Pre-existing Disease Research Articles

12213 Is Atrial Fibrillation An Adverse Cardiovascular Effect Of Romosozumab

Abstract Disclosure: S. Martinez: None. D. Anez: None. M. Shahid: None. Osteoporosis and cardiovascular disease are both common in older populations. Therefore, it is not uncommon to find the two disorders in a single individual and yet it may be difficult to establish whether the diseases are coincident or the result of complex hormonal processes interacting with multiple systems, including possibly sclerostin. Indeed, pre-existent cardiovascular disease predisposes to osteoporotic bone loss and increased fracture risk. To date, a number of studies have linked the incidence of major adverse cardiovascular events (MACE) with various osteoporosis treatments while other treatments have demonstrated no associated or a reduced cardiovascular risk. Here we discuss the possibility of romosozumab-induced sudden, new onset atrial fibrillation (a fib) in a 70-year-old female with no known risk factors other than age. A 70-year-old female with a 20-year history of osteoporosis presented to establish care. After 5 years of alendronate therapy, she was switched to denosumab injections, 60 mg every 6 months. During Covid the patient’s physicians closed their office and denosumab therapy was interrupted for approximately 18 months. Therefore, when the patient established care with a new rheumatologist she was started on romosozumab. After 6 months of romosozumab the patient developed new onset atrial fibrillation. The cardiovascular safety of romosozumab, in particular, has been adjudicated in two large trials describing predominantly major cardiovascular events such as myocardial infarction, stroke, heart failure and cardiovascular death. In one of those trials, two reports of atrial fibrillation were also included in the adverse events but further details were not available. These increased MACEs prompted a safety warning from the FDA such that use of romosozumab in patients who have experienced a myocardial infarction or stroke within the year prior to its use is contraindicated. Recently atrial fibrillation and congestive heart failure were documented in 78-year-old woman who had been receiving romosozumab for three months for the treatment of osteoporosis. Our case represents a second report of a temporal relationship between the initiation of romosozumab and the onset of atrial fibrillation raising the question of a possible cause and effect. Disclaimer: This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities. Presentation: 6/3/2024

7699 Unanticipated Harmony: PD-L1 Inhibitor Treatment for Urothelial Cancer Resolving Graves' Disease in a Patient - A Case of Immune Modulation Surprises

Abstract Disclosure: K. Tiwari: None. C.A. Resta: None. Introduction: Programmed death ligand 1(PD-L1) inhibitors constitute a class of immune checkpoint inhibitors (ICI) employed in treating various cancers. Thyroid-related immune-related adverse events (irAEs), such as hypothyroidism, are found to be in 3.9% of patients with PD L1 treatments. This case explores a unique scenario where a patient with pre-existing Graves' disease, undergoing PD-L1 inhibitor therapy for cancer, experienced an unexpected sequence of events leading to the default treatment of Graves' disease and subsequent progression to hypothyroidism. Case Presentation: A 59-year-old male, who had been effectively managed on methimazole for Graves' disease over two years and had chosen not to pursue definitive therapy for the condition, presented with tremors and a bilaterally enlarged thyroid gland during treatment for urothelial carcinoma. Laboratory findings included a TSH of 0.03 mIU/L (nl 0.40-4.50 mIU/L), fT4 of 3.4 ng/dL (nl 0.8-1.8 ng/dl), and tT3 of 284ng/dl (nl 76-181 ng/dl). The patient had recently started treatment with Avelumab, a PD-L1 inhibitor, as maintenance therapy following 4 cycles of gemcitabine/cisplatin cycles. Concerned about worsening Graves' disease, the methimazole dose was increased, and follow-up labs were performed after three weeks. These results showed low-normal fT4 of 0.8 ng/dL, TSH of 1.01 mIU/L(N), and low T3 of 58 ng/dL. TSI was mildly elevated at 168%. Due to rapidly changing thyroid function tests and suspicion of thyroiditis, methimazole was stopped. A PET scan a week later indicated diffuse thyroid uptake consistent with thyroiditis. Repeat labs 10 days later revealed a TSH of 67.36 mIU/L(H) and fT4 of 0.4 ng/dL(L), indicative of overt primary hypothyroidism. The patient exhibited symptoms including fatigue, constipation, and cold intolerance. The patient was initiated on levothyroxine therapy to address overt primary hypothyroidism, likely secondary to destructive thyroiditis from ICI. Discussion: Thyroid irAEs are typically incidentally discovered during routine monitoring of ICI treatment. It includes thyrotoxicosis, subclinical hypothyroidism, and overt hypothyroidism. These events commonly occur in patients lacking pre-existing thyroid conditions. In contrast, our patient, with a history of Graves' disease, experienced resolution of Graves' disease following treatment with PD-L1 inhibitor use with subsequent progression to hypothyroidism. Conclusion: This case emphasizes the importance of recognizing atypical presentations of thyroid irAEs in individuals with pre-existing thyroid disorders undergoing ICI treatment. Presentation: 6/3/2024

7404 Evaluation Of Cortisol Reserve And Adrenal Imaging In Patients With Graves’ Disease Before And Six Months After Treatment

Abstract Disclosure: P. Sharma: None. S. Mir: None. S. Mohd Patto: None. A.H. Bhat: None. B. Dar: None. M. Bhat: None. Introduction: There is scarcity of data regarding the effect of thyrotoxicosis on cortisol metabolism and adrenal gland size. An increase in cortisol metabolism can deplete the functional reserve of adrenal cortex and lead to adrenocortical insufficiency even when there is no pre-existing Addison's disease. In developing countries patients with Graves’ disease present in advanced states of thyrotoxicosis. Besides they are also exposed to a variety of environmental stresses such as recurrent febrile illnesses, salt, and water loss due to manual labour in hot and humid climates etc., which can precipitate an adrenal crisis in the presence of compromised adrenal reserve. So present study was undertaken to assess cortisol reserve and adrenal gland size in patients with treatment naive Graves' disease. Objectives- The present study, was undertaken to assess cortisol reserve and adrenal imaging in patients with treatment naive Graves' disease. Specific information in this regard would help alert physicians dealing with clinical thyrotoxicosis in developing countries of tropics to the possibility of co-existing adrenal decompensation and adopt appropriate life saving measures promptly. Material & Methods: We examined 38 treatment-naive Graves' Disease patients at GMC, SSH, Srinagar, Kashmir, INDIA. Basal cortisol and cortisol response to ACTH were measured before and after six months of treatment, alongside adrenal CT imaging. Results: In hyperthyroid state, Graves' patients exhibited significantly lower basal cortisol compared to euthyroid and healthy controls (306 vs. 410 vs. 421 nmol/l, p < 0.05). 23.6% patients had subnormal cortisol response to ACTH(250ug). Those with T3 ≥ 400 ng/dl had lower cortisol response (560±133 nmol/l) and delta cortisol response than T3 < 400 ng/dl (724 ± 294 nmol/l, 213+/-73 vs. 428+/-265 nmol/l). After achieving euthyroid state, cortisol levels improved significantly (410±213 nmol/l vs. 306 ± 103 nmol/l, p < 0.05). Adrenal CT scans in 34 patients was done out of which 19 showed statistically significant increases in gland thickness, width, and AP diameter compared to controls (p < 0.01, p < 0.05. Repeat CT in 26 patients demonstrated resolution of hyperplasia (p < 0.05). Conclusion: Treatment-naive Graves' disease patients have compromised adrenocortical reserve and adrenal gland enlargement. Adrenal changes are reversible after achieving euthyroid state. These findings support steroid supplementation in impending thyrotoxic crisis and highlight a unique feature of reversible adrenal gland enlargement in this context. Keywords: Graves’ Disease, Adrenal hyperplasia, Cortisol reserve. Presentation: 6/3/2024

7659 Iodinated Contrast Induced Thyrotoxicosis Leading to Takotsubu Cardiomyopathy

Abstract Disclosure: A. Jain: None. E. Naous: None. S. Sedrakyan: None. A.T. Sweeney: None. Background: Thyrotoxicosis may cause many cardiovascular manifestations including tachycardia, hypertension, atrial fibrillation and heart failure. Iatrogenic exposure to iodinated contrast media (ICM) precipitating iodine induced thyrotoxicosis (or the Jod-Basedow phenomenon) is often overlooked. Here, we describe a case of iodine induced thyrotoxicosis leading to takotsubu cardiomyopathy, following multiple exposures to ICM. Case Presentation: An 88-year-old male with a history of hypertension, dyslipidemia, chronic obstructive pulmonary disease, and an ED visit one month ago for hemoptysis for which a CT Angiography (CTA) of the chest was obtained (which excluded Pulmonary Embolism(PE)), presented with fever and shortness of breath. On physical examination his temperature was 100.3F, heart rate was 104bpm, blood pressure 130/62mmHg, respiratory rate was 20/min and saturation was 88% (room air). He was frail but his examination was otherwise unremarkable. Electrocardiogram (EKG) revealed sinus tachycardia. Chest CTA excluded PE. Transthoracic echocardiogram (TTE) showed an ejection fraction (EF) of 73% and no wall motion abnormalities. He was admitted to the hospital for a viral upper respiratory infection and was treated conservatively with bronchodilators. Odynophagia prompted a CT with contrast of the neck soft tissue, which was unrevealing. He was planned to be discharged the next day, but overnight developed severe abdominal pain, and atrial fibrillation with a rapid ventricular response (Troponin t was 191 ng/L (normal {nl}: <9 ng/L)). EKG showed new T-wave inversions in the anterolateral leads, raising a suspicion of myocardial ischemia. A repeated TTE revealed a new drop in EF from 73 to 41%, with new apical akinesis, suspicious for takotsubo cardiomyopathy. CT of the abdomen with contrast was unrevealing. Lab results showed a suppressed TSH of <0.01uIU/mL (nl: 0.34-5.60 uIU/mL), elevated FT4 of 13ng/dL (nl: 0.93-1.70 ng/dL), and TSI 4.97 IU/ L (nl: 0-0.55 IU/ L). Endocrinology was consulted. His thyroid examination was normal, and he had no eye findings. Neck ultrasound revealed a homogeneous thyroid gland without any nodules. His clinical course was consistent with the diagnosis of acute thyrotoxicosis precipitating takotsubu cardiomyopathy. He likely developed iodine induced thyrotoxicosis from multiple exposures to ICM, in a background of previously undiagnosed Graves’ disease. Discussion: Screening for thyroid disease is critical in patients with new onset tachyarrhythmias and stress cardiomyopathy. Iodine induced thyrotoxicosis typically presents after patients with underlying thyroid disease are exposed to iodinated contrast. Prior to ordering studies requiring ICM, it is important to thoroughly evaluate patients for possible pre-existing thyroid disease. Presentation: 6/2/2024

6637 A Rare Case of a Possible Non-functional (Clinically Silent Biochemically Negative) Adrenal Pheochromocytoma

Abstract Disclosure: V.K. Babu: None. M.T. Corwin: None. S.T. Olatunbosun: None. Introduction: Adrenal pheochromocytomas (pheo) are rare neuroendocrine tumors arising from the chromaffin cells of the adrenal medulla. Their incidence is around 0.8 per 100,000 patient years. They are usually sporadic, with about 40% having a pre-existing familial genetic disease. About 3% of adrenal incidentalomas prove to be pheo. They have a heterogenous presentation and are diagnosed by measuring urinary and plasma fractionated metanephrines (met) and catecholamines (catecho). The diagnosis becomes challenging in patients presenting with small tumors and normal levels of biochemical metabolites, as in our patient. Clinical Case: A 32-year-old male with no significant past medical history was referred to us with a left adrenal incidentaloma of 1.2 cm x 1 cm with 23 Hounsfield units during a non-contrast CT scan performed for abdominal pain. He denied spells of headaches, excessive perspiration, palpitations, history of hypertension, hypokalemia, history of kidney stones, fractures, muscle weakness, easy bruisability, new abdominal striae, change in weight, steroid use, or family history of endocrine tumors. MRI with adrenal protocol 3 months later showed a 1.2 cm x 1.4 cm left adrenal nodule that was markedly hyperintense on T2-weighted and hypointense on T1-weighted images without microscopic fat, suspicious for a pheo. It also demonstrated peripheral enhancement with progressive central filling on the delayed images without washout. Plasma met and catecho were normal: normetanephrines (normet) (45.2 pg/mL), met (36.4 pg/mL), epinephrine (epi) (34 pg/mL), norepinephrine (norepi) (295 pg/mL) and dopamine (<30 pg/mL). Subsequent 24-hour urine testing revealed normal met (155 mcg/day, 154 mcg/day), and normal normet (248 mcg/day, 236 mcg/day) on two separate occasions, and normal epi (9 mcg/L), norepi (36 mcg/day), and dopamine (228 mcg/day). The patient was subsequently referred to Endocrine Surgery for evaluation. Conclusion: Our patient likely has a non-functional pheo. Another possibility is an adrenal hemangioma, which would show discontinuous peripheral nodular enhancement in addition to progressive central filling. Patients with pheo less than 2 cm may present with normal biochemical testing. The size of a pheo is usually proportional to the levels of its biochemical metabolites. This case is unique because patients with a similar sized pheo are expected to have 3 times higher levels of plasma met and catecho, even if still within normal limits. It is important to take tumor size into consideration when interpreting labs to determine its functional status. This may help in determining the need for a pre-operative alpha blockade prior to adrenal surgery. A definitive diagnosis of a pheo’s non-functional status can only be confirmed after histopathological examination of the tumor tissue. Presentation: 6/3/2024

Not Just CTEPH: A Narrative Review on the Spectrum Approach to Postpulmonary Embolism Conditions.

Three mutually exclusive entities can underlie a postpulmonary embolism syndrome (PPES): not obstructed postpulmonary embolism syndrome (post-PE dyspnea), chronic thromboembolic pulmonary disease (CTEPD), and chronic thromboembolic pulmonary hypertension (CTEPH). Cardiorespiratory impairment in CTEPH and CTEPD underlies respiratory and hemodynamic mechanisms, either at rest or at exercise. Gas exchange is affected by the space effect, the increased blood velocity, and, possibly, intracardiac right to left shunts. As for hemodynamic effects, after a period of compensation, the right ventricle dilates and fails, which results in retrograde and anterograde right heart failure. Little is known on the pathophysiology of post-PE dyspnea, which has been reported in highly comorbid with lung and heart diseases, so that a "two-hit" hypothesis can be put forward: it might be caused by the acute myocardial damage caused by pulmonary embolism in the context of preexisting cardiac and/or respiratory diseases. More than one-third of PE survivors develops PPES, with only a small fraction (3-4%) represented by CTEPH. A value of ≈3% is a plausible estimate for the incidence of CTEPD. Growing evidence supports the role of CTEPD as a hemodynamic phenotype intermediate between post-PE dyspnea and CTEPH, but it still remains to be ascertained whether it constantly underlies exercise-induced pulmonary hypertension and if it is a precursor of CTEPH. Further research is needed to improve the understanding and the management of CTEPD and post-PE dyspnea.

Age, anticoagulants, hypertension and cardiovascular genetic traits predict cranial ischaemic complications in patients with giant cell arteritis

ObjectivesThis project aimed to determine whether cranial ischaemic complications at the presentation of giant cell arteritis (GCA) were associated with pre-existing cardiovascular (CV) risk factors, CV disease or genetic risk...

Investigation of 5-fluorouracil cardiotoxicity in combinational therapy: Influence of risk factors and demographics in a Pakistani population.

5-Fluorouracil (5-FU) is a chemotherapeutic agent used to treat various types of cancers. Although widely used, it has consistently been attributed to cardiotoxicities after administration. The purpose of this study was to assess the parameters and predictors of cardiotoxicities associated with various 5-FU-based chemotherapeutic protocols in patients with GI/colorectal cancer, as well as the correlation of these cardiotoxic events with age, sex, cumulative dose, and risk factors such as obesity, hypertension, and family history of cardiac diseases. A prospective study consisting of 396 patients of both sexes was conducted in the oncology ward of Nishtar Hospital in Multan, Pakistan. Patients were grouped according to the therapeutic protocol they received (5-FU monotherapy or in combination, with different dosing regimens). Electrocardiography and serum troponin levels were used to assess 5-FU-induced cardiotoxicity. In cases where cardiotoxicity was detected, 5-FU treatment was interrupted; nitroglycerin, nitrates, and calcium channel blockers were administered; and cardiac monitoring was initiated. 5-FU was discontinued in all cases of acute myocardial infarction. Of the 396 patients, 28.5% reported different cardiotoxic symptoms after receiving various 5-FU-containing protocols. 35% had anginal pain, 13% suffered a myocardial infarction, 11% developed hypertension, and 10% presented heart failure. Patients receiving 5-FU combination therapy showed cardiotoxic events that were significantly different from those on 5-FU monotherapy. Based on the ECG results, only the QTc-d interval increased significantly (p < 0.001) after therapy. 68% of the patients had troponin levels > 2 ng/mL at the end of treatment. Pre-existing cardiac diseases, treatment duration, smoking, and obesity were found to be influential components in the development of cardiotoxicity, and patients with cancer should be closely monitored during 5-FU chemotherapy.

Spontaneous Coronary Sinus Infective Endocarditis in a 9-year-old: a rare case report with a favorable outcome

Coronary sinus infective endocarditis is extremely rare, more so in children. We report a case of coronary sinus infective endo- carditis diagnosed by echocardiography in a 9-year-old boy with no pre-existing heart disease or any of the usual risk factors known to predispose to infective endocarditis. He was successfully managed non-surgically.

Effectiveness of recently-approved oral antiviral medications on the outcome of patients with mild-to-moderate COVID-19 and preexisting chronic obstructive pulmonary diseases

ABSTRACT Objectives This study assessed the effectiveness of the oral antiviral agents nirmatrelvir – ritonavir (NMV-r) and molnupiravir (MOV) for treating mild-to-moderate coronavirus disease 2019 (COVID-19) in patients with COPD. Methods This retrospective cohort study extracted data from the TriNetX platform and examined 94,984 COVID-19 patients with preexisting COPD from 1 January 2022, to 1 October 2023. Patients receiving NMV-r or MOV (study group) were compared with those not receiving oral antiviral agents (control group) after propensity score matching (PSM). Results After PSM, 7,944 patients were classified into the study and control groups. The primary composite outcome of all-cause hospitalization, or death in 30 days was reported in 458 (5.7%) patients in the study group and 566 (7.1%) patients in the control cohort, yielding a hazard ratio [HR] of 0.79 (95% confidence interval [CI]: 0.70–0.89; Table 2). Compared with the control group, the study group had a significantly lower risk of all-cause hospitalization (HR, 0.87; 95% CI: 0.76–0.99) and death (HR: 0.21, 95% CI: 0.13–0.35). Conclusions This study revealed that oral antivirals – NMV-r or MOV might improve clinical outcomes in patients with preexisting COPD and COVID-19. However, only a small proportion of preexisting COPD patients with COVID-19 received oral antiviral treatment.

A-332 Identifying At-Risk Patients Pre-IV Contrast Administration via POCT Creatinine Measurement

Abstract Background The use of intravenous iodinated contrast in computerized tomography studies is associated with a small risk of acute kidney injury. Pre-existing chronic kidney disease is a recognized factor and assessment of renal function prior to contrast administration is essential. This study assessed the ability of the Abbott iSTAT creatinine assay to correctly identify IV-contrast patient risk using lab-based eGFR as the gold standard. Methods This was a retrospective study comparing POCT creatinine (whole blood, Abbott iSTAT enzymatic) and lab creatinine (plasma, Beckman Coulter AU5800 Jaffe) results on simultaneous samples collected in the emergency department. Anonymised data records were extracted from the laboratory database for 2020-2023. IV contrast risk was calculated using eGFR (CKD-EPI 2021) and classified as high risk (HR: eGFR &amp;lt; 30 mL/min/1.73 m2), moderate risk (MR: eGFR 30-59) and low risk (LR: eGFR &amp;gt;=60) as per the Royal Australian and New Zealand College of Radiologists 2018 guidelines, using the Beckman-based eGFR as the gold standard. Results 132 paired samples patients were available for analysis (61% male, average age 69 y (23-98), 70% Chinese, eGFR (iStat) 3-143, eGFR (Beckman) 3-121 mL/min/1.73 m2). The proportions of Beckman-based eGFR HR:MR:LR cases were 53:39:40. The prevalence of HR/MR cases was 70%. The diagnostic performance of the iSTAT-based eGFR to accurately identify HR/MR patients was: sensitivity 93.5%, specificity 95%, PPV 97.7%, NPV 86.4%, accuracy 93.9%. For different Beckman-derived eGFR categories, the mean difference in eGFR (iSTAT - Beckman), 95% lower limit of agreement (LOA) and upper LOA was: &amp;lt;30 mL/min/1.73 m2: -1.0, -3.2, -1.1; 30-60 mL/min/1.73 m2: 0.9, -13.3, 15.1; &amp;gt;60 mL/min/1.73 m2: 1.6, -16.8, 20.1. Linear regression fit (Passing-Bablok): CKD-EPI Beckman = 1.193 + 0.9773 CKD-EPI iSTAT. Correlation coefficient was 0.981. Kappa for the 3 categories of risk classification was 0.814. Conclusions The iSTAT creatinine assay could reliably identify patients at medium/high risk of acute kidney injury following intravenous contrast administration. Performance was best for low and high risk patients with 100% of high risk patients being correctly identified. It is a useful screening test but differences in eGFR of up to 20 mL/min/1.73 m2 may be seen between the Beckman and iSTAT eGFR values at higher levels, meaning numeric eGFR results are not interchangeable.

A-233 Wastewater-based surveillance for SARS-CoV-2 Subvariants using the Nanopore Sequencing in South Korea

Abstract Background Genomic tools to identify and characterize SARS-CoV-2 and its various subvariants were adapted from clinical settings. Wastewater-based surveillance (WBS) has since been recognized as tool of transformative potential, providing real-time objective, comprehensive data on the prevalence and distribution of the target pathogen across the space and time. We conducted wastewater-based epidemiology (WBE) at sewage treatment plants to find a more efficient mutation monitoring method, and respond to pre-existing infectious diseases. Methods In our study, domestic sewage collected every weeks from 6 sewage treatment plants in urban region from June 2023 to November 2023 was used to concentrate and isolate viruses using wastewater ultra nucleic acid isolation kits with virus enrichment kits. Positive samples confirmed were subjected to SARS-CoV-2 whole genome sequencing (WGS) using GridION (Oxford Nanopore Technologies). The experimental data was aligned through Epi2me, analyzed using Nextclade, that was compared with KCDC official reports and our monitoring results (total 780 cases) ongoing at SCL. Results Various mutations were identified at each collection time, occurring new subvariants over time. The mutations (orf1a:A690V, S:F456L) sequentially confirmed from the sample collected on Aug. 23rd are specific mutations of XBB.1.9.2 and EG.5. In addition, the mutations orf1b: D54N, S:L455F, which were sequentially confirmed from the sample collected on Sep. 6th, are HK.3, a descendent lineage of EG.5, and FLip variants, which show growth advantage, were confirmed. Furthermore, the detection rate of FLip variants detected from Sep.6th gradually increased from 17% to 67% (Fig.1). Taken together, we confirmed the similarity between monthly detected mutations and changes in dominant species over time by comparing with ‘monthly COVID-19 mutation trends’ and ‘HK.3 dominance announcement by KCDC’(Fig.2). Conclusions WBS would be a useful tool for proactively responding to infectious diseases including COVID-19 by exploring new mutations and predicting changes in dominant species.

Clinical macular edema following uneventful cataract surgery in eyes without pre-existing fundus diseases: risk factors and treatment prognosis

BackgroundTo investigate the risk factors and prognosis of clinical pseudophakic cystoid macular edema (PCME) after uneventful phacoemulsification surgery in patients without pre-existing fundus diseases.MethodsThis was a retrospective case-control study. Medical records between August 2020 and August 2023 were reviewed for patients who had no previous fundus diseases and developed clinical PCME. A control group was randomly chosen and the risk factors for PCME was analyzed by binary logistic regression. Structure and visual prognosis of the PCME cohort were observed and compared among subgroups undergoing different treatment measures.ResultsForty-seven eyes of 47 patients with PCME were included. The development of PCME was associated with higher systolic blood pressure (OR, 1.048; 95%CI 1.002, 1.097; P = .042), no posterior vitreous detachment (OR, 0.215; 95%CI: 0.553, 0.887; P = .032) and shorter axial lengths (OR, 0.401; 95%CI 0.161, 0.997; P = .049) compared to controls. During a mean follow-up of 8.26 months, 36 eyes (76.6%) showed visual improvement with decreased macular thickness. Different treatment modalities, including observation, topical NSAIDs, and intervention therapy, have no significant differences on the visual prognosis (P = 1.000). However, the intervention group had a shorter recovery time compared to the observation group (28.6 vs. 45.9 days, P = .037).ConclusionPCME remains an encountered morbidity in patients without pre-existing fundus diseases. Shorter axial lengths, absence of posterior vitreous detachment, and higher systolic blood pressure are risk factors of PCME. Active intervention failed to improve the prognosis of PCME but could shorten the recovery time.

Using Doppler duplex ultrasound to determine hemodynamic alterations in renal vasculature: Crucial pathophysiological event preceding renal dysfunction in decompensated cirrhosis

BackgroundRenal dysfunction is a watershed event in cirrhosis, often preceded by renal vasoconstriction. However, our reliability on elevated serum creatinine often delays interventions. Measurement of Renal Resistive Index (RI) and Renal Venous Stasis Index (RVSI) by Doppler ultrasound offers insight into renal vasoconstriction. MethodsFifty participants with decompensated cirrhosis with ascites and normal serum creatinine underwent renal Doppler ultrasound for the measurement of RI and RVSI. All patients were compliant with a salt-restricted diet. Individuals aged <18 years, hepatocellular carcinoma, non-cirrhosis-related ascites, pre-existing renal disease, obstructive uropathy, or history of nephrotoxic medication use were excluded. Statistical analyses, including Pearson correlation, regression analysis, and Chi-square/Fisher’s exact tests, were performed to assess the statistical significance between RI, RVSI, and renal parameters. Additionally, the association of RI with the model for end-stage liver disease sodium (MELD-Na) and Child-Turcotte-Pugh (CTP) scores was also assessed. ResultsMajority were males (88%), average CTP score was 11.7, mean MELD-Na score was 20.92, and mean serum creatinine was 1.05 mg/dL. Renal parameters had varying RI values among renal arteries, with the main right and left arteries at 0.615 [standard deviation (SD): 0.089] and 0.638 (SD: 0.083), respectively. RI and RVSI are significantly correlated with serum creatinine. Further, significant correlation between, RI, RVSI values noted with MELD-Na score even when serum creatinine values are normal. ConclusionStrong correlations between serum creatinine, RI, and MELD-Na scores hints at predictive clinical potential. Future research with larger cohorts and extended follow-up is required to gauge clinical utility and its impact on outcomes.

Classifying early apple scab infections in multispectral imagery using convolutional neural networks

Multispectral imaging systems combined with deep learning classification models can be cost-effective tools for the early detection of apple scab (Venturia inaequalis) disease in commercial orchards. Near-infrared (NIR) imagery can display apple scab symptoms earlier and at a greater severity than visible-spectrum (RGB) imagery. Early apple scab diagnosis based on NIR imagery may be automated using deep learning convolutional neural networks (CNNs). CNN models have previously been used to classify a range of apple diseases accurately but have primarily focused on identifying late-stage rather than early-stage detection. This study fine-tunes CNN models to classify apple scab symptoms as they progress from the early to late stages of infection using a novel multispectral (RGB-NIR) time series created especially for this purpose.This novel multispectral dataset was used in conjunction with a large Apple Disease Identification (ADID) dataset created from publicly available, pre-existing disease datasets. This ADID dataset contained 29,000 images of infection symptoms across six disease classes. Two CNN models, the lightweight MobileNetV2 and heavyweight EfficientNetV2L, were fine-tuned and used to classify each disease class in a testing dataset, with performance assessed through metrics derived from confusion matrices. The models achieved scab-prediction accuracies of 97.13 % and 97.57 % for MobileNetV2 and EfficientNetV2L, respectively, on the secondary data but only achieved accuracies of 74.12 % and 78.91 % when applied to the multispectral dataset in isolation. These lower performance scores were attributed to a higher proportion of false-positive scab predictions in the multispectral dataset. Time series analyses revealed that both models could classify apple scab infections earlier than the manual classification techniques, leading to more false-positive assessments, and could accurately distinguish between healthy and infected samples up to 7 days post-inoculation in NIR imagery.

Neck Reflex Points: A New Clinical Test? Prevalence in Two Cohorts and Its Covariates.

Background: Neck reflex points (NRPs) are 2 × 6 potentially tender areas of the neck, denominated NRP-C0 to NRP-C7. They are different from muscular trigger points and become tender in response to chronic trigeminal irritation. NRP examination has a high inter-rater reproducibility. We investigated the prevalence of NRPs in two populations to investigate their usefulness as a clinical test for trigeminal irritation. Methods: In total, 165 patients with chronic pain and 431 students were examined for NRP tenderness using a three-level pain scale: absent pain (PI = 0), mild tenderness (PI = 1), or marked tenderness (PI = 2). Results: In patients, we found more tender NRPs than in the student group (p < 0.001), and on the left side, more tender NRPs were found in NRP-C0-C4. Left and right NRPs appeared independently (kappa 0.1-0.4), except for NRP-C7 (kappa 0.55). Females had more tender NRPs (p < 0.001). Tenderness was independent of age, BMI, and pre-existing diseases. Conclusions: NRP tenderness occurs more frequently in patients than in students, independent from potential covariates. Our results, together with previous findings, support the use of NRP examination as a clinical test for chronic silent inflammation of the trigeminal region. These data provide a base for further studies investigating correlations of NRPs with clinical findings.

Effects of Laser Acupuncture on Metabolic Functions of Sedentary People: A Double-Blind Randomized Clinical Trial.

Background: Laser acupuncture regulates energy flow and restores body fluid metabolism. Objective: To evaluate the effects of the laser acupuncture protocol (LAP) on hepatic and renal metabolism in sedentary people. Methods: Longitudinal, double-blind, and randomized clinical trial with 29 participants, adults, both sexes, sedentary, without pre-existing metabolic diseases, subdivided into control and laser groups. Based on the STandards for Reporting Interventions in Clinical Trials of Acupuncture 2010 guidelines, 10 laser applications (660 nm ±10 nm wavelength, 100 mW power. The irradiation tip has a diameter of 5 mm, which corresponds to an area of 0.19 cm2, totaling a power density of 0.52 W/cm2 and considering the irradiation time of 90 s, the energy density applied was 47.3 J/cm2) were performed on the acupoints of metabolic functions (LR3, SP6, ST36, and LI4) and blood samples were collected for fasting glycemia, lipid profile (HDL, LDL, total cholesterol, and triglycerides), liver function (AST/GOT and ALT/GPT), and renal function (serum creatinine and urea). A repeated measures analysis of variance (ANOVA) with Bonferroni corrected post hoc comparisons was applied to compare statistical differences between groups and times, adopting p < 0.05 as the null hypothesis. Results: The laser stimulated changes in serum lipid profile values and renal and hepatic functions. There was a significant (p = 0.014) reduction in LDL ("bad" cholesterol) from 105.75 ± 32.83 pre- to 84.32 ± 18.38 mg/dL postintervention, associated with cardioprotective function. Positive significant (p = 0.035) impacts were also observed in the reduction of creatinine (0.86 ± 0.12 mg/dL to 0.75 ± 0.12 mg/dL) and the enzyme AST/GOT (33.73 ± 12.95 U/L to 20.80 ± 4.99 U/L, p = 0.002). Conclusion: LAP applied to basal metabolism acupoints promoted positive metabolic changes in the lipid profile (LDL), and in main markers of the liver (AST/GOT) and kidney (creatinine) functions, contributing to risk control of cardiovascular diseases.

The optimal antibiotic treatment duration for community-acquired pneumonia in adults diagnosed in general practice in Denmark (CAP-D): an open-label, pragmatic, randomised controlled trial

BackgroundUse of antibiotics is the main driver of antimicrobial resistance which is considered one of the biggest threats to human health. In Denmark, most antibiotics are prescribed in general practice. Acute lower respiratory tract infections, including community-acquired pneumonia (CAP), are among the most frequent indications for antibiotic prescribing. Phenoxymethylpenicillin is established as first-line treatment in general practice in Denmark. However, the treatment duration with phenoxymethylpenicillin is mostly based on traditions. Both 5 and 7 days of treatment is recommended in Danish guidelines, and when asking the general practitioners about what treatment duration, they prescribe the variation is even bigger. Several hospital-based studies have proven short course (≤ 6 days) antibiotic treatment non-inferior to long course (≥ 7 days) treatment of CAP. No evidence exists on the optimal treatment duration for CAP in non-hospitalised patients.This randomised controlled trial aim to investigate the optimal treatment duration with phenoxymethylpenicillin for CAP in adults diagnosed in general practice in Denmark.MethodsThis is an open-label, pragmatic, randomised controlled, five-arm DURATIONS trial. Participants will be recruited from at least 24 general practices in Denmark. Eligible participants are adults, with no pre-existing lung disease, presenting with symptoms of CAP, and in whom the general practitioner finds it relevant to treat with antibiotics. The study will compare treatment with phenoxymethylpenicillin 1.2 MIE q.i.d. in 3, 4, 5, 6, and 7 days.DiscussionThis study will provide evidence for the optimal antibiotic treatment duration of CAP in general practice and inform future guidelines on CAP in all countries using phenoxymethylpenicillin for the treatment of acute respiratory tract infections in adults. The results of this study might also be used to guide treatment recommendations in other countries using phenoxymethylpenicillin.Moreover, a (potential) reduction in antibiotic use might lower the development of antimicrobial resistance, increase patient treatment adherence, reduce risks of adverse events, and lower the economical expTrial registrationClinicalTrials.gov: NCT06295120. Registered 28 February 2024. The Scientific Ethics Committee for the North Denmark Region: N-20230039.

Histological analysis of the spleen of rats immunized with SARS-CoV-2 S protein

SARS-CoV-2 infection can lead to pathological disorders in various organs due to the ubiquitous of angiotensin-converting enzyme 2 (ACE2), which serves as a receptor for SARS-CoV-2. However, tissue damage may not only be the result of viral infection. SARS-CoV-2 has been shown to induce the production of autoantibodies to ACE2, and their presence is associated with disease severity. The spleen is one of the targets for COVID-19. The presence of ACE2 in the red pulp sinus endothelium cells of the spleen and in tissue-resident CD169+ macrophages positioned in the splenic marginal zone makes these cells a potential target of autoimmune reactions to ACE2 triggered by SARS-CoV-2. In addition, antibodies to the SARS-CoV-2 S protein cross-react with a wide range of human tissue proteins and can cause tissue damage. The most common splenic pathologies in deceased COVID-19 patients are lymphocyte depletion and subsequent hemaphagocytosis. Since the spleen plays a fundamental role in the immune response regulation, splenic damage could be one of the causes of immune perturbations associated with severe COVID-19. To test the hypothesis of the autoimmune nature of COVID-19, we developed a non-infectious experimental model of autoimmune multiorgan damage caused by immunization with SARS-CoV-2 S protein. The purpose of this work was to study the spleen in rats with induced multiorgan damage caused by immunization with SARS-CoV-2 S protein, as well as the influence of pre-existing autoimmune disease on the severity of splenic damage caused by an immune response against S protein. Intact Wistar rats and Wistar rats with completed experimental autoimmune encephalomyelitis were immunized with S protein in incomplete Freund’s adjuvant (IFA). Control rats received an injection of IFA. No changes were detected in the secondary follicles number in the spleen of rats immunized with the SARS-CoV-2 S protein. However, in the spleen of rats with previously induced autoimmune encephalomyelitis, immunization with SARS-CoV-2 S protein caused a significant decrease in the number of secondary follicles relative to the control group. Hemosiderin deposits and macrophage hyperplasia of the marginal zones of the white pulp were detected in both groups immunized with S protein. Thus, immunization with the S protein of SARS-CoV-2 causes changes in the spleen of rats similar to those detected in patients who died from COVID-19. Damage to the spleen is more varied and pronounced in rats with previous experimental encephalomyelitis.

The effect of the immune response to SARS-CoV-2 S protein on angiotensin II levels in rats

Autoantibodies against key molecules of the renin-angiotensin system (RAS) are found in some patients infected with SARS-CoV-2. These autoantibodies include antibodies against angiotensin II and angiotensin converting enzyme 2 (ACE2). The presence of antibodies to the RAS-related molecules is associated with episodes of hypotension or hypertension. The aim of this work was to study the effect of antibodies to SARS-CoV-2 S protein and autoantibodies to ACE2 on angiotensin II levels in a model of induced multiple organ damage caused in rats by immunization with SARS-CoV-2 S protein. The effect of pre-existing autoimmune encephalomyelitis on change in angiotensin II level caused by immunization with S protein is also was studied. Wistar rats were immunized with S protein of SARS-CoV-2 emulsified in incomplete Freund’s adjuvant (IFA). At the time of injection of S protein 6 of the rats were intact (S group), in 4 of the rat experimental autoimmune encephalomyelitis was previously induced by immunization with guinea pig myelin basic protein (EAE + S group). The control group of rats was injected with IFA. Antibodies to S protein, autoantibodies to ACE2, and angiotensin II level were determined in blood plasma by enzyme linked immunosorbent assay. It was found that immunization with S protein leads to a transient decrease in the blood level of angiotensin II. The blood angiotensin II level was lower than normal in 3 out of 6 rats (50%) in group S, and in 3 out of 4 (75%) in the EAE + S group at week 6 after immunization. The decrease in angiotensin II level was significant in the EAE + S group relative to the control group (ANOVA, p = 0.0423). A deeper decrease in the angiotensin II level in the blood of EAE + S group than in S group was associated with a higher level of antibodies to S protein: the level of antibodies to S protein was significantly higher in the EAE + S group for 1-6 weeks after immunization with S protein compared to the S group of rats. Immunization of rats with S protein did not cause the production of anti-ACE2 autoantibodies in the EAE + S group, and in the S group it was weak and was not accompanied by an increase in angiotensin II levels. Thus, in rats immunized with S protein, a transient decrease in the level of angiotensin II was detected at the peak of production of antibodies to S protein, which may indicate that antibodies to S protein may contribute to a decrease in angiotensin II level in SARS-CoV-2 infection. In addition, pre-existing autoimmune disease leads to a stronger response to S protein, accompanied by a stronger decrease in angiotensin II level.