Differences In Clinical Course Research Articles

#1039 Characteristics and outcome of IgA nephropathy in Switzerland – a single center perspective

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide leading to end-stage kidney disease (ESKD) in roughly 40% of affected patients by ten years. Geographic differences in clinical course and response to treatment may partly result from different disease entities. The purpose of this retrospective cohort analysis was to study all cases of IgAN from a single tertiary center with respect to clinical and histological characteristics, treatment practices and outcome. Method This retrospective cohort analysis identified 158 cases of adult biopsy-proven IgAN by chart review diagnosed between 1980 and 2017. Detailed phenotypisation including clinical, paraclinical, histological, treatment and outcome parameters was performed. Remission status was defined as described previously (Reich 2007). Statistical analysis was performed using Excel and SPSS software and included standard descriptive methods and included standard descriptive methods and student's t-test on a significance level of 0.05. Results Subjects were majorly male and of Caucasian descent. Mean estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration formula at diagnosis was 55.3 ml/min/1.73 m2, mean proteinuria was 3.2 g/d. 70.3% of patients were hypertensive at presentation. Clinical presentation varied according to age. Thus, younger patients (18-39 years) presented more frequently with macrohematuria, asymptomatic urine abnormalities and by trend acute kidney injury whereas nephrotic syndrome and extrarenal symptoms were recorded in similar proportions of patients (Fig. 1). 28.5% of initial biopsies showed moderate to severe tubular atrophy and interstitial fibrosis (IFTA), 38% included crescents, 1.9% > 50% crescents. 86.1% of the patients were treated by renin-angiotensin-aldosterone-system inhibitors, 46.8% received immunosuppressive therapy including steroids in 46.2% and other immunosuppressive medications in 19.6% the most common being azathioprine (Fig. 2). There were 33.5% complete and 13.3% partial remissions. Progression to ESKD was noted in 42.1%. 51.4% of patients treated with immunosuppressive therapy experienced remission. Recurrence rate after transplantation was 18.4%. Patients treated by immunosuppressants had higher levels of baseline proteinuria (3.2 ± 2.3 vs. 1.6 ± 1.6 g/d, p < 0.00001), lower baseline eGFR (50 ± 31 vs. 61 ± 30 ml/min/1.73 m2, p = 0.04), higher number of crescents (9.4 ± 15.0 vs 2.3 ± 8.5%, p = 0.001), higher IFTA scores (1.7 ± 0.8 vs. 1.3 ± 0.6, p = 0.007) and higher fluorescence intensity scores for C3 (2.0 ± 0.9 vs. 1.6 ± 0.9, p = 0.02) on initial biopsy as compared to patients treated conservatively. Patients progressing to ESKD presented with higher blood pressure (146 ± 26 vs. 135 ± 18 mmHg systolic, p = 0.005; 89 ± 14 vs. 82 ± 14 mmHg diastolic, p = 0.006), lower eGFR (41 ± 29 vs. 64 ± 28 ml/min/1.73 m2, p = 0.00001), higher levels of proteinuria (3.4 ± 2.0 vs. 1.8 ± 1.9 g/d, p = 0.0001), higher number of crescents (9 ± 17 vs. 4 ± 9%, p = 0.03) and higher IFTA scores (1.8 ± 0.8 vs. 1.3 ± 0.6, p = 0.00001) as compared to patients without ESKD at last follow up. Baseline blood pressure (134 ± 18 vs. 147 ± 26 mmHg systolic, p = 0.004; 82 ± 14 vs. 89 ± 15 mmHg diastolic, p = 0.01), eGFR (60 ± 29 vs. 41 ± 27 mmHg, p = 0.0007), proteinuria (2.3 ± 1.9 vs. 3.2 ± 2.3 g/d, p = 0.03) and severity of IFTA (1.4 ± 0.6 vs. 1.8 ± 0.9, p = 0.003) differed significantly between patients who experienced any remission vs. those who did not achieve remission respectively. Conclusion This analysis gives insight into the characteristics and treatment practices of a Swiss single center cohort of IgAN patients from 1980-2017.

Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis.

Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. Although the detection of autoantibodies is important for distinguishing the disease from other neuropathies that present with autonomic dysfunction, other factors are important for accurate diagnosis. Here, we provide a comprehensive review of the clinical features of AAG, highlighting differences in clinical course, clinical presentation, and laboratory findings from other neuropathies presenting with autonomic symptoms. The first step in diagnosing AAG is careful history taking, which should reveal whether the mode of onset is acute or chronic, followed by an examination of the time course of disease progression, including the presentation of autonomic and extra-autonomic symptoms. AAG is a neuropathy that should be differentiated from other neuropathies when the patient presents with autonomic dysfunction. Immune-mediated neuropathies, such as acute autonomic sensory neuropathy, are sometimes difficult to differentiate, and therefore, differences in clinical and laboratory findings should be well understood. Other non-neuropathic conditions, such as postural orthostatic tachycardia syndrome, chronic fatigue syndrome, and long COVID, also present with symptoms similar to those of AAG. Although often challenging, efforts should be made to differentiate among the disease candidates.

Postoperative Care of Zenker Diverticula: Contemporary Perspective from the Prospective OUtcomes Cricopharyngeaus Hypertonicity (POUCH) Collaborative.

The aim of the study was to identify trends in postoperative management of persons undergoing surgery for Zenker diverticula (ZD) by evaluating length of stay (LOS), diet on discharge, and imaging with or without surgical complication. Prospectively enrolled adult patients with cricopharyngeal muscle dysfunction with diverticula undergoing surgery from August 1, 2017 to February 1, 2023 were included. Data were extracted from a multi-institutional REDCap database, summarizing means, medians, percentages, and frequencies. Fisher's exact or chi squared analyses were utilized, as appropriate, to compare subsets of data. Descriptive analysis assessed differences in clinical course and the relationship to postoperative management. There were 298 patients with a mean (standard deviation) age of 71.8 (11.2) years and 60% male. Endoscopic surgery was performed in 79.5% (237/298) of patients versus 20.5% (61/298) open surgery. Sixty patients (20.1%) received postoperative imaging, with four leaks identified. Complications were identified in 9.4% of cases (n = 29 complications in 28 patients), more commonly in open surgery. Most (81.2%) patients were discharged within 23 h. About half of patients (49%) were discharged from the hospital on a pureed/liquid diet; 36% had been advanced to a soft diet. In patients without complications, LOS was significantly longer following open cases (p = 0.002); postoperative diet was not different between open and endoscopic (p = 0.26). Overall, most patients are discharged within 23 h without imaging. However, LOS was affected by surgical approach. Postoperative complications are different in endoscopic versus open surgery. Complications with either approach were associated with prolonged LOS, need for imaging, and diet restriction. Level III Laryngoscope, 134:2678-2683, 2024.

Cavernous Malformations and Hemangioblastomas of the Spinal Cord Show Distinct Differences in Clinical Course - A Retrospective Single-Center Analysis of 112 Patients.

Retrospective cohort study. Cavernous malformations (CMs) and hemangioblastomas (HBs) of the spinal cord exhibit distinct differences in histopathology but similarities in the neurological course. The aim of our study was to analyze the clinical differences between the vascular pathologies and a benign tumor of the spinal cord in a perioperative situation. We performed a retrospective analysis of patients who had undergone surgery for lesions in the spinal cord between 1984 and 2015. Patients were screened for CMs and HBs as the primary inclusion criteria. General patient information, surgical data, and disease-specific data were collected from the records. Cooper-Epstein scores for clinical symptoms were evaluated preoperatively, at discharge, and at the 6-month follow-up. A total of 112 patients were included, of which 46 had been diagnosed with CMs and 66 with HBs. Patients with CMs often demonstrated more preoperative neurological deterioration compared to those with HBs (P < .05); accordingly, in took longer to diagnose HBs. Complete resection was possible for 96.8% of all patients with CMs and 90% of those with HBs. At the 6-month follow-up, patients with HBs more often presented with persisting neurologic impairment of the upper extremities compared to the CM patients (P < .001). CMs and HBs of the spinal cord have similarities but also exhibit significant differences in neurological presentation and perioperative course. Surgical therapy is the treatment of choice for symptomatic lesions, and complete surgical resection is possible in the majority of cases for both entities. Neurologic outcomes are usually favorable, although patients with HBs retain neurologic deficits more often.

EP01.01-14 Gender Differences in Clinical Course and Patient-Reported Outcomes among Patient with Early-Stage Non-Small Cell Lung Cancer

EP01.01-14 Gender Differences in Clinical Course and Patient-Reported Outcomes among Patient with Early-Stage Non-Small Cell Lung Cancer

Spectrum of diabetes mellitus in patients with Shwachman-Diamond syndrome: case report and review of the literature

BackgroundShwachman-Diamond syndrome (SDS) is a rare congenital disorder caused by mutations in the SBDS gene and characterized by exocrine pancreatic deficiency, hematologic dysfunction, and skeletal growth failure. Although the hematologic features and characteristics of the somatic disorders commonly associated with SDS are well known, emerging data from case reports and patient registries suggest that SDS may also be associated with an increased risk of diabetes mellitus. However, currently available data on SDS-associated diabetes are limited and do not allow conclusions regarding prevalence and incidence rates, clinical course, and outcomes.Case presentationHere we report the case of a 5-year-old girl with SDS who underwent bone marrow transplantation at the age of 3 months and developed autoantibody-positive type 1 diabetes mellitus at the age of 1.8 years. The manifestation and course of diabetes development were mild, complicated by concurrent spontaneous episodes of hypoglycemia even before the onset of antidiabetic treatment. Currently, adequate metabolic control can be achieved by dietary intervention.ConclusionsConsidering that the SBDS protein regulates mitosis and ribosomal biosynthesis and that its suppression may cause immunologic instability and chronic inflammation, this case provides insight into the phenotype of rare Shwachman-Diamond syndrome-associated diabetes mellitus, which may be characterized by significant age-dependent differences in clinical course.

Utility of circulating tumor DNA (ctDNA) in the management of appendiceal adenocarcinoma (AA).

226 Background: Appendiceal adenocarcinoma (AA) is a rare and heterogenous cancer with marked differences in clinical course between high- and low-grade tumors. Unlike colorectal cancer (CRC) and other gastrointestinal malignancies, AA virtually never has hematogenous metastases, rather, metastasis is limited to the peritoneum. Here we present a retrospective, single institution study of AA to identify the prevalence of detectable ctDNA, evaluate the clinical predictive value of positive ctDNA, and assess what clinical, pathologic, or molecular features predict positive ctDNA. Methods: 160 blood samples from 147 patients with AA metastatic to the peritoneum were profiled with a CLIA approved 73 gene mutational panel as part of routine clinical practice. Paired tumor sequencing was available for 73 patients. Survival was measured starting from day ctDNA was drawn. Mutations that most likely represented clonal hematopoiesis were removed from analysis. Results: Out of 160 ctDNA samples, 120 were taken in the setting of radiographically apparent metastatic disease. Of these, 46 (38.3%) had any detectable mutation. 40 ctDNA tests were performed when patients had no radiographic evidence of disease (NED); 15 (37.5%) of which had any detectable mutation. High-grade tumors were more likely to have detectable ctDNA with detection rates of 10/46 (21.7%), 18/46 (39.1%), and 33/68 (48.5%) for well, moderately, and poorly-differentiated tumors, respectively. Restricting analysis to the 73 patients with paired tissue and blood samples and 73 genes sequenced in both, of 81 mutations detected in tumor only, 21 were detected in blood (sensitivity of 26%). Sensitivity was highest for mutation in TP53 (53.8%) suggesting these tumors may have a greater propensity to shed DNA into circulation. Overall, the sensitivity of ctDNA detection in metastatic AA was markedly less than what was observed in a cohort of 274 metastatic CRC patients from the same institution (288/581 = 49.6%). For AA patients with detectable ctDNA, variant allele frequency (VAF) in AA was significantly lower compared to CRC (median VAF 0.04% vs. 6%, p = &lt;0.0001). Detectable ctDNA was associated with shorter overall survival (46.2 mo for positive ctDNA vs. not-yet-reached for negative ctDNA, HR = 2.5, p = 0.016) and shorter disease free survival (DFS) (60 mo vs. not-yet-reached, HR = 3.4, p = 0.05). As expected, patients with radiographic evidence of disease did worse than patients with NED (HR = 2.1. p = 0.08), but of note this hazard ratio was less than that for positive ctDNA. Conclusions: In patients with AA, the presence of detectable ctDNA is associated with shorter overall and disease-free survival. Sensitivity of ctDNA detection in metastatic AA is overall markedly lower than CRC, with detection more likely in high-grade tumors and higher sensitivity in tumors containing TP53 mutation.

Sex Difference in General Cognition Associated with Coupling of Whole-brain Functional Connectivity Strength to Cerebral Blood Flow Changes During Alzheimer’s Disease Progression

Alzheimer’s disease (AD) is a progressive age-related neurodegenerative disorder that results in irreversible cognitive impairments. Nonetheless, there are numerous sex-dependent differences in clinical course. We examined potential contributions of neurovascular coupling deficits to sex differences in AD progression. T1-weighted three-dimensional structural magnetic resonance images, functional blood oxygen level dependent and arterial spin labeling images were acquired from 50 AD patients (28 females), 52 amnesic mild cognitive impairment patients (31 females), and 59 healthy controls (36 females). Short- and long-range functional connectivity strength (FCS) and cerebral blood flow (CBF) values were calculated for all participants. Then, the CBF/FCS coupling ratio, which represented the amount of blood supply per unit of connectivity strength, was calculated for each voxel. Two-way ANOVA was performed to identify group × sex interactions and main effects of group. Correlation analysis was used to assess associations between CBF/FCS ratios and Mini-Mental State Examination (MMSE). There were significant group × sex interaction effects on short-range coupling ratios of right middle temporal gyrus, left angular gyrus, left inferior orbital frontal gyrus, and left superior frontal gyrus as well as on the long-range coupling ratios of right middle temporal gyrus, left precuneus, left posterior cingulate cortex, and left angular gyrus. There were significant negative correlations between MMSE scores and CBF/FCS ratios for all regions with significant group × sex interactions among female patients, while positive correlations were found among male patients. Our results demonstrate significant sex differences in neurovascular coupling mechanisms associated with cognitive function during the course of AD.

Characteristics of Hospitalized Pediatric Patients in the First Five Waves of the COVID-19 Pandemic in a Single Center in Poland-1407 Cases.

This is a single-center, prospective study that compared the clinical presentation and laboratory findings of hospitalized children during the first five waves of the COVID-19 pandemic. Data were collected, according to a standardized questionnaire, from 1407 children from 23 March 2020 to 30 April 2022. Significant differences in clinical courses were found among the five waves probably due to different SARS-CoV-2 variants. The median age was 95.8 months in the first wave versus 14.6-23 months in the others. The number of patients with upper respiratory infection was the highest in the fifth wave (74.4% versus 43.8-56.9% in the others) and for lower respiratory infection in the first wave (50.0% versus 16.4-32.5%). Gastroenterocolitis was more common in the fifth wave (24.4% versus 8.9-16.5%); neurological diagnoses appeared more frequently in the fourth wave (16.6% versus 0.6-9.9%), while anosmia and ageusia were higher in the fifth wave (13% versus 1.5-4%). Life-threatening courses were relatively rare. However, children with pneumonia, dehydration from high fever, gastrointestinal symptoms, loss of smell and taste, and neurological symptoms required hospitalization.

Differences in Clinical Course and Management of Sars-CoV2 Infection in Patients with Chronic Lymphocytic Leukemia between the Sequential Pandemic Phases: An Eric Study

BACKGROUND. Infection by SARS-CoV2 remains a worldwide health burden. Previous studies by the ERIC (European Research Initiative on CLL) showed that patients with chronic lymphocytic leukemia (CLL) have a very-high risk of severe Coronavirus disease 19 (COVID19). In particular, age, CLL-directed treatment, and cardiac failure were identified as significant risk factors of overall survival (OS). Since the beginning of 2020 different treatment strategies have been used to fight COVID19 and different SARS-CoV2 variants alternated during the pandemic, however very few studies analyzed their impact on patients with CLL. AIMS. The aims of this study were to investigate different manifestations, treatments and outcome of COVID19 in patients with CLL/SLL (small lymphocytic lymphoma), and MBL (monoclonal B-cell lymphocytosis). METHODS. This is a retrospective international multicenter ERIC study from Jan 2020 till May 2022. CLL diagnosis, COVID-19 management, review of medical history, and assessment of patient status were performed by local investigators following international guidelines. Ninety institutions participated in the study. Statistical analyses were conducted using R software. During the pandemic we identified 4 phases: 1st Jan 2020 - Jun 2020, 2nd Jul 2020 - Feb 2021, 3rd Mar 2021 - Dec 2021 and 4th Jan 2022 - May 2022. RESULTS. We gathered data from 1540 patients (93.8% CLL, 4.1% SLL and 2.1% MBL), 65% males, the median age at COVID19 was 69 years, median CIRS score was 4 (IQR 2-7), 49.6% were treated in the last 12 months before COVID19, 38.8% was on treatment at COVID19 onset (BTK inhibitor-based 51.1%, BCL2 inhibitor-based 20.7%, chemo/chemoimmunotherapy 21.5%, 6.7% others). Overall, 34.4% of patients was managed at home, 49.9% needed hospitalization and 15.7% was admitted to the intensive care unit (ICU). After a median follow-up of 2.7 months, the infection was resolved in 1124/1540 (73%) cases, while 23% died and 3.6% were still under medical observation. Distribution of patients among time is shown in Fig. 1A. Three hundred and four (19.8%) patients were infected during the 1st, 737 (48%) during the 2nd, 137 (8.9%) during the 3rd and 357 (23.3%) during the last 4th phase. Comparing the features of patients infected in different phases, age at COVID19 and distribution of biological markers were similar, but more patients in the latter phases suffered from arrhythmias (8.2% vs 10.5% vs 16.1% vs 14.2%, p=0.01), chronic renal disease (3.9% vs 5.9% vs 8.9% and 11.1%, p=0.003) and other malignancies (0.3% vs 1.8% vs 2.2% vs 3.6%, p=0.04). Vaccinated patients (0% vs 0.4% vs 45.7% vs 89.1%, p<0.001) and those treated for CLL in the last 12 months (44.1% vs 44.1% vs 55.7% vs 66.1%, p<0.001) were also more common in the last phases. COVID19 signs and symptoms differed between early and late phases, with less fever (p<0.001) and dyspnea (p=0.028) but more fatigue (p<0.001), cough (p<0.001), headache (p<0.001), anosmia/ageusia (p<0.001) and myalgia/arthralgia (p<0.001) in the later phases. COVID19 management also changed over time, with less patients receiving a SARS-CoV2 therapy (87.6% vs 74.7% vs 78.1% vs 67.9%, p<0.001). In particular, hydroxychloroquine, azithromycin, steroids and anti-IL6/IL6R were more commonly used in the first 2 phases while antiviral and monoclonal antibodies (mAb) were mainly employed in the last 2 phases. Less patients were hospitalized (84.5% vs 67.3% vs 60.3% vs 45.8%, p<0.001), needed ICU admission (20.6% vs 17.2% vs 13.3% vs 8.1%, p<0.001) or died (29.8% vs 25.5% vs 21.8% vs 15.8%, p=0.002) through these phases. These improvements in patients' management led to an increase of OS, with 2-month OS of 70%, 74%, 81% and 83% for patients diagnosed during the 1st, 2nd,3rd and 4th phase (p=0.0015, Fig. 1B). CONCLUSION. We analyzed one of the largest series of patients with CLL infected by SARS-CoV2 over more than 2 years of COVID19 pandemic. Patients infected during the most recent phases, though carrying a higher comorbidity burden, were less frequently hospitalized, only rarely needed ICU admission and died due to the SARS-CoV2 infection in a lower proportion compared to initial phases. The improvement in COVID-19 management with effective antiviral drugs, mAb and the high rate of vaccination together with the change in SARS-CoV2 variants over time may have played an important role in this outcome. AV, LS, TC, AK, CD and GK equally contributed. KS and PG are both last authors. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 15083: Chronicity of Heart Failure, In-Hospital Clinical Trajectory, and Post-Discharge Outcomes Among Patients Hospitalized for Heart Failure

Introduction: Among patients hospitalized for HF, patients hospitalized with worsening chronic heart failure (WCHF) are at increased risk for morbidity and mortality compared with those who are recently diagnosed with HF. Whether there are differences in clinical course during hospitalization for HF is unclear. Methods: We pooled 735 participants hospitalized for HF in the DOSE, CARRESS, and ROSE trials. We grouped participants by whether HF was recently diagnosed (≤12 months) or WHCF (&gt;12 months). We compared changes in congestion, kidney function, and symptoms during hospitalization, as well as early post-discharge kidney and mortality outcomes. Results: Overall, 132 (18%) had recently diagnosed HF and 603 (82%) had WCHF. Compared with WCHF, patients with recently diagnosed HF tended to have lower serum creatinine and higher systolic blood pressure, ejection fraction, and serum NT-proBNP (all p&lt;0.05). In the first 72 hours, changes in body weight, global well-being visual analog scale, serum creatinine, and serum NT-proBNP, as well as net fluid loss were similar between patients with recently diagnosed versus WCHF (all p&gt;0.15) ( Figure ). Recently diagnosed HF showed improved dyspnea at 72 hours (p=0.03). There was no difference in change in serum creatinine from baseline to 60 days (p=0.75). There was a trend toward significantly increased odds of mortality during study follow-up (adjusted odds ratio 1.96 [95% confidence interval 0.97-3.94], p=0.06). Conclusion: Patients hospitalized for recently diagnosed and WCHF have generally similar in-hospital clinical trajectories, and similar changes in kidney function early post-discharge. Despite these similarities and adjustment for other clinical factors, patients with WCHF remain at increased risk for post-discharge mortality as compared with patients who are more recently diagnosed.

Clinical Characteristics, Prognostic Factors and Treatment Outcomes of Patients with Bone-Only Metastatic Breast Cancer.

IntroductionBone is the most frequent site of breast cancer metastasis. Differences between those who present with de novo bone-only metastasis (BOM) and those who progress to bone-only disease following a diagnosis of early-stage breast cancer are not clear. Such differences in clinical course might have an impact on the aggressiveness of treatment. This study presents the clinical and pathological features, along with treatment outcomes, of breast cancer patients with BOM in relation to the timing and type of bone metastasis.Patients and MethodsPatients with breast cancer and BOM were retrospectively reviewed. De novo BOM was defined as bone metastasis diagnosed at presentation or within the first 4 months of follow-up. Treatment outcomes of patients with de novo, compared to those with subsequent BOM, are presented.Results242 patients, median age (range) at diagnosis was 52 (27–80) years were enrolled. The majority of the patients (77.3%) had de novo BOM with multiple sites of bone involvement (82.6%). At a median follow-up of 37.7 months, the median overall survival (OS) for patients with de novo BOM disease was significantly shorter than those who developed so subsequently; 40.8 months (95% CI, 51.1–184.1) compared to 80.9 months (95% CI, 36.4–47.9), p < 0.001. Tumor grade, hormone receptor status and type of bone lesions (lytic versus sclerotic) had a significant impact on survival outcomes.ConclusionBreast cancer with de novo BOM is a distinct clinical entity with unfavorable prognosis and is associated with shorter survival. Several risk factors for poor outcomes were identified and might inform treatment plans.

Heterogeneity of obesity and the main pathogenetic factors of its development (a review of resources)

Introduction. Among medical and social problems, obesity (Ob) occupies one of the leading places. This is related to the established pathogenetic connection of Ob with type 2 diabetes mellitus, arterial hypertension, acute vascular events, dementia, osteoarthritis, obstructive sleep apnea and some forms of cancer. Ob is also associated with social problems and reduced work capacity. Despite numerous studies on the study of Ob, a number of unresolved issues and controversial points of view remain. The aim – is to analyze the currently existing data on the heterogeneity of Ob and the main pathogenetic factors of its development based on the study of literary sources, mainly for a period of 10 years. Materials and methods – an electronic search was carried out in MEDLINE/PubMed, Google Scholar and Web of Science databases using the keywords "obesity", "obesity heterogeneity", "obesity etiopathogenesis" with subsequent analysis of literature sources published mainly in the last 10 years. The results. To date, there is no single universally accepted classification of Ob, and those currently used in clinical practice and during scientific research are based on one or another criterion. Such criteria include etiopathogenetic factors, type of adipose tissue deposition, degree of weight gain, etc. The use of bioimpedancemetry became the basis for the assertion about the heterogeneity of Ob with the selection of its separate forms, namely: metabolically healthy Ob; metabolic Ob with normal body weight, sarcopenic and metabolically unhealthy Ob. Despite the lack of clear diagnostic criteria for each of these forms, their differences in clinical course, pathogenetic factors of development and degree of cardiovascular risk have been established. Considering the indicated heterogeneity, the selection of the leading etiological factor of Ob remains a rather controversial and difficult issue. The exceptions, obviously, should include cases of the secondary form of this pathology, when Ob is one of the symptoms and is pathogenetically related to the underlying disease. In general, it is believed that, being hereditary, Ob is the result of the interaction between genetic, hormonal-metabolic, behavioral and environmental factors. Conclusions. Ob is a chronic multifactorial and heterogeneous disease, the individual clinical forms of which differ in the course and level of metabolic disorders. Etiopathogenetic factors of the development and progression of Ob are multifactorial and include genetic predisposition, factors of the external and internal environment, eating behavior and hormonal and metabolic shifts. According to the data obtained today regarding the heterogeneity of Ob and the pathogenetic mechanisms of its development, a new generally accepted characteristic and classification of this pathology should be accepted.

SO-40 Measurement of circulating tumor DNA (ctDNA) in appendiceal adenocarcinoma (AA): Prevalence, predictors, and correlation with clinical outcome

Appendiceal adenocarcinoma (AA) is a rare and heterogenous cancer with marked differences in clinical course between high- and low-grade tumors. Unlike colorectal cancer (CRC) and other gastrointestinal malignancies, AA virtually never has hematogenous metastases, rather, metastasis is limited to the peritoneum. Here we present a retrospective, single institution study of AA to identify the prevalence of detectable ctDNA, evaluate the predictive value of positive ctDNA, and assess what clinical, pathologic, or molecular features predict positive ctDNA.

Essential Management of Pediatric Brain Tumors.

Brain tumors are the most common solid tumors in children and are associated with high mortality. The most common childhood brain tumors are grouped as low-grade gliomas (LGG), high grade gliomas (HGG), ependymomas, and embryonal tumors, according to the World Health Organization (WHO). Advances in molecular genetics have led to a shift from pure histopathological diagnosis to integrated diagnosis. For the first time, these new criteria were included in the WHO classification published in 2016 and has been further updated in the 2021 edition. Integrated diagnosis is based on molecular genomic similarities of the tumor subclasses, and it can better explain the differences in clinical courses of previously histopathologically identical entities. Important advances have also been made in pediatric neuro-oncology. A growing understanding of the molecular-genetic background of tumorigenesis has improved the diagnostic accuracy. Re-stratification of treatment protocols and the development of targeted therapies will significantly affect overall survival and quality of life. For some pediatric tumors, these advances have significantly improved therapeutic management and prognosis in certain tumor subgroups. Some therapeutic approaches also have serious long-term consequences. Therefore, optimized treatments are greatly needed. Here, we discuss the importance of multidisciplinary collaboration and the role of (pediatric) neurosurgery by briefly describing the most common childhood brain tumors and their currently recognized molecular subgroups.

72P The risk factors of developing severity in immune checkpoint inhibitors-related pneumonitis in advanced lung cancer patients

Immune checkpoint inhibitors (ICIs) have increasingly become an indispensable treatment strategy in advanced lung cancer, but may be associated with life-threaten immune checkpoint inhibitors-related pneumonitis (ICIP). Currently, there are no clear predictor factors for the development severity of ICIP. In this study, we evaluated the potential risk factors for the presence of severe ICIP in lung cancer patients treated with immunotherapy. This was a retrospective study. We included patients treated with immunotherapy between January 2017 to December 2021 in Shanghai Chest Hospital. The diagnosis and classification of ICIP according to the Common Terminology Criteria for Adverse Events (4.0). The clinical and treatment information in ICIP patients were collected and evaluated. A total of 524 lung cancer patients were included in the analysis, 55 (10.5%) were diagnosed with ICIP. The patients were divided into two groups based on clinical and radiological severity, of which 24 patients (43.6%) were divided into the severe groups and 31 patients (56.4%) were non-severe groups. No significant differences in clinical course, baseline characteristics, and peripheral-blood biomarkers between the two groups. However, the patients with prior radiotherapy history have an increased risk of severity (P<0.01). Among patients were diagnosed with ICIP, the history with prior radiotherapy is an independent predictor risk factor for developing severity in patients.

Treatment strategy for surgical site infection post posterior lumbar interbody fusion: A retrospective study

IntroductionPosterior lumbar interbody fusion (PLIF) has been widely used to treat various degenerative spinal diseases. However, surgical site infection (SSI) post-PLIF is often difficult to cure. This study aimed to clarify the difference in clinical course due to the causative organism and develop a treatment strategy for SSI post-PLIF. MethodsBetween January 2011 and March 2019, 581 PLIF surgeries were performed at our hospital. Deep SSI occurred in 14 patients who were followed up for more than 2 years. Causative bacterial species were diagnosed by preoperative puncture and/or intraoperative drainage or by tissue culture in 13 patients and by intradiscal puncture in one patient who underwent conservative treatment. Of the 13 patients who underwent surgeries for infection, 10 had Propionibacterium acnes (Group A; n = 4) or coagulase-negative Staphylococcus (CNS) (Group B; n = 6) as the causative bacterial species. Groups A and B were retrospectively compared in terms of age, sex, number of segments, presence of diabetes mellitus, operation time, blood loss, C-reactive protein on hematological examination, the elapsed time to diagnosis (ETD), the presence of clinical findings such as heat, redness, swelling, and discharge from the wound and healing time. ResultsAll infections were eradicated with surgery except in one patient whose causative bacteria was CNS; cages were finally removed in 11 patients. There was a significant difference (P = 0.0105) in the ETD and clinical findings (P = 0.0476) between Groups A and B. Posterior one-stage simultaneous revision (POSSR) was performed in nine patients, of whom eight were cured and one required additional surgery. ConclusionsThe ETD and clinical findings were significantly different in SSI cases caused by different bacteria, which will be useful in predicting the causative bacteria in future cases. For the treatment of deep SSI post-PLIF, POSSR was effective.

Sex-Dependent Differences in Predictive Value of the C2HEST Score in Subjects with COVID-19-A Secondary Analysis of the COLOS Study.

Background: Since the outbreak of the COVID-19 pandemic, a growing number of evidence suggests that COVID-19 presents sex-dependent differences in clinical course and outcomes. Nevertheless, there is still an unmet need to stratify the risk for poor outcome at the beginning of hospitalization. Since individual C2HEST components are similar COVID-19 mortality risk factors, we evaluated sex-related predictive value of the score. Material and Methods: A total of 2183 medical records of consecutive patients hospitalized due to confirmed SARS-CoV-2 infections were analyzed. Subjects were assigned to one of two of the study arms (male vs. female) and afterward allocated to different stratum based on the C2HEST score result. The measured outcomes included: in-hospital-mortality, three-month- and six-month-all-cause-mortality and in-hospital non-fatal adverse clinical events. Results: The C2HEST score predicted the mortality with better sensitivity in female population regarding the short- and mid-term. Among secondary outcomes, C2HEST-score revealed predictive value in both genders for pneumonia, myocardial injury, myocardial infarction, acute heart failure, cardiogenic shock, and acute kidney injury. Additionally in the male cohort, the C2HEST value predicted acute liver dysfunction and all-cause bleeding, whereas in the female arm-stroke/TIA and SIRS. Conclusion: In the present study, we demonstrated the better C2HEST-score predictive value for mortality in women and illustrated sex-dependent differences predicting non-fatal secondary outcomes.

Small Towns, Big Cities: Rural and Urban Disparities Among Hospitalized Patients With COVID-19 in the Central Savannah River Area.

BackgroundThere is a lack of data surrounding the impact of coronavirus disease 2019 (COVID-19) among rural and urban communities. This study aims to determine whether there are differences in epidemiologic characteristics and clinical outcomes among individuals with COVID-19 among these communities.MethodsThis was a retrospective analysis of 155 patients admitted to a single-center tertiary academic hospital located in Augusta, Georgia, with a large proportion of hospitalized patients transferred from or residing in rural and urban counties. Hospitalized adult patients were included in the study if they were admitted to AUMC between March 13, 2020, and June 25, 2020, and had a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 regardless of the presence or absence of symptomatology. Demographics, admission data, and 30-day outcomes were examined overall and by geographical variation.ResultsUrban patients were more likely to be admitted to the general medical floor (P = .01), while rural patients were more likely to require an escalation in the level of care within 24 hours of admission (P = .02). In contrast, of the patients who were discharged or expired at day 30, there were no statistically significant differences in either total hospital length of stay or intensive care unit length of stay between the populations.ConclusionsThere may be many social determinants of health that limit a rural patient’s ability to seek prompt medical care and contribute to decompensation within the first 24 hours of admission. This study provides insight into the differences in clinical course among patients admitted from different community settings and when accounting for comorbid conditions.

Identification of a specific immunophenotype associated with a consistent pattern of genetic mutations including SRFS2 and gene expression profile in MDS.

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of diseases classified by comprehensive diagnostics. Identification of homogeneous subgroups is desirable to understand differences in clinical course and to develop targeted treatment approaches. We identified a specific CD11b/CD16 expression pattern in granulocytes associated with reduced CD45 expression in myeloid progenitor cells (MPC) in MDS cases and assessed its genetic background by whole genome (WGS) and whole transcriptome sequencing (WTS). The cohort consisted of 32 MDS cases with the specific aberrant immunophenotype. Since all these 32 cases were found to be SRSF2 mutated additional 51 SRSF2 mutated MDS cases without this specific immunophenotype were selected as controls. For all cases WGS and WTS were performed. The immunophenotype newly identified in SRSF2 mutated MDS patients is characterized (1) by a specific maturation pattern, i.e. an increase of CD11b expression without CD16 expression followed by an increase in CD16 expression without further CD11b expression and (2) by only dim CD45 expression of MPC. STAG2 mutations were exclusively found in MDS cases with the specific immunophenotype (17/32, 53% vs. 0%, p< 0.001). Hence, >50% of cases with the specific immunophenotype were characterized by co-mutations in SRSF2 and STAG2. In addition, cluster analysis revealed a specific gene expression profile of such cases. We here for the first time describe a specific immunophenotype which defines MDS cases with SRSF2 mutations and a consistent and specific mutational and gene expression profile. This comprehensive data warrants analysis of further such cases to assess the feasibility of defining a new sub-entity of MDS.