Early Initiation Of Treatment Research Articles

Histological chorioamnionitis and its predictors among mothers with premature rupture of membranes delivering at tertiary hospitals in Uganda: a multicenter cross-sectional study

BackgroundHistological chorioamnionitis (HCA) is a significant global threat to maternal and fetal health, with an increasing prevalence in resource-limited settings. However, data on its burden and predictors remain scarce in Africa, including Uganda. This study aimed to determine the prevalence and predictors of HCA among mothers with premature rupture of membranes (PROM) at three tertiary hospitals in Uganda.MethodsThis multicenter cross-sectional study was conducted over a three-month period, from July to October 2023, at three tertiary hospitals in Uganda. A total of 106 women diagnosed with PROM were consecutively enrolled. Data were collected using a structured questionnaire that captured routine history-taking and physical examinations. Key information gathered included the history of liquor drainage, clinical signs of chorioamnionitis (fever, uterine tenderness, and foul-smelling liquor), labor history, and placental samples obtained after delivery for histopathological analysis. Descriptive statistics and binary logistic regression analyses were performed using STATA version 14.2. Statistical significance was set at P < 0.05, with a 95% confidence interval. Results were presented using bar charts, pie charts, and tables.ResultsAmong the 106 participants with PROM, 44 (41.5%) had histological chorioamnionitis. The most common histological finding was neutrophil infiltration in 22 cases (50.0%), followed by funisitis in 13 cases (29.6%). Referral status (aOR = 4.5, 95% CI: 1.511–13.315, p = 0.007) and lack of prenatal care (PNC) attendance (aOR = 9.8, 95% CI: 2.802–14.504, p = 0.000) were independently associated with histological chorioamnionitis.Conclusions and recommendations.The prevalence of HCA in this study was notably higher than previously reported data from Uganda. Neutrophil infiltration was the most frequently observed histological lesion. Patients with PROM who were referred from other health facilities or had not attended PNC were at a higher risk of developing HCA. These findings highlight the critical need for early detection and management of HCA in mothers with PROM, particularly in resource-limited settings. Routine screening for HCA should be implemented for all women presenting with PROM, with special attention to referred cases and those without PNC. Early initiation of treatment should be considered until the diagnosis is definitively ruled out. Further research is needed to explore the underlying causes of HCA to inform targeted preventive measures.

Development and validation of a model to predict cognitive impairment in traumatic brain injury patients: a prospective observational study.

Traumatic brain injury (TBI) is a significant public health issue worldwide that affects millions of people every year. Cognitive impairment is one of the most common long-term consequences of TBI, seriously affect the quality of life. We aimed to develop and validate a predictive model for cognitive impairment in TBI patients, with the goal of early identification and support for those at risk of developing cognitive impairment at the time of hospital admission. The training cohort included 234 TBI patients, all of whom were admitted to the Department of Neurosurgery at the Third Affiliated Hospital of Soochow University from May 2017 to April 2020. These patients were selected from our previously published studies. Baseline characteristics, medical history, clinical TBI characteristics, treatment details, and vital signs during hospitalization were screened via least absolute shrinkage and selection operator (LASSO) and logistic regression to construct a predictive net risk score. The derived score represents an estimate of the risk of developing cognitive impairment in patients with TBI. A nomogram was constructed, and its accuracy and predictive performance were evaluated with the area under the receiver operating characteristic curve (AUC), calibration curves, and clinical decision curves. For the validation cohort, data were prospectively collected from TBI patients admitted to the Department of Neurosurgery at the Third Affiliated Hospital of Soochow University from March 1, 2024 to August 30, 2024, according to the inclusion and exclusion criteria. This study is registered with the Chinese Clinical Trial Registry (ChiCTR) at http://www.chictr.org.cn/ (registration number: ChiCTR2400083495). The training cohort included 234 patients. The mean (standard deviation, SD) age of the patients in the cohort was 47.74 (17.89) years, and 184 patients (78.63%) were men. The validation cohort included 84 patients with a mean (SD) age of 48.44 (14.42) years, and 68 patients (80.95%) were men. Among the 48 potential predictors, the following 6 variables were significant independent predictive factors and were included in the net risk score: age (odds ratio (OR)=1.06, 95% confidence interval (CI): 1.03-1.08, P=0.00), years of education (OR=0.80, 95% CI: 0.70-0.93, P=0.00), pulmonary infection status (OR=4.64, 95% CI: 1.41-15.27, P=0.01), epilepsy status (OR=4.79, 95% CI: 1.09-21.13, P=0.04), cerebrospinal fluid leakage status (OR=5.57, 95% CI: 1.08-28.75, P=0.04), and the Helsinki score (OR=1.53, 95% CI: 1.28-1.83, P=0.00). The AUC in the training cohort was 0.90, and the cut-off value was 0.71. The AUC in the validation cohort was 0.87, and the cut-off value was 0.63. The score was translated into an online risk calculator that is freely available to the public (https://yuanxiaofang.shinyapps.io/Predict_cognitive_impairment_in_TBI/). This model for predicting post-TBI cognitive impairment has potential value for facilitating early predictions by clinicians, aiding the early initiation of preventative interventions for cognitive impairment. This research was supported by Science and Technology Development Plan Project of ChangZhou (CJ20229036); Science and Technology Project of Changzhou Health Commission (QN202113).

P-1406. Racial Disparities in HIV Prevalence and Complications in Hospitalized Patients

Abstract Background Racial and ethnic disparities in HIV care and outcomes are well known. Multiple causes have been reported including inequalities in access to care and pre-exposure prophylaxis (PrEP), housing instability, lack of antiretroviral insurance coverage, and economic disadvantages. We aim to evaluate the disparities in HIV prevalence and outcomes in hospitalized patients. Methods We analyzed the 2020 United States National Inpatient Sample (NIS) data of all patients with a diagnosis of HIV admitted inpatient. The NIS database is the largest publicly available database of patients hospitalized in the United States and contains approximately 20% stratified samples of all hospital discharges in the United States. Results There were 38,666 admissions with a diagnosis of HIV in 2020, of which 30.3% were females. 51.6% of the HIV patients were Blacks, 30% Whites, 13.7% Hispanics, 0.7% Asians, 0.6% Native Americans, and 3.4% others. The mean age was 50.8 years, and the mean length of stay was 6.4 days. In the bivariate analysis, the Hispanics were more likely compared to others to have Kaposi Sarcoma (1.8% vs. 1.1%, p&amp;lt; 0.001), cryptococcal meningitis (1.5% vs. 0.6%, p&amp;lt; 0.001), disseminated coccidioidomycosis (0.2% vs 0.0%, p&amp;lt; 0.001), hepatitis C (6.7% vs. 5.3%, p&amp;lt; 0.001), Covid-19 infection (7.9% vs. 4.9%, p&amp;lt; 0.001) and pneumocystis jiroveci pneumonia (3.2% vs. 2.3%, p&amp;lt; 0.001). The multivariate analysis showed no statistically significant racial or ethnic difference in all-cause mortality (p=0.17). However, patients in the highest income quartile had significantly lower all-cause mortality compared to those in the lowest quartile after adjusting for variables including race, ethnicity, and HIV complications (OR 0.69, 95% CI 0.54-0.89, p=0.004). Conclusion Our study showed that the prevalence of HIV is still disproportionally high in Blacks. While about 16% of all patients in our dataset are Black, about 52% of the HIV patients are Black. However, Hispanic patients appear to have more HIV complications. Cultural appropriate interventions to prevent HIV acquisition, increase HIV screening, and early initiation of treatment in racial and ethnic minorities are warranted. Mining a national database can provide insights into morbidity and mortality trends in patients living with HIV. Disclosures All Authors: No reported disclosures

P-1150. Prospective case-control study to examine clinical, biochemical, and serological indicators to predict Staphylococcal scalded skin syndrome

Abstract Background Staphylococcal scalded skin syndrome (SSSS) typically affects infants &amp; children, with rare occurrences in adults. There is no rapid tool or any scoring system to diagnose SSSS, where early diagnosis is the key to successful outcome. Methods This study evaluates specific clinical &amp; serological indicators to distinguish between maculopapular eruption &amp; SSSS upon initial presentation. Additionally, we investigate the correlation between serum levels of thymus and activation-regulated chemokine (TARC) &amp; the severity of SSSS &amp; the extent of organ involvement. In this observational study conducted prospectively, 25 patients diagnosed with SSSS &amp; 25 control subjects with maculopapular rash were enrolled. Results The diagnostic efficacy of various factors, including TARC level ( &amp;gt;612.25 pg/ml), total body surface area (TBSA &amp;gt;30%), hsCRP ( &amp;gt;5mg/l), leucocytosis ( &amp;gt;12X 109 cells/L), &amp; aspartate transaminase ( &amp;gt;90 U/L), showed statistical similarity to the diagnosis of SSSS. While baseline serum TARC levels proved to be a reliable screening tool, they did not predict the severity or outcome of SSSS. However neutrophil extracellular traps (NETs) level did correlate positively with disease severity &amp; duration of hospital stay. Through multivariable regression analysis, we have formulated a novel model that integrates TBSA at baseline, neutrophil percentage in leucocytosis, &amp; hsCRP, surpassing the predictive capacity of these parameters when considered individually. The resulting equation with the highest odds for diagnosing SSSS is as follows: Odds of SSSS (present) = Antilog [-11.26 + 0.3 x Total BSA + 0.30 x hsCRP – 0.1 x neutrophil (%)]. This composite model (incorporating TBSA at baseline, neutrophil percentage, and hsCRP) achieved a sensitivity of 96% and specificity of 100% at a cutoff point of 7.8. Conclusion The equation developed from our research is straightforward to apply and suitable for use in settings with limited resources. It facilitates the identification of patients who are more likely to have SSSS, enabling the early initiation of definitive treatment. Likewise, it helps in minimizing unnecessary extensive investigations for patients unlikely to have SSSS. Neutrophil extracellular traps (NET) can be definitely used as a prognostic marker in patients with severe SSSS. Disclosures All Authors: No reported disclosures

632. Cytomegalovirus Infections in Patients with Relapsed/Refractory Multiple Myeloma on Novel T-Cell Redirecting Therapy

Abstract Background The advent of T-cell redirecting therapies such as chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs) has reshaped the treatment of relapsed/refractory multiple myeloma (R/R MM), but their immunomodulatory effects potentially increase the risk of infections, including cytomegalovirus (CMV). We compared the rate of CMV viremia, clinically significant CMV infection (CS-CMVi), CMV end organ disease, and CMV related mortality in R/R MM patients receiving BsAbs, CAR T cells or non-T-cell redirecting standard of care (SOC) treatment. Patients’ characteristics Abbreviations: SOC: standard of care; CRS: cytokine release syndrome; ICANS: immune effector cell-associated neurotoxicity syndrome Methods We conducted a retrospective cohort study in patients with R/R MM who underwent treatment with BsAbs, CAR-T cell or SOC regimens from January 2023 to June 2023. Patient demographics, oncologic history, complications related to therapy as well as CMV characteristics and outcomes were collected. The primary outcomes of interest included CMV viremia, CS-CMVi, CMV end organ disease and mortality within 6 months after initiating cancer therapy. Comparison between the 3 groups was performed by Fischer exact test or Wilcoxon Rank sum as appropriate. Characteristics of CMV infections Abbreviations: SOC: standard of care; CMV: cytomegalovirus; PCR: polymerase chain reaction; CS-CMVi: clinically significant CMV viremia Results A total of 118 patients were screened; 6 did not receive any therapy of interest, 4 did not undergo follow up, therefore 108 patients were included in the analysis. Of those, 24, 32 and 52 R/R MM patients received BsAbs, CAR T cell and SOC therapy respectively. Patient characteristics are depicted in table 1. The rates of CMV viremia were higher in BsAb and CAR T cell recipients (46% and 44%) compared to SOC (8%). CS-CMVi was also higher in BsAb and CAR T cell recipients (8% and 13%) compared to SOC (2%) but this was not statistically significant (p=0.14) (Table 2). Three cases of CMV end organ disease were identified; all had CMV pneumonitis. There was one death due to CMV recorded. Conclusion CMV viremia occurs more commonly amongst R/R MM undergoing treatment with T-cell redirecting therapies, such as BsAbs and CAR T cell in comparison with patients receiving SOC therapy. Further studies are needed to help determine the best strategies for CMV surveillance and viral load thresholds in these populations to mitigate the risk of CS-CMVi by early initiation of anti-CMV treatment. Disclosures Fareed Khawaja, MBBS, Eurofins Viracor: Grant/Research Support|Symbio: Grant/Research Support Krina Patel, MD, Abbvie: Advisor/Consultant|Arcellx: Advisor/Consultant|Astra Zeneca: Advisor/Consultant|BMS: Advisor/Consultant|BMS: Scientific committee/chair|Caribou Sciences: Advisor/Consultant|Celgene: Advisor/Consultant|Genentech: Advisor/Consultant|Janssen: Advisor/Consultant|Kite: Advisor/Consultant|Kite: Scientific committee/chair|Merck: Advisor/Consultant|Oricel: Scientific committee/chair|Pfizer: Advisor/Consultant|Regeneron: Advisor/Consultant|Sanofi: Advisor/Consultant Hans C. Lee, MD, Abbvie: Advisor/Consultant|Allogene Therapeutics: Advisor/Consultant|Bristol Myers Squibb: Advisor/Consultant|Bristol Myers Squibb: Grant/Research Support|Genentech: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Regeneneron: Advisor/Consultant|Regeneneron: Grant/Research Support|Sanofi: Advisor/Consultant|Takeda Pharmaceuticals: Advisor/Consultant|Takeda Pharmaceuticals: Grant/Research Support Roy F. Chemaly, MD/MPH, AiCuris: Advisor/Consultant|AiCuris: Grant/Research Support|Ansun Pharmaceuticals: Advisor/Consultant|Ansun Pharmaceuticals: Grant/Research Support|Astellas: Advisor/Consultant|Eurofins-Viracor: Grant/Research Support|InflaRX: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck/MSD: Advisor/Consultant|Merck/MSD: Grant/Research Support|Moderna: Advisor/Consultant|Oxford Immunotec: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Roche/Genentech: Advisor/Consultant|Roche/Genentech: Grant/Research Support|Shinogi: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Tether: Advisor/Consultant

P-2038. A Pharmacist-Run Treatment Decision Program for High-Risk Outpatients with Mild-Moderate COVID-19 at an Urban Veteran's Affairs Medical Center

Abstract Background Antiviral treatment is recommended for high-risk outpatients with mild-moderate COVID-19 to prevent progression to severe disease. Antiviral treatment decisions remain challenging due to the need for early initiation of treatment and the potential for drug-drug interactions with first-line therapy. Methods This single center, retrospective review evaluated the impact of a Pharmacist-run treatment decision program for high-risk outpatients with mild-moderate COVID-19 from 1/1/2022 through 12/28/2023. All outpatient treatment candidates were reviewed by a Clinical Pharmacist prior to initiation of oral antiviral treatment. A 5-day course of oral ritonavir-boosted nirmatrelvir (RNM) was considered first-line. A 5-day course of oral molnupiravir (MNP) was used as an alternative in situations where oral RNM was not clinically appropriate. The Clinical Pharmacist determined the optimal antiviral treatment, the appropriate medication dose, reviewed for drug-drug interactions, helped implement any necessary medication adjustments and/or monitoring plans, and assisted with patient education. Patient characteristics and the number of pharmacist interventions related to RNM drug-drug interactions were summarized. Results From 1/1/2022 to 12/28/2023, 455 high-risk outpatients were treated with oral antivirals for mild-moderate COVID-19 through the Pharmacist-run treatment decision program. Four-hundred and two patients (88.35%) were treated with RNM and 53 patients (11.65%) were treated with MNP. Patient ages ranged from 23 to 97 years (mean 66.4, SD 12.1). The mean duration of COVID-19 symptoms for patients who received oral antiviral treatment was 3 days (SD 1.12). The Clinical Pharmacist intervened on a total of 624 drug-drug interactions related RNM. The most common reason for use of MNP was the presence of major drug-drug interactions related to RNM (47/53; 88.7%), followed by severe renal impairment (6/53; 11.3%). Conclusion A Pharmacist-run treatment decision program for high-risk outpatients with mild-moderate COVID-19 was effective at initiating appropriate oral antiviral treatment in a timely fashion and ensuring patient safety by managing drug-drug interactions related to RNM. Disclosures All Authors: No reported disclosures

A Comprehensive Review of Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome

Background: Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare autoimmune disorder, characterized by acute tubulointerstitial nephritis and uveitis. It poses diagnostic challenges due to the mostly asynchronous onset of renal and ocular manifestations, as well as the variety of differential diagnoses. This review provides an overview of the epidemiology, pathogenesis, clinical features, diagnostic criteria, and management strategies. Methods: A comprehensive review of the peer-reviewed literature, including studies and case reports, was conducted. Results: The etiology of TINU syndrome involves an autoimmune reaction to renal and ocular antigens, leading to interstitial inflammation and tubular damage in the kidneys, and anterior uveitis with acute onset of flares. Diagnostic criteria based on ocular examination, laboratory parameters, and renal biopsy emphasize the need to exclude other systemic diseases. TINU syndrome accounts for approximately 2% of all uveitis cases. Primary treatment consists of corticosteroids, while immunomodulatory therapies (methotrexate, azathioprine, mycophenolate mofetil, or biologic agents) are reserved for refractory cases. Recurrence of uveitis appears to be more common than that of nephritis. Conclusions: TINU syndrome is rare and requires clinical suspicion for accurate diagnosis. Early diagnosis and initiation of treatment are crucial for achieving favorable outcomes. Advances in the understanding of its pathogenesis and treatment have improved patient outcomes. Further research is needed to investigate the underlying triggers and mechanisms in order to develop targeted therapies.

Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023

BackgroundCerebral creatine deficiency disorders (CCDD) are rare diseases caused by defects in the enzymes L-arginine: glycine amidinotransferase (AGAT) or guanidinoacetate-N-methyltransferase (GAMT), which are involved in synthesis of creatine; or by a defect in the creatine transporter (CRTR), which is essential for uptake of creatine as important energy source into the target cells. Patients with CCDD can present with a variety of unspecific symptoms: global developmental delay, speech-language disorder, behavioral abnormalities and seizures. Early treatment initiation is essential in AGAT and GAMT deficiencies to achieve a favorable outcome. This study describes the CCDD patient cohort in a single center, and an analysis of the referrals to two Swiss laboratories in Lausanne and Zurich between 2015 and 2023 for the two marker metabolites guanidinoacetate and creatine.ResultsThe patient cohort comprised 6 patients (defects: 2 GAMT, 4 CRTR), who were initially seen by different subspecialties depending on first symptoms. There was a diagnostic and therapeutic delay between 3 and 32 months (mean 13.8). Numbers of biomarker requests showed a constant increase during the study period, with a majority of tests performed in urine, the preferred sample for CCDD detection. Almost all samples (93.3%) were sent in by large hospitals (mainly from neurology, developmental pediatrics and metabolism) and only few (5.2%) by pediatricians in private practice, although those usually see the patients first.ConclusionsThe data from this study demonstrate a relevant delay in identifying patients with these rare conditions, and a predominance of biomarker analysis requested from pediatric subspecialties that are involved in patient management often long after occurrence of symptoms. To reduce the diagnostic delay and the outcome of patients, the current practice of sample referral should be reflected and first-contact healthcare providers should be encouraged to initiate selective screening.

P0993 Prevention of Postoperative Recurrence of Crohn’s Disease: Comparison of Two Therapeutic Strategies

Abstract Background Postoperative recurrence of Crohn’s disease affects half of patients within 10 years, making prevention crucial. The ECCO recommends immediate postoperative prophylactic treatment for patients with at least one risk factor for recurrence. While this strategy is proven effective for those with multiple risk factors, data on its benefits compared to endoscopy-guided prophylaxis in patients with only one risk factor is lacking. The study aimed to compare immediate postoperative prophylactic treatment with endoscopy-guided prophylaxis in patients with a single risk factor Methods This retrospective bicentric study included patients who underwent ileocolic resection for Crohn’s disease between January 2011 and December 2021, each with one risk factor for postoperative recurrence. Patients were divided into two groups G1 received immediate postoperative prophylactic treatment, while G2 received prophylactic treatment guided by colonoscopy within the first year after surgery. The primary outcome was the frequency of endoscopic recurrence within one year :Rutgeerts score ≥ i2. Secondary outcomes included severe endoscopic recurrence (i4) within 12 months and clinical recurrence at 6 and 24 months. Statistical analysis was conducted using SPSS26 Results This study included 41 patients divided into two groups. Group 1 (24 patients) had an average age of 34 years, with 58.33% being active smokers.Postoperative treatments were as follows: infliximab (4 patients), infliximab-azathioprine combination (3 patients), adalimumab (4 patients), ustekinumab (1 patient), and azathioprine monotherapy (12 patients). A Rutgeerts score of i2 or higher was found in 13 patients after a median of 9 months post-surgery, with an average follow-up of 3 years Group 2 (17 patients) had an average age of 38 years, with 64.7% being active smokers. Postoperative colonoscopy was performed after a median delay of 8 months. A Rutgeerts score of i2 or higher was found in 10 patients. The treatments initiated after colonoscopy were as follows: infliximab (3 patients), infliximab-azathioprine combination (2 patients), adalimumab (7 patients), azathioprine monotherapy (4 patients), and ustekinumab (1 patient). The average follow-up after surgery was 3 years No significant differences were observed between the groups in terms of endoscopic or severe endoscopic recurrence, or clinical recurrence at 6 and 24 months post-surgery Conclusion In our study, early initiation of prophylactic postoperative treatment for patients with a single risk factor did not reduce clinical or endoscopic recurrence rates. This suggests that avoiding such early treatment could help prevent unnecessary exposure to immunosuppressants and biologics, thereby reducing risks of side effects and high costs

P1117 A 24-year, single-centre perianal fistulizing Crohn’s disease cohort: documentation of demographics and factors influencing clinical and radiological remission

Abstract Background Radiological remission (RR), is the ultimate treatment goal in treatment of complex perianal fistula (cPAF) in Crohn’s disease (CD). In this study, we analysed cPAF disease characteristics and RR-related factors in a CD cohort. Methods Patients with CD (1999–2023) and MRI-confirmed cPAF (per AGA 2003 criteria, reviewed by 4 radiologists) were analyzed. Clinical remission (CR) was defined as no drainage under compression for ≥3 months, and RR as fibrotic fistula closure. Results Among 1688 CD patients, PAF prevalence was 24.7% (n=417), with 19% (n=79) classified as simple fistulas. Detailed analysis included 223 cPAF patients with sufficient follow-up. Male predominance was noted (65.5%), with a median CD diagnosis age of 28(IQR: 20) years and cPAF onset at 8(53) months. Median follow-up was 58(79) months. Isolated PAF occurred in 8.5%. Patients had a median of 2 fistulas, with ≥1 fistula in 51.6%. Common cPAF types were ISF (77%) and TSF (46%), with branching formation evident in 38.6%. Immunomodulator (IM) use was 94%, Anti-TNF+IM combination 87%, and multiple Anti-TNF exposure 35%. IFX was given to 31.8% at 5mg/8w and 51.9% at higher doses (up to 15mg/kg/4w). CR was achieved in 71% and RR in 43.5% of patients following a stepwise treatment approach including antibiotics, IM, Anti-TNF dose escalation, and diverting stoma (Figure 1). In the RR group, cPAF onset after CD diagnosis, non-mucosal (B2-B3) involvement, and abscess-related low fistulas were more frequent, while multiple cPAF, branching formation, and TSF were more common in the non-RR group (Table 1). Time-dependent analyses showed better RR associated with cPAF onset after CD diagnosis (log-rank &amp;lt;0.001), fewer fistulas (LR=0.035), abscess-related low fistulas (LR&amp;lt;0.001), and early Anti-TNF initiation (&amp;lt;0.008). Poor RR was linked to branched fistulas (LR=0.003), TSF (LR=0.042), and multiple Anti-TNF exposure (LR=0.017). The development of cPAF after CD diagnosis during follow-up, fistulas other than TSF, the absence multiple Anti-TNF exposure, and early initiation of Anti-TNF treatment were independently associated with better RR rates in multivariate analyses. Conclusion With a appropriate stepwise approach, including dose adjustments and stoma, RR can be achieved in 43.5% of cPAF patients. TSF-type fistulas are associated with poorer outcomes, while low perianal fistulas complicated by abscesses show better prognosis. Multiple Anti-TNF exposure predicts a poor response, whereas cPAF onset during follow-up and early Anti-TNF initiation are strongly associated with achieving RR.

Predicting Postoperative Infection After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy with Splenectomy.

Hematologic changes after splenectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) can complicate postoperative assessment of infection. This study aimed to develop a machine-learning model to predict postoperative infection after cytoreductive surgery (CRS) and HIPEC with splenectomy. The study enrolled patients in the national TriNetX database and at the Johns Hopkins Hospital (JHH) who underwent splenectomy during CRS/HIPEC from 2010 to 2024. Demographics, comorbidities, vital signs, daily laboratory values, and documented infections were collected. The patients were divided into infected and non-infected cohorts within 14 days postoperatively. Extreme gradient boost (XGBoost) machine-learning was used to predict postoperative infection. An initial model was generated using the TriNetX dataset and externally validated in the JHH cohort. From TriNetX, 1016 patients were included: 802 in the non-infected group (79%) and 214 (21%) in the postoperative infection group. The mean age was 61 ± 13 years, and 597 (56%) of the patientswere female. Most of the patients underwent CRS/HIPEC with splenectomy for appendiceal cancer (n = 590, 56%), followed by colorectal malignancy (n = 299, 29%). The remainder (n = 127, 15%) underwent CRS/HIPEC with splenectomy for gastric, pancreatic, ovarian, and small bowel malignancies or peritoneal mesothelioma. In detecting any infection, XGBoost exhibited excellent prediction accuracy (area under the receiver operating characteristic curve [AUC], 0.910 ± 0.073; F1 score, 0.915 ± 0.040) and retained high accuracy upon external validation with 96 demographically similar JHH patients (AUC, 0.823 ± 0.08; F1 score, 0.864 ± 0.03). A novel machine-learning algorithm was developed to predict postoperative infection after CRS/HIPEC with splenectomy that could aid in the early diagnosis and initiation of treatment.

Thrombopenia and hemolytic anemia in acute and emergency medicine : Detailed view at thrombotic microangiopathies

Recognizing anemia and thrombpenia in acute and emergency medicine is easy. Acute (microangiopathic hemolytic) anemia and thrombopenia can be asign of thrombotic microangiopathy (TMA). TMA syndromes are potentially life-threatening diseases. Diagnosing aTMA syndrome, causal differentiation and treatment require specialist knowledge that is not always available in acute and emergency medicine. Many differential diagnoses and examinations are usually necessary to make acorrect diagnosis. Therefore, astandardized diagnostic algorithm is helpful for early diagnosis and treatment initiation.

Multiple sclerosis: peculiarities of providing high-quality medical care to patients in the realities of Ukraine

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system, which is one of the most common causes of progressive disability among young people. This disease significantly affects the quality of life of patients and their families and is also accompanied by significant economic costs. Early diagnosis and early initiation of treatment of patients with MS help prevent the development of exacerbations, disability, premature death and improve quality of life. Today, awareness of MS has increased, more effective methods of diagnosis and therapy of patients with MS have become available. This has led to a reduction in the diagnostic delay between the detection of symptoms and making a reliable diagnosis, as well as to the postponement of severe disability. Multidisciplinary co-operation of specialists at all levels of medical care and close co-operation between the doctor and the patient is essential for optimal clinical management. The article systematizes current know-ledge on the main approaches to the diagnosis and treatment of patients with MS in Ukraine.

NORSE secondary to anti-GAD65 antibody-positive encephalitis treated with novel adjunctive rapid titrationVNS protocol.

New Onset Refractory Status Epilepticus (NORSE) is a rare and severe condition characterized by refractory seizures in individuals without a prior history of epilepsy. This case report describes a 37-year-old woman diagnosed with anti-glutamic acid decarboxylase 65 (anti-GAD65) antibody-positive encephalitis-related NORSE. Her seizures were refractory to multiple interventions, including anti-seizure medications, anesthetics, immunotherapies, a ketogenic diet, and electroconvulsive therapy. Seizures recurred twice during the tapering of anesthetic medications. However, after 32 days of treatment, the seizures were successfully controlled. To maintain seizure control and facilitate the weaning of anesthetics, a Vagus Nerve Stimulator (VNS) was implanted using a novel rapid titration protocol. This allowed for the successful tapering of anesthetics by day 50, with no recurrence of seizures. At her 9-month follow-up, the patient remained seizure-free and had an improved quality of life. This case highlights that early initiation of immunosuppressive treatment may lead to a favorable prognosis. The novel application of VNS therapy assisted seizure control in NORSE, thus encouraging further research investigating the potential role of VNS in this condition. PLAIN LANGUAGE SUMMARY: New Onset Refractory Status Epilepticus (NORSE) is a rare and severe condition characterized by relentless seizures in individuals without a prior epilepsy history. This report shares the case of a 37-year-old woman with NORSE, associated with a high anti-glutamic acid decarboxylase 65 antibody titer. Her seizures were super-refractory, requiring multiple anti-seizure medications, anesthetics, immunotherapies, a ketogenic diet, and electroconvulsive therapy. Seizures recurred twice during the tapering of anesthetic medications. However, by hospital day 32, the seizures were successfully controlled with these interventions. To further stabilize seizure control and enable the successful discontinuation of anesthetics, a Vagus Nerve Stimulator (VNS) was implanted. The patient had no further seizures and gradually recovered back to her pre-disease baseline. This case suggests that a novel rapid VNS titration protocol could be a promising treatment option for NORSE, warranting further investigation.

Fever in the Trauma Bay: A Marker for Greater Risk of Adverse Outcomes.

Purpose: Previous work identified a sub-group of trauma patients at risk for bacteremia who presented with signs of infection, including fever. A majority were older adult falls who had early onset bacteremia. Hypothesis: Fever in the trauma bay is associated with a greater risk of adverse outcomes and identifies patients who might benefit from early initiation of interventions for sepsis. Methods: Trauma patients ≥18 years, drawn from a system-wide electronic medical record (EMR) (2017-2020), were included. Fever+ patients (temperature >38°C) were compared with Fever- patients (36°C-38°C). Multi-variable logistic regressions assessed the association of fever status with outcomes. The interaction between fever, age, and outcomes was assessed. Results: A total of 140,647 patients were included from 89 centers. Eight hundred ninety (0.6%) were Fever+ and had worse unadjusted outcomes. After adjustment, Fever+ patients had significantly greater mortality (adjusted odds ratios [aOR], 95% confidence interval: 1.05 [1.04-1.07]), intensive care unit use (1.08 [1.04-1.11]), and ventilator use (1.11 [1.09-1.13]). Fever+ status was associated with a significantly larger aOR of severe sepsis in older versus younger patients (≥65 y: 1.12 [1.11-1.13]; <65 y: 1.04 [1.03-1.05]). Fever+ status was also associated with a significantly larger aOR of bacteremia in older versus younger patients (≥65 y: 1.09 [1.08-1.10]; <65 y: 1.04 [1.03-1.05]). Implications: Although uncommon, fever at presentation is an ominous sign for trauma patients and portends significantly greater risks for bacteremia, sepsis, and mortality. These risks increase with age. These findings suggest older adults who present with fever warrant early aggressive intervention and may sustain injury as a consequence of debility from systemic infection.

Disparities in time to treatment initiation of invasive lung cancer among Black and White patients in Tennessee

Background Early initiation of treatment for lung cancer has been shown to improve patient survival. The present study investigates disparities in time to treatment initiation of invasive lung cancer within and between Black and White patients in Tennessee. Methods A population-based registry data of 42,970 individuals (Black = 4,480 and White = 38,490) diagnosed with invasive lung cancer obtained from the Tennessee Cancer Registry, 2005–2015, was analyzed. We conducted bivariate ANOVA tests to examine the difference in time to treatment initiation among independent factors, and multivariable Cox proportional hazard models to identify independent factors that influence median time to treatment initiation after diagnosis. Results When considering the estimate of the proportion of time to treatment initiation based on the combined influence of all independent factors (sex, age, race, marital, county of residence, health insurance, cancer stage, and surgical treatment), Black patients were generally more at risk of delayed treatment compared to Whites. Black patients aged &lt;45 years (adjusted hazard ratio [aHR] = 1.40; 95% confidence interval [CI] = 1.01–1.94) and married White patients (aHR = 1.13; 95% CI = 1.07–1.18) had the highest increased risk of late treatment among their respective racial subgroups. In the general sample, patients with private health insurance had (aHR = 1.08; 95% CI = 1.01–1.16) higher risk of late treatment beyond 2.7 weeks compared to self-pay/uninsured patients. This was consistent among both Black and White subsamples. Patients with localized and regional lung cancer stages had a decreased risk of delayed treatment compared to those diagnosed at the distant stage among both Black and White patients. Conclusions Black patients were often at greater risk of late initiation of treatment for invasive lung cancer in Tennessee. Additional research is needed to understand factors influencing time to treatment initiation for Black patients in Tennessee. Further, cancer care resources are needed in Black communities to ensure timely treatment of invasive lung cancer, reduce disparities, and promote equitable care for all cancer patients.

Epstein-Barr Virus Encephalitis as a Cause of Status Epilepticus – A Rare Encounter

Epstein-Barr virus (EBV) is associated with infectious mononucleosis and is known to cause various neurological complications, albeit rarely. EBV encephalitis is a rare manifestation, and even rarer is its presentation as status epilepticus. To date, fewer than ten cases of EBV encephalitis presenting as status epilepticus have been reported globally. We report a case of an 18-year-old girl who presented with fever followed by seizures. She went into status epilepticus the next day. Cerebrospinal fluid (CSF) analysis showed lymphocytic predominance. Brain imaging showed bilateral symmetric hyperintense lesions in the caudate and the putamen. EBV IgG and IgM were found to be positive. The patient was treated with ganciclovir and anti-epileptics and she improved gradually. Our case emphasizes the importance of considering EBV encephalitis as a potential cause of status epilepticus, even in individuals without immunodeficiency. Recognizing atypical presentations and appropriate diagnostic investigations can facilitate early diagnosis and treatment initiation.

CARDIOVASCULAR-DERIVED CELL-FREE DNA: ASSOCIATIONS WITH FRAILTY AND AGING-RELATED COMORBIDITIES

Abstract Cell-free genomic DNA (cf-gDNA) fragments are released into the bloodstream following cell death processes and higher levels are associated with age-related physical and cognitive decline. It remains unclear which tissues release cf-gDNA fragments in community-dwelling older adults with frailty. Serum cf-gDNA from 190 participants in the Religious Orders Study and Rush Memory and Aging Project (ROS-MAP) had DNA methylation performed via Illumina Methylation EPIC array. Hierarchical clustering derived distinct sub-populations based on cf-gDNA tissue of origin. Linear regression and mixed-effects models examined associations between tissue origin and physical measures. After neutrophils, vascular endothelial cells (5.3%), erythrocyte progenitors (4.8%), and monocytes (4.3%) were the most frequent cell types of origin. Hierarchical clustering demonstrated three sub-populations distinguished by cf-gDNA tissue origin: Cardiovascular, Erythrocyte Progenitor, and Immune Cell. Individuals in the Cardiovascular sub-group had enrichment of fragments from myocardial and vascular endothelial cells, demonstrated higher frailty scores, and had increased prevalence of myocardial infarction, congestive heart failure, and stroke compared to other sub-groups. The Cardiovascular sub-group also had DNA fragments with increased biological age compared to the other groups (via GrimAge calculation), suggesting the cf-gDNA was released from older cells in the Cardiovascular group. Our study reveals a sub-group enriched with fragments originating from cardiovascular tissue that demonstrate higher future occurrence of frailty and cardiovascular disease and have cf-gDNA release from older cells compared to the other sub-groups. Using cf-gDNA to identify these at-risk individuals can allow for early initiation of treatments to attenuate progression to severe cardiovascular disease and frailty.

The Use of Biologic and Targeted Synthetic Disease-Modifying Drugs in the Treatment of Psoriatic Arthritis

Psoriatic arthritis (PsA) is a systemic inflammatory condition affecting the joints, spine, and entheses, as well as the skin and nails. It affects about 6–42% of patients with psoriasis (PsO), with a prevalence of 1–2 per 1000. PsA can precede skin disease in 7–14% of patients. Different clinical domains may be involved, including psoriatic skin disease, peripheral arthritis, axial involvement, dactylitis, enthesitis, and nail disease. Psoriatic arthritis is a complex, systemic inflammatory condition. While the exact mechanisms underlying PsA are not fully understood, it is believed that the disease arises from a combination of genetic predisposition and environmental triggers that lead to inflammatory processes in both the skin and joints. The treatment approach for PsA focuses on controlling inflammation, improving symptoms, and preventing joint damage. Early initiation of treatment is crucial for achieving better functional outcomes. Various therapeutic agents are available that target different inflammatory pathways. In this review article, various treatment options, focusing on biologic and targeted synthetic disease-modifying antirheumatic drugs, are discussed.

Completed suicide risk factors among people living with HIV in Hunan Province identified through a psychological autopsy case–control study

Accumulating evidence has shown an increased risk of suicide among people living with HIV/AIDS (PLWHA). However, few studies have explored the risk factors associated with completed suicide among PLWHA. This study aimed to identify the characteristics and causes of completed suicide among PLWHA to guide future targeted suicide prevention and intervention programs. A 1:1 matched case–control psychological autopsy study was conducted among PLWHA in Hunan Province. We recruited 63 PLWHA who died by suicide from January 1, 2013, to December 31, 2019, and 63 living controls matched for age, gender, and employment. Two informants for each participant were interviewed to collect data on participants’ sociodemographic characteristics, depressive symptoms, HIV-related stress, hopelessness, and social support. The median survival time from HIV diagnosis to completed suicide was 3.9 months (IQR: 0.57–14.13). Most completed suicides occurred within six months of HIV diagnosis (71.4%), with poisoning (34.9%) and hanging (22.2%) as the primary methods. After controlling for confounding factors, we identified four risk factors of completed suicide: not receiving antiretroviral treatment (OR = 6.805; 95% CI: 1.227 to 37.738), receiving low-income subsidy (OR = 16.272; 95% CI: 3.245 to 81.598), HIV-related stress (OR = 1.332; 95% CI: 1.089 to 1.629), and hopelessness (OR = 2.910; 95% CI: 1.378 to 6.144). PLWHA are at a high risk of suicide within the first six months of HIV diagnosis, indicating an urgent need for immediate suicide screening and timely intervention. Suicide risk is affected by multiple factors, including sociodemographic, clinical, and psychological factors, indicating the need for a multifactorial approach to suicide prevention, which may involve early initiation of ART treatment and provision of economic and psychosocial support.