Mild Clinical Presentation Research Articles

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< 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 <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<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.

The Impact of Using Standardized Autism Screening on Referral to Specialist Evaluation for Young Children on the Autism Spectrum: A Cluster-Randomized Controlled Trial

We tested whether the implementation of standardized, high-fidelity screening for autism during routine well-child check-ups results in the following: increasing the number of children with suspected autism referred to diagnostic evaluation; lowering the age at which they are referred; and facilitating autism diagnosis for children across a more diverse range of demographic backgrounds and clinical presentations, including those with subtle manifestations. As part of a multi-site cluster randomized trial, pediatric practices were randomly assigned to an experimental condition involving training and supervision in the universal, standardized, high-fidelity implementation of the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F), or a usual care condition. Children in both conditions identified as having a high likelihood of autism during well-child visits were referred to a diagnostic evaluation conducted by clinicians naive to referral source. Children referred to the diagnostic evaluation from the practices in the experimental condition were more numerous (n= 186) and younger (mean age= 20.65 months) than those referred from the practices in the usual care condition (n= 39; mean age= 23.58 months). Children referred by experimental practices who received an autism diagnosis had milder clinical presentations across measures of cognitive, language, adaptive, and social-communication functioning, compared to those referred from usual care practices. Demographic characteristics were similar across groups. Standardized, high-fidelity implementation of autism screening during pediatric well-child visits facilitates the identification of children with high autism likelihood at a younger age, including those presenting with more subtle clinical manifestations. Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes; https://clinicaltrials.gov/; NCT03333629.

Tailoring Management of May-Thurner Syndrome : Case Comparison

Background: May-Thurner syndrome (MTS) is a post-thrombosis syndrome (PTS) of the lower extremity. This disorder results from compression and/or irritation from adjacent crossing the right common iliac artery to the left iliac venous. In this report, we present two management comparisons of patients with left lower DVT with consideration of MTS. Case Illustration: The first patient is a 49-year-old male soldier presented with chronic unilateral left leg edema and a mild clinical presentation for 9 months. Previous Doppler ultrasonography (DUS) revealed a thrombus in the left venous femoralis. Anticoagulant was given for six months. DUS and CT venography following anticoagulant treatment revealed a thrombus in the left venous femoralis. Venography revealed entire blockage of the left common femoral and left iliac veins, with adequate collateral flow. PTV was attempted twice and failed both times. The patient was following a conservative therapy (walking exercise and stocking compression) that yielded positive outcomes. The second patient is a 53-year-old male soldier has had unilateral left leg edema for three years, which has increased during the previous three months with ulceration and active bleeding. Previous Doppler ultrasonography revealed a thrombus in the left iliac externa. Anticoagulants and compression stockings were given for eight months, but the symptoms persisted. CT and venography revealed a complete blockage from the left popliteal vein to the iliac vein. Femoral crossover bypass surgery yielded favorable results. Conclusion: Clinically moderate MTS demonstrated fair results with conservative treatment, whereas clinically severe MTS showed superior results with bypass surgery. Keyword: Anticoagulant, May-Thurner Syndrome, Palma Procedure.

International expert consensus recommendations for the use of dermocosmetics in acne.

A wide variety of dermocosmetics (products with both active skincare and cosmetic activity) are available for the management of acne vulgaris. These products are important because they may be the first line of approach for patients desiring to self-treat and they can also have beneficial effects-reducing lesion counts and improving global acne severity. When used in conjunction with medical therapy, dermocosmetics can improve tolerability and enhance results. We reviewed available evidence and combined it with our clinical experience to help guide clinicians in selecting skincare products with acne-targeting ingredients. An international panel of dermatologists with an interest and expertise in managing acne performed a literature review, formulated clinical questions related to the role of dermocosmetics in the acne setting, used a modified GRADE approach to evaluate available evidence and then utilized an online iterative Delphi process to create consensus recommendations. It should be noted that due to the limited number of available studies, the category of dermocosmetics was evaluated rather than specific ingredients. The quality of evidence was found to be low to moderate. Key recommendations were made based on available evidence for the use of dermocosmetics in acne to improve acne global assessment, reduce acne lesion counts, reduce superficial skin oiliness and serve as maintenance therapy after medical treatment, while providing a good tolerability. Recommendations were also made for using dermocosmetics as adjuncts to medical treatment. While there is a need for better quality evidence, dermocosmetics have demonstrated some benefit for acne both when used alone in its milder clinical presentations or in maintenance post acne medication and as adjunct to acne treatments.

#198 Different patterns of renal thrombotic microangiopathy

Abstract Background and Aims Thrombotic microangiopathy (TMA) is a renal lesion often associated with microangiopathic hemolysis. However, there are cases of TMA that present without hemolysis, hematuria or even proteinuria, sometimes being an incidental histopathological finding. In these situations, little is known about the long-term effects on renal function. The aim of our study is to describe the clinical and histopathological presentation of patients with renal TMA biopsied in our center, focusing on those without hemolysis and with low clinical suspicion of TMA. Method We conducted a retrospective observational unicentric study. Clinical and histological parameters were collected from patients biopsied between 2015 and 2023, whose renal biopsy (RB) showed TMA, with a minimum follow-up of 6 months. We excluded renal transplant recipients. Results Data were collected from 41 patients (17 men, 24 women), with a mean age at the time of RB of 54 ± 16 years and a mean eGFR of 80 ± 23 ml/min/1.72 m2. 12 of them (29%) had chronic kidney disease (CKD). Twenty-seven patients (66%) did not have hemolysis at diagnosis. Compared to patients with hemolysis, they were of older age (58 vs 47 years, p = 0.030) and had higher prevalence of CKD (41% vs 7%, p = 0.028). They had a milder clinical presentation, with lower creatinine (168 vs 419 μmol/L, p = 0.029), lower need for renal replacement therapy (RRT) (4% vs 50%, p = 0.001), less hematuria (33% vs 79%, p = 0.008) and proteinuria (67% vs 100%, p = 0.035). Histologically, patients without hemolysis had less fibrosis (56% vs 86%, p = 0.084) and fewer chronic TMA lesions (double contours, wrinkling of the basement membrane) (52% vs 93%, p = 0.009), despite delayed renal biopsy compared to patients with hemolysis (99 ± 118 vs 28 ± 30 days since clinical presentation, p = 0.036). The causes of TMA that were most commonly associated with the absence of hemolysis were drugs (89% without hemolysis) and glomerulopathies such as IgA nephropathy, minimal change disease and fibrillary glomerulonephritis (100% without hemolysis). Within this group of patients without hemolysis, 13 (32%) had a low clinical suspicion of TMA, defined as the absence of hemolysis, hypertension and predisposing factors, in some cases being an incidental finding in the RB. As expected, they also had a mild presentation and did not require RRT. In some cases, they even presented without proteinuria (7 patients, 64%). When comparing the severity of the lesions in renal tissue with patients with high clinical suspicion of TMA, patients with low clinical suspicion presented a similar prevalence of mesangiolysis, vascular damage and a similar proportion of affected glomeruli. Chronic TMA lesions were present in both groups (Table 1). When analysing the evolution of renal function, there are several confounding factors to consider (higher prevalence of CKD in patients without hemolysis, targeted treatment in patients with hemolysis, different time of follow-up between groups...). In our results, there were no statistically significant differences in the evolution of creatinine and proteinuria between groups, even when TMA was an incidental finding. In our sample, these findings were not attributable to a larger number of other histopathological lesions in patients with low suspicion of TMA, as there were no differences between groups (see Table 1). Conclusion Renal TMA should be suspected even in the absence of hemolysis, hypertension or proteinuria, as in our sample one third of diagnoses were incidental and their mild presentation may have delayed renal biopsy. The severity of histological lesions and the evolution of renal function in these cases are comparable to those of patients with a high clinical suspicion. Therefore, its prompt identification, etiological study and treatment are equally important. Currently, we have insufficient data to provide the different clinical scenarios in which TMA should be suspected. However, based on our findings, in the presence of drugs TMA should be considered in the differential diagnosis along with Acute Interstitial Nephritis, even in the absence of urinary abnormalities.

External validation of the SI2NCAL2C score for outcomes following cerebral venous thrombosis

ObjectivesPrognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI2NCAL2C score in an international cohort. Materials and methodsThe SI2NCAL2C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI2NCAL2C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. ResultsMortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI2NCAL2C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year. ConclusionsThe SI2NCAL2C score had acceptable to good performance in an international external validation cohort. The SI2NCAL2C score warrants additional validation studies in diverse populations and clinical implementation studies.

Abstract TMP108: External Validation of the SI 2 NCAL 2 C Score for Mortality Following Cerebral Venous Thrombosis

Background: Prognostication following cerebral venous thrombosis (CVT) remains challenging. Mortality is an uncommon yet catastrophic outcome after CVT. We sought to externally validate the SI 2 NCAL 2 C score for mortality in an international cohort. Methods: The SI 2 NCAL 2 C score was developed from the International CVT Consortium Registry to predict mortality by 30 days and one year using the factors: female- s ex-specific risk factors, i ntracerebral hemorrhage, CNS i nfection, n eurological focal deficits, c oma, a ge, hemoglobin l evel, glucose l evel, and c ancer. ACTION-CVT was an international retrospective study that enrolled consecutive patients with CVT across 27 centers. Model performance was evaluated using the area under the curve (AUC) of the time-dependent receiver operating characteristic curve and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. Results: After exclusion of one site which contributed data to the derivation cohort, 950 of 1,025 patients enrolled in ACTION-CVT were analyzed. Compared to the derivation cohort, the ACTION-CVT cohort was older (median 44 vs 40 years), less female (63.4% vs 69.8%), and with milder clinical presentation (focal deficits 38.6% vs 57.1%; seizures 22.6% vs 36.7%). Mortality was 2.5% by 30 days and 6.0% by one year. The SI 2 NCAL 2 C score achieved an AUC of 0.716 [95% CI 0.603-0.823] for mortality by 30 days and 0.820 [0.761-0.878] for mortality by one year. Calibration plots demonstrated an overestimation of predicted risk among patients with low observed mortality, concordant with score derivation (Fig 1, A-D). Conclusions: The SI 2 NCAL 2 C score had acceptable performance in an international validation cohort despite differences in baseline characteristics between cohorts. The SI 2 NCAL 2 C score warrants additional validation studies in diverse populations and clinical implementation studies.

Clinical characteristics and outcomes of vaccinated patients hospitalised with SARS-CoV-2 breakthrough infection: Multi-IPV, a multicentre study in Northern Italy

BackgroundDespite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. MethodsData collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson’s Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. ResultsData from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039–0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582–1.703, p = 0.987). ConclusionsThis study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates.

Exploring the Various Radiological Observations and Appearances in Patients with Dengue Fever; A Retrospective Observational Approach

Objective: To assess the range of radiological observations in patients testing positive for dengue serology. Methodology: This retrospective, observational study was conducted at Islamabad Diagnostic Center, Islamabad from September 2022 to March 2023. The Ethical Committee approved this study. All the individuals who arrived at the IDC, Islamabad, complaining of fever and tested positive for dengue serology, from September 2022 to March 2023, were included in our study. A total of 240 patients met these criteria. Patient details, including age and gender, were obtained from the center’s computer system. Results: Severe cases of dengue fever, including thrombocytopenia, were observed in 62 out of 240 patients (25.83%), while mild clinical presentations were noted in rest of the 178 patients (74.16%). The most mutual radiological outcome was wall edema of the gall bladder (figure 2a), seen in 113 out of 240 patients (47.08%). This was followed by ascites (2b), that were observed in 38.33% (n=92) cases. Hepatomegaly was noted in 10.83% (n=26) (2c), splenomegaly in 3.75% (n=9) (2d) respectively. Conclusion: Dengue fever presents with a variety of manifestations. Imaging techniques, especially ultrasound, can be employed to promptly identify the characteristics and complications of dengue fever in emergency situations, even when serological tests are unavailable or delayed.

Identification of Key Disulfidptosis-Related Genes and Their Association with Gene Expression Subtypes in Crohn's Disease.

Crohn's disease (CD) is a persistent inflammatory condition that impacts the gastrointestinal system and is characterized by a multifaceted pathogenesis involving genetic, immune, and environmental components. This study primarily investigates the relationship between gene expression and immune cell infiltration in CD, focusing on disulfidptosis-a novel form of cell death caused by abnormal disulfide accumulation-and its impact on various immune cell populations. By identifying key disulfidptosis-related genes (DRGs) and exploring their association with distinct gene expression subtypes, this research aims to enhance our understanding of CD and potentially other autoimmune diseases. Gene expression data from intestinal biopsy samples were collected from both individuals with CD and healthy controls, and these data were retrieved from the GEO database. Through gene expression level comparisons, various differentially expressed genes (DEGs) were identified. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to reveal the biological processes and pathways linked to these DEGs. Later, immune cell infiltration was evaluated. Hub candidate DRGs were identified using machine learning algorithms. Validation of the expression of hub DRGs was carried out using quantitative real-time polymerase chain reaction. The hub DRGs were subjected to unsupervised hierarchical clustering to classify CD patients into subtypes. The characteristics of each subtype were then analyzed. Two hub DRGs (NDUFA11 and LRPPRC) were identified. NDUFA11 showed a significantly positive association with the abundance of Th17 cells. Conversely, higher expression levels of LRPPRC were associated with a reduced abundance of various immune cells, particularly monocytes. CD patients were classified into two disulfidptosis-related subtypes. Cluster B patients exhibited lower immune infiltration and milder clinical presentation. LRPPRC and NDUFA11 are identified as hub DRGs in CD, with potential roles in disulfidptosis and immune regulation. The disulfidptosis subtypes provide new insights into disease progression.

Epidemiological Characteristics of COVID-19 during Seven Consecutive Epidemiological Waves (2020-2022) in the North Bačka District, Serbia.

The COVID-19 pandemic continues to pose a threat to global public health. The purpose of this research was to determine the epidemiological characteristics of COVID-19 in the North Bačka district while observing seven pandemic waves. The cross-sectional study was based on data from the COVID-19 surveillance database of the Institute for Public Health of Vojvodina during the period from March 2020 to December 2022. A total of 38,685 primary infections and 4067 reinfections caused by SARS-CoV-2 were notified. Pandemic waves caused by the Delta variant (cumulative incidence rate of 2482.37/100,000) and by the Omicron variant (cumulative incidence rate of 2994.45/100,000) emerged as significant focal points during the surveillance period. Over the course of three consecutive years (2020-2022), women were more affected (50.11%, 54.03%, and 55.68%, respectively). The highest incidence rates in age-specific categories were recorded in 2021 for the age group 40-49 (1345.32 per 10,000 inhabitants), while in 2022, they shifted towards the elderly population. Regarding vaccination status at the time of diagnosis, in 2021, around 15% of patients were vaccinated, while in 2022, the number increased to 37%. The most widely received vaccine was BBIBP-CorV (67.45%), followed by BNT162b2 (19.81%), Gam-COVID-Vac (9.31%), and ChAdOx1 nCoV-19 (3.42%) vaccine. The implementation of stringent public health measures and their mitigation, together with the emergence of new variants, influenced the dynamics of COVID-19 pandemic waves in the North Bačka district. Notably, throughout the study period, the working-age population was the most affected, along with females, with a mild clinical presentation dominating. Reinfections were most frequently recorded during the latter pandemic waves. Dealing with this pandemic has provided some valuable lessons for the development of future strategies in the case of a similar public health crisis.

Pathobiological alterations affecting the distinct clinical courses of pediatric versus adult COVID-19 syndrome.

The clinical presentation of pediatric coronavirus disease 2019 (COVID-19) is associated with a milder disease course than the adult COVID-19 syndrome. The disease course of COVID-19 has three clinicobiological phases: initiation, propagation, and complication. This study aimed to assess the pathobiological alterations affecting the distinct clinical courses of COVID-19 in pediatric age groups versus the adult population. We hypothesized that critical biogenomic marker expressions drive the mild clinical presentations of pediatric COVID-19. Blood samples were obtained from 72 patients with COVID-19 hospitalized at Ankara City Hospital between March and July 2021. Peripheral blood mononuclear cells were isolated using Ficoll-Paque and density-gradient sedimentation. The groups were compared using a t-test and limma analyses. Mean standardized gene expression levels were used to hierarchically cluster genes employing Euclidean Gene Cluster 3.0. The expression levels of identified genes were determined using reverse transcription-polymerase chain reaction. This study found that ANPEP gene expression was significantly downregulated in the pediatric group (p < 0.05, FC: 1.57) and IGF2R gene expression was significantly upregulated in the adult group (p < 0.05, FC: 2.98). The study results indicated that the expression of critical biogenomic markers, such as the first-phase (ACE2 and ANPEP) and second-phase (EGFR and IGF2R) receptor genes, was crucial in the genesis of mild clinical presentations of pediatric COVID-19. ANPEP gene expression was lower in pediatric COVID-19. The interrelationship between the ANPEP and ACE2 genes may prevent the progression of COVID-19 from initiation to the propagating phase in pediatric patients. High IGF2R gene expression could potentially contribute to a protective effect and may be a contributing factor for the mild clinical course observed in pediatric patients.

Combined PMM2-CDG and hereditary fructose intolerance in a patient with mild clinical presentation

We report a patient with an extremely rare, combined diagnosis of PMM2-CDG and hereditary fructose intolerance (HFI). By comparing with other patients, under-galactosylation was identified as a feature of HFI. Fructose/sorbitol/sucrose restriction was initiated right afterwards. The patient is at the mild end of the PMM2-CDG spectrum, raising the question of sorbitol's role in the pathogenesis of PMM2-CDG and whether fructose/sorbitol/sucrose restriction could benefit other PMM2-CDG patients. Additionally, epalrestat, an emerging potential PMM2-CDG therapy, may benefit HFI patients.

Systematic genomic analysis of SARS-CoV-2 co-infections throughout the pandemic and segregation of the strains involved.

SARS-CoV-2 recombinants involving the divergent Delta and Omicron lineages have been described, and one of them, "Kraken" (XBB.1.5), has recently been a matter of concern. Recombination requires the coexistence of two SARS-CoV-2 strains in the same individual. Only a limited number of studies have focused on the identification of co-infections and are restricted to co-infections involving the Delta/Omicron lineages. We performed a systematic identification of SARS-CoV-2 co-infections throughout the pandemic (7609 different patients sequenced), not biassed towards the involvement of highly divergent lineages. Through a comprehensive set of validations based on the distribution of allelic frequencies, phylogenetic consistency, re-sequencing, host genetic analysis and contextual epidemiological analysis, these co-infections were robustly assigned. Fourteen (0.18%) co-infections with ≥ 8 heterozygous calls (8-85 HZs) were identified. Co-infections were identified throughout the pandemic and involved an equal proportion of strains from different lineages/sublineages (including pre-Alpha variants, Delta and Omicron) or strains from the same lineage. Co-infected cases were mainly unvaccinated, with mild or asymptomatic clinical presentation, and most were at risk of overexposure associated with the healthcare environment. Strain segregation enabled integration of sequences to clarify nosocomial outbreaks where analysis had been impaired due to co-infection. Co-infection cases were identified throughout the pandemic, not just in the time periods when highly divergent lineages were co-circulating. Co-infections involving different lineages or strains from the same lineage were occurring in the same proportion. Most cases were mild, did not require medical assistance and were not vaccinated, and a large proportion were associated with the hospital environment.

Poster 170: First-Time Anterior Shoulder Instability Events in Subluxators versus Dislocators: A Comparison of Clinical Presentation, Extent of Injury, and Revision

Objectives: The objective of this study was to characterize epidemiology and postoperative outcomes in subluxators and dislocators after a first-time anterior instability (FTAI) event. We hypothesized that subluxators would have a milder clinical presentation, lesser degree of pathology on imaging, and fewer anchors placed intraoperatively in comparison to dislocators. Methods: Surgically managed FTAI patients from a single institution between 2013-2020 were included. Exclusion criteria included multidirectional instability and recurrent instability. Demographics and surgical details were retrospectively collected. Instability was categorized into dislocation, in which another person reduced the shoulder, or subluxation, in which there was no documentation of another person reducing the shoulder. Labral tear location was determined using the clock method and labral tear size was determined by assigning 1 point to each hour around the clock for a maximum value of 12. Results: 146 patients (97 subluxators, 79 dislocators) were available for analysis. There were no significant differences in baseline demographics. Rates of bony Bankarts were equivalent, but Hill-Sachs lesions were reported more in dislocators (88.1% vs. 52.6%, p&lt;0.001). Table 1. Preoperative and postoperative ROM and strength was equivalent between cohorts. There was no difference in either labral total tear size or incidence of concomitant posterior or superior labrum tears. There was no difference in the number of anchors used, although remplissage was performed more in dislocators (18.9% for dislocators vs. 6.0%, p = 0.002). Revision rates were not significantly different between cohorts. Conclusions: Subluxators and dislocators had similar clinical presentations with no difference in the extent of injury except for greater frequency of Hill-Sachs lesions in dislocators with similar surgical outcomes. Given comparable injury characteristics, a tendency to bias subluxation events as “less severe” should be reconsidered. Further investigations may be necessary to determine demographic and anatomic predictive risk factors that influence outcomes between these two populations. [Table: see text]

Children diagnosed with presymptomatic type 1 diabetes through public health screening have milder diabetes at clinical manifestation.

We aimed to determine whether disease severity was reduced at onset of clinical (stage 3) type 1 diabetes in children previously diagnosed with presymptomatic type 1 diabetes in a population-based screening programme for islet autoantibodies. Clinical data obtained at diagnosis of stage 3 type 1 diabetes were evaluated in 128 children previously diagnosed with presymptomatic early-stage type 1 diabetes between 2015 and 2022 in the Fr1da study and compared with data from 736 children diagnosed with incident type 1 diabetes between 2009 and 2018 at a similar age in the DiMelli study without prior screening. At the diagnosis of stage 3 type 1 diabetes, children with a prior early-stage diagnosis had lower median HbA1c (51 mmol/mol vs 91 mmol/mol [6.8% vs 10.5%], p<0.001), lower median fasting glucose (5.3 mmol/l vs 7.2 mmol/l, p<0.05) and higher median fasting C-peptide (0.21 nmol/l vs 0.10 nmol/l, p<0.001) compared with children without previous early-stage diagnosis. Fewer participants with prior early-stage diagnosis had ketonuria (22.2% vs 78.4%, p<0.001) or required insulin treatment (72.3% vs 98.1%, p<0.05) and only 2.5% presented with diabetic ketoacidosis at diagnosis of stage 3 type 1 diabetes. Outcomes in children with a prior early-stage diagnosis were not associated with a family history of type 1 diabetes or diagnosis during the COVID-19 pandemic. A milder clinical presentation was observed in children who participated in education and monitoring after early-stage diagnosis. Diagnosis of presymptomatic type 1 diabetes in children followed by education and monitoring improved clinical presentation at the onset of stage 3 type 1 diabetes.

Inherited human ZNF341 deficiency.

Typical hyper-IgE syndromes (HIES) are caused by autosomal-dominant-negative (DN) variants of STAT3 (Signal Transducer And Activator Of Transcription 3) or IL6ST (Interleukin 6 Cytokine Family Signal Transducer), biallelic partial loss-of-function (LOF) variants of IL6ST, or biallelic complete LOF variants of ZNF341 (Zinc Finger Protein 341). Including the two new cases described in this review, only 20 patients with autosomal-recessive (AR) ZNF341 deficiency have ever been reported. Patients with AR ZNF341 deficiency have clinical and immunological phenotypes resembling those of patients with autosomal-dominant STAT3 deficiency, but with a usually milder clinical presentation and lower NK (Natural Killer) cell counts. ZNF341-deficient cells have 50% the normal level of STAT3 in the resting state. However, as there is no clear evidence that STAT3 haploinsufficiency causes HIES, this decrease alone is probably insufficient to explain the HIES phenotype observed in the ZNF341-deficient patients. The combination of decreased basal expression level and impaired autoinduction of STAT3 observed in ZNF341-deficient lymphocytes is considered a more likely pathophysiological mechanism. We review here what is currently known about the ZNF341 gene and ZNF341 deficiency, and briefly discuss possible roles for this protein in addition to its control of STAT3 activity.

Gitelman syndrome with Graves’ disease leading to rhabdomyolysis: a case report and literature review

A 14-year-old male patient who suffered from limb numbness, fatigue, and hypokalemia was considered Graves’ disease (GD) complicated with thyrotoxic periodic paralysis (TPP) at the first diagnosis. Although with the treatment of antithyroid drugs, he developed severe hypokalemia and rhabdomyolysis (RM). Further laboratory tests revealed hypomagnesemia, hypocalciuria, metabolic alkalosis, hyperrenin, and hyperaldosteronemia. Genetic testing revealed compound heterozygous mutations in the SLC12A3 gene (c.506-1G > A, c.1456G > A) encoding the thiazide-sensitive sodium-chloride cotransporter, which presented a definitive diagnosis of Gitelman syndrome (GS). Moreover, gene analysis revealed his mother diagnosed with subclinical hypothyroidism due to Hashimoto’s thyroiditis carried the c.506-1G > A heterozygous mutation in the SLC12A3 gene and his father carried the c.1456G > A heterozygous mutation in the SLC12A3 gene. His younger sister who had hypokalemia and hypomagnesemia carried the same compound heterozygous mutations as the proband and was diagnosed with GS as well, but with a much milder clinical presentation and better treatment outcome. This case suggested the potential relationship between GS and GD, clinicians should strengthen the differential diagnosis to avoid missed diagnosis.

Clinical Update on Congenital Adrenal Hyperplasia: Recommendations from a Multidisciplinary Adrenal Program.

Congenital adrenal hyperplasia (CAH) is a common genetic disorder in endocrinology, especially its milder clinical presentation, often caused by a partial or total deficiency of the 21-hydroxylase enzyme located in the adrenal cortex. CAH is characterized by the overproduction of androgen, along with variable degrees of cortisol and aldosterone deficiency. The age at diagnosis can provide some information about underlying mutations, with those diagnosed at birth/early infancy more likely to have severe enzymatic defects, which may include adrenal insufficiency, sexual development disorders, short stature in adulthood, hirsutism, and a higher risk for metabolic syndrome and infertility. Non-classic CAH, a milder form of CAH, is usually manifested later in life and is a common differential diagnosis of Polycystic Ovary Syndrome and should be actively evaluated during initial studies of clinical or biochemical hyperandrogenism. The main goals of CAH treatment are hormone supplementation for severe cases, controlling adrenal androgen overproduction to minimize long-term side effects, managing fertility and genetic counseling, and optimizing patients' quality of life.

Clinical Characteristics and Pattern of Imaging Change of Pediatric COVID-19

Introduction: COVID-19 infection in children is relatively milder and vary from that in adults. Higher fatality rate of children in Bangladesh from COVID-19 infection does not matched with other country may be due to malnutrition, air pollution, poverty, poor parental education about health hygine, inadequate access to high-quality acute healthcare. Chest X-ray is initial imaging technique which is done in children with mild respiratory infections with or without dyspnea. Few studies have reported the radiological findings of COVID-19 in children. Objective: In this study, our main goal was to investigate the clinical and imaging features of pediatric COVID-19 patients in child corona unit of Dhaka Medical College Hospital, Bangladesh. Materials and Methods: This single center observational study was conducted in Child Corona Unit of Dhaka Medical College Hospital between January 2022 to September 2022. A total of 123 COVID-19 positive pediatric patients detected by RT-PCR were purposively included in the study. Patients with comorbidities were excluded from the study. Results: Among 123 children with COVID-19, 43 had no symptoms, 71 had low grade fever and 9 presented with cough, nasal congestion, diarrhea, headache, or fatigue. Normal X-ray findings present in 50(40.6%), unilateral patchy shadowing in 28 (22.8%), bilateral patchy shadowing in 22(17.9%), ground glass opacity in 11(8.9%), consolidation in 7(5.8%) and Interstitial abnormalities in 5(4.0%). Conclusion: This study throw light on the cases of COVID-19 in the pediatric population. Children usually have mild or moderate clinical and imaging presentations. Understanding of the clinical and imaging findings helps in reducing misdiagnosis rate for those with concealed and atypical symptoms. Medicine Today 2023 Vol.35(1): 7-11