations, and their potential applications in the development of novel medicines.

Surveillance of Waterborne Disease Outbreaks Associated with Drinking Water - United States, 2015-2020.

Public health agencies in U.S. states, territories, and freely associated states investigate and voluntarily report waterborne disease outbreaks to CDC through the National Outbreak Reporting System (NORS). This report summarizes NORS drinking water outbreak epidemiologic, laboratory, and environmental data, including data for both public and private drinking water systems. The report presents outbreak-contributing factors (i.e., practices and factors that lead to outbreaks) and, for the first time, categorizes outbreaks as biofilm pathogen or enteric illness associated. 2015-2020. CDC launched NORS in 2009 as a web-based platform into which public health departments voluntarily enter outbreak information. Through NORS, CDC collects reports of enteric disease outbreaks caused by bacterial, viral, parasitic, chemical, toxin, and unknown agents as well as foodborne and waterborne outbreaks of nonenteric disease. Data provided by NORS users, when known, for drinking water outbreaks include 1) the number of cases, hospitalizations, and deaths; 2) the etiologic agent (confirmed or suspected); 3) the implicated type of water system (e.g., community or individual or private); 4) the setting of exposure (e.g., hospital or health care facility; hotel, motel, lodge, or inn; or private residence); and 5) relevant epidemiologic and environmental data needed to describe the outbreak and characterize contributing factors. During 2015-2020, public health officials from 28 states voluntarily reported 214 outbreaks associated with drinking water and 454 contributing factor types. The reported etiologies included 187 (87%) biofilm associated, 24 (11%) enteric illness associated, two (1%) unknown, and one (<1%) chemical or toxin. A total of 172 (80%) outbreaks were linked to water from public water systems, 22 (10%) to unknown water systems, 17 (8%) to individual or private systems, and two (0.9%) to other systems; one (0.5%) system type was not reported. Drinking water-associated outbreaks resulted in at least 2,140 cases of illness, 563 hospitalizations (26% of cases), and 88 deaths (4% of cases). Individual or private water systems were implicated in 944 (43%) cases, 52 (9%) hospitalizations, and 14 (16%) deaths.Enteric illness-associated pathogens were implicated in 1,299 (61%) of all illnesses, and 10 (2%) hospitalizations. No deaths were reported. Among these illnesses, three pathogens (norovirus, Shigella, and Campylobacter) or multiple etiologies including these pathogens resulted in 1,225 (94%) cases. The drinking water source was identified most often (n = 34; 7%) as the contributing factor in enteric disease outbreaks. When water source (e.g., groundwater) was known (n = 14), wells were identified in 13 (93%) of enteric disease outbreaks.Most biofilm-related outbreak reports implicated Legionella (n = 184; 98%); two nontuberculous mycobacteria (NTM) (1%) and one Pseudomonas (0.5%) outbreaks comprised the remaining. Legionella-associated outbreaks generally increased over the study period (14 in 2015, 31 in 2016, 30 in 2017, 34 in 2018, 33 in 2019, and 18 in 2020). The Legionella-associated outbreaks resulted in 786 (37%) of all illnesses, 544 (97%) hospitalizations, and 86 (98%) of all deaths. Legionella also was the outbreak etiology in 160 (92%) public water system outbreaks. Outbreak reports cited the premise or point of use location most frequently as the contributing factor for Legionella and other biofilm-associated pathogen outbreaks (n = 287; 63%). Legionella was reported to NORS in 2015 and 2019 as the cause of three outbreaks in private residences (2). The observed range of biofilm and enteric drinking water pathogen contributing factors illustrate the complexity of drinking water-related disease prevention and the need for water source-to-tap prevention strategies. Legionella-associated outbreaks have increased in number over time and were the leading cause of reported drinking water outbreaks, including hospitalizations and deaths. Enteric illness outbreaks primarily linked to wells represented approximately half the cases during this reporting period. This report enhances CDC efforts to estimate the U.S. illness and health care cost impacts of waterborne disease, which revealed that biofilm-related pathogens, NTM, and Legionella have emerged as the predominant causes of hospitalizations and deaths from waterborne- and drinking water-associated disease. Public health departments, regulators, and drinking water partners can use these findings to identify emerging waterborne disease threats, guide outbreak response and prevention programs, and support drinking water regulatory efforts.