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Best Practices for Delivering Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma
No full textIMPORTANCE: Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined.
OBJECTIVE: To develop consensus best practices for delivering NT to patients with localized PDAC.
DESIGN, SETTING, AND PARTICIPANTS: This study used a modified Delphi approach consisting of 2 rounds of voting, and a series of virtual conferences (from October to December 2023) to reach expert consensus on candidate best practice statements generated from a systematic review of the literature and expert opinion. An interdisciplinary panel was formed including 47 North American experts from surgical, medical, and radiation oncology, radiology, pathology, gastroenterology, integrative oncology, anesthesia, pharmacy, nursing, cancer care delivery research, and nutrition as well as patient and caregiver stakeholders.
MAIN OUTCOME AND MEASURES: Statements that reached 75% agreement or greater were included in final consensus statements.
RESULTS: Of the 47 participating panel members, 27 (57.64%) were male, and the mean (SD) age was 47.6 (8.2) years. Physicians reported completing training a mean (SD) 14.6 (8.6) years prior and seeing a mean (SD) 110.6 (38.4) patients with PDAC annually; 35 (77.7%) were in academic practice. Final consensus was reached on 82 best practices for delivering NT. Of these, 38 statements focused on pre-NT practices, including diagnosis and staging (n = 15), evaluation and optimization (n = 20), and decision-making (n = 3); 29 statements defined best practices during NT, including initiation (n = 3), delivery of therapy (n = 8), restaging practices (n = 12), and management of complications during NT (n = 6); and 15 best practices were identified to guide treatment post-NT, focusing on surgery (n = 7), pathology (n = 4), and follow-up (n = 3).
CONCLUSIONS: Using a modified Delphi consensus technique, best practice guidelines were developed focusing on the optimal standards for delivering NT to patients with localized PDAC. Given the prognostic importance of completing multimodality therapy, efforts to standardize and optimize the delivery of NT represent an immediate opportunity to decrease care variation and improve outcomes for patients with PDAC. Future research should focus on validating and implementing best practice standards into clinical practice
Practical management of adverse events in patients receiving tarlatamab, a delta-like ligand 3-targeted bispecific T-cell engager immunotherapy, for previously treated small cell lung cancer
No full textTarlatamab is a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 (DLL3) and the cluster of differentiation 3 (CD3) molecule. In the phase 2 DeLLphi-301 trial of tarlatamab for patients with previously treated small cell lung cancer, tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial demonstrated that the most common treatment-emergent adverse events were cytokine release syndrome (53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and an emia (30%). Cytokine release syndrome was mostly grade 1 or 2 in severity, occurred primarily after the first or second tarlatamab dose, and was managed with supportive care, which included the administration of antipyretics (e.g., acetaminophen), intravenous hydration, and/or glucocorticoids. Other treatment-emergent adverse effects of interest included neutropenia (16%) and immune effector cell-associated neurotoxicity syndrome and associated neurologic events (10%). Given that tarlatamab is the first T-cell engager approved for the treatment of small cell lung cancer, raising awareness with regard to the monitoring and management of tarlatamab-associated adverse events is essential. Here, the authors describe the timing, occurrence, and duration of these adverse events and review the management and risk-mitigation strategies used by clinical investigators during the DeLLphi-301 trial
Non-bacterial thrombotic endocarditis: a clinical and pathophysiological reappraisal
No full textNon-bacterial thrombotic endocarditis (NBTE), formerly recognized as marantic endocarditis, represents a rare cardiovascular pathology intricately linked with hypercoagulable states, notably malignancy and autoimmune disorders. Characterized by the development of sterile vegetations comprised of fibrin and platelets on cardiac valves, NBTE poses a diagnostic challenge due to its resemblance to infective endocarditis. Therapeutic endeavours primarily revolve around addressing the underlying aetiology and instituting anticoagulant regimens to forestall embolic events, with surgical intervention seldom warranted. Non-bacterial thrombotic endocarditis frequently coexists with malignancies and autoimmune conditions, such as lupus and antiphospholipid antibody syndrome, and, more recently, has been associated with COVID-19. Its pathogenesis is underpinned by a complex interplay of endothelial dysfunction, hypercoagulability, hypoxia, and immune complex deposition. Clinical manifestations typically manifest as embolic phenomena, particularly cerebrovascular accidents, bearing substantial mortality rates. Diagnosis necessitates a high index of suspicion and meticulous exclusion of infective endocarditis, often facilitated by advanced cardiac imaging modalities. Anticoagulation, typically employing low molecular weight heparin or warfarin, constitutes the cornerstone of pharmacological intervention. Surgical recourse may be warranted in instances of refractory heart failure or recurrent embolic events. Given its multifaceted nature, the management of NBTE mandates a multidisciplinary approach, with prognosis contingent upon individual clinical intricacies. Future endeavours should prioritize further research to refine therapeutic strategies and enhance patient outcomes
Craniofacial Pain Locations and Outcomes After Endoscopic Sinus Surgery for Unilateral Sphenoid Sinusitis: A Multi-Institutional Study
No full textINTRODUCTION: Unilateral sphenoid sinus opacification on computed tomography is caused by a variety of pathologies including inflammatory and infectious sinusitis, benign and malignant tumors, and encephaloceles. The purpose of this study was to report craniofacial pain locations and outcomes in inflammatory unilateral sphenoid sinusitis (USS) patients who underwent endoscopic sinus surgery (ESS).
METHODS: A multi-institutional retrospective cohort study was conducted on all adult patients who had ESS for USS from 2015 to 2022. Patient demographics, presenting symptoms and nasal endoscopy findings, extent of surgical dissection, and craniofacial pain locations and outcomes were recorded. Exclusion criteria included age \u3c18 \u3eyears, non-inflammatory etiology, immunodeficiency, invasive fungal sinusitis, lack of follow-up, lack of preoperative pain location, and neoplasia. Descriptive statistics were calculated.
RESULTS: Of 57 patients with USS, 44 (77.2%) reported craniofacial pain at one or more locations. Retrobulbar (n = 19, 43.2%) was the most common pain location followed by frontal (n = 17, 38.6%) and occipital (n = 10, 22.7%). Surgical intervention resulted in pain resolution in 33/44 patients (75%), with a mean follow-up of 83.7 (±97.8) days. There were no significant associations between presenting symptoms, imaging findings, endoscopy, surgical extent, or final pathology and the presence or resolution of facial pain (p \u3e 0.05).
CONCLUSION: In USS patients, the most common craniofacial pain locations were retrobulbar, occipital, and frontal, with a minority being vertex. Based on short-term follow-up, ESS resolved the craniofacial pain in 75% of cases. There were no clinical variables that predicted the presence or resolution of craniofacial pain.
LEVEL OF EVIDENCE: IV Laryngoscope, 2025
Influenza vaccine effectiveness against medically attended outpatient illness, United States, 2023-24 season
No full textBACKGROUND: The 2023-24 U.S. influenza season was characterized by a predominance of A(H1N1)pdm09 virus circulation with co-circulation of A(H3N2) and B/Victoria viruses. We estimated vaccine effectiveness (VE) in the United States against mild-to-moderate medically attended influenza illness in the 2023-24 season.
METHODS: We enrolled outpatients aged ≥8 months with acute respiratory illness in 7 states. Respiratory specimens were tested for influenza type/subtype by reverse-transcriptase polymerase chain reaction (RT-PCR). Influenza VE was estimated with a test-negative design comparing odds of testing positive for influenza among vaccinated versus unvaccinated participants. We estimated VE by virus sub-type/lineage and A(H1N1)pdm09 genetic subclades.
RESULTS: Among 6,589 enrolled patients, 1,770 (27%) tested positive for influenza including 796 A(H1N1)pdm09, 563 B/Victoria, and 323 A(H3N2). Vaccine effectiveness against any influenza illness was 41% (95% Confidence Interval [CI]: 32 to 49): 28% (95% CI: 13 to 40) against influenza A(H1N1)pdm09, 68% (95% CI: 59 to 76) against B/Victoria, and 30% (95% CI: 9 to 47) against A(H3N2). Statistically significant protection against any influenza was found for all age groups except adults aged 50-64 years. Lack of protection in this age group was specific to influenza A-associated illness. We observed differences in VE by birth cohort and A(H1N1)pdm09 virus genetic subclade.
CONCLUSIONS: Vaccination reduced outpatient medically attended influenza overall by 41% and provided protection overall against circulating influenza A and B viruses. Serologic studies would help inform differences observed by age groups
Validation of UniverSeg for Interventional Abdominal Angiographic Segmentation
No full textAutomatic segmentation of angiographic structures can aid in assessing vascular disease. While recent deep learning models promise automation, they lack validation on interventional angiographic data. This study investigates the feasibility of angiographic segmentation using in-context learning with the UniverSeg model, which is a cross-learning segmentation model that lacks inherent angiographic training. A retrospective review, after IRB approval, identified 234 patients who underwent interventional fluoroscopy of the celiac axis with iodinated contrast from January 1, 2019, to December 31, 2022. From 261 acquisitions, 303 maximum contrast images were selected, each generating a 128 × 128 pixel partition for arterial detail analysis and binary mask creation. Image-mask pairs were divided into three classes of 101 pairs each, based on arterial diameter and bifurcation number. UniverSeg was tested class independently in a fivefold nested cross-validation. Performance analysis for in-context learning determined average model convergence for class sizes from 1 to 81 pairs. The model was further validated by repeating the tests on the inverse segmentation task. Dice similarity coefficients for decreasing diameters were 78.7%, 72.5%, and 59.9% (σ = 5.96, 7.99, 14.29). Balanced average Hausdorff distances were 0.86, 0.71, and 1.16 (σ = 0.37, 0.52, 0.68) pixels, respectively. Inverted mask testing aligned with UniverSeg expectations for out-of-context problem sets. Performance improved with support class size, vessel diameter, and reduced bifurcations, plateauing to within ± 1.34 Dice score at N = 51. This study validates UniverSeg for arterial segmentation in interventional fluoroscopic procedures, supporting vascular disease modeling and imaging research
Institutional experience with implanted cardiac device risk level assessment: Comparing calculation and measurement
No full textBACKGROUND: The use of in-vivo dosimetry is a long-standing but also labor-intensive component of risk-level assessment for patients with implanted devices. A calculation-only approach, using treatment planning system (TPS)-calculated doses along with imaging doses estimates when relevant, has the potential to streamline the physics workflow without negatively impacting patient safety.
PURPOSE: To evaluate the feasibility of using a calculation-only approach for risk level assessment for patients with implanted electronic medical devices.
METHODS: A total of 86 patients were included in this retrospective study. For each patient, in-vivo dosimetry measurements using optically stimulated luminescent dosimeter (OSLD) were compared to calculated doses (based on TPS calculated doses and an estimate of imaging doses when relevant). The comparison of OSLD doses and estimated predicted doses was structured in the following manner: (1) direct comparison of both absolute dose difference and percent difference for measured and calculated doses, (2) risk level assessment comparison using measured and estimated doses, and (3) sensitivity and positive predictive value assessment of each method for TG-203 risk level assessment.
RESULTS: For all cases, the calculation-based approach yielded a risk level that was equivalent to or more conservative than the risk level from OSLD measurement. For 79 of 86 patients (91.9%), the calculated and measured doses provided the same risk level. For 7 of 86 patients (8.1%), the calculated dose yielded the more conservative risk level. The calculation-based dose estimate provided a sensitivity of 1.00 with a positive predictive value of 0.92.
CONCLUSIONS: The use of a calculation-only approach has the potential to reduce workload while maintaining the efficacy of risk-level assessment for patients with implanted devices
The increasing global burden of cancer: implications for anaesthesia and peri-operative medicine
No full textINTRODUCTION: Most patients with cancer will require surgery at some point in their lifetime. As the global burden of cancer continues to increase, changes and challenges in cancer epidemiology and care are also borne peri-operatively.
METHODS: Due to its broad scope, a formal systematic electronic literature search was not performed. This narrative review examines how an increasing global burden of cancer affects anaesthesia and peri-operative medicine. We aimed to describe current cancer statistics; economic implications; the increasing survival of individuals with cancer; and the role of anaesthetists in enhancing the quality of life and survival after oncological surgery.
RESULTS: Epidemiological reports show wide variation in cancer incidence and mortality worldwide. Countries with a lower human development index will be disproportionately affected by greater increases in cancer burden. At the same time, these countries will also suffer larger deficits in the surgical and anaesthetic workforce. Cancer has significant macro- and micro-economic implications. Thus, public health and policy should address the large economic burden of cancer surgery and care. The improvement in cancer-related survival can be attributed to research focused on a deeper understanding of tumour biology; effective awareness education campaigns and screening programmes; early diagnosis; newer cancer therapies; and patient-centred precision care. Increasing survival brings new global challenges, such as delivering an adequate survivorship care plan and addressing long-term psychosocial concerns in survivors. Anaesthetists are involved in all phases of a patient\u27s cancer journey including facilitating diagnostic procedures; providing comprehensive peri-operative care needs for ablative procedures; provision of critical care; addressing acute and chronic pain; and provision of integrative and palliative care services.
DISCUSSION: Deeper engagement of anaesthetists in cancer care programmes will be instrumental in reducing postoperative complications; improving the quality of life for patients; enhancing population health; and contributing to improved global economies
The impact of post-nephroureterectomy surgically induced chronic kidney disease on survival outcomes
No full textOBJECTIVE: To investigate the prevalence, predictors and impact of surgically induced chronic kidney disease (CKD-S) on survival outcomes in patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU).
METHODS: Utilising the ROBUUST 2.0 registry, a multicentre retrospective analysis was conducted in patients with UTUC undergoing RNU between 2006 and 2022 who did not have baseline chronic kidney disease (CKD) stages 3-5. We calculated the prevalence of postoperative CKD-S3a (estimated glomerular filtration rate [eGFR] 59-45 mL/min/1.73 m(2)) and CKD-S3b (eGFR \u3c45 mL/min/1.73 m(2)) as measured by the Chronic Kidney Disease Epidemiology Collaboration 2021 equation. The analytical cohort was stratified by postoperative CKD stage [no CKD-S [eGFR ≥60 mL/min/1.73 m(2)]; CKD-S3a [eGFR 59-45 mL/min/1.73 m(2)] and CKD-S3b [eGFR \u3c45 mL/min/1.73 m(2)]). The primary outcome was all-cause mortality (ACM). Predictors for development of CKD-S3a/3b and ACM/cancer-specific mortality (CSM) were analysed using logistic and Cox regression, respectively. Kaplan-Meier analysis was used to analyse overall survival (OS) and cancer-specific survival (CSS) among postoperative CKD groups.
RESULTS: We analysed 1862 patients; 34.7% (646) and 39.6% (738), respectively, developed CKD-S3a and CKD-S3b. Predictors of CKD-S3b included increasing age (odds ratio [OR] 1.03, P = 0.029), decreasing preoperative eGFR (OR 1.06, P \u3c 0.001) and receipt of neoadjuvant (OR 2.07, P = 0.006) and adjuvant chemotherapy (OR 1.41, P = 0.012). Worsened ACM was associated with CKD-S3b (hazard ratio 1.42, P = 0.032), but not CKD-S3a (P = 0.766). Development of CKD-S3a (P = 0.812) and CKD-S3b (P = 0.316) were not associated with CSM. The 5-year OS rate was significantly worse in CKD-S3b (no-CKD 71%, CKD-S3a 70%, CKD-S3b 59%; P = 0.017). No differences between CKD-S groups were noted for 5-year CSS (no-CKD 78%, CKD-S3a 77%, CKD-S3b 82%; P = 0.44).
CONCLUSIONS: A significant proportion of UTUC patients undergoing RNU developed CKD-S. Development of CKD-S3b was associated with worse ACM. Increasing age, preoperative eGFR, and chemotherapy were associated with developing CKD-S3b. Our findings call for further exploration and refinement of nephron-preserving surgical strategies and non-nephrotoxic systemic therapy to improve survival outcomes in UTUC
