Patient Demise Research Articles

Subependymal Giant Cell Astrocytoma: The Molecular Landscape and Treatment Advances.

Subependymal giant cell astrocytoma (SEGA) is most often found in patients with TSC (Tuberous Sclerosis Complex). Although it has been classified as a benign tumor, it may create a serious medical problem leading to grave consequences, including young patient demise. Surgery and chemotherapy belong to the gold standard of treatment. A broader pharmacological approach involves the ever-growing number of rapalogs and ATP-competitive inhibitors, as well as compounds targeting other kinases, such as dual PI3K/mTOR inhibitors and CK2 kinase inhibitors. Novel approaches may utilize noncoding RNA-based therapeutics and are extensively investigated to this end. The purpose of our review was to characterize SEGA and discuss the latest trends in the diagnosis and therapy of this disease.

Impact of patient death on physicians’ mental health

IntroductionPhysicians often encounter stressful situations that can impact their mental well-being. The death of a patient represents one of the most difficult situations in routine medical practice. Literature notably lacks comprehensive studies into physicians’ personal experiences with patients’ deaths. However, it does underscore heightened levels of sorrow, guilt, and stress stemming from the passing of terminally ill patients. As a majority of studies in this realm adopt qualitative methodologies, there is merit in supplementing existing research with a quantitative approach that employs validated psychometric scales. Furthermore, the study of phenomena associated with stress, particularly the perceived professional support by physicians in stressful events, can contribute to the implementation of preventive measures to help physicians cope. ObjectiveOur study aims to measure the traumatic impact on resident and intern physicians at national university hospitals following the death of patients, as well as to assess the perceived level of professional support among these physicians. Materials and methodsWe conducted a nationwide cross-sectional, descriptive, and analytical study. Participants included interns and residents from various specialties (medical, surgical and laboratory) at national university hospitals in Morocco. Assessing the traumatic impact of patients’ death on doctors was conducted using two psychometric scales: the Peri-Traumatic Distress Inventory (PDI) and the Revised Impact of Event Scale (IES-R). Additionally, we used the Perceived Professional Social Support Scale (QSSP-P) to evaluate how supportive the professional environment was towards these doctors. All scales utilized in the study are validated in the French language. ResultsThe study included 96 participants, with 67.7% being female. The average age was 26.8 years, ranging from 23 to 39 years. The majority of participants managed more than nine patients simultaneously (58.3%) while 41.7% were scheduled for more than six 24h shifts per month. During their training, over 64.6% of interns and residents faced more than ten patients’ death incidents, and 68.8% considered their first patient death as the most traumatizing. Half of the physicians evaluated the patients’ care as moderately appropriate, with 46.9% believing that the incident could have been prevented. Notably, 70.8% of interns and residents involved in patient care experienced self-blame and attributed a share of responsibility to themselves for the patient's demise. The majority of participants, 82.3%, exhibited peri-traumatic distress with a PDI score exceeding 15. Among the studied factors, only the perceived responsibility and a management system centered on a single physician (rather than a team) demonstrated a noteworthy correlation with PDI scores. The mean score on the IES-R scale was 25.6, with almost half of the sample (54.2%) reporting moderate to severe PTSD symptoms. The severity of these symptoms was significantly correlated with higher age, high number of patient's deaths experienced and the physician's perceived sense of responsibility. Participants in our study were more satisfied with support from colleagues compared to support functions (paramedical staff, administrative officials) or superiors. Moreover, only colleagues’ support was statistically significantly associated with low scores on the traumatic impact scales. ConclusionPhysicians maintain a unique relationship and therapeutic alliance with their patients. Therefore, the death of a patient can have a significant psychological impact on the physician. This study allowed us to objectively measure this psychological impact and evaluate professional support. The results of these studies encourage further exploration of the issue and the implementation of measures to reduce this psychological impact.

Advancements in Pharmacological Interventions and Novel Therapeutic Approaches for Amyotrophic Lateral Sclerosis.

(1) Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease in which the patient suffers from an affection of both upper and lower motor neurons at the spinal and brainstem level, causing a progressive paralysis that leads to the patient's demise. Gender is also considered a predisposing risk factor for developing the disease. A brief review of the pathophysiological mechanisms of the disease is also described in this work. Despite the fact that a cure for ALS is currently unknown, there exists a variety of pharmacological and non-pharmacological therapies that can help reduce the progression of the disease over a certain period of time and alleviate symptoms. (2) We aim to analyze these pharmacological and non-pharmacological therapies through a systematic review. A comprehensive, multidisciplinary approach to treatment is necessary. (3) Drugs such as riluzole, edaravone, and sodium phenylbutyrate, among others, have been investigated. Additionally, it is important to stay updated on research on new drugs, such as masitinib, from which very good results have been obtained. (4) Therapies aimed at psychological support, speech and language, and physical therapy for the patient are also available, which increase the quality of life of the patients.

Metabolic gene therapy in a canine with pulmonary hypertension secondary to degenerative mitral valve disease.

Myxomatous mitral valve disease (MMVD) stands out as the most prevalent acquired canine heart disease. Its occurrence can reach up to 40% in small breed dogs and escalates in geriatric canine populations. MMVD leads to thickening and incomplete coaptation of valve leaflets during systole, resulting in secondary mitral valve regurgitation. Serious complications may arise concurrently with the worsening of mitral valve regurgitation, including left-and right-sided congestive heart failure, and pulmonary hypertension (PH). Ultimately, the PH progression might contribute to the patient's demise or to the owner's decision of euthanasia. Most currently available FDA-approved therapies for PH are costly and aim to address the imbalance between vasoconstriction and vasodilation to restore endothelial cell function. However, none of these medications impact the molecular dysfunction of cells or impede the advancement of pulmonary vascular and right ventricular remodeling. Recent evidence has showcased successful gene therapy approaches in laboratory animal models of PH. In this manuscript, we summarize the latest advancements in gene therapy for the treatment of PH in animals. The manuscript incorporates original data showcasing sample presentations, along with non-invasive hemodynamic assessments. Our findings demonstrate that the use of metabolic gene therapy, combining synthetic adeno-associated virus with acid ceramidase, has the potential to significantly reduce the need for drug treatment and improve spontaneously occurring PH in dogs.

Total management of hemangiopericytoma/solitary fibrous tumor of the buttock: A case report.

Solitary fibrous tumors can manifest at various anatomical sites, predominantly occurring at extrapleural sites with a peak incidence between 40 and 70 years. SFT necessitates long-term follow-up owing to its tumor characteristics. However, comprehensive reports covering the period from initial diagnosis to the patient's demise are lacking. Herein, we present a case of a malignant SFT of the buttocks that was treated at our hospital from the time of initial diagnosis to the end of life, with a literature review. A 54-year-old woman had a T1 low-to-isobaric and T2 isobaric-to-hyperintense mass in the psoas muscle on magnetic resonance imaging, diagnosed as an SFT. Wide excision was performed, followed by postoperative radiotherapy and chemotherapy. Multiple lung metastases were treated, while bone metastases appeared in the left femur. Multiple spinal metastases developed, causing respiratory distress due to pleural effusion. Best support care was initiated; however, a thrombus appeared in the inferior vena cava. Despite anticoagulant therapy, the patient died 11 years and 6 months after the initial surgery. Herein, marginal resection resulted in a relatively short operative time and average blood loss. The radiotherapy dose was 66 Gy; no complications occurred, and local recurrence was prevented. Tumor arthroplasty was performed to stabilize the affected limbs, and the patient required careful follow-up. Despite the poor prognosis, the patient survived >11 years after surgery and had a favorable outcome. Long-term monitoring for potential complications remains necessary.

Usefulness of bicarbonate-based Impella purge solution in a patient with heparin-induced thrombocytopenia: the first case report of long-term management in Japan.

Percutaneous mechanical circulatory support utilizing micro-axial flow pumps, such as the Impella group of devices, has become a life-saving technique in the treatment of refractory cardiogenic shock, with ever-increasing success rates. A 30-year-old man presented with acute decompensated heart failure and a severely reduced left ventricular ejection fraction (17%). Despite initial treatment with inotropic drugs and intra-aortic balloon pump support, his hemodynamic status remained unstable. Transition to Impella CP mechanical circulatory support was made on day 6 owing to persistently low systolic blood pressure. A significant decline in platelet count prompted suspicion of heparin-induced thrombocytopenia (HIT), later confirmed by positive platelet-activated anti-platelet factor 4/heparin antibody and a 4Ts score of 6 points. Argatroban was initially used as the purge solution, but owing to complications, a switch to Impella 5.0 and a bicarbonate-based purge solution (BBPS) was performed. Despite additional veno-arterial extracorporeal membrane oxygenation support on day 24, the patient, aiming for ventricular assist device treatment and heart transplantation, died from infection and multiple organ failure. Remarkably, the Impella CP continued functioning normally until the patient's demise, indicating stable Impella pump performance using BBPS. This case highlights the usefulness of BBPS as an alternative to conventional Impella heparin purge solution when HIT occurs.

Challenging of ECMO application in pediatric restrictive cardiomyopathy: case report of a novel TNNI3 variant

BackgroundRestrictive cardiomyopathy (RCM) represents a rare cardiovascular disorder stemming from filament-associated genes. Nonetheless, treating RCM presents considerable challenges, particularly concerning device implantation and mechanical support. Furthermore, elucidating the molecular function of specific variants holds promise in benefiting patients and enhancing prognosis, given the significant heterogeneity among RCM variants.Case presentationThe proband, an eight-year-old female, was admitted to our hospital post cardiopulmonary resuscitation due to sudden cardiac arrest. Echocardiography revealed bilateral atrial enlargement. Whole-exome sequencing uncovered a novel heterozygous mutation (c.509G>A, p.R170Q) in TNNI3. Evaluation using the MutationTaster application deemed c.509G>A pathogenic (probability = 0.99). Following clinical manifestations, imaging assessments, and genetic screening, the proband received an RCM diagnosis. ECMO was recommended along with continuous renal replacement therapy. However, persistent atrial flutter ensued post-ECMO withdrawal. Attempts to restore cardiac rhythm with cardioversion, metoprolol, and amiodarone proved futile. Subsequent heart failure led to the patient's demise due to cardiac shock. Based on crystal protein structural analysis, we observed that cTnI-R170Q and R170W exerted similar impacts on protein structural stability and formation. However, both differed significantly from cTnI-R170G, primarily influencing amino acid regions 32–79 and 129–149, involved in TnC and actin binding. Therefore, cTnI-R170Q was revealed to induce RCM via the same molecular mechanism as cTnI-R170W.ConclusionManaging RCM remains a critical challenge. This study underscores the discouragement of device implantations for cardiac pump functional support in RCM, particularly for non-short-term scheduled HTx. Additionally, considering catheter ablation for atrial fibrosis-induced AFs is recommended. Mechanistically, cTnI-R170Q primarily diminishes troponin-actin interactions and destabilizes thin filaments.

Targeting Integrin α3 Blocks β1 Maturation, Triggers Endoplasmic Reticulum Stress, and Sensitizes Glioblastoma Cells to TRAIL-Mediated Apoptosis.

Glioblastoma (GBM) is a devastating brain cancer for which new effective therapies are urgently needed. GBM, after an initial response to current treatment regimens, develops therapeutic resistance, leading to rapid patient demise. Cancer cells exhibit an inherent elevation of endoplasmic reticulum (ER) stress due to uncontrolled growth and an unfavorable microenvironment, including hypoxia and nutrient deprivation. Cancer cells utilize the unfolded protein response (UPR) to maintain ER homeostasis, and failure of this response promotes cell death. In this study, as integrins are upregulated in cancer, we have evaluated the therapeutic potential of individually targeting all αβ1 integrin subunits using RNA interference. We found that GBM cells are uniquely susceptible to silencing of integrin α3. Knockdown of α3-induced proapoptotic markers such as PARP cleavage and caspase 3 and 8 activation. Remarkably, we discovered a non-canonical function for α3 in mediating the maturation of integrin β1. In its absence, generation of full length β1 was reduced, immature β1 accumulated, and the cells underwent elevated ER stress with upregulation of death receptor 5 (DR5) expression. Targeting α3 sensitized TRAIL-resistant GBM cancer cells to TRAIL-mediated apoptosis and led to growth inhibition. Our findings offer key new insights into integrin α3's role in GBM survival via the regulation of ER homeostasis and its value as a therapeutic target.

Unicompartmental knee arthroplasty in obese patients, poorer survivorship at 15 years

IntroductionThe preclusion of obese patients from unicompartmental knee arthroplasty (UKA) has increasingly been challenged. This study aimed to evaluate the impact of Body Mass Index (BMI) on UKA at 15-year follow-up. Materials and methods169 unilateral UKA patients from 2003 to 2007 were followed-up prospectively for at least 15 years. 70 patients were left for analysis after accounting for patient demise, revision surgery and loss to follow-up. 48 of these patients (69%) were in the Control group (BMI <30 kg/m2) and 22 (31%) were in the Obese group (BMI ≥30 kg/m2). Patients were assessed before and after operation using the Knee Society Function Score (KSFS), Knee Society Knee Score (KSKS), Oxford Knee Score (OKS), and Physical (PCS) and Mental (MCS) component of the Short Form 12. Survivorship analysis was also performed. ResultsObese patients went through UKA at an earlier age than the non-obese patients (54.7 ± 4.7 years compared to 59.9 ± 7.8 years, p = 0.005). At 2, 10, and 15-year follow-up, both groups achieved clinically significant improvements in outcomes. There was no significant association found between obesity and outcome using multiple linear regression. While propensity matching found PCS improvement at 2 years to be greater in obese patients, no significant association between obesity and 15-year outcome was found. All 13 patients who required revision, underwent total knee arthroplasty (TKA). The overall 15-year survivorship was 74.2% within the obese group and 92.4% within the control group. ConclusionCompared to non-obese patients, obese patients had poorer 15-year survivorship with greater odds of requiring revision surgery. However, assuming implant survival, obese patients can expect a non-inferior outcome relative to their non-obese counterparts in all patient reported outcome measures 15 years after surgery.

Abstract 4432: Molecular biomarkers of non-Hodgkin lymphomas and subtypes identified by mass spectrometry-based metabolomics

Abstract Non-Hodgkin lymphomas (NHLs) constitute a diverse collection of lymphoid neoplasms, each characterized by distinct biological features. Approximately 90% of all lymphomas in the United States stem from B lymphocytes, with the remainder originating from T cells. The therapeutic approach for NHLs hinges on the neoplastic histology and the tumor stage, guiding the determination of whether radiotherapy, chemotherapy, or a combination thereof represents the most effective treatment strategy. Following an indolent phase, 50% of patients experience disease transformation into an aggressive form of lymphoma, leading to rapid deterioration and patient demise. While extensive efforts have been directed towards understanding the genetics of transformation, the contribution of altered tumor metabolism, induced by these genetic lesions, to disease aggressiveness remains unclear. Therefore, there exists an urgent need to better understand the metabolic changes during lymphoma transformation and treatment. Given the metabolic adaptations supporting bioenergetics, biosynthesis, and redox in malignant cells, here in this study we aimed to identify unique metabolic signatures in prominent lymphoma subsets—diffuse large B-cell (DLBCL), mantle cell (MCL), and follicular lymphomas (FL). Employing unbiased mass spectrometry-based metabolomics, we screened sera samples from n=30 patients with lymphoma and n=25 aged and BMI-matched healthy controls for molecular biomarkers that may be indicative of the subtypes. Principal component analysis revealed distinct clustering of the disease and control groups, indicating unique metabolic profiles induced by lymphoma presence. A total of 36 metabolites, including adenine, trans-aconitic acid, and citric acid, were significantly deregulated between groups (FC &amp;gt; 2, FDR p &amp;lt; 0.05). Functionally, enriched pathways included tryptophan metabolism and the tricarboxylic cycle (FDR p &amp;lt; 0.05), supporting our previous findings that lymphomas rely on oxidative phosphorylation for sustained proliferation. Comparing metabolic profiles of different lymphomas subtypes demonstrated unique clustering, emphasizing the distinct metabolic flexibility of each malignancy. Interestingly, cystine was the primary metabolite driving separation of the groups in our partial least squares discriminant analysis (PLS-DA), with DLBCLs demonstrating the highest abundance of this amino acid. In summary, our research uncovered that there are distinctive metabolic shifts resulting from the transformation of lymphomas. The findings stemming from our unbiased metabolic screening enables a better understanding of the complex metabolic intricacies in lymphomas and paves the way for prominent biomarker detection for improved patient outcomes. Citation Format: Fouad Choueiry, Satishkumar Singh, Lalit Sehgal, Jiangjiang (Chris) Zhu. Molecular biomarkers of non-Hodgkin lymphomas and subtypes identified by mass spectrometry-based metabolomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4432.

Stress in the metastatic journey - the role of cell communication and clustering in breast cancer progression and treatment resistance.

Breast cancer stands as the most prevalent malignancy afflicting women. Despite significant advancements in its diagnosis and treatment, breast cancer metastasis continues to be a leading cause of mortality among women. To metastasize, cancer cells face numerous challenges: breaking away from the primary tumor, surviving in the circulation, establishing in a distant location, evading immune detection and, finally, thriving to initiate a new tumor. Each of these sequential steps requires cancer cells to adapt to a myriad of stressors and develop survival mechanisms. In addition, most patients with breast cancer undergo surgical removal of their primary tumor and have various therapeutic interventions designed to eradicate cancer cells. Despite this plethora of attacks and stresses, certain cancer cells not only manage to persist but also proliferate robustly, giving rise to substantial tumors that frequently culminate in the patient's demise. To enhance patient outcomes, there is an imperative need for a deeper understanding of the molecular and cellular mechanisms that empower cancer cells to not only survive but also expand. Herein, we delve into the intrinsic stresses that cancer cells encounter throughout the metastatic journey and the additional stresses induced by therapeutic interventions. We focus on elucidating the remarkable strategies adopted by cancer cells, such as cell-cell clustering and intricate cell-cell communication mechanisms, to ensure their survival.

The Outcomes of Peripherally Inserted Central Catheter (PICC) Insertion in Pediatric Patients at Siriraj Hospital

Objective: Peripherally Inserted Central Catheters (PICC) are widely used for intermediate to long term venous access. Venipunctures and catheterizations in pediatric patients can be challenging and traumatizing to children’s veins due to frequent and painful needle sticks. This study aims to demonstrate the outcomes of PICC insertion and management in pediatric patients by the Anesthesia Line Service Team (ALiST) at Siriraj Hospital. Materials and Methods: This is a retrospective, descriptive study collecting data from January 2018 to December 2021. The inclusion criteria were pediatric patients aged 15 years and under, body weight equal to or exceeding 5 kg with no history of previous complicated central venous accesses. The primary outcome is the success rate of insertion. Results: 124 PICCs were inserted in pediatric patients. The median age of patients was 5.0 years, with a median height of 107.8 cm, and a median weight of 10.0 kg. The successful insertion rate was 96.92%, and all insertions were inserted using ultrasound-guided technique, with or without fluoroscopy. No acute complications were noted during insertion. Most patients received either intravenous sedation (39.5%) or general anesthesia (26.6%) during the procedure. The mean duration of catheter indwelling was 66.48 days. Reasons for removal of PICC included completion of therapy and patient demise (70.97%), catheter malformation (8.06%), accidental removal (4.03%), infection (8.06%), and patient non-adherence (1.61%). Conclusion: Our research demonstrates a notably high rate of successful PICC placement among pediatric patients, with data indicating a minimal occurrence of complications and an extended duration of catheter usage.

Prediction of Subclinical and Clinical Multiple Organ Failure Dysfunction in Breast Cancer Patients-A Review Using AI Tools.

This review explores the interconnection between precursor lesions of breast cancer (typical ductal hyperplasia, atypical ductal/lobular hyperplasia) and the subclinical of multiple organ failure syndrome, both representing early stages marked by alterations preceding clinical symptoms, undetectable through conventional diagnostic methods. Addressing the question "Why patients with breast cancer exhibit a tendency to deteriorate", this study investigates the biological progression from a subclinical multiple organ failure syndrome, characterized by insidious but indisputable lesions, to an acute (clinical) state resembling a cascade akin to a waterfall or domino effect, often culminating in the patient's demise. A comprehensive literature search was conducted using PubMed, Google Scholar, and Scopus databases in October 2023, employing keywords such as "MODS", "SIRS", "sepsis", "pathophysiology of MODS", "MODS in cancer patients", "multiple organ failure", "risk factors", "cancer", "ICU", "quality of life", and "breast cancer". Supplementary references were extracted from the retrieved articles. This study emphasizes the importance of early identification and prevention of the multiple organ failure cascade at the inception of the malignant state, aiming to enhance the quality of life and extend survival. This pursuit contributes to a deeper understanding of risk factors and viable therapeutic options. Despite the existence of the subclinical multiple organ failure syndrome, current diagnostic methodologies remain inadequate, prompting consideration of AI as an increasingly crucial tool for early identification in the diagnostic process.

Frequent expression of PD-L1 in BLS-type diffuse large B-cell lymphoma: implications for aggressiveness and immunotherapy

BLS-type diffuse large B-cell lymphoma (DLBCL) denotes an uncommon, aggressive variant of DLBCL presenting initially in bone marrow, liver and spleen without lymphadenopathy or mass lesion. Patients with BLS-type DLBCL present frequently with haemophagocytic syndrome which often leads to early patient demise. Programmed death ligand 1 (PD-L1) plays a negative regulatory role on effector T cells and is an important target of immunotherapy. Assessment of PD-L1 expression in BLS-type DLBCL may carry therapeutic implications and provide mechanistic insights. Standard immunohistochemical analysis for PD-L1 was performed in seven cohorts for this study: (1) DLBCL-not otherwise specified (NOS) (n=201); (2) Epstein-Barr virus (EBV)-positive DLBCL (n=26); (3) thymic (primary mediastinal) DLBCL (n=12); (4) intravascular LBCL (n=3); (5) high-grade B-cell lymphoma, NOS (n=12); (6) BLS-type DLBCL (n=37); and (7) systemic DLBCL involving bone marrow (n=28). We found that PD-L1 was positive in 12.9% of DLBCL-NOS cases, 46.2% of EBV-positive DLBCL, 91.7% of thymic LBCL, none of intravascular LBCL, 8.3% of high-grade B-cell lymphoma-NOS, and 56.8% of BLS-type DLBCL. By comparison, only 14.3% of bone marrow cases involved by systemic DLBCL were positive for PD-L1 (p<0.001). Interestingly, BLS-type DLBCL more frequently showed activated B-cell phenotype (86.5% vs 65.2%, p=0.010), a high Ki-67 proliferative index (97.1% vs 63.3%, p<0.001), MYC overexpression (90.9% vs 56.2%, p=0.023), presence of haemophagocytic syndrome (86.5% vs 4.0%, p<0.001), and poorer overall survival (p<0.001) than DLBCL-NOS. These data suggest that the poor prognosis of BLS-type DLBCL may be explained by both extrinsic tumour microenvironment factors and intrinsic genetic factors of tumour cells, such as PD-L1-associated inactivation of anti-tumour immunity for the former, and MYC pathway activation-related aggressiveness for the latter.

Orbital Metastasis of Cervical Squamous Cell Cancer during Treatment with Pembrolizumab

Purpose: This case report presents a rare occurrence of squamous cell carcinoma metastasizing to the orbit from the cervix.Case summary: A 48-year-old female with cervical cancer and multiple bone metastases experienced binocular diplopia two days prior to admission to the Department of Gynecology for scheduled chemotherapy. She was undergoing treatment with pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, for metastatic cervical cancer. The patient exhibited unilateral ptosis and restricted eyeball movement in the right eye. Brain MRI revealed a well-defined lobulated lesion attached to the superior rectus muscle in the right orbit and orbital apex. In suspicion of metastasis, radiation therapy with a dosage of 3,600 cGy was administered to the right orbital area, resulting in a reduction in size of the metastatic lesion. However, distant metastases subsequently developed in the bone and soft tissue, leading to the patient's demise one month later.Conclusions: This report emphasizes the importance of considering orbital metastasis from cervical cancer in patients undergoing advanced stage chemotherapy. It highlights the rarity of such cases and underscores the need for heightened awareness of this malignancy in patients with underlying cancer.

Tidal volume expandability and ventilatory efficiency as predictors of mortality in Taiwanese male patients with chronic obstructive pulmonary disease: A 10-year follow-up study – Is V̇O2peak or FEV1% the gold standard?

Despite our knowledge of the risk factors for mortality associated with chronic obstructive pulmonary disease (COPD), the mortality rate for this condition continues to increase. This study aimed to investigate the predictive power of physiological variables on all-cause mortality in COPD patients compared to peak oxygen uptake ([Formula: see text]O2peak) and forced expired volume in one second (FEV1). We conducted a retrospective study of 182 COPD patients with complete lung function tests, cardiopulmonary exercise testing (CPET), and survival data. Cox regression analysis was used to estimate the hazard ratios for all-cause mortality. The median follow-up period was 6.8 (IQR 3.9-9.2) years. Out of the 182 patients in our study, sixty-two (34.1%) succumbed to various causes. Of these, 27.4% ( n = 17) experienced acute exacerbations, 24.2% ( n = 15) had advanced cancer, and 12.9% ( n = 8) had cardiovascular disease as the primary cause of death. Another 25.8% ( n = 16) passed away due to other underlying conditions, while 6.5% ( n = 4) had an unknown cause of death. One patient's demise was attributed to a benign tumor, and another's to a connective tissue disease. The ratio of tidal volume to total lung capacity (VTpeak/TLC) and the ratio of minute ventilation and [Formula: see text]O2 at nadir ([Formula: see text]E/[Formula: see text]O2nadir) (AUR 0.83, 95% CI 0.76-0.91) were superior predictors of all-cause mortality compared to [Formula: see text]O2peak and FEV1%. A mortality prediction formula was derived using these variables. This study highlights the potential of VTpeak/TLC and [Formula: see text]E/[Formula: see text]O2nadir as predictive markers for COPD all-cause mortality in COPD. CPET is an effective tool for evaluating COPD mortality; however, the predictive equation requires further validation.

SAT281 Screening For Adrenocortical Insufficiency In Patients With X-linked Adrenoleukodystrophy

Abstract Disclosure: J. Berquist: None. R.N. Kiani: None. M.P. Wahl: None. Background: A 41-year-old male initially presented to neurology clinic for complaints of poor balance, lower extremity weakness, and numbness. He previously had exam findings of lower extremity spasticity and hyperreflexia, distal vibratory loss, positive Romberg, and difficulty with Tandem gait. His symptoms had been progressive following an ankle sprain 8 years earlier and he was treated with physical therapy and baclofen. He is highly active otherwise and enjoys rock climbing, which was difficult to do given his symptoms. Clinical Case: Genetic screening was performed to evaluate for hereditary spastic paraparesis, which resulted positive for a mutation in the ABCD1 gene with a p.Lys336Glu mutation of uncertain significance. Interestingly, this ABDC1 variant was not detected in submitted maternal sample, hence patient’s mutation likely occurred de novo. This variant is not established in population databases (gnomAD no frequency) but has been observed in at least one individual with clinical features of adrenomyeloneuropathy. X-linked adrenoleukodystrophy causes impairment of beta oxidation that leads to accumulation of saturated very long chain fatty acids (VFLA) in multiple tissues. There are many clinical phenotypes, but they are hallmarked by neurologic signs and symptoms. Although neurologic symptoms can often develop in childhood, they can be delayed and present in adulthood, as can adrenal insufficiency (AI). However, males are overwhelmingly likely to develop adrenocortical insufficiency compared to females. Our patient presented with a BMI of 22.94, HR 50 bpm, and blood pressure 120/76; reflecting his active lifestyle. Recent electrolytes were within normal limits, AM cortisol was 13.0, and ACTH 544.0 Given the elevated ACTH and known cause of adrenal insufficiency, we proceeded with ACTH stimulation test. Peak cortisol resulted at 13.1 (at 60 minutes) and he was started on replacement glucocorticoid therapy per body-surface area. Upon further literature review, patients can also develop loss of mineralocorticoid production. Renin and aldosterone were ordered and were both within normal limits. Conclusion: Males with adrenoleukodystrophy are at a much higher risk of developing adrenal insufficiency (AI) compared to females. Additionally, AI will often develop later in life, so a low threshold for screening should be present for the endocrinologist. Mineralocorticoid deficiency can also develop, although not as commonly. Loss of adrenal function can lead to patient demise, and therefore adrenal function needs to be closely evaluated in people with leukodystrophy. Presentation: Saturday, June 17, 2023

Stereotactic Radiosurgery for Contrast-Enhancing Satellite Nodules in Recurrent Glioblastoma: A Rare Case Series From a Single Institution.

Introduction Glioblastoma (GBM) is the most common malignant adult brain tumor and is invariably fatal. The standard treatment for GBM involves resection where possible, followed by chemoradiation per Stupp's protocol. We frequently use stereotactic radiosurgery (SRS) as a single-fraction treatment for small (volume ≤ 1cc) nodular recurrent GBM to the contrast-enhancing target on T1 MRI scan. In this paper, we aimed to evaluate the safety and efficacy of SRS for patients with contrast-enhancing satellite nodules in recurrent GBM. Methods This retrospective study analyzed the clinical and radiological outcomes of five patients who underwent CyberKnife (AccurayInc., Sunnyvale, California) SRS at the institute between 2013 and 2022. Results From 96 patients receiving SRS for GBM, five (four males, one female; median age 53) had nine distinct new satellite lesions on MRI, separate from their primary tumor beds. Those nine lesions were treated with a median margin dose of 20 Gy in a single fraction. The three-, six, and 12-month local tumor control rates were 77.8%, 66.7%, and 26.7%, respectively. Median progression-free survival (PFS) was seven months, median overall survival following SRS was 10 months, and median overall survival (OS) was 35 months. Interestingly, the only lesion that did not show radiological progression was separate from the T2-fluid attenuated inversion recovery (FLAIR) signal of the main tumor. Conclusion Our SRS treatment outcomes for recurrent GBM satellite lesions are consistent with existing findings. However, in a unique case, a satellite nodule distinct from the primary tumor's T2-FLAIR signal and treated with an enlarged target volumeshowed promising control until the patient's demise. This observation suggests potential research avenues, given the limited strategies for 'multicentric' GBM lesions.

Massive Hemorrhage and Mortality Following Thyroid Radiofrequency Ablation.

Radiofrequency ablation (RFA) provides a relatively safe and noninvasive option for treating benign thyroid nodules and thyroid cancer that is cosmetically superior to surgery. Following a loss of consciousness 1 h after thyroid RFA, a 56-year-old patient was transferred to the emergency room. Despite undergoing coronary angiography due to 3 cardiac arrests, the results were normal. Although brain, chest, and abdominal computed tomography scans were performed, the emergency physician failed to detect any hematoma formation. Despite the use of mechanical ventilation and extracorporeal membrane oxygenation, the patient exhibited persistent hypoventilation. It was later discovered that an aggravated massive hemorrhage had occurred, due to which inferior thyroid artery embolization and surgical hematoma evacuation were performed. Unfortunately, prolonged brain hypoperfusion resulting from airway compromise and common carotid artery occlusion resulted in brain death and, ultimately, the patient's demise. In conclusion, massive hemorrhages caused by RFA require immediate diagnosis and hemostasis.

Detecting Diabetic Ketoacidosis with Infection: Combating a Life-Threatening Emergency with Practical Diagnostic Tools.

Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes mellitus and can lead to patient demise if not immediately treated. From the recent literature, the diabetic ketoacidosis mortality rate, depending on age, is 2-5%. Insulin discontinuation and infection remain the two most common triggers for diabetic ketoacidosis. About 50% of cases of ketoacidosis result from bacterial infections like urinary tract infections and pneumonia. It is also important to diagnose the presence of infection in diabetic ketoacidosis patients to prevent the excessive use of antibiotics, which may lead to antibiotic resistance. Although performing bacterial culture is confirmatory for the presence or absence of bacterial infection, the time required to obtain the result is long. At the same time, emergency treatment needs to be started as early as possible. This narrative review examines various septic markers to identify the appropriate tools for diagnosis and to distinguish between diabetic ketoacidosis with and without infection. Electronic databases were searched using the Google engine with the keywords "Diabetes Mellitus", "Diabetic Ketoacidosis", "Infection with Diabetic Ketoacidosis", "biomarkers for infection in Diabetic Ketoacidosis", "Procalcitonin", "Inflammatory cytokines in DKA", "Lactic acidosis in DKA", and "White blood cell in infection in DKA". This narrative review article presents the options for diagnosis and also aims to create awareness regarding the gravity of diabetic ketoacidosis with infection and emphasizes the importance of early diagnosis for appropriate management. Diabetes mellitus is a clinical condition that may lead to several acute and chronic complications. Acute diabetic ketoacidosis is a life-threatening condition in which an excess production of ketone bodies results in acidosis and hypovolemia. Infection is one of the most common triggers of diabetic ketoacidosis. When bacterial infection is present along with diabetic ketoacidosis, the mortality rate is even higher than for patients with diabetic ketoacidosis without infection. The symptoms and biomarkers of diabetic ketoacidosis are similar to that of infection, like fever, C reactive protein, and white blood cell count, since both create an environment of systemic inflammation. It is also essential to distinguish between the presence and absence of bacterial infection to ensure the appropriate use of antibiotics and prevent antimicrobial resistance. A bacterial culture report is confirmatory for the existence of bacterial infection, but this may take up to 24 h. Diagnosis needs to be performed approximately in the emergency room upon admission since there is a need for immediate management. Therefore, researching the possible diagnostic tools for the presence of infection in diabetic ketoacidosis patients is of great importance. Several of such biomarkers have been discussed in this research work.