Mild Disease Course Research Articles

BN SO35 - A Novel Ambulatory Pathway in the Management of Acute Pancreatitis

Abstract Background Acute Pancreatitis (AP) accounts for 20000 admissions per year, resulting in an average hospital stay of 5 days. Over 90% of patient have mild or moderate disease severity. Validated risk stratification tools such as the Harmless Acute Pancreatitis (HAP) score utilised alongside biochemical markers and clinical acumen can predict up to 97% of patients with a mild disease course. A pathway was introduced at two NHS centres to enable diagnosis and ambulatory management of patients with predicted mild AP with the aim of improving patient experience by preventing unnecessary admission, reducing pressure on surgical departments and providing safe outpatient management. Method The study took place at two sites: a district general hospital (DGH) and a tertiary referral centre. Pathway development occurred in parallel to pilot. Ambulation was defined as no overnight stay in a hospital bed. An initial retrospective review of all AP admissions was undertaken to understand current burden of disease and severity in our centres. Suitable patients were identified prospectively and data (demographics, biochemical markers, modified HAP score, severity of disease, complications, re-admission rate, surgical or endoscopic intervention) were collected for up to 30 days after discharge. AP ‘proforma’ were created to understand surgeons decision-making surrounding ambulation versus admission. Results Between November 2023 and May 2024, 99 patients with AP presented to the DGH surgical unit. Causes of AP included gallstones (n=55), idiopathic (n=21), alcohol (n=17), and post-ERCP (n=2). 38 patients (38%) were ambulated, with 23/38 (61%) returning for planned review within 72 hours. There were no mortalities in the ambulatory group. Three (7%) ambulated patients were re-admitted within 30 days for pain control (n=2) and post-cholecystectomy complications (n=1). Reasons for non-ambulation included: pain (n=30), inpatient cholecystectomy (n=4), poor oral intake (n=4), social reasons (n=3). In 4-week tertiary data collection, 5/17 (29%) eligible patients were ambulated, with 1 (20%) re-admission. Conclusion Pilot of a novel pathway to identify and ambulate patients with a predicted mild course of AP has been successful across two NHS centres. Use of validated risk scores alongside biochemical markers and clinical acumen produces a safe, sustainable and effective pathway that reduces burden on inpatient surgical resources. It is safe and feasible to ambulate patients with AP whilst undertaking diagnostic imaging, managing symptoms, facilitating expedited cholecystectomy and arranging specialist review in the outpatient setting. Further work is required with stakeholders to refine the pathway and replicate these results in other surgical units.

Misprocessing of Alpha-Galactosidase A, Endoplasmic Reticulum Stress, and the Unfolded Protein Response

Background Classic Fabry disease is caused by GLA mutations that result in loss of enzymatic activity of alpha-galactosidase A, lysosomal storage of globotriaosylceramide, and a resulting multisystemic disease. In non-classic Fabry disease, patients have some preserved alpha-galactosidase A activity and a milder disease course. Heterozygous females may also be affected. While Fabry disease pathogenesis has been mostly attributed to catalytic deficiency of mutated alpha-galactosidase A, lysosomal storage and impairment of lysosomal functions, other pathogenic factors may contribute, especially in non-classic Fabry disease. Methods We characterized the genetic, clinical, biochemical, molecular, cellular and organ pathology correlates of the p.L394P alpha-galactosidase A variant that was identified initially in six individuals with kidney failure by the Czech national screening program for Fabry disease and by further screening in additional 24 family members. Results Clinical findings in affected males revealed a milder clinical course with ∼15% residual alpha-galactosidase A activity with normal plasma lyso-globotriaosylceramide levels and abnormally low ratio of these values. None of the four available kidney biopsies showed lysosomal storage. Laboratory investigations documented intracellular retention of mutated alpha-galactosidase A with resulting endoplasmic reticulum stress and the unfolded protein response, which were alleviated with BRD4780, a small molecule clearing misfolded proteins from the early secretory compartment. We observed similar findings of endoplasmic reticulum stress and unfolded protein response in five kidney biopsies with several other classic and non-classic Fabry disease missense alpha-galactosidase A variants. Conclusions We identified defective proteostasis of mutated alpha-galactosidase A resulting in chronic endoplasmic reticulum stress and unfolded protein response of alpha-galactosidase A expressing cells as a contributor to Fabry disease pathogenesis.

Primary hyperoxaluria type 3: from infancy to adulthood in a genetically unique cohort.

Primary hyperoxaluria type 3 (PH3) is a rare autosomal recessive disorder caused by bi-allelic genetic variants in the 4 hydroxy-2 oxoglutarate aldolase (HOGA-1) gene. We report the natural history of PH3 in a 16-patient cohort, 15 from a unique genetically isolated population. This retrospective single-center study followed PH3 patients between 2003 and 2023 with demographic, clinical, radiographic, genetic, and biochemical parameters. Genetic population screening was performed in four villages to determine carrier frequency and identify couples at risk in a genetically isolated population. Sixteen patients with biallelic (or homozygous) pathogenic variants (PV) in HOGA-1 (c.944_946 del, c.119C > A, c.208C > T) were included in the study, 15 Druze and one Jewish, aged 0-63years at diagnosis (4 adults and 12 pediatric patients). All symptomatic patients had clinical or imaging signs of nephrolithiasis. One developed chronic kidney disease (CKD) stage 5; biopsy showed focal mesangial sclerosis and chronic tubulo-interstitial changes with few oxalate deposits. Two other patients had CKD stage 2 (eGFR 87 and 74mL/min/1.73m2) upon their last visit. The remaining cohort showed preserved kidney function until the latest follow-up. Of 1167 healthy individuals screened, 90 carriers were found, a rate of 1:13 in the genetically unique cohort screened. A high prevalence of PH3 patients was found among a unique cohort, but probably still underdiagnosed due to relatively mild disease course. The carrier rate is high. There is no specific therapy for PH3, but early diagnosis can prevent redundant diagnostic efforts and provide early treatment for kidney stone disease. Even in our homogeneous cohort, kidney stone disease severity and CKD degree were variable, supporting a suspected contribution of yet unknown genetic or environmental factors.

Cancer Risks in Attenuated and Classical Familial Adenomatous Polyposis: A Nationwide Cohort with Matched, Non-Exposed Individuals: Cancer and surgery in AFAP and FAP patients.

Familial adenomatous polyposis (FAP) is caused by pathogenic variants in the APC gene. FAP is usually categorized according to phenotype: classical FAP (CFAP) and attenuated FAP (AFAP); the latter is considered to have a milder disease course. We aimed to assess the risk of overall and specific cancers in CFAP and AFAP patients compared to matched, non-exposed individuals. All known Danish FAP patients were classified as either CFAP or AFAP and assigned four matched, non-exposed individuals. The risk of overall and specific cancers, and mortality were analyzed. The analysis included 311 CFAP patients, 134 AFAP patients, and 1,600 non-exposed individuals. The overall cancer risk was significantly higher for both CFAP and AFAP patients than for non-exposed individuals, with hazard ratios (HR) of 4.77 (95% confidence interval (CI), 3.61-6.32; P<0.001) for CFAP and 3.22 (95% CI, 2.16-4.80; P<0.001) for AFAP. No significant difference was observed when comparing CFAP and AFAP (HR=1.48; 95% CI, 0.98-2.25; P=0.0646). The HR of colonic cancer was 2.16 (95% CI, 0.99-7.72; P=0.0522) and 2.72 (95% CI, 1.19-6.22; P=0.0177 for CFAP and AFAP), respectively compared to non-exposed and did not differ between CFAP and AFAP patients (HR=0.80; 95% CI, 0.32-2.00; P=0.6278). Mortality was significantly higher in CFAP (HR=2.96; 95% CI, 2.04-4.28; P<0.001), but not in AFAP (HR=1.40; 95% CI, 0.73-2.69; P=0.311). Nationwide data reveal differing risk profiles for specific cancers and mortality in AFAP and CFAP compared to non-exposed individuals. The cancer burden of AFAP necessitates consistent monitoring of these patients.

The role of angiotensin II and endothelin receptor antibodies in COVID19 patients with HFpEF

Abstract Background The infection caused by the coronavirus SARS-COV-2, is associated with an unusual pattern of organ damage in comparison to other viral-induced pathologies. A theory of autoimmunity induced by ACE-2/SARS-COV-2 spike protein complex or its degradation products, was proposed as a possible explanation for the versatile and multiorgan damage in COVID-19. Aim The aim of the study is to determine whether antibodies against angiotensin II receptor type 1 (AT1R) or endothelin-1 receptor type A (ETAR) do exist in plasma of COVID -19 patients with heart failure with preserved ejection fraction and whether they correlate to the severity of the disease. Methods A total of 61 patients with COVID-19 and heart failure with preserved ejection fraction and 48 controls (free of COVID19) with heart failure with preserved ejection fraction were included. Patients were divided into two groups: patients with severe disease (admitted at the intensive care (n=30)), patients with milder clinical presentation that remained in the general therapeutical department (n=31). The plasma levels of IL-6 and auto-antibodies against AT1R or ETAR in peripheral blood were measured and compared between COVID19 patients with severe and milder disease and age matched controls. Clinical and standard laboratory parameters were also collected and their association with the research biomarkers was analysed. Results Auto-antibodies against AT1R were significantly increased in severe disease course (median 19.60 U/mL, IQR 4.8-34.75) compared to milder disease (median 10.95 U/mL, IQR 7.69 – 17.67, p=0.017) and the control group (median 6.79 U/mL, IQR 5.10 – 14.05, p&amp;lt; 0.001). ETAR antibody titers were also significantly increased in severe disease (median 14.52, IQR 6.76-32.94), compared to milder disease course (median 8.73 U/mL, IQR 6.59 –13.45, p=0.023) and to the control group (median 6.64, IQR 6.79 – 17.92, p &amp;lt;0.001). The same was the trend regarding IL-6 antibodies. Severe disease (median 12.11 U/mL, IQR 5.59–19.38); milder disease disease (median 8.64U/mL, IQR 1.84 – 14.13, p=0.039); control group (median 4.28U/mL, IQR 0.11–1.43, p&amp;lt;0.001).Both AT1R and ETAR correlated to IL-6 plasma levels. The results did not show association with the concomitant therapy. Conclusion In conclusion, we establishеd the presence of AT1R and ETAR autoantibodies in COVID-19 patients with heart failure with preserved ejection fraction. They correlated to IL-6 plasma levels (systemic inflammation) and are associated with severe form of the disease.

Pediatric Inflammatory Bowel Disease Type Unclassified: A Nationwide Cohort Study in Scotland With up to 20 Years Follow-up Shows Reclassification in the Majority and Mild Course in Those Whose Diagnosis Is Unchanged.

Given the paucity of long-term longitudinal data for inflammatory bowel disease type unclassified (IBDU), we aimed to clarify IBDU disease course and reclassification rate by presenting nationwide data with up to 20 years of follow-up. We analyzed a prospectively identified 11-year cohort of pediatric patients diagnosed with IBDU between January 1, 2003 and December 31, 2013 at all Scottish pediatric IBD centers and followed up into adult services until December 31, 2022. Data were obtained from electronic medical records at fixed timepoints (5 and 10 years post-diagnosis) and at the final follow-up. Overall, 102 patients were included in the analysis (57/102 [56%] male, median [interquartile range {IQR}] age at diagnosis: 11.5 [9.1-13.2] years) with a median (IQR) follow-up length of 10.5 (8.6-14.0) years. A change of diagnosis was made in 61 of 102 patients (60%); of these, 30 patients (29%) were reclassified to Crohn's disease (CD) and 31 patients (30%) to ulcerative colitis (UC). Patients who remained with IBDU had higher 1- to 5-year remission rates (IBDU 30/39 [77%] vs reclassified 16/57 [28%], P < .05), with lower rates of moderate-to-severe disease (IBDU 3/39 [8%] vs reclassified 31/57 [54%], P < .05) and less need for biologics across all timepoints (IBDU vs reclassified: first timepoint 1/39 [3%] vs 17/57 [30%], second timepoint 1/33 [3%] vs 26/56 [46%], third timepoint 0/18 [0%] vs 16/33 [49%]; all P < .05). Higher rates of surgical resections were observed in reclassified patients (reclassified 11/61 [18%] vs IBDU 1/41 [2%], P = .02). In our nationwide pediatric IBDU cohort, 60% of patients were reclassified to either UC or CD over 10.5 years of median follow-up; those who remained with IBDU had a milder disease course.

Cold case: COVID-19-triggered type 1 cryoglobulinemia

A 42-year-old male was referred to the internal medicine department because of renal failure and persistent malaise after a recent SARS-CoV-2 infection. Blood results showed anemia and severe renal insufficiency (hemoglobin of 10.3 g/dL and a creatinine of 2.19 mg/dL). Additional tests revealed a type I cryoglobulinemia with a cryoprecipitate composed of dual IgM (kappa and lambda). Further investigations on the cryoprecipitate revealed that the immunoglobulins were directed against SARS-CoV-2 antigens. In the meanwhile, our patient noticed improvement of his symptoms accompanied by resolution of laboratory abnormalities. Three months later, the cryoglobulin could no longer be detected.Type 1 cryoglobulinemia is usually associated with lymphoproliferative disorders and is characterized by various symptoms caused by cryoprecipitates occluding small blood vessels. This is, to our knowledge, the first case of type I cryoglobulinemia with proven precipitation of SARS-CoV-19 antibodies. COVID-19 induced cryoglobulinemia appears to have a mild disease course and to be self-limiting upon viral clearance.

PIMS-TS Complicating SARS-CoV-2 Infection: A Report of 10 Pediatric Cases

SARS-CoV-2, or COVID-19, is a betacoronavirus identified by the WHO as the cause of the 2020 pandemic. Unlike most respiratory virus, children exhibit lower susceptibility to COVID-19 and generally develop milder disease courses, with reduced mortality rates. Recently, there have been reports of clustered cases characterized by shock states associated with elevated cardiac biomarkers and vasoplegia, necessitating treatment with inotropes, vasopressors, and fluid resuscitation. This clinical presentation has been linked to the emergence of Pediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS), also known as Kawasaki-like syndrome. This study is a retrospective analysis of 10 pediatric patients diagnosed with PIMS-TS secondary to COVID-19 infection, who were admitted to Mohammed VI International University Hospital in Casablanca, Morocco, from January 2021 to October 2023. The cohort&amp;apos;s ages ranged from 2 to 13 years, with a mean age of 6 years, and demonstrated a male predominance (sex ratio 9M:1F). Clinical manifestations included prolonged fever, gastrointestinal disturbances, rash, conjunctivitis, and cheilitis. Laboratory findings revealed elevated levels of CRP, PCT, and ferritin, indicative of an atypical Kawasaki syndrome. These patients responded to intravenous immunoglobulin therapy, with adjunctive corticosteroids administered as needed. All patients experienced favorable outcomes, with resolution of systemic involvement and normalization of inflammatory markers, and no relapses or fatalities were recorded. The risk factors for PIMS-TS complicating COVID-19 infection remain unclear. However, there are noted parallels between PIMS-TS and Kawasaki syndrome diagnostic criteria, suggesting possible pathophysiological overlap. In conclusion, a novel multisystem inflammatory syndrome associated with COVID-19 infection, resembling Kawasaki syndrome, has been identified in pediatric patients. This emerging syndrome enhances our understanding of the complex pathophysiology associated with COVID-19 and underscores the need for continued research into its etiology and optimal management strategies.

Clinical profiling, treatment characteristics and outcome in Behcet's Disease (BD)-A retrospective cohort study from Karnataka Rheumatology Association (KRA).

Behcet's disease (BD) has a heterogeneous and unpredictable phenotype that differs in various geographical areas. To describe the clinical phenotype & outcome of Behcet's disease(BD) from Karnataka, India and compare them with large cohorts from endemic regions. Databases of practising rheumatologists from Karnataka were reviewed to retrieve clinical characteristics, course of illness, prescribing information and outcome at last follow-up of patients clinically diagnosed as BD. The classification criteria, namely revised International criteria for Behcet's disease (rICBD) and International study group (ISG) criteria were applied. Outcome was defined as complete or partial remission, persistent disease or relapse. We included 72 patients, equal gender distribution and mean age 37.4 ± 12.8years from 8 rheumatology centres. Commonest presentations were recurrent oral aphthosis 58(80.6%), genital ulcers 36(50%) and ocular manifestations 40(55.6%). Three-quarters [51/72(70.8%)] fulfilled rICBD criteria whereas only half [36/72(50%)] fulfilled ISG criteria. Apart from glucocorticoids [53/72(73.6%)], frequently prescribed therapies were colchicine 39(54.2%) and azathioprine 35(48.6%). Eleven-patients received biologics(anti-TNF-α) and JAK inhibitors to treat severe organ involvement. HLA-B*51 and pathergy tests were positive in 27/45(60%) and 12/34(35.3%) patients respectively. Outcomes were documented in 94.4%(68/72) patients at median follow-up of 24 (12;36) months. Majority [46/68(67.6%)] had complete remission, 17/68(25%) had partial remission, 4/68(5.9%) had persistent while 1/68(1.5%) had relapsing course. Majority of BD patients had orogenital aphthosis and ocular manifestations and an excellent response to treatment. Key Points • In our region, Behçet's Disease primarily manifests with recurrent oral aphthae and ocular involvement, with comparatively lower incidence of severe genital ulcers and neurological involvement than in endemic regions. • Apart from glucocorticoids, colchicine and azathioprine are the most commonly used agents. Biologics and JAK inhibitors are prescribed infrequently, primarily in cases of severe organ involvement. • A significant proportion of patients achieved either complete or partial remission during follow-up, with no observed mortality suggesting a milder disease course and better outcome compared to endemic regions. • Gender, HLA-B*51 status, and pathergy response did not exert any significant influence on the clinical profile or outcome in BD patients in Karnataka.

Pulmonary rehabilitation in follow-up and inpatient rehabilitation for Long COVID: twelve months of follow-up.

Individuals with persistent impairments due to Coronavirus disease 2019 (COVID-19) can receive pulmonary rehabilitation in Germany. To date, there is no evidence of the medium- or long-term effects of pulmonary rehabilitation on Long COVID. This study examined changes in health and occupational outcomes over time and described the therapeutic content of pulmonary rehabilitation and aftercare. This analysis also compared two rehabilitation groups after COVID-19 who had different levels of access to rehabilitation. Longitudinal observational study with multicenter and prospective data collection. Pulmonary rehabilitation in four different rehabilitation facilities in Germany. Individuals with a mild course of disease and long-lasting impairments (inpatient rehabilitation, IR) and patients with a severe course after hospitalization (follow-up rehabilitation, FuR). Participants had to be between 18 and 65 years of age. Written questionnaires were administered at the beginning and end of rehabilitation, as well as six and twelve months after rehabilitation. Health-related quality of life (HrQoL), fatigue, participation restrictions, COVID-19 symptoms, mental and physical health were assessed, as well as occupational outcomes and questions about rehabilitation and aftercare. IR patients were predominantly female (68.0%) and 52 years of age on average, while 66.1% of Long COVID rehabilitees in FuR were male and three years older. Over the course of rehabilitation, most COVID-19 symptoms decreased with statistical significance. The subjective health scales showed improvements with medium to large effect sizes (ES) over time in IR (P<0.01; ES between 0.55 (cognitive fatigue) and 1.40 (physical fatigue)) and small to large effects in FuR (P<0.01; ES between 0.45 (anxiety) and 1.32 (physical fatigue)). One year after rehabilitation, most effects remained at a moderate level. After twelve months, an increase in neurocognitive symptoms was observed in FuR patients. More than 80% of employed people returned to work one year after rehabilitation, although FuR patients returned to work a median of four weeks later (P<0.01). The comparative analysis showed that rehabilitees in different forms of rehabilitation attended rehabilitation with different impairments and rehabilitation goals, which are partly considered in treatment and aftercare. To provide needs-based rehabilitation to different rehabilitation groups with Long COVID, knowledge of their health histories and preferences is necessary.

Pediatric Respiratory Infections ‎After the COVID-19 Pandemic: A Single-Center Experience.

Background Pediatric respiratory infections, mainly bronchiolitis, are a substantial clinical burden. The most common etiology is respiratory syncytial virus (RSV). Other viruses include human rhinovirus, human metapneumovirus, influenza, adenovirus, coronavirus, and parainfluenza viruses. Objective We aimed to study the epidemiology and clinical characteristics of children with confirmed viral bronchiolitis and flu after the COVID-19 pandemic season and compare the behavior of each virus. Methods This retrospective observation study was done over seven months, from October 2022 to April 2023. All children (0-14) were included in the study if they met the clinical diagnosis of bronchiolitis or flu. Viral etiology is confirmed by PCR, using the respiratory panel available in our center which included the detection of four viruses: COVID-19, RSV, influenza A, and B. Clinical data, lab results, and X-rays were collected and correlated with each viral infection for all admitted patients. Results We recruited 237 children with bronchiolitis and flu symptoms from October 2022 to April 2023. The peak of infections (41%) was in November. Seasonal variations for each virus showed distinct patterns across the year. RSV peaked at the beginning of the season, gradually declining after that. In contrast, influenza A and B maintained a relatively consistent presence throughout the season. Meanwhile, COVID-19 reached its peak during March and April. One hundred forty-four (60%) of the patients were under two years of age. RSV was predominant in 150 patients (63.3%). COVID-19 was only detected in 25 patients (10%), whereas influenza A and B were equally isolated in 31 (13%) patients each. Fifty-one children (21%) were initially sick and required pediatric intensive care unit (PICU) admission, with no deaths reported. Notably, COVID-19 had a milder disease course, a shorter length of stay (LOS) in the hospital (two days) and a shorter duration of illness (five days) compared to other viruses. RSV infection was linked to more profound hypoxia and more sick children with more extended hospital stays. Conclusion Our study showed that, following the pandemic and the release of lockdown measures, there was another peak of upper respiratory tract infections (URTI) and flu, which was more aggressive, primarily due to other viruses, especially RSV. This resurgence was associated with more severe respiratory symptoms and an increased need for hospitalization. Notably, children with COVID-19 were in better condition compared to those with RSV.

CD74 is a functional MIF receptor on activated CD4+ T cells

Next to its classical role in MHC II-mediated antigen presentation, CD74 was identified as a high-affinity receptor for macrophage migration inhibitory factor (MIF), a pleiotropic cytokine and major determinant of various acute and chronic inflammatory conditions, cardiovascular diseases and cancer. Recent evidence suggests that CD74 is expressed in T cells, but the functional relevance of this observation is poorly understood. Here, we characterized the regulation of CD74 expression and that of the MIF chemokine receptors during activation of human CD4+ T cells and studied links to MIF-induced T-cell migration, function, and COVID-19 disease stage. MIF receptor profiling of resting primary human CD4+ T cells via flow cytometry revealed high surface expression of CXCR4, while CD74, CXCR2 and ACKR3/CXCR7 were not measurably expressed. However, CD4+ T cells constitutively expressed CD74 intracellularly, which upon T-cell activation was significantly upregulated, post-translationally modified by chondroitin sulfate and could be detected on the cell surface, as determined by flow cytometry, Western blot, immunohistochemistry, and re-analysis of available RNA-sequencing and proteomic data sets. Applying 3D-matrix-based live cell-imaging and receptor pathway-specific inhibitors, we determined a causal involvement of CD74 and CXCR4 in MIF-induced CD4+ T-cell migration. Mechanistically, proximity ligation assay visualized CD74/CXCR4 heterocomplexes on activated CD4+ T cells, which were significantly diminished after MIF treatment, pointing towards a MIF-mediated internalization process. Lastly, in a cohort of 30 COVID-19 patients, CD74 surface expression was found to be significantly upregulated on CD4+ and CD8+ T cells in patients with severe compared to patients with only mild disease course. Together, our study characterizes the MIF receptor network in the course of T-cell activation and reveals CD74 as a novel functional MIF receptor and MHC II-independent activation marker of primary human CD4+ T cells.

Coexistence of familial Mediterranean fever and seronegative spondyloarthritis: peculiarities of the course

Familial Mediterranean fever (FMF) is an autosomal recessive disease distributed among populations of Mediterranean origin - Armenians, Sephardi Jews, Arabs, Turks. There are numerous clinical observations regarding combination of FMF, as a classical representative of autoinflammatory diseases, with systemic diseases of connective tissue. Seronegative spondyloarthritis (SpA) are the most interesting disorders from this point of view, as far as sacroiliitis - an essential feature of SpA, may also present as a part of joint syndrome in FMF. The main objective of this clinical study was the investigation of the peculiarities of courses of FMF and SpA in case of their coexistence. We studied 126 patients with FMF, SpA and coexistence of both. According to results, patients with the overlap of FMF with SpA had relatively milder course of disease in comparison with each disease separately. Comparative clinical and instrumental characteristics of FMF-associated disorders had shown that in FMF-SpA overlap the symptoms of both diseases are less severe.

Comparatively analyzed pattern of Delta and Omicron SARS-CoV-2 genovariant dominated COVID-19 incidence in the population of the Saratov region

Despite the stable decline in SARS-CoV-2 virus-caused COVID-19 incidence in most countries worldwide by the end of 2023, spreading of this infection on a global scale remains relevant. Among all known SARS-CoV-2 genovariants, within the last about two years Omicron remains dominant. The distinctive properties of this genovariant are presented by short incubation period (1–5 days), high contagiousness, and a relatively mild disease course due to largest number of genomic mutations among all SARS-CoV-2 genovariants. The first case of Omicron genovariant-caused infection in Russia was recorded in early December 2021. Over many month-monitoring after active spread of the genovariant in Russia, it is obvious that in a number of key characteristics it differs profoundly from previous SARS-CoV-2 genovariants. Analyzing major patterns inherent in COVID-19 epidemic process particularly uncovering geographic features is one of the most crucial activities in COVID-19 surveillance. Here, we provide a comparatively analyzed pattern of Delta and Omicron SARS-CoV-2 genovariant dominated COVID-19 incidence in the population of the Saratov region. For this, there was used statistical reporting from the Office of Rospotrebnadzor for the Saratov Region. The main research method is based on epidemiological analysis. The study data showed that upon Omicron genovariant dominance, an increased percentage in COVID-19 cases among children of varying age, increased rate of infected subjects with unknown source of infection as well as improved clinical disease course were recorded. Regardless of the circulating genovariant, elderly people remain to be in risk group. Thus, after three years of the COVID-19 pandemic, the mutual adaptation for SARS-CoV-2 and human population can be observed, which is accompanied by altered biological properties of the former and the accumulation of herd immunity. Alleviated disease symptoms and decreased mortality rate among Omicron genovariant-infected individuals evidence in favor of further COVID-19 transformation into a seasonal infection.

Prospective Evaluation of the Prediction Score for a Mild Course of Crohn's Disease (PreMiCC) in Newly Diagnosed Patients With Crohn's Disease: The PROGNOS Study.

The course of Crohn's disease (CD) is highly variable. The Prospektive Evaluation eines Score zur Vorhersage eines milden Verlaufsbei neu diagnostizierten Morbus Crohn-Patienten in gastroenterologischen Fachpraxen (PROGNOS) study aimed to determine the frequency of a mild disease course and validate a proposed prediction score. The PROGNOS study is a prospective study of CD patients who were newly diagnosed and, except for 1 course of 5-aminosalicylic acid or steroids for ≤10 days, therapy-naïve. Among other predefined inclusion criteria, the initial diagnosis had to be made ≤6 weeks before enrollment. All inception cohort patients were diagnosed and screened consecutively in participating gastroenterology practices in Germany specialized in inflammatory bowel disease. All screened CD patients were scored and, if possible, included in the study for up to 5 years (NCT02193048). A total of 201 CD patients were included in the study (43.3% male; mean age 33 years, mean follow-up 38 months). Altogether, 29.5% of the patients had a mild course at 36 months. Among those with a score ≤2, therapy escalation at 36 months was necessary for only 24.2%, whereas in the group with a score >2, therapy escalation was necessary for 70.2% of patients. In the Kaplan-Meier curve showing time to therapy escalation in the 2 groups, there was a pronounced and statistically significant divergence of the curves starting at 3 months and extending to 48 months (P < .001). In this prospective study, about 30% of incident CD patients had a mild disease course. Our suggested PreMiCC (prediction score for a mild course of Crohn's disease) successfully predicted this.

Long-term effectiveness of zoledronic acid in patients with Paget's disease of bone - a retrospective cohort study.

The aims of the current study were to describe clinical and biochemical features of patients with Paget disease of bone (PDB) followed at our medical center, and to examine the long-term effectiveness of zoledronate. Retrospective cohort study included consecutive patients≥18 years with a diagnosis of PDB, followed in the Rabin Medical Center (RMC) Institute of Endocrinology from 1973 to 2023. The cohort comprised two groups: patients treated/not treated with zoledronic acid (ZOL/NZOL). The primary outcome was the percentage of patients who achieved a biochemical therapeutic response. Overall, 101 patients with PDB were included, 68 in the ZOL group and 33 in the NZOL group. The mean age was 65.2 ± 10.0 years, and 47% were female. Notably, 77% exhibited monostotic involvement, and only 3% had experienced fractures attributed to PDB. Mean ALP level at diagnosis was 160 ± 70.6 U/L. The median follow-up duration was 17 years since PDB diagnosis, comparable between the groups. Primary outcome was more prevalent in the ZOL compared to the NZOL group [42 patients (88%) VS 11 patients (52%) respectively, P = 0.004]. At the end of follow-up, mean ALP levels in the NZOL group were significantly higher than the levels in the ZOL group irrespective of the number of infusions received. The majority of patients with PDB experience a mild disease course, marked by monostotic involvement and a low prevalence of fractures. Zoledronic acid effectively manages PDB, providing sustained biochemical response. The necessity for multiple zoledronic acid injections remains questionable, often implemented due to osteoporosis.

PCR-based study on viral pathogens circulation among cervids in the Moscow region

A molecular survey of selected viruses in free-ranging cervids was conducted in 15 different districts of Moscow region. Samples were collected from 178 game animals including 144 moose (Alces alces), 19 roe deer (Capreolus capreolus) and 15 deer without species information. Nasal swabs and tissue samples including parts of the nasal septum, upper tracheal rings, lung, heart, liver, kidneys and pooled organ samples were tested using polymerase chain reaction (PCR). Samples were studied for pestiviruses, herpesviruses, coronaviruses, group A rotaviruses, adenoviruses, hepatitis e and parainfluenza type 3 virus. None of the samples were positive for Bovine Coronavirus and SARS-COV-2, hepatitis E virus and parainfluenza type 3 virus. PCR results were positive for bovine herpesviruses (5.05%), pestiviruses (0.56%), rotaviruses (1.68%). DNA of a new adenovirus, presumably causing a mild course of animal respiratory disease, was detected in samples of 6 animals (3.37%). In conclusion, the conducted studies have shown that game animals of the Moscow region can be a natural reservoir of cattle viruses, and this must be taken into account when planning and organizing measures for the control and eradication of such notifiable diseases as bovine viral diarrhoea and infectious bovine rhinotracheitis. Monitoring studies and general disease surveillance of wild animal populations provide additional information on the epidemiology of infectious diseases in the region and allow timely measures to be taken to protect wild animals, domestic animals and the public.

Healthy Lifestyle Is a Protective Factor from Moderate and Severe Relapses and Steroid Use in Inflammatory Bowel Disease: A Prospective Cohort Study.

A healthy lifestyle, including good adherence to a Mediterranean diet (MD) and regular physical exercise, may be an important factor during the course of inflammatory bowel disease (IBD). Our aim is to determine whether adherence to MD, physical activity, and the combination of both can impact on IBD course. This prospective cohort study includes 693 IBD outpatients who were in remission with a median follow-up time of 27 months (interquartile range 22-29 months). Each patient completed a survey to assess their adherence to the MD and physical activity. Healthy lifestyle was considered to be a proper adherence to both MD and an active lifestyle. Relapse during follow-up, severity of relapses, need for systemic steroids, and therapy changes were recorded. During the follow-up period, 188 patients (27.1%) experienced relapse, of which 56.1% were moderate or severe. Among patients with relapse, 85 (45%) required treatment with corticosteroids, and 15 (7.9%) were hospitalized. Patients with ulcerative colitis (CU) were more adherent to healthy lifestyle than patients with Crohn's disease (P = .011). Healthy lifestyle was associated with lower risk of moderate and severe relapses (adjusted Hazard ratio [aHR], 0.250; 95% confidence interval [CI], 0.093-0.670) and steroids use (aHR 0.292; 95% CI, 0.103-0.828) in IBD patients and with lower risk of moderate and severe relapses (aHR 0.270; 95% CI, 0.093-0.789) in UC patients. Healthy lifestyle has a favorable influence on promoting a milder disease course, and thus should be a crucial part of clinical management of patients with IBD.

Predicting acute kidney injury onset with a random forest algorithm using electronic medical records of COVID-19 patients: the CRACoV-AKI model.

Acute kidney injury (AKI) is a serious and common complication of SARS‑CoV‑2 infection. Most risk assessment tools for AKI have been developed in the intensive care unit or in elderly populations. As the COVID‑19 pandemic is transitioning into an endemic phase, there is an unmet need for prognostic scores tailored to the population of patients hospitalized for this disease. We aimed to develop a robust predictive model for the occurrence of AKI in hospitalized patients with COVID‑19. Electronic medical records of all adult inpatients admitted between March 2020 and January 2022 were extracted from the database of a large, tertiary care center with a reference status in Lesser Poland. We screened 5806 patients with SARS‑CoV‑2 infection confirmed with a polymerase chain reaction test. After excluding individuals with lacking data on serum creatinine levels and those with a mild disease course (<7 days of inpatient care), a total of 4630 records were considered. Data were randomly split into training (n = 3462) and test (n = 1168) sets. A random forest model was tuned with feature engineering based on expert advice and metrics evaluated in nested cross‑validation to reduce bias. Nested cross‑validation yielded an area under the curve ranging between 0.793 and 0.807, and an average performance of 0.798. Model explanation techniques from a global perspective suggested that a need for respiratory support, chronic kidney disease, and procalcitonin concentration were among the most important variables in permutation tests. The CRACoV‑AKI model enables AKI risk stratification among hospitalized patients with COVID‑19. Machine learning-based tools may thus offer additional decision‑making support for specialist providers.

Post-COVID fatigue: Reduced quality-of-life associated with clinically relevant fatigue in mild disease courses

ABSTRACT Fatigue is a pervasive symptom experienced by many individuals after COVID-19. Despite its widespread occurrence, fatigue remains a poorly understood and complex phenomenon. Our aim is to evaluate the subjective experience of mental fatigue after COVID-19 and to assess its significance for daily life functioning. In this online questionnaire study (N = 220), the Fatigue Severity Scale (FSS), World Health Organization Quality-of-Life assessment (WHOQoL) and a subjective severity rating of the COVID-19 disease progression were used. For our statistical analyses we utilized independent samples t-tests, one-way ANOVA with post-hoc analyses, and a multiple regression. As expected our findings revealed the COVID group reported significantly higher levels of subjective fatigue compared to the control group. Moreover, there was a significant difference between experienced fatigue across the four severity groups. Participants who had a milder course of disease also experienced severe subjective fatigue. Subjective fatigue explained 40% variance in quality-of-life. In conclusion, severe subjective fatigue appears to be associated with increased self-reported COVID-19 symptom severity and lower quality-of-life but is already observable in milder cases. This underscores, firstly, the importance of considering also less severe cases and, secondly, the need to develop rehabilitation and psychological interventions for fatigue.