Proven Disease Research Articles

303. The A-Stop Study: Rapid Tests for Candida Infection in Non-neutropenic Critically-ill Patients - A Multicentre Diagnostic Test Accuracy Study

Abstract Background Among critically-ill patients, antifungal therapy is usually driven by risk rather than a confirmed diagnosis. This leads to overtreatment, due to both low confidence in culture-based diagnostics and the time-critical nature of antifungal treatment. Such overtreatment undermines antimicrobial stewardship which could be improved if rapid, non-culture, tests reliably exclude disease. Methods This was a prospective multicentre diagnostic test accuracy study of three rapid tests for Candida infection: beta-D-glucan (BDG), Associates of Cape Cod, and two PCR-based tests (Fungiplex Candida, Bruker Corporation; & T2Candida, T2 Biosystems). In brief, patients were eligible for recruitment within 24hr of being started empirically on antifungal therapy for suspected Candida infection if they were not neutropenic. In the primary analysis, diagnostic accuracy metrics were derived by comparing index test results to the EORTC/MSGERC definition of proven Candida disease for patients in intensive care units (ICU). In a secondary analysis, the tests were compared with a constructed reference standard for proven + probable Candida disease. Since the purpose of these tests was to rule-out disease, sensitivity and negative predictive value (NPV) were the focus. Results Of 4005 patients screened for eligibility, 1251 participants were recruited from 57 UK ICUs between 2018-2023. Of these, 1223 were evaluable against the definition of proven disease and 54 met that definition. In total, 1215, 1217, and 507 participants had an evaluable BDG, Fungiplex, and T2Candida test, respectively. For proven disease, the most sensitive test was BDG (69%), followed by T2Candida (44%) and Fungiplex (28%); the NPV of each of these three tests was 97%. The sensitivity was predictably lower for the proven + probable disease group (N=124), ranging from 18%-58%, yet NPV remained above 90% for all three tests. Conclusion There is an opportunity to reduce unnecessary antifungal prescribing in this patient group. Each of the tests evaluated had lower sensitivity than previously reported but, because of low disease prevalence, they had high NPV. Modelling the effects of using the tests to stop empiric treatment may further guide how best to apply the tests in practice. Disclosures All Authors: No reported disclosures

633. Incidence and Outcomes of Pediatric Allogeneic Hematopoietic Cell Transplant (allo-HCT) Recipients Under Surveillance and Not Under Surveillance for Human Adenovirus (HAdV) in the Post-HCT Period

Abstract Background Human Adenovirus (HAdV) can cause life-threatening illness in pediatric allo-HCT recipients, but studies to define incidence and outcomes of HAdV in allo-HCT patients are limited. Use of PCR-based HAdV surveillance varies by HCT center, in part because there are no approved HAdV-directed therapies. This study describes the epidemiology of HAdV infection and disease in pediatric allo-HCT patients who did and did not undergo HAdV surveillance. Methods An allo-HCT cohort was assembled from July 2018 to June 2021 at ten US pediatric HCT centers. Patients were followed for 180 days from HCT to document presence of HAdV infection and disease and were considered under surveillance if ≥ 2 HAdV blood tests were run in the first 14 days post-HCT. Published HAdV disease and attributable death definitions were applied to patients with positive HAdV PCR tests from any site and adjudicated by a central review committee. HAdV events were designated asymptomatic infection or possible, probable, or proven disease. HAdV DNAemia and disease incidence, time to event, and mortality and attributable case fatality rates were described. Results The cohort included 831 allo-HCT recipients: 645 under surveillance & 186 not (Table 1). 15.5% of patients under surveillance had DNAemia; median time to DNAemia was 31.0 days from HCT (Table 2). Probable/proven disease was documented in 11.9% and 3.8% of patients under and not under surveillance, with median time to disease 37.0 days and 66.0 days from HCT, respectively (Table 3). Overall mortality rates were 7.6% and 8.6% in patients under and not under surveillance (Table 4). Attributable case fatality rates for those with probable or proven disease were 13.0% and 14.3% in those under and not under surveillance, respectively. Conclusion HAdV infection and disease events were frequent; however, incidence was higher in patients under surveillance, suggesting detection bias. HAdV disease was identified as a frequent cause of death. Attributable case fatality rates were similar regardless of surveillance, suggesting early detection did not improve outcomes. Future analyses of these data will determine patient factors that identify allo-HCT patients at high risk for HAdV infection and disease to target for novel prophylaxis or pre-emptive therapy studies. Disclosures Michael D. Green, MD, MPH, ADMA: Advisor/Consultant|Bristol Myers Squibb: Advisor/Consultant|ITB-MED: Advisor/Consultant|kamada: Honoraria Monica I. Ardura, DO, MSCS, Karius: Advisor/Consultant|Miravista: Grant/Research Support Jeffrey Auletta, MD, Ascella Health: Advisor/Consultant Diego R. Hijano, MD, MSc, FDA: Grant/Research Support|Merck: Grant/Research Support|National Institute of Health: Grant/Research Support William J. Muller, MD, Ansun Biopharma: Grant/Research Support|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|DiaSorin: Advisor/Consultant|DiaSorin: Honoraria|Eli Lilly and Company: Grant/Research Support|Enanta Pharmaceuticals: Advisor/Consultant|Enanta Pharmaceuticals: Grant/Research Support|F. Hoffmann-LaRoche Ltd (Roche): Grant/Research Support|Finley Law Firm, P.C.: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Melinta Therapeutics, Inc.: Grant/Research Support|Merck Sharpe & Dohme: Grant/Research Support|Moderna: Grant/Research Support|Nabriva Therapeutics, plc: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Pfizer: Grant/Research Support|ProventionBio: Advisor/Consultant|Sanofi: Advisor/Consultant|Sanofi: Honoraria|Tetraphase Pharmaceuticals, Inc.: Grant/Research Support Michael Grimley, MD, SymBio Pharmaceuticals Limited: Advisor/Consultant Lara A. Danziger-Isakov, MD, MPH, Aicuris: clinical research contract, paid to institutio|Ansun BioPharma: clinical research contract, paid to institution|Astellas: Advisor/Consultant|Astellas: clinical research contract, paid to institutio|Merck: clinical research contract, paid to institutio|Pfizer: Grant/Research Support|Takeda: clinical research contract, paid to institutio Brian T. Fisher, DO, MPH/MSCE, Allovir: Grant/Research Support|Astellas: Data Safety Monitoring Board|Merck: Grant/Research Support|Pfizer: Grant/Research Support

Endoscopic sleeve gastroplasty plus lifestyle intervention in patients with MASH: a multicentre, sham-controlled, randomized trial.

Metabolic dysfunction-associated steatohepatitis(MASH) is commonly seen in biopsy proven steatotic liver disease(SLD). Life-style intervention reaching a weight loss higher than 10% promotes MASH resolution, but this goal is only achieved by a small number of patients. Endoscopic sleeve gastroplasty(ESG) has recently emerged as a safe and effective option to promote weight loss in obese population. We report the results of a multicenter, randomized, controlled and double-blind study to evaluate the effectiveness and safety of ESG in MASH patients METHODS: Forty patients were randomized 1:1 to ESG plus lifestyle modification vs. sham endoscopy (SE) plus lifestyle intervention. Inclusion criteria included biopsy proven MASH with NAS≥3 and fibrosis stage F0-F3. Eighteen patients from the ESG group and 19 from the ESI group completed follow-up during 72 weeks. Baseline to end of follow-up changes in body weight, liver tests, liver stiffness(VCTE) and liver histology were recorded RESULTS: Total Body weight loss(TBWL) was 9.47%(±9.38) in ESG group vs 3.91%(±5.43) in ESI group(p<0.05). Liver stiffness decreased 5.63(±7.17) KPa in ESG group vs 0.2(±5.38) KPa in ESI group(p<0.05). Steatosis was significantly reduced in ESG group(-0.94±0.87) vs ESI group(-0.26±0.99)[p= 0.033]. No differences on NAS(-1.89±2.11 vs -1.47±2.01) score neither fibrosis(-0.1±0.91 vs -0.84±1.21) was seen. In patients achieving weight loss>10% we found a significant improvement on NAS score(-4±0.94 vs. -0.81±1.62, p<0.01), but not in fibrosis stage(-0.3±1.06 vs -0.59±1.25). Only 2 patients of ESG group had adverse events that required admission that resolved conservatively in 72 hours CONCLUSION: ESG is an effective and safe method to promote weight reduction associated with significant improvement in patients with MASH and obesity.

Comparison of Salivary Opiorphin in Burning Mouth Syndrome and Healthy Subjects and Its Correlation With Psychiatric Disorders

ABSTRACTObjectivesBurning mouth syndrome (BMS) is a chronic disease in which the patient experiences a burning sensation in the oral mucosa without any pathological cause. Opiorphin is a pentapeptide that prevents pain and can have an antidepressant effect. The aim of this study was to evaluate salivary opiorphin concentration in BMS and healthy subjects. In addition, opiorphin concentration in BMS patients before and after psychiatric treatment was compared and the association between burning severity and psychiatric scores with salivary opiorphin concentration was examined.Materials and MethodsThis cross‐sectional study included 28 BMS patients and 40 healthy individuals referred to the Department of Oral and Maxillofacial Medicine, Faculty of Dentistry, Mashhad, from September 2018 to August 2019. Patients with proven disease based on clinical and psychiatric examinations were included in the study. Unstimulated salivary opiorphin levels were assessed by ELISA. Statistical analysis was performed using SPSS version 24.ResultsSalivary opiorphin levels were significantly higher in BMS patients (2.16 ± 0.30 ng/mL) than in healthy subjects (1.80 ± 0.36 ng/mL) (p &lt; 0.001). Opiorphin levels in BMS patients increased insignificantly after psychiatric therapy (p = 0.212). In addition, there was no significant association between opiorphin levels and age, gender, menopause, burning severity, anxiety, and depression status.ConclusionsThe opiorphin concentration in saliva is higher in BMS patients than in healthy subjects. Most BMS patients also suffer from anxiety and depression.

Epidemiology of Infections in Lung Transplant Recipients Treated With Belatacept.

Belatacept is a costimulatory blocker that can be used to prevent and treat rejection in lung transplant recipients (LuTRs). The epidemiology of infections in belatacept-treated LuTRs has not been systematically evaluated. We performed a single-center retrospective study of all adult LuTRs who received belatacept as prevention or treatment of antibody-mediated rejection (desensitization) or as part of maintenance immunosuppression from January 1, 2011, to June 30, 2022. We assessed the epidemiology of infections that occurred within 12 months following the first belatacept dose. Fifty-two LuTRs received at least one dose of belatacept as either desensitization (n = 32) or maintenance immunosuppression (n = 20). Among 45 patients who were cytomegalovirus (CMV) donor and/or recipient seropositive, nine (20%) developed CMV infection. Seven (77%) CMV infections occurred despite valganciclovir prophylaxis and four (44%) were associated with antiviral resistance. Three (6%) LuTRs developed Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (PTLD). Twenty-five (48%) LuTRs developed 43 bacterial infections and five (10%) developed proven or probable invasive fungal disease. Incidence rates of viral, bacterial, and fungal infections were similar between the desensitization and maintenance groups: incidence rate ratios (95% confidence interval) were 0.70 (0.32-1.57), 1.31 (0.70-2.46), and 2.82 (0.31-25.2), respectively. Infection/PTLD prompted belatacept discontinuation in eight (15%) patients. In the first year after belatacept initiation, LuTRs commonly developed CMV infections, EBV+ PTLD, and bacterial infections. Multicenter collaborations are needed to better understand infection risks in LuTRs treated with belatacept.

Mycophenolate mofetil for the treatment of cicatrizing conjunctivitis secondary to ocular pemphigoid

PurposeTo characterize the use of mycophenolate mofetil (MMF) in a large cohort of patients undergoing treatment for ocular mucous membrane pemphigoid (ocMMP). DesignThis was a retrospective consecutive observational chart review of patients with cicatrizing conjunctivitis associated with pemphigoid (ocMMP) at the University of Texas Southwestern Medical Center in Dallas, TX from 2016 to 2023 who underwent treatment with MMF. MethodsData collection included patient demographics, medical and ocular history, clinical findings, slit lamp photographs, biopsy results, additional testing, disease stage, time on MMF, patient response to treatment, and side effects of treatment. The data was analyzed with logistic regression using IBM SPSS (version 29). The dependent variable was remission status. ResultsA total of 52 patients with cicatrizing conjunctivitis associated with pemphigoid were treated with MMF, of which 37 (71.2 %) patients had biopsy proven disease. Of the cohort, 29 (55.8 %) patients were female and 23 (44.2 %) patients were male. The mean age at initiation of MMF therapy was 65.1 years (range 35–93). The best degree of response achieved by each patient in our cohort was as follows: no response (4, 7.7 %), partial response (28, 53.8 %), clinical remission with steroids (4, 7.7 %), steroid-free remission (14, 26.9 %), and durable drug-free remission (2, 3.8 %). The mean time of treatment with MMF was 35.5 months (range 2–118), with a mean follow up time of 42.7 months (range 3–123). The mean time to clinical remission was 6.7 months (range 1–18), while the mean time to steroid-free remission was 7.2 months (range 2–18). Of the entire cohort, 16 (30.8 %) patients reported side effects. The most common side effect was nausea (7 patients). There was one adverse event (anemia, 1, 1.9 %). Overall, 30 (57.7 %) patients discontinued MMF, most commonly due to side effects (11 patients) or inadequate disease control (11 patients). ConclusionMycophenolate mofetil (MMF) can be beneficial in ocMMP as a steroid-sparing alternative. Although effective, side effects and discontinuation of treatment were common.

Impact of manual therapy on body posture-3-D analysis with rasterstereography – pilotstudy

IntroductionThe relationship between posture and temporomandibular disease (TMD) is unclear. The aim of our study was to determine the influence of manual therapy (MT) on posture in TMD patients compared with healthy subjects.Material/methodAfter consideration of inclusion and exclusion criteria, 30 subjects were included. These were divided into two groups: group A comprised 15 healthy subjects and group B 15 patients with present proven TMD disease. Rasterstereographic images were taken at different times. Group A subjects were scanned twice within half a year and group B before initiation as well as after the first MT and after completion of the prescribed MT. The different posture variables were calculated using DIERS Formetric software.ResultsTo illustrate the differences between the two groups, 10 different postural variables were examined. Significant differences between the two groups were observed in pelvic tilt, surface rotation, and kyphotic apex. Pelvic tilt: mean = 7.581, p-value = 0.029; surface rotation: mean = 3.098, p = 0.049; and mean kyphotic apex = 11.538 and 11.946, respectively, with p-values of 0.037 and 0.029, respectively.ConclusionMT leads to a change in posture in TMD patients. This could influence the course of TMD treatment.

Molecular and serological prevalence rates of Neospora caninum infection in dogs from Jordan.

Neosporosis is a proven disease of farm animals and dogs caused by Neospora caninum. This cross-sectional study investigates N. caninum prevalence and seroprevalence among 268 dogs. Nc5 gene PCR was carried out on dog faeces and confirmed by sequencing. Seroprevalence was detected using an indirect fluorescent antibody test (IFAT). Three age groups, gender, locality (Amman, Irbid, and Zarqa Governorates), dog type (stray, pet, and breeding), place of living (indoor/outdoor), food type (raw/cooked), having diarrhoea, having abortion in the area, and having animals nearby were tested as independent variables for associations with positivity to N. caninum using univariate and multivariable logistic regression analyses. The true prevalence of N. caninum was 34.3% (95% CI 28.4, 40.5) using the Nc5-PCR test. The true seroprevalence rate of N. caninum among dogs in Jordan was 47.9% (95% CI 41.4, 54.5) using IFAT. The sequenced isolates of Nc5-PCR products (n = 85) matched three N. caninum strains, namely, NcHareGre (n = 70, 82.4%, 95% CI 72.6-89), NC MS2 (n = 14, 16.5%, 95% CI 9.3-26.1), and L218 (n = 1, 1.2%, 95% CI 0.03-6.4). The three strains were isolated previously from three different countries and continents. N. caninum shedding is associated with abortion among dogs and animals in the area (odds ratio = 3.6). In Amman and Zarqa, living indoors reduced seroprevalence at 0.45, 0.24, and 0.02 odds ratios, respectively. Jordan shares three molecular N. caninum strains with three different countries and continents.

Axillary management and long-term oncologic outcomes in breast cancer patients with clinical N1 disease treated with neoadjuvant chemotherapy

BackgroundLow false negative rates can be achieved with sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients with clinical N1 (cN1) disease. We examined changes in axillary management and oncologic outcomes in BC patients with cN1 disease receiving NAC.MethodsBC patients with biopsy proven cN1 disease treated with NAC were selected from our institutional cancer registry (2014–2017). Patients were grouped by axillary management, axillary lymph node dissection (ALND), SLNB followed by ALND, or SLNB alone. Univariable and multivariable survival analysis for recurrence-free survival (RFS) and overall survival (OS) were performed.Results81 patients met inclusion criteria: 31 (38%) underwent ALND, 25 (31%) SLNB + ALND, and 25 (31%) SLNB alone. A SLN was identified in 45/50 (90%) patients who had SLNB. ALND was performed in 25/50 (50%) patients who had SLNB: 18 for a + SLNB, 5 failed SLNB, and 2 insufficient SLNs. 25 patients had SLNB alone, 17 were SLN- and 8 SLN+. In the SLNB alone group, 23/25 (92%) patients received adjuvant radiation (RT). 20 (25%) patients developed BC recurrence: 14 distant (70%), 3 local (15%), 2 regional + distant (10%), and 1 contralateral (5%). In the SLNB alone group, there was 1 axillary recurrence in a patient with a negative SLNB who did not receive RT. Univariable survival analysis showed significant differences in RFS and OS between axillary management groups, ALND/SLNB + ALND vs. SLNB alone (RFS: p = 0.006, OS: p = 0.021). On multivariable survival analysis, worse RFS and OS were observed in patients with TNBC (RFS: HR 3.77, 95% CI 1.70–11.90, p = 0.023; OS: HR 8.10, 95% CI 1.84–35.60, p = 0.006).ConclusionsSLNB alone and RT after NAC in BC patients with cN1 disease who have negative SLNs at surgery provides long-term regional disease control. This analysis provides support for the practice of axillary downstaging with NAC and SLNB alone.

Cardiovascular risk reduction in type 2 diabetes: What the non-specialist needs to know about current guidelines.

In the US, approximately 11% of the population have diagnosed diabetes and nearly 40% have prediabetes. In addition, chronic kidney disease (CKD) affects 14% of the US population including up to 40% of those with diabetes. Cardiovascular disease (CVD) remains the leading cause of death worldwide where it affects approximately half of adults. The presence of CKD or diabetes doubles the risk of cardiovascular events. When both CKD and diabetes occur in the same patient the risks are further increased. The clinical problems of hypertension, hyperglycemia, and hyperlipidemia are all closely related with obesity, metabolic syndrome, Type 2 diabetes, CKD, atherosclerotic cardiovascular disease, heart failure and non-alcoholic fatty liver disease and metabolic dysfunction-associated steatohepatitis. The increasing frequency of obesity has driven increases in all of these medical comorbidities. These conditions frequently cluster together in the same patient exacerbating the risk of morbidity and mortality. They are also associated with cognitive dysfunction/dementia, pulmonary diseases, cancers, gastrointestinal diseases, immune system abnormalities, and inflammatory disorders. Only 6.8% of adults in US meet all targets for cardiovascular risk management with significant disparities based on race and ethnicity. Given the complexity of these multisystem problems in people with diabetes and obesity, it would seem reasonable to attempt to diagnose and treat many of the comorbidities earlier in the course of disease rather than wait for substantial end organ dysfunction to occur. The American Diabetes Association (ADA) has recently published a consensus statement recommending early screening for the diagnosis of heart failure, CKD and diabetes, recognizing both the frequency and gravity of this combination. Likewise, there are recommendations in the guidelines to facilitate screening for microalbuminuria, blood pressure, glycemic control and lipids earlier in patients at risk rather than wait and treat as a secondary prevention program. Thus, the general principle is to facilitate earlier recognition and diagnosis and provide treatment before downstream target organ complications occur. This review will focus on CVD and risk management based on newest recommendations and standards of care in people with diabetes by the ADA. The main considerations in the treatment of people with diabetes are glycemic control, blood pressure, lipids, and the use of medications with proven cardiorenal disease progression capability to prevent or delay.

Common carotid artery intima media thickness (CIMT) in patients with prediabetes and newly diagnosed type 2 diabetes mellitus

AimTo evaluate the relationship between common carotid artery intima media thickness (CIMT) in patients with prediabetes and new-onset diabetes mellitus without proven cardiovascular disease and some classic cardio-metabolic risk factors. Patients and methodsThe study included 461 obese patients with an average age of 53.2 ± 10.7 years, divided into three groups - group 1 without carbohydrate disturbances (n = 182), group 2 with prediabetes (n = 193) and group 3 with newly diagnosed diabetes mellitus (n = 86). ResultsThe patients with new-onset diabetes had significantly higher mean CIMT values compared to those with prediabetes or without carbohydrate disturbances and a higher frequency of abnormal IMT values. CIMT correlated significantly with age, systolic BP, diastolic BP and fasting blood glucose and showed a high predictive value for the presence of diabetic neuropathy and sudomotor dysfunction. Patients with abnormal CIMT values had a higher incidence of arterial hypertension, dyslipidemia, metabolic syndrome, peripheral neuropathy, and sudomotor dysfunction. Patients who developed type 2 diabetes during follow-up had a significantly higher initial mean CIMT, which showed the highest predictive value for the risk of new-onset diabetes, with CIMT≥0.7 mm having 53 % sensitivity and 83 % specificity for the risk of progression to diabetes mellitus. ConclusionPatients with new-onset diabetes mellitus had significantly greater intima media thickness of the common carotid artery and a greater frequency of abnormal CIMT values compared to those with normoglycemia and prediabetes. CIMT has a high predictive value for the presence of diabetic neuropathy, sudomotor dysfunction and the risk of new onset diabetes.

Associations of the variable site rs2010963 of the VEGF-A gene with multifocal atherosclerosis in aluminum industry workers with chronic occupational intoxication with fluoride compounds

Introduction. The aluminum industry occupies a leading position among non-ferrous metallurgy industries in revealing somatic pathologies in workers that occur against the background of chronic fluoride intoxication. Long-term exposure to fluorides on the body has a cardiovasotoxic effect, leads to structural and functional disorders of the myocardium and the development of comorbid cardiovascular pathology. This dictates the need for a risk-oriented approach to its diagnosis, including one based on molecular genetic analysis, for the timely identification of risk groups for the development of atherosclerosis and the elaboration of preventive measures aimed at preserving the health and maintaining working longevity of the studied occupational cohort. Materials and methods. There were examined ninety seven metallurgists with a previously proven diagnosis of chronic occupational intoxication with fluoride compounds, engaged in aluminum production. The comparison group consisted of 33 workers of this enterprise without a proven occupational disease. All respondents underwent ultrasound investigation of the main arteries. Genotyping of the rs2010963 polymorphic locus of the VEGF-A gene was carried out in a 96-well format using TaqMan technology (allele-specific real-time PCR). Results. The associative connection of the G/G VEGF-A genotype is determined in metallurgists with the risk of developing chronic occupational intoxication with fluoride compounds and heterozygous G/C genotype in subjects with multifocal atherosclerosis. The high level of predictive value of the polymorphism -634 G/C (rs2010963) of the VEGF-A gene allows considering it a marker of the risk for the developing atherosclerosis in workers exposed to long-term impact to fluoride compounds on the body. Limitations. The study was limited to the number of long-term work experienced subjects undergoing periodic medical examinations and undergoing inpatient treatment at the Research Institute for Complex Problems of Hygiene and Occupational Diseases. Conclusion. It is recommended to conduct a screening molecular and genetic analysis in a clinical hospital setting for timely assessment of the prognostic significance of risk markers for the development of atherosclerosis and its complications in workers of basic occupations engaged in aluminum production.

Intensity Score of Vessel Wall Contrast Enhancement in MRI Allows Prediction of Disease Progression in Moyamoya Angiopathy.

The underlying pathophysiological cause of moyamoya angiopathy (MMA) is still unclear. High-resolution vessel wall imaging has become a useful tool. The aim was to study vessel wall contrast-enhancement (VW-CE) as an imaging marker to predict disease progression in MMA. Patients with MMA, who had undergone serial contrast-enhanced high-resolution MRI with concomitant and follow-up digital subtraction angiography, were analyzed retrospectively. VW-CE was semiquantified by measurement of the signal intensity of the vessel wall in in contrast-enhanced high-resolution MRI. A comparative quotient with the contrast-intensity of the pituitary stalk was calculated and graded accordingly from grade 1 to 5. VW-CE status was correlated with disease status, stroke, cerebrovascular reactivity in CO2-triggered blood-oxygen level-dependent MRI, angiographic disease progression, revascularization surgery, and follow-up imaging. Forty eight patients met the inclusion criteria. N = 56 MRI and digital subtraction angiography time-intervals were evaluated for 12 vessel sections per hemisphere each (N = 1344). N = 38 (79%) patients showed VW-CE and N = 10 (21%) did not. VW-CE was only observed in the terminal internal carotid artery and the proximal circle of Willis (N = 96/1344). Notably, patients with VW-CE significantly more often presented with acute infarction in the concomitant MRI. The incidence of angiographically proven disease progression was significantly associated with the incidence of VW-CE, and time to disease progression was earlier in higher grades of VW-CE compared with lower grades. VW-CE is a semiquantifiable marker for disease activity in patients with MMA and associated with disease progression and increased risk of stroke. VW-CE analysis can be routinely performed in patients with MMA to estimate the risk for disease progression and stroke.

Registration of ‘CP 15‐1407’ sugarcane for muck soils

AbstractThe complex hybrid sugarcane (Saccharum spp.) cultivar ‘CP 15‐1407’ (Reg. no. CV‐217; PI 704105) was made available to growers in June 2022 for cultivation on muck soils in Florida. This development took 10 years thanks to collaborative research by the USDA–ARS, the Florida Sugar Cane League Inc., and the University of Florida. It started at Canal Point (CP) as a bi‐parental cross between ‘CP 08‐1110’ (female) and CP 05‐1616 (male). Due to its high stalk weight, adequate disease resistance, higher recoverable sugar, and equivalent cane yield to best check ‘CP 96‐1252’ on muck soils, the Florida Sugarcane Variety Committee recommended releasing CP 15‐1407. It has demonstrated resistance to brown rust, orange rust, sugarcane mosaic, smut, leaf scald, and ratoon stunt and is moderately susceptible to yellow leaf. In late‐stage, on‐farm yield trials, CP 15‐1407 stalk weights were 27.8% heavier than that of CP 96‐1252, while cane yields and economic index (EI) did not differ from CP 96‐1252. Florida sugarcane output and crop sustainability are predicted to benefit from CP 15‐1407's sustained cane production capacity and proven disease resistance.

Patients with Coronary Heart Disease with Lipid Profile

Background: The lipid profile and their ratio are important in management and follow up of patients with coronary heart disease. We studied the lipid profile and their ratios with proven coronary artery disease. Methods: It was retrospective study to determine the lipid profile and their ratios in patients with proven coronary artery disease at Shakuntala Pathology Lab., Nagpur. 200 patients were studied. Results: Out of 200 patients studied, 126 (63%) were males while 74 (37%) were females. out of 126 males,12 (9.52%) had raised cholesterol values of &gt;200 mg/dL. 20 (15.87%) had raised triglyceride values of &gt;200 mg/dL. 30 (23.80%) had lower HDL values of 150 mg/dL. 90 (71.42%) had raised values of &gt;3.5 for cholesterol to HDL ratio. Out of 74 female patients, 20 (27.02%) patients had raised cholesterol values. 12 (16.21%) patients had raised triglycerides values. 13 (17.56%) patients had lower HDL values. 6 (8.10%) patients had raised LDL values. 50 (67.56%) patients had raised values for cholesterol to HDL ratio. Conclusions: Our study shows more prevalence of coronary heart disease in males than females. Hypercholesteremia and hypertriglyceridemia was more prevalent in females. HDL values were lowered in more number of males than females. LDL values were raised in more number of females than males. Total cholesterol to HDL ratio was raised in more number of males than females.

Surgical strategy for hiatal hernias

The indications for surgical treatment of hiatus hernias differentiate between type I and types II, III and IV hernias. The indications for a type I hernia should include a proven reflux disease but the indications for surgical treatment of types II, III and IV hernias are mandatory due to the symptoms with problems in the passage of food and due to the sometimes very severe possible complications. The primary aims of surgery are the repositioning of the herniated contents and a hiatoplasty, which includes a surgical narrowing of the esophageal hiatus by suture implantation. In addition, depending on the clinical situation other procedures, such as hernia sac removal, mesh implantation, gastropexy and fundoplication can be considered. There are various approaches to the repair, all of which have individual advantages and disadvantages. An adaptation to the specific needs situation of the patient and the expertise of the surgeon is therefore essential.

Influence of sex and disease etiology on the development of papilledema and optic nerve sheath extension in the setting of intracranial pressure elevation in children

IntroductionDilatation of the optic nerve sheath diameter and swelling of the optic disc are known phenomena associated with intracranial pressure elevation. Research questionDo sex and disease etiology have an impact on the development of optic disc elevation and optic nerve sheath extension in children in the setting of ICP elevation? Fundoscopic papilledema and point-of-care-ultrasound techniques-optic nerve sheath diameter (US-ONSD) and optic disc elevation (US-ODE) - were compared in this regard. Material and methods72 children were included in this prospective study; 50 with proven pathology (e.g. pseudotumor cerebri, tumor), 22 with pathology excluded. Bilateral US-ONSD and US-ODE were quantified by US using a 12-MHz-linear-array-transducer. This was compared with fundoscopic optic disc findings and in 28 patients with invasive ICP values, stratified for sex and etiology. ResultsIn patients with proven disease, significant more girls (69%) had fundoscopic papilledema compared with boys (37%, p < 0.05). Girls had also larger US-ODE values (0.86 ± 0.36 mm vs. 0.65 ± 0.40 mm in boys). 80% of tumor patients had initial papilledema (100% girls, 79% boys), compared with 50% in pseudotumor cerebri (PTC) (83% girls, 30% boys). US-ONSD had no sex- and no etiology-specificity. Discussion and conclusionPresence of papilledema appears to be influenced by sex and etiology, whereas US-ONSD is not. Girls seem more likely to develop papilledema under similar conditions. Male sex and PTC appear as risk factors for being undetected by fundoscopic findings. US-ONSD and US-ODE seem useful tools to identify pathologies with potentially increased ICP requiring treatment in children regardless of sex and etiology.

Treatment of Molecular Relapses in Pediatric AML Saves Toxicities Prior to Hematopoietic Stem Cell Transplantation (HSCT) - Results of AMoRe2017 Trial

Introduction The long-term survival for children with AML has increased to 70 % - but relapsed AML patients still have a poor prognosis (about 30 %). Recent data suggest that in AML residual leukemic cells below the 5 % limit required for a morphologic CR can adversely affect outcome and that increasing levels of Minimal Residual Disease (MRD) are almost always followed by clinical relapse. Early MRD detection provides an opportunity to implement pre-emptive therapies as a bridge-to-transplant approach, to potentially prevent hematological relapse and increase the probability of successful HSCT. A promising approach is the use of Azacitidine (Aza) for treatment of molecular relapse which we evaluated within the clinical trial “AMoRe2017”. Aza has been shown to reverse epigenetic changes in malignant cells, restoring the normal function of genes critical for differentiation and cell cycle control. The trials' primary objective was the evaluation of the effect of Aza treatment in AML subjects at molecular relapse after CR1 regarding molecular response prior to further treatment (reinduction/HSCT). Patients and Methods AMoRe2017 enrolled children with AML (N=20), &amp;gt;3 months &amp;lt; 21 yrs., of which n=1 dropped out due to laboratory measurement error. The median age was 10.9 yrs. (range 1.7-18.9 yrs.). N=10 (53 %) had a CBFB-AML, n=5 (27 %) KMT2A-rearrangement, n=1 (5 %) NUP98::NSD1, n=1 (5 %) FLT3-ITD, n=1(5 %) PICALM::MLLT10 and n=1 (5 %) NPM1. N=8 (42 %) were classified to subgroup M2, n=4 (21 %) to M5, n=3 (16 %) into M1 and n=4 (21 %) to M4/M4 Eo. At baseline, the white blood cell count averaged 3.8x10 9/l (range 0.1-6.6x10 9/l), without leukemic blasts in PB or BM. Each patient had at least one quantifiable genetic marker (rt-PCR), achieved CR with molecular remission, following initial therapy, and subsequently had a molecular relapse (defined as an increase of the MRD level by at least 1 log, less than 5 % BM myeloblasts and absence of proven extramedullary disease). Patients were treated for up to 6 cycles with 75 mg/m 2 i.v. Aza on days 1 to 7 in a 28-day cycle. Molecular response was categorized as molecular stabilization (&amp;lt; 1 log decrease or increase from baseline), molecular progression (≥ 1 log increase from baseline without hematological relapse), molecular improvement (≥ 1 log decrease from baseline), and hematological relapse (at least 5 % blasts in PB and/or BM and/or proven histological extramedullary relapse). Results During Aza treatment, 10 patients (53 %) had an open relapse, which occurred in n=9 after 1 st or 2 nd cycle. These patients were monitored for KMT2A::SEPTIN6 (n=1), KMT2A::MLLT3 (n=2), PICALM::MLLT10 (n=1), FLT3-ITD (n=1), NUP98::NSD1 (n=1), CBFB::MYH11 (n=1) and RUNX1::RUNX1T1 (n=3). 9 patients (47 %; RUNX1::RUNX1T1 n=5, CBFB::MYH11 n=1, NPM1 n=1, KMT2A::ELL n=2) showed a molecular response to Aza and proceeded to HSCT without receiving intensive re-induction treatment. 16 out of the 19 patients are alive (overall survival 84 %), 2 died from HSCT-associated side effects (VOD, infection), and 1 from disease progression. Considering genetics, 7 out of 11 patients with favorable genetics (core-binding leukemia n=10 or NPM1 n=1) responded to the Aza therapy ( RUNX1::RUNX1T1 n=5, CBFB::MYH11 n=1, NPM1 n=1). By contrast, in cases with KMT2A-rearrangements, NUP98::NSD1 or FLT3-ITD, 2 out of 8 patients showed improvement or stabilization. In total 152 adverse events (AEs) associated to Aza were reported, the majority classified as grade 1 or 2 (n= 114; 75 %). Mainly affected was the hematopoietic system (40 %), the gastrointestinal tract (15 %), kidney and liver (14 %). Cardiotoxicity was not reported. Discussion The use of Aza as pre-emptive “bridge-to-transplant” approach treating the molecular relapse showed efficacy in patients with RUNX1::RUNX1T1, CBFB::MYH11, NPM1, and KMT2A::ELL, who could be transplanted directly. This pilot provided proof of principle that molecular relapses could be treated, and MRD levels be reversed, at least in subgroups. In addition, avoiding intensive re-induction therapy prior to HSCT is feasible. Conversely, the relatively slow-acting mechanism of epigenetic therapy seems to be ineffective in highly proliferative subgroups of AML with KMT2A-rearrangements or FLT3-ITD. Further studies are mandatory to define treatment options for molecular relapses of non-favorable pediatric AML and to confirm potential improvement of outcome post-HSCT.

Transorbital point-of-care ultrasound versus fundoscopic papilledema to support treatment indication for potentially elevated intracranial pressure in children

PurposeTo compare transorbital point-of-care ultrasound techniques —optic nerve sheath diameter (US-ONSD) and optic disc elevation (US-ODE)— with fundoscopic papilledema to detect potentially raised intracranial pressure (ICP) with treatment indication in children.MethodsIn a prospective study, 72 symptomatic children were included, 50 with later proven disease associated with raised ICP (e.g. pseudotumour cerebri, brain tumour, hydrocephalus) and 22 with pathology excluded. Bilateral US-ONSD and US-ODE were quantified by US using a 12-MHz-linear-array transducer. This was compared to fundoscopic optic disc findings (existence of papilledema) and, in 28 cases, invasively measured ICP values.ResultsThe sensitivity and specificity of a cut-off value of US-ONSD (5.73 mm) to detect treatment indication for diseases associated with increased ICP was 92% and 86.4%, respectively, compared to US-ODE (0.43 mm) with sensitivity: 72%, specificity: 77.3%. Fundoscopic papilledema had a sensitivity of 46% and a specificity of 100% in this context. Repeatability and observer-reliability of US-ODE examination was eminent (Cronbach’s α = 0.978–0.989). Papilledema was detected fundoscopically only when US-ODE was > 0.67 mm; a US-ODE > 0.43 mm had a positive predictive value of 90% for potentially increased ICP.ConclusionIn our cohort, transorbital point-of-care US-ONSD and US-ODE detected potentially elevated ICP requiring treatment in children more reliably than fundoscopy. US-ONSD and US-ODE indicated the decrease in ICP after treatment earlier and more reliably than fundoscopy. The established cut-off values for US-ONSD and US-ODE and a newly developed US-based grading of ODE can be used as an ideal first-line screening tool to detect or exclude conditions with potentially elevated ICP in children.

Effects of the multidomain intervention with nutritional supplements on cognition and gut microbiome in early symptomatic Alzheimer's disease: a randomized controlled trial.

The SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN) is a part of the World-Wide Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (WW-FINGERS) network. This study aimed to demonstrate the effects of the SUPERBRAIN-based multidomain intervention with nutritional supplements in amyloid positive emission tomography (PET) proven early symptomatic Alzheimer's disease patients. Forty-six participants who were diagnosed with mild cognitive impairment or mild dementia and were positive in the amyloid PET study randomized into three groups: group A, the multidomain intervention with nutritional supplements; group B, nutritional supplements only; and a control group. The primary outcome was a change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score after an 8-week intervention. Secondary outcomes, including gut microbiome data, were also analyzed. The RBANS total scale index score improved significantly in group A compared with group B (p < 0.032) and compared with the control group (p < 0.001). After intervention, beta diversity of the gut microbiome between group A and the control group increased, and patients in group A were more enriched with Bifidobacterium. SUPERBRAIN-based multidomain intervention with nutritional supplements improves cognition and gut microbiota in patients with early symptomatic Alzheimer's disease who were amyloid-positive by PET.