Treatment Considerations Research Articles

Evidence-based assessment and treatment of military/Veteran PTSD: Reflections on 15 years of practice

LAY SUMMARY This reflection following 15 years of military/Veteran clinical practice reviews special assessment and treatment considerations, with a focus on prolonged exposure therapy for posttraumatic stress disorder. It discusses common assumptions about evidence-based psychotherapy that can negatively impact treatment outcome and patient motivation and participation in treatment. The widely varying clinical presentations of the Canadian military population and unique nature of military service, as well as its impact on mental health, are reviewed. Key practice suggestions include the importance of identifying the index trauma, using outcome monitoring, and understanding the theory of each of the gold-standard trauma-focused psychotherapies, as well as the rationale for each included intervention, so that clinicians can tailor treatments to patients as clinically required. Common misunderstanding and complexities related to trauma-focused psychotherapies are discussed, including the goal of treatment and clinician hesitation to implement evidence-based psychotherapies. The intention of this reflection is to increase discussion, contribute to a greater understanding and deeper appreciation for the uniqueness of military/Veteran patients, and promote advancement and innovation in research and clinical practice.

Beyond the binary: A transformative implementation science initiative to improve LGBTQ+ cancer care.

11010 Background: Patient, provider, and system-level barriers contribute to significant disparities in care of LGBTQ+ persons, including delays in screening and diagnosis, and poorer outcomes. This implementation science initiative was designed to identify and address root causes of disparities in care for LGBTQ+ patients (pts) and drive sustainable change to improve health equity in LGBTQ+ cancer care. Methods: In 2023, a steering committee of 3 expert oncologists and 5 LGBTQ+ cancer pts convened to develop survey instruments and a point-of-care LGBTQ+ Cancer Care Toolkit. Next, LGBTQ+ pts with cancer (N = 817) and oncology providers (OPs) from 2 academic and 5 community-based practices (N = 115) completed surveys to reveal alignments and discordances in beliefs, perceptions, and practices regarding cancer care. OPs participated in audit-feedback (AF) sessions to critically assess system-specific practice gaps, prioritize areas for improvement, and develop action plans for improving LGBTQ+ cancer care. Results: Provider-reported top challenges in care included: unsure how sexual orientation/gender identity (SOGI) affect treatment considerations (35%), unsure how to discuss SOGI (30%),and systemic barriers that limit inclusion (29%). While most providers (84%) were at least moderately comfortable treating LGBTQ+ pts, these data suggest they overestimated the level of comfort of their pts. For example, only 24% of pts reported feeling safe disclosing their LGBTQ+ identity, while 65% of providers thought pts felt safe. Additionally, while most providers (73%) thought it was important to know a pt’s gender identity, only 46% thought it was important to know sexual orientation, and only 3% of providers reported routinely discussing SOGI with new pts. Patients and providers were not concordant in several other key areas, including the experience of pts’ partners, measures of inclusivity, and supportive care services offered, such as fertility preservation. Survey data also revealed systemic barriers to equitable care, such as EMR documentation of SOGI. In AF sessions, teams reviewed survey outcomes, and developed action plans for improvement, including integrating the toolkit, updating EMR documentation, developing LGBTQ+ education, and adopting measures of inclusivity. Notably, following the intervention, there were considerable gains in provider confidence and knowledge, and ~70% of providers committed to discussing SOGI with their pts at first introduction. Conclusions: Through this QI initiative, teams identified patient-, provider-, and systemic-level barriers that affect LGBTQ+ cancer care in their own practices and implemented action plans to address key challenges. The sustainable changes implemented in this QI initiative represent key opportunities for improvement that can be implemented in clinics across the country to improve equitable LGBTQ+ cancer care.

Bioethics of over- and undertreatment in older adults with cancer.

9046 Background: Over-/undertreatment are pervasive in older adults with cancer, despite oncologists prescribing with best intentions. What “ought” to be prescribed with limited evidence creates challenges in adhering to the principles of bioethics: beneficence, nonmaleficence, justice, and respect for autonomy. Our objective for this study was to elucidate whether and how tensions among these ethical principles can contribute to over-/undertreatment in older patients. Methods: We designed a modified Delphi study, convening a panel of 13 experts in biomedical ethics (5 male, 8 female; 4 MD, 4 PhD, 2 MD/MA, 1 MD/PhD, 1 JD/MDiv, 1 DNP) from U.S. and Canadian institutions for three iterative rounds of data collection. In the first round—an electronic questionnaire—we presented definitions of overtreatment and undertreatment in older adults with cancer (DuMontier, J Clin Oncol, 2020) and asked questions delineating which ethical principles related to each definition, followed by questions regarding how over-/undertreatment might occur from conflicts among different ethical principles. Consensus for each question was defined as ≥75% of experts answering “agree” or “strongly agree”. The second round consisted of a virtual synchronous focus group of 9 of the panel experts led by a qualitative researcher to review round one results and discuss questions that did not reach consensus, followed by a second questionnaire including these questions. Results: After the first round, experts reached consensus that bioethical principles applied to over-/undertreatment in older adults with cancer. Specifically, 92% felt that overtreatment can occur when oncologists overemphasize beneficence that values the potential benefit of cancer treatments, while underemphasizing non-maleficence with respect to treatment adverse effects. Moreover, 77% felt that overtreatment can also occur when oncologists prioritize patient autonomy (preference to be treated) over non-maleficence (oncologists' concerns that treatment harms outweigh benefits). 84% felt that undertreatment can occur due to a lack of justice in equitable consideration of cancer treatments that could provide similar benefits in older adults as they would in younger adults. Moreover, 77% felt that undertreatment can occur when oncologists underemphasize patient autonomy, failing to consider patient preferences regarding which benefits to pursue and risks to take. Data collection for the second questionnaire and qualitative analysis of the focus group are underway. Conclusions: Our findings suggest that tension in ethical principles can lead to over- and undertreatment in older adults with cancer. The “right” treatment in older patients in the context of limited evidence is not simply one that aims to aggressively target their cancer, but that balances both benefits and harms in light of the whole patient and their preferences, while not restricting therapies based on age alone.

Distal Medium Vessel Occlusion Strokes: Understanding the Present and Paving the Way for a Better Future.

Distal medium vessel occlusions (DMVOs) are thought to cause as many as 25% to 40% of all acute ischemic strokes and may result in substantial disability amongst survivors. Although intravenous thrombolysis (IVT) is more effective for distal than proximal vessel occlusions, the overall efficacy of IVT remains limited in DMVO with less than 50% of patients achieving reperfusion and about 1/3 to 1/4 of the patients failing to achieve functional independence. Data regarding mechanical thrombectomy (MT) among these patients remains limited. The smaller, thinner, and more tortuous vessels involved in DMVO are presumably associated with higher procedural risks whereas a lower benefit might be expected given the smaller amount of tissue territory at risk. Recent advances in technology have shown promising results in endovascular treatment of DMVOs with room for future improvement. In this review, we discuss some of the key technical and clinical considerations in DMVO treatment including the anatomical and clinical terminology, diagnostic modalities, the role of IVT and MT, existing technology, and technical challenges as well as the contemporary evidence and future treatment directions.

Botulinum Treatment Induced Dropped Head Syndrome in a Patient With Chronic Migraines and Multiple Sclerosis

BACKGROUND: Chronic migraine treatment typically is treated medically by use of medications, such as nonsteroidal anti-inflammatory drugs and triptans; however, for a subset of patients, botulinum toxin (or Botox) has effectively been shown to be an alternative medication. CASE REPORT: Following Botox administration for chronic headaches, our patient developed unforeseen adverse effects and presented with severe neck stiffness, facial droop, and dysphagia, collectively known as dropped head syndrome, prompting them to seek emergency care. In order to counteract botulinum toxicity, we administered neostigmine, but unexpectedly induced cholinergic toxicity, which led to severe secretions and blurry vision. Glycopyrrolate was administered with responsive resolution of symptoms. CONCLUSIONS: This case highlights the complexities of managing adverse reactions to Botox and raises considerations for alternative treatments, such as atropine, or concurrent neostigmine treatment with glycopyrrolate. KEY WORDS: Botox, botulinum, dropped head syndrome, chronic migraine, migraine, multiple sclerosis

Discovering Inflammation in Atherosclerosis: Insights from Pathogenic Pathways to Clinical Practice.

This comprehensive review explores the various scenarios of atherosclerosis, a systemic and chronic arterial disease that underlies most cardiovascular disorders. Starting from an overview of its insidious development, often asymptomatic until it reaches advanced stages, the review delves into the pathophysiological evolution of atherosclerotic lesions, highlighting the central role of inflammation. Insights into clinical manifestations, including heart attacks and strokes, highlight the disease's significant burden on global health. Emphasis is placed on carotid atherosclerosis, clarifying its epidemiology, clinical implications, and association with cognitive decline. Prevention strategies, lifestyle modifications, risk factor management, and nuanced antithrombotic treatment considerations are critical to managing cardiovascular complications, thus addressing a crucial aspect of cardiovascular health.

Kikuchi-Fujimoto Disease: A Rare Lymphadenitis with Diagnostic Challenges and Treatment Considerations

Kikuchi-Fujimoto disease (KFD) is a rare form of lymphadenitis that primarily affects young women in Japan and other parts of Asia. It is caused by unknown agents, possibly viruses that trigger an autoimmune response in genetically susceptible individuals. KFD is often misdiagnosed due to its resemblance to other benign and malignant conditions, including SLE-related lymphadenitis and lymphoma. Diagnosis of KFD requires a lymph node biopsy, which reveals characteristic features such as histiocytic necrotizing lymphadenitis. Additional diagnostic tests, including skin biopsy, MRI, and cerebrospinal fluid analysis, can aid in confirming the diagnosis. KFD is self-limiting, and most patients recover within a few months with symptomatic treatment. However, early intervention with corticosteroids and hydroxychloroquine is crucial for effective management, particularly in cases with extra-nodal involvement or neurological symptoms. Lymph node removal can also be an effective therapeutic measure, and Hemophagocytic lymphohistiocytosis (HLH), a potential complication of KFD, is managed with a combination of immunoglobulins and steroids. While KFD is a benign condition, its diagnosis and treatment can be challenging, requiring close monitoring and follow-up.

Solitary median maxillary central incisor syndrome: cone beam computed tomography illustrated review

The solitary median maxillary central incisor syndrome (SMMCI) is a rare autosomal dominant genetic syndrome characterized by the presence of a single central incisor positioned along the midline in both primary and permanent dentition. It is often associated with the holoprosencephaly spectrum, a group of brain and facial malformations. The etiopathogenesis of SMMCI is believed to involve embryonic developmental defects occurring between the 35th and 38th day of gestation, primarily affecting midline facial structures. Several genetic factors, including mutations in the Sonic Hedgehog gene on chromosome 7 and other genetic variants, have been implicated in SMMCI development. Diagnosis is typically made through clinical examination, prenatal ultrasound, and postnatal dental evaluation. Management of SMMCI requires a multidisciplinary approach involving pediatricians, otolaryngologists, neuro-pediatricians, and genetic counselors. Dental interventions may include extraction and space maintenance, orthodontic treatment, prosthodontic options, or esthetic considerations. Further research is needed to understand better the underlying mechanisms and genetic factors associated with SMCI, which will contribute to improved diagnosis and management of this syndrome.

Impact of functional gene groups on outcomes after ablation of ventricular tachycardia in patients with inherited left ventricular cardiomyopathy: an international multicentre study

Abstract Background Advances in genetic testing has enabled identification of pathogenic variants of different functional gene groups associated with non-dilated left ventricular cardiomyopathy (NDLCM)/dilated cardiomyopathy (DCM) and ventricular tachycardia (VT). However, there is limited data on the impact of functional groups on VT ablation outcome. Aim We aimed to assess the impact of likely pathogenic/pathogenic variants (LP/Pv) of different functional gene groups on heart failure (HF) outcomes and VT recurrence in patients with NDLCM/DCM after VT ablation. Methods Patients with NDLCM/DCM who underwent genetic testing (next-generation sequencing) and were referred for VT ablation were enrolled at 6 participating centers. Patients were followed for VT recurrence, HF-related adverse outcomes (death, left ventricular assist device [LVAD], or heart transplantation due to HF), and all-cause mortality. Results A total of 239 patients (age 55±14yrs; male n=193; LVEF 40±12%; amiodarone at admission n=103; ICD n=180) were included. LP/Pv were identified in 128 patients (54%), predominantly found in genes encoding sarcomeric (n=36/128, [28%]; titin n=20, myosin binding protein C n=12), followed by nuclear membrane (n=27/128, [22%]; lamin A/C; n=26), desmosomal (n=23/128, [18%]; desmoplakin n=11, plakophilin n=9), cytoskeleton (n=12/128, [9%]; filamin C n=8), and sarcoplasmic reticulum proteins (n=12/128, [9%]; phospholamban n=10). Variants of unknown significance (n=32) were grouped with patients who tested negative. Acute complete ablation success, defined as non-VT inducibility of any sustained monomorphic VT, was achieved in 113 patients (47%), 63 (56%) with LP/Pv. During a median follow-up of 32 months, 108 patients (45%) had VT recurrence, 41 (17%) had HF-related adverse outcomes (death with/without LVAD in 34, LVAD in 2, heart transplantation in 5) and 47 (20%) died. Patients with LP/Pv were more likely to have VT recurrence, HF-related adverse outcomes and had a higher mortality compared to those without (VT, 68 [53%] vs. 40 [36%]; HF-related adverse outcomes, 30 [23%] vs. 11 [10%]; mortality, 30 [23%] vs. 17 [15%]; log-rank, P<0.01 for all). As compared to patients without LP/Pv, those with LP/Pv in genes encoding nuclear membrane or sarcomeric proteins had significantly worse (P<0.01 for both) and those with LP/Pv in genes encoding desmosomal proteins had similar HF and VT recurrence outcomes (Figure). Of interest, patients with LP/Pv in genes encoding cytoskeleton proteins had favorable HF-related adverse outcomes, but worse VT recurrence (P=0.02) compared to those without LP/Pv (Figure). Conclusion In patients with NDLCM/DCM and VT, the impact of LP/Pv on HF and VT-recurrence outcomes after ablation differs across functional groups. Integrating genetic testing in the comprehensive evaluation of patients with NDLCM/DCM undergoing VT ablation may facilitate personalized ablation strategies and early consideration of alternative HF treatments.

Considerations of Pico-second and Nano-second Laser Treatments for Pigmented Lesions in Skin: Our 10 years’ Clinical Experience

Considerations of Pico-second and Nano-second Laser Treatments for Pigmented Lesions in Skin: Our 10 years’ Clinical Experience

Home-based primary care providers' perspectives on the unique challenges of working with late life posttraumatic stress disorder within their population of Veterans.

Posttraumatic stress disorder (PTSD) is more prevalent in medically ill older Veterans in Home-Based Primary Care (HBPC) settings than in the general population, raising unique considerations. The aim of this qualitative project was to explore HBPC mental health providers' perceptions of the presentation and treatment of PTSD and trauma-related symptoms in this population of older Veterans, many of whom face additional barriers to treatment due to living in rural settings. Five focus groups and one one-on-one interview were conducted with 23 HBPC mental health providers serving rural or rural/urban mixed communities across the United States. We applied qualitative content analysis to the data. Three themes were found: (1) Presentation of Trauma-Related Symptoms and PTSD in HBPC Population; (2) Treatment Challenges in HBPC; and (3) PTSD Treatment Strategies. Each theme had multiple subthemes which illustrate unique issues in this population. Results of this project contribute to key insights surrounding the unique presentation of PTSD and trauma-related processes and treatment considerations in a medically, cognitively, and psychosocially complex group of veterans. Efforts to improve access to care should consider the specific needs of veterans who are homebound, live in rural settings and identify with rural cultural norms, and have difficulty engaging in specialized PTSD treatment due to the convergence of these factors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

#1814 Infection associated pancreatitis in peritoneal dialysis, a case report

Abstract Background and Aims Peritoneal dialysis (PD) patients seem to have a higher incidence of acute alithiasic pancreatitis. Though rare and with some suggested triggers described in the literature, this is still a poorly understood and potentially life-threatening complication. We present a 60 years old woman concluding antimicrobial therapy with an icodextrin night-dwell regimen for peritonitis presenting with epigastric pain. This work reviews our approach to cloudy effluent from non-infectious causes during an infection while managing acute pancreatitis in the PD setting. We report diagnostic difficulties and treatment considerations with a positive outcome. Method We present a 60 years old woman on PD for one year presenting to the emergency room in November of 2023 with severe epigastric pain, nausea and emesis. She suffered from stage 5 chronic kidney disease due to autosomal dominant polycystic kidney disease and had disease complications as anemia and secondary hyperthyroidism controlled within targets. She was on automated PD (APD) with glucose based solutions. She was on the 17th of 21 days antibiogram guided treatment (ceftazidime) for a Enterobacter ludwigii PD-related peritonitis with good clinical evolution and peritoneal effluent (PE) leukocyte count per μl from 1258 to 91 in 5 days. In the previous 3 months she had had 2 other infectious episodes. A bacteremic urinary tract infection to E. coli associated with peritonitis treated with antibiogram guided therapy (ceftazidime) followed by C. difficile colitis treated with oral vancomycin. During each infection period she transitioned from APD to continuous ambulatory peritoneal dialysis with an icodextrin night dwell. On admission she presented with normal vital signs, no fever, and abdominal distention with severe epigastric tenderness to palpation without muscular guarding. Her dwell exchange showed blood-tinged cloudy PE. She had hemoglobin of 11.3 g/dl, otherwise normal blood cell counts, and raised amylase (213 UI/l) and lipase (1467 UI/l). There was no elevation of transaminases, cholestatic enzymes, C-reactive protein or procalcitonin and lipidemia or hyperbilirubinemia were normal. PE cell count showed 213/μl leukocytes and 202/μl erythrocytes. Abdominal ultrasound showed no evidence of an obstructive cause. She was admitted in the surgical care unit for a conservative and watchful approach. Results On presentation we accounted for the peritonitis still under treatment, acute pancreatitis, drug therapy and recently introduced icodextrin solution. The acute alithiasic pancreatitis diagnosis was established but there was still a possible causative role of icodextrin or infection and refractory peritonitis could also not be promptly excluded. The literature suggests icodextrin and other drugs as causes for acute pancreatitis in some patients but also mentions the possibility of cloudy or hemorrhagic effluent due to abdominal inflammation processes. Considering the clinical stability, the multiple possible contributing causative agents and the differential diagnosis of refractory peritonitis we closely monitored PE cell count evolution keeping the icodextrin dwell and ceftazidime prescriptions and collected samples for bacterial and fungal culture. The cultures were negative and stability of leukocyte count and mononuclear cell predominance (Fig. 1) helped us exclude the peritonitis hypothesis and attribute the PE changes to the pancreatitis process. Conclusion Inpatient monitoring and identifying all possible causes are essential to ensure good outcomes in PD patients suffering from acute pancreatitis. Full anamnesis, physical examination and close attention to laboratory findings were key in allowing adequate antibiotic therapy and resolution of the abdominal inflammatory process at hand while maintaining an adequate PD prescription.

Access to Care Considerations for the Endodontic Treatment of Immature Permanent Teeth: A National Survey of Pediatric Dentists and Endodontists

IntroductionThis study aimed to investigate access to care and financial considerations associated with the endodontic treatment of immature permanent teeth. MethodsSurveys were distributed to endodontists (n = 2,457) and pediatric dentists (n = 3,974) in the United States. Data were analyzed using X2 analysis and logistic regression. The level of significance was set to 0.05. ResultsThe response rate was 13% (n = 840). Respondent specialist groups were similar by age and years since specialty residency completion, but significantly different with regard to primary practice setting (eg private practice, Federally Qualified Health Center, hospital), (P = .001). The majority (91%) of respondents reported participation with dental insurance. Pediatric dentists (69%) were significantly more likely than endodontists (17%) to participate with public-payer dental insurance (P < .001). The majority of respondents (82%) indicated that patients reported economic factors (time or money) as a barrier to accessing endodontic treatment. Pediatric dentists were significantly more likely to consider economic factors when planning for treatment (P < .001). Pediatric dentists were more likely than endodontists to have the opinion that endodontic procedures for treatment of necrotic immature permanent teeth should cost less than root canal therapy (apexification, P < .001; regenerative endodontic procedures, P = .002). Pediatric dentists (33%) reported encountering barriers when attempting to refer their patients to an endodontist. Inability to find an endodontist that participates with dental insurance was the most frequently cited barrier. ConclusionsLimited clinician participation with dental insurance and gaps in insurance coverage for endodontic procedures appear to contribute to access to care barriers for pediatric patients.

Thyroid papillary carcinoma combined with primary follicular lymphoma: a case report

BackgroundPapillary thyroid carcinoma (PTC) stands out as the most prevalent epithelial malignant thyroid tumor. Thyroid primary follicular lymphoma (PFL) represents a rare malignant tumor originating from mesenchymal tissues. The concurrent occurrence of PTC and PFL is exceptionally rare, particularly in the context of Hashimoto’s thyroiditis, presenting significant challenges in clinical diagnosis and treatment.Case demonstrationA 44-year-old female patient presented with a neck mass persisting for over 1 month. The patient underwent surgery, and the incised tissues were subjected to pathology examinations, along with immunohistochemistry and next-generation sequencing tests suggestive of an EZH2 gene mutation in the tumor cells. The final pathological diagnosis confirmed the presence of PTC combined with PFL. Following a 27-month follow-up, the patient displayed no signs of recurrence or metastasis.ConclusionsThe concurrent occurrence of PTC and PFL poses notable challenges in clinical practice, requiring careful consideration in diagnosis and treatment. Herein, we present a rare case of PTC combined with PFL featuring an EZH2 gene mutation, which can be easily overlooked in the context of Hashimoto’s thyroiditis. The patient’s favorable response to surgical and radiotherapeutic interventions underscores the importance of accurate diagnosis and tailored treatment strategies in similar cases.

Systematic review and meta-analysis of Tuberculosis and COVID-19 Co-infection: Prevalence, fatality, and treatment considerations.

Tuberculosis (TB) and COVID-19 co-infection poses a significant global health challenge with increased fatality rates and adverse outcomes. However, the existing evidence on the epidemiology and treatment of TB-COVID co-infection remains limited. This updated systematic review aimed to investigate the prevalence, fatality rates, and treatment outcomes of TB-COVID co-infection. A comprehensive search across six electronic databases spanning November 1, 2019, to January 24, 2023, was conducted. The Joanna Briggs Institute Critical Appraisal Checklist assessed risk of bias of included studies, and meta-analysis estimated co-infection fatality rates and relative risk. From 5,095 studies screened, 17 were included. TB-COVID co-infection prevalence was reported in 38 countries or regions, spanning both high and low TB prevalence areas. Prevalence estimates were approximately 0.06% in West Cape Province, South Africa, and 0.02% in California, USA. Treatment approaches for TB-COVID co-infection displayed minimal evolution since 2021. Converging findings from diverse studies underscored increased hospitalization risks, extended recovery periods, and accelerated mortality compared to single COVID-19 cases. The pooled fatality rate among co-infected patients was 7.1% (95%CI: 4.0% ~ 10.8%), slightly lower than previous estimates. In-hospital co-infected patients faced a mean fatality rate of 11.4% (95%CI: 5.6% ~ 18.8%). The pooled relative risk of in-hospital fatality was 0.8 (95% CI, 0.18-3.68) for TB-COVID patients versus single COVID patients. TB-COVID co-infection is increasingly prevalent worldwide, with fatality rates gradually declining but remaining higher than COVID-19 alone. This underscores the urgency of continued research to understand and address the challenges posed by TB-COVID co-infection.

Respiratory pathogen and clinical features of hospitalized patients in acute exacerbation of chronic obstructive pulmonary disease after COVID 19 pandemic

Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p < 0.001) than patients of AECOPD before the outbreak. Hospital stay was longer after the outbreak than before the outbreak (10 vs. 8 days. p < 0.001). After the COVID-19 outbreak, the identification rates of S. pneumoniae (15.3 vs. 6.2%, p < 0.001) and Hemophilus influenzae (6.4 vs. 2.4%, p = 0.002) decreased, whereas the identification rates of P. aeruginosa (9.4 vs. 13.7%, p = 0.023), Klebsiella pneumoniae (5.3 vs. 9.8%, p = 0.004), and methicillin-resistant Staphylococcus aureus (1.0 vs. 2.8%, p = 0.023) increased. After the outbreak, the identification rate of influenza A decreased (10.4 vs. 1.0%, p = 0.023). After the outbreak, the number of patients hospitalized with AECOPD was lower and the identification rates of community-transmitted pathogens tended to decrease, whereas the rates of pathogens capable of chronic colonization tended to increase. During the period of large-scale viral outbreaks that require quarantine, patients with AECOPD might be given more consideration for treatment against strains that can colonize chronic respiratory disease rather than community acquired pathogens.

Genetic Predisposition to Sarcoma: What Should Clinicians Know?

Pathogenic germline variants in the setting of several associated cancer predisposition syndromes (CPS) may lead to the development of sarcoma. We would consider testing for a CPS in patients with a strong family history of cancer, multiple primary malignancies, and/or pediatric/adolescent/young adult patients diagnosed with other malignancies strongly associated with CPS. When a CPS is diagnosed in a patient with sarcoma, additional treatment considerations and imaging options for those patients are required. This applies particularly to the use of radiation therapy, ionizing radiation with diagnostic imaging, and the use of alkylating chemotherapy. As data and guidelines are currently lacking for many of these scenarios, we have adopted a shared decision-making process with patients and their families. If the best chance for cure in a patient with CPS requires utilization of radiation therapy or alkylating chemotherapy, we discuss the risks with the patient but do not omit these modalities. However, if there are treatment options that yield equivalent survival rates, yet avoid these modalities, we elect for those options. Considering staging imaging and post-therapy evaluation for sarcoma recurrence, we avoid surveillance techniques that utilize ionizing radiation when possible but do not completely omit them when their use is indicated.

Differential efficacy of medical therapies for ulcerative colitis according to disease extent: patient-level analysis from multiple randomized controlled trials

Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to severely active UC vary according to disease extent at enrollment. We analyzed patient level data from 11 Phase 2 and 3 clinical trials of advanced therapies in patients with moderate-to-severe UC to assess modifications of advanced therapy effects by disease extent. Primary outcome was clinical response and secondary outcomes were clinical remission, endoscopic response/remission and endoscopic improvement, and Mayo clinic subscore for both induction and maintenance studies. Binary and continuous outcomes were analyzed using the modified Poisson regression model and the mixed-effects model, respectively, adjusting for age, sex, disease duration, concomitant steroid use and prior anti-TNF use. Effect modifications with binary outcomes were quantified by ratios of risk ratio for left-sided to that for extensive colitis while effect modifications with the Mayo subscores were quantified by differences of the differences between mean scores of the left-sided and extensive colitis. Results were presented with point estimates and 95% confidence intervals as well as p-values. Eleven clinical trials enrolling 5450 UC patients (infliximab=2, adalimumab=2, golimumab=2, vedolizumab=2, tofacitinib=3) were included. In induction trials, there was evidence to suggest effect modification by disease extent for clinical response with tofacitinib (the ratio of RRs 0.67, 95% CI [0.45, 0.99], p=0.049) and clinical remission with infliximab (ratio of RRs 0.33, 95% CI [0.13, 0.85], p=0.020) favoring patients with extensive colitis. There was no evidence to suggest effect modification for endoscopic improvement and clinical outcomes. There was evidence to suggest effect modification by disease extent for clinical remission with tofacitinib (ratio of RRs 0.44, 95% CI [0.22, 0.89], p=0.020) favoring patients with extensive colitis. For symptom subscores from the Mayo Clinic score, tofacitinib was associated with a greater reduction in both stool frequency (difference of differences 0.37, 95% CI [0.08, 0.65], p=0.012) and rectal bleeding scores (difference of differences 0.25, 95% CI [0.03, 0.47], p=0.026) in patients with extensive colitis compared to left sided. These findings underscore the possibility of differential efficacy of medical therapies according to disease distribution. These results warrant further exploration in forthcoming trials to better inform treatment strategies and consideration of disease distribution as a baseline stratification factor in clinical trials. This study did not receive any financial support.

Abstract PO3-05-13: A Multi-Institutional Review of Contralateral Axillary Metastases: Time for Reclassification as Local-Regional Event?

Abstract Background Current American Joint Committee on Cancer (AJCC) breast cancer staging considers contralateral axillary metastasis (CAM) stage IV disease (M1). Retrospective studies suggest that women with CAM have improved overall survival (OS) compared to those with distant metastasis (M1) and/or comparable OS to locally advanced breast cancer (LABC). These studies support consideration of curative intent treatment; however, they contain heterogeneous cohorts with highly variable treatment strategies. We sought to evaluate treatment and outcomes in a well-defined CAM cohort treated with contemporary systemic and locoregional therapy. Methods We performed a retrospective multi-institution cohort study to compare OS of patients with CAM matched 1:3 on age +/- 5 years to LABC (defined as cN2-3 and/or pN2-3), and to non-CAM M1. CAM patients classified as type 1) de novo CAM, synchronous with the contralateral primary, 2) metachronous isolated CAM in the setting of prior surgical and/or radiation treatment to primary index cancer, 3) synchronous with, or 4) metachronous after an in-breast or axillary nodal recurrence of the primary index cancer. The M1 cohort included de novo and recurrent metastasis with varied sites and number of metastasis. OS was defined as time from CAM diagnosis to death or last follow-up for CAM patients; time from primary diagnosis to death or last follow-up for LABC; and time from metastatic diagnosis to death or last follow-up for M1. Unadjusted OS was estimated with the Kaplan-Meier method, and Cox proportional hazards models were used to estimate the association of group with OS after adjustment for covariates Results We identified 57 CAM and 155 LABC from 8 institutions (2016-2022), and 632 M1 from a single institution. The median age was similar between groups (CAM=59 years, LABC=58, M1=57, p=0.44), and there were no statistically significant differences in hormone receptor status (p=0.25). There were more Non-Hispanic Black patients in the M1 cohort compared to CAM or LABC (p&amp;lt; 0.001). The majority of CAM cases were delayed metachronous from the index cancer (type 2, 35.1%), or synchronous with a recurrence (type 3, 33.3%). Type 1 (de novo, 14%) and type 4 (delayed metachronous after breast cancer recurrence, 17.5%) were less frequent. Among CAM patients, 49.1% were hormone receptor positive (HR+)/HER2-negative (HER2-), 22.8% HR-/HER2-, 10.5% HR+/HER2+, and 5.3% HR-/HER2+. Comparing CAM versus LABC, invasive ductal carcinoma (IDC) was more commonly seen in CAM (82.5% vs 66.5%), as was grade 3 (45.6% vs 35.5%), and triple negative (22.8% vs 13.5%). Conversely, in LABC, treatment of the primary index cancer more frequently included chemotherapy (CAM=71.9%, LABC=92.3%), mastectomy (CAM=54.4%, LABC 74.2%), and adjuvant radiation (CAM=73.7%, LABC=90.3%). On multivariable analysis adjusting for age, race/ethnicity, and hormone receptor status, both CAM and M1 had inferior survival to LABC (Table 1), but with a 2.4-fold difference for CAM (95% CI 1.42-4.07, p=0.001) versus a 6.3-fold difference for M1 (95% CI 4.29-9.23, p=&amp;lt; 0.001). Discussion In this contemporary, multi-institution study, we demonstrated that CAM patients selected for presumed curative intent treatment experienced improved OS when compared to stage IV (M1) patients. Our data adds additional support for re-evaluating the current stage IV designation, in favor of N3, and consideration of curative intent treatment in this disease. Table. Adjusted* Overall Survival Comparing Patients with Breast Cancer Contralateral Axillary Metastasis (CAM) to those with Locally Advanced Breast Cancer (LABC) and Metastatic Disease (M1) *Adjusted for age, race/ethnicity, hormone receptors. Citation Format: Meghan R. Flanagan, Stephanie Downs-Canner, Samantha Thomas, Astrid Botty van de bruele, Margaret Lillie, Kristalyn Gallagher, Tammeza Gibson, James Jakub, Alexandra Verosky, Sarah Tevis, Malia Brennan, Francys Verdial, Jennifer Q. Zhang, Leisha Elmore, Jennifer Plichta, Laura Rosenberger. A Multi-Institutional Review of Contralateral Axillary Metastases: Time for Reclassification as Local-Regional Event? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-13.

Treatment considerations for bluetongue virus serotype‐3 cases in sheep

Background: Bluetongue virus (BTV) serotype‐3 (BTV‐3) has been circulating in the Netherlands since September 2023 and was first reported in Kent in the UK in November 2023, picked up via the annual bluetongue surveillance programme. It is a highly pathogenic strain in sheep with limited preventive measures once virus is circulating in the biting midge population. At the time of publication there is no BTV‐3 vaccine available and no cross‐protection from other BTV vaccine strains. There are no specific antiviral medicines available, and therapy focuses on nursing care and anti‐inflammatory medicines to reduce clinical signs, although early euthanasia decisions need to be considered on the grounds of animal welfare.Aim of the article: This article takes the experiences of vets from the Netherlands and describes what practitioners might be able to do to treat clinical cases of BTV‐3, with thanks to Schapendokter (2023) for sharing their practice protocols.