Functional Status and Quality of Life in Light-Chain Amyloidosis: Advanced Imaging, Longitudinal Changes, and Outcomes.

BACKGROUND: In light-chain (AL) amyloidosis, whether functional status and heart failure-related quality of life (HF-QOL) correlate with cardiomyopathy severity, improve with therapy, and are associated with major adverse cardiac events (MACE) beyond validated scores is not well-known. OBJECTIVES: The authors aimed to: 1) correlate functional status and HF-QOL with cardiomyopathy severity; 2) analyze their longitudinal changes; and 3) assess their independent associations with MACE. METHODS: This study included 106 participants with AL amyloidosis, with 81% having AL cardiomyopathy. Functional status was evaluated using the NYHA functional class, the Karnofsky scale, and the 6-minute walk distance (6MWD), and HF-QOL using the MLWHFQ (Minnesota Living with Heart Failure Questionnaire). Cardiomyopathy severity was assessed by cardiac 18F-florbetapir positron emission tomography/computed tomography, cardiac magnetic resonance, echocardiography, and serum cardiac biomarkers. MACE were defined as all-cause death, heart failure hospitalization, or cardiac transplantation. RESULTS: NYHA functional class, Karnofsky scale, 6MWD, and MLWHFQ were impaired substantially in participants with recently diagnosed AL cardiomyopathy (P < 0.001), and correlated with all markers of cardiomyopathy severity (P ≤ 0.010). NYHA functional class, 6MWD, and MLWHFQ improved at 12 months in participants with cardiomyopathy (P ≤ 0.013). All measures of functional status and HF-QOL were associated with MACE (P ≤ 0.017), independent of Mayo stage for 6MWD and MLWHFQ (P ≤ 0.006). CONCLUSIONS: Functional status and HF-QOL were associated with AL cardiomyopathy severity, improved on therapy within 12 months, and were associated with MACE, independently of Mayo stage for 6MWD and MLWHFQ. They may be validated further in addition to prognostic scores and as surrogate outcomes for future studies.

Myocardial Characteristics, Cardiac Structure, and Cardiac Function in Systemic Light-Chain Amyloidosis.

BACKGROUND: In systemic light-chain (AL) amyloidosis, cardiac involvement portends poor outcomes. OBJECTIVES: The authors' objectives were to detect early myocardial alterations, to analyze longitudinal changes with therapy, and to predict major adverse cardiac events (MACE) in participants with AL amyloidosis using cardiac magnetic resonance imaging (MRI). METHODS: Recently diagnosed participants were prospectively enrolled. AL amyloidosis with and without cardiomyopathy (AL-CMP, AL-non-CMP) were defined based on abnormal cardiac biomarkers and wall thickness. MRI was performed at baseline, 6 months in all participants, and 12 months in participants with AL-CMP. MACE were defined as all-cause death, heart failure hospitalization, and cardiac transplantation. Mayo stage was based on troponin T, N-terminal pro-B-type natriuretic peptide, and difference in free light chains. RESULTS: This study included 80 participants (median age 62 years, 58% men). Extracellular volume (ECV) was abnormal (>32%) in all participants with AL-CMP and in 47% of those with AL-non-CMP. ECV tended to increase at 6 months (median +2%; AL-CMP P = 0.120; AL-non-CMP P = 0.018) and returned to baseline values at 12 months in participants with AL-CMP. Global longitudinal strain (GLS) improved at 6 months (median -0.6%; P = 0.048) and 12 months (median -1.2%; P < 0.001) in participants with AL-CMP. ECV and GLS were strongly associated with MACE (P < 0.001) and improved the prognostic value when added to Mayo stage (P ≤ 0.002). No participant with ECV ≤32% had MACE, while 74% of those with ECV >48% had MACE. CONCLUSIONS: In patients with systemic AL amyloidosis, ECV detects subclinical myocardial alterations. With therapy, ECV tends to increase at 6 months and returns to values unchanged from baseline at 12 months, whereas GLS improves at 6 and 12 months in participants with AL-CMP. ECV and GLS offer additional prognostic performance over Mayo stage. (Molecular Imaging of Primary Amyloid Cardiomyopathy [MICA]; NCT02641145).

Prognostic Value of Left Ventricular 18F-Florbetapir Uptake in Systemic Light-Chain Amyloidosis.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) with 18F-florbetapir, a novel amyloid-targeting radiotracer, can quantify left ventricular (LV) amyloid burden in systemic light-chain (AL) amyloidosis. However, its prognostic value is not known. OBJECTIVES: The authors' aim was to evaluate the prognostic value of LV amyloid burden quantified by 18F-florbetapir PET/CT, and to identify mechanistic pathways mediating its association with outcomes. METHODS: A total of 81 participants with newly diagnosed AL amyloidosis underwent 18F-florbetapir PET/CT imaging. Amyloid burden was quantified using 18F-florbetapir LV uptake as percent injected dose. The Mayo stage for AL amyloidosis was determined using troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain levels. Major adverse cardiac events (MACE) were defined as all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months. RESULTS: Among participants (median age, 61 years; 57% males), 36% experienced MACE, increasing from 7% to 63% across tertiles of LV amyloid burden (P < 0.001). LV amyloid burden was associated with MACE (HR: 1.46; 95% CI: 1.16-1.83; P = 0.001). However, this association became nonsignificant when adjusted for Mayo stage. In mediation analysis, the association between LV amyloid burden and MACE was mediated by NT-proBNP (P < 0.001), a marker of cardiomyocyte stretch and heart failure, and a component of Mayo stage. CONCLUSIONS: In this first study to link cardiac 18F-florbetapir uptake to subsequent outcomes, LV amyloid burden estimated by percent injected dose predicted MACE in AL amyloidosis. This effect was not independent of Mayo stage and was mediated primarily through NT-proBNP. These findings provide novel insights into the mechanism linking myocardial amyloid deposits to MACE.

Mechanisms of left ventricular systolic dysfunction in light chain amyloidosis: a multiparametric cardiac MRI study.

Background: Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly understood. Purpose: This study aims to analyze the effects of extracellular volume (ECV) expansion, a surrogate marker of amyloid burden on myocardial blood flow (MBF), myocardial work efficiency (MWE), and left ventricular (LV) systolic dysfunction in AL amyloidosis. Methods: Subjects with biopsy-proven AL amyloidosis were prospectively enrolled (April 2016-June 2021; Clinicaltrials.gov ID NCT02641145) and underwent cardiac magnetic resonance imaging (MRI) to quantify rest MBF by perfusion imaging, LV ejection fraction (LVEF) by cine MRI, and ECV by pre- and post-contrast T1 mapping. The MWE was estimated as external cardiac work from the stroke volume and mean arterial pressure normalized to the LV myocardial mass. Results: Rest MBF in 92 subjects (62 ± 8 years, 52 men) with AL amyloidosis averaged 0.87 ± 0.21 ml/min/g and correlated with MWE (r = 0.42; p < 0.001). Rest MBF was similarly low in subjects with sustained hematologic remission after successful AL amyloidosis therapy (n = 21), as in those with recently diagnosed AL amyloidosis. Both MBF and MWE decreased by ECV tertile (p < 0.01 for linear trends). The association of ECV with MWE comprised a direct effect (84% of the total effect; p < 0.001) on MWE from adverse interstitial remodeling assessed by ECV and an indirect effect (16% of the total effect; p < 0.001) mediated by MBF. There was a significant base-to-apex gradient of rest MBF in subjects with higher amyloid burden. Conclusions: In AL amyloidosis, both MBF and MWE decrease as cardiac amyloid burden and ECV expansion increase. Both structural and vascular changes from ECV expansion and myocardial amyloid burden appear to contribute to lower MWE.

Deciphering the triad of endothelial glycocalyx, von Willebrand Factor, and P-selectin in inflammation-induced coagulation.

This review examines the endothelial glycocalyx's role in inflammation and explores its involvement in coagulation. The glycocalyx, composed of proteins and glycosaminoglycans, interacts with von Willebrand Factor and could play a crucial role in anchoring it to the endothelium. In inflammatory conditions, glycocalyx degradation may leave P-selectin as the only attachment point for von Willebrand Factor, potentially leading to uncontrolled release of ultralong von Willebrand Factor in the bulk flow in a shear stress-dependent manner. Identifying specific glycocalyx glycosaminoglycan interactions with von Willebrand Factor and P-selectin can offer insights into unexplored coagulation mechanisms.

Influenza burden averted with a cell-based quadrivalent seasonal influenza vaccine compared with egg-based quadrivalent seasonal influenza vaccine.

BACKGROUND: Cell-based quadrivalent inactivated influenza vaccines (IIV4c) avoid egg-adaptive mutations found in egg-based production, improving vaccine effectiveness (VE). Studies demonstrate improved VE for IIV4c relative to egg-based quadrivalent inactivated influenza vaccines (IIV4). RESEARCH DESIGN AND METHODS: We built on a static compartmental model developed by the CDC to estimate the influenza burden in persons 0-64 years that would be additionally averted by vaccination with IIV4c vs. IIV4. Model inputs were based on published data from 2017-2018, 2018-2019, and 2019-2020 Northern Hemisphere influenza seasons for the US. RESULTS: Over 3 influenza seasons, relative to IIV4, IIV4c would avert 31-39% more symptomatic cases, 29-40% more outpatient visits, 29-38% more hospitalizations and ICU admissions, and 34-49% more deaths vs. IIV4. In a deterministic sensitivity analysis, the main drivers were the relative VE of IIV4c vs. IIV4 in the 2017-2018 season and influenza burden estimates for the 2018-2019 and 2019-2020 seasons. Probabilistic sensitivity analysis showed that the interquartile range of symptomatic cases was ± 13% of baseline in 2017-2018, ±8% in 2018-2019, and ± 7% in 2019-2020. CONCLUSIONS: IIV4c prevented significantly more symptomatic cases, outpatient visits, hospitalizations, and deaths than IIV4 in persons aged 0-64 years over 3 influenza seasons.

XR and mental wellbeing: state of the art and future research directions for the Metaverse.

Introduction: The purpose of this study is to provide an overview of extant research regarding XR technology and its effect on consumer wellbeing. With the hopes of informing marketing practitioners on XR consumer psychology, in preparation for the Metaverse. Methods: To achieve the above aim, two types of analysis took place. Firstly, a bibliometric analysis was conducted which was then followed by a framework-based structured literature review. The latter entailed an analysis of 81 articles evaluated from a positive psychological approach. Findings: Following the TCCM framework, the analysis revealed the most common psychological theories demonstrating potential avenues for XR to impact consumer wellbeing. Moreover, researchers found preliminary links between, theory, characteristics, and contexts. Giving a preliminary description of how theory manifests into reality. Finally, the overview of extant literature was used to propose new avenues for future research pertaining to marketing, the Metaverse, and consumer effects. Conclusion: In conclusion, the paper provides stakeholder insights which can ensure minimal consumer risk and sustainable use of the XR technology and Metaverse. While addressing the need for more research that uncovers the psychological effects of emerging technologies, so to prepare for the Metaverse. This is especially important when considering the current upsurge of these technologies and the uncertainties associated with their novelty and the idea of an 'always on' consumer.

Quantification of right ventricular amyloid burden with 18F-florbetapir positron emission tomography/computed tomography and its association with right ventricular dysfunction and outcomes in light-chain amyloidosis.

AIMS: In systemic light-chain (AL) amyloidosis, quantification of right ventricular (RV) amyloid burden has been limited and the pathogenesis of RV dysfunction is poorly understood. Using 18F-florbetapir positron emission tomography/computed tomography (PET/CT), we aimed to quantify RV amyloid; correlate RV amyloid with RV structure and function; determine the independent contributions of RV, left ventricular (LV), and lung amyloid to RV function; and associate RV amyloid with major adverse cardiac events (MACE: death, heart failure hospitalization, cardiac transplantation). METHODS AND RESULTS: We prospectively enrolled 106 participants with AL amyloidosis (median age 62 years, 55% males) who underwent 18F-florbetapir PET/CT, magnetic resonance imaging, and echocardiography. 18F-florbetapir PET/CT identified RV amyloid in 63% of those with and 40% of those without cardiac involvement by conventional criteria. RV amyloid burden correlated with RV ejection fraction (EF), RV free wall longitudinal strain (FWLS), RV wall thickness, RV mass index, N-terminal pro-brain natriuretic peptide, troponin T, LV amyloid, and lung amyloid (each P < 0.001). In multivariable analysis, RV amyloid burden, but not LV or lung amyloid burden, predicted RV dysfunction (EF P = 0.014; FWLS P < 0.001). During a median follow-up of 28 months, RV amyloid burden predicted MACE (P < 0.001). CONCLUSION: This study shows for the first time that 18F-florbetapir PET/CT identifies early RV amyloid in systemic AL amyloidosis prior to alterations in RV structure and function. Increasing RV amyloid on 18F-florbetapir PET/CT is associated with worse RV structure and function, predicts RV dysfunction, and predicts MACE. These results imply a central role for RV amyloid in the pathogenesis of RV dysfunction.

Incidence of Squamous Cell Carcinoma in Situ Upstaged to Invasive Squamous Cell Carcinoma During Mohs Surgery.

Objective: We sought to record the incidence and risk factors associated with upstaging squamous cell carcinoma in situ (SCCIS) to squamous cell carcinoma (SCC) during Mohs surgery with the largest sample size to date. Methods: Patient records of preoperative biopsy-proven SCCIS being treated with Mohs between January 2019 to March 2022 were identified and reviewed. Postoperative diagnoses of invasive SCC proven by dermal infiltration on pathology were identified as upstaged SCCIS. Results: From 2,043 cases of preoperative diagnosed SCCIS, 47 (2.3%) were upstaged to SCC during Mohs surgery. Of the 47 invasive tumors, a large proportion on the hands (29.8%) and lesions with larger preoperative sizes had a higher risk of being upstaged to invasive SCC in this study. Limitations: All of the patients included were from rural and suburban areas of North Carolina. The only sections obtained were those reviewed for margin analysis, which may significantly underestimate the actual number of invasive SCC, as only the deepest and furthest portions were examined. Conclusion: This retrospective study concluded that 2.3 percent of preoperatively diagnosed SCCIS were upstaged to SCC during treatment with Mohs surgery. Large lesions (>2cm) and lesions on the hand were more likely to be upstaged (29.8%). Treatment must be individualized considering the size of the lesion, the anatomic location, and the possibility that in some cases the initial biopsy may not have been able to accurately distinguish SCCIS from SCC. Although there is a myriad of treatment options for SCC, select patients with increased risk factors for upstaged SCC must be considered for margin assessed treatment modalities.

Myocardial Characterization for Early Diagnosis, Treatment Response Monitoring, and Risk Assessment in Systemic Light-Chain Amyloidosis.

Aims: In systemic light-chain (AL) amyloidosis, cardiac involvement portends poor prognosis. Using myocardial characteristics on magnetic resonance imaging (MRI), this study aimed to detect early myocardial alterations, to analyze temporal changes with plasma cell therapy, and to predict risk of major adverse cardiac events (MACE) in AL amyloidosis. Methods and Results: Participants with recently diagnosed AL amyloidosis were prospectively enrolled. Presence of AL cardiomyopathy (AL-CMP vs. AL-non-CMP) was determined by abnormal cardiac biomarkers. MRI was performed at baseline and 6 months, with 12-month imaging in AL-CMP cohort. MACE was defined as all-cause death, heart failure hospitalization, or cardiac transplantation. Mayo AL stage was based on troponin T, NT-proBNP, and difference in free light chains. The study cohort included 80 participants (median age 62 years, 58% males). Median left ventricular extracellular volume (ECV) was significantly higher in AL-CMP (53% vs. 30%, p<0.001). ECV was abnormal (>32%) in all AL-CMP and in 47% of AL-non-CMP. ECV tended to increase at 6 months and decreased significantly from 6 to 12 months in AL-CMP (median -3%, p=0.011). ECV was strongly associated with MACE (p<0.001), and improved MACE prediction when added to Mayo AL stage (p=0.002). ECV≤32% identified a cohort without MACE, while ECV>48% identified a cohort with 74% MACE. Conclusions: In AL amyloidosis, ECV detects subclinical cardiomyopathy. ECV tends to increase from baseline to 6 months and decreases significantly from 6 and 12 months of plasma cell therapy in AL-CMP. ECV provides excellent risk stratification and offers additional prognostic performance over Mayo AL stage.

Prognostic Value of Left Ventricular 18 F-Florbetapir Uptake in Systemic Light-Chain Amyloidosis.

Background: Myocardial immunoglobulin light-chain (AL) amyloid deposits trigger heart failure, cardiomyocyte stretch and myocardial injury, leading to adverse cardiac outcomes. Positron emission tomography/computed tomography (PET/CT) with 18 F-florbetapir, a novel amyloid-targeting radiotracer, can quantify left ventricular (LV) amyloid burden, but its prognostic value is not known. Therefore, we aimed to evaluate the prognostic value of LV amyloid burden quantified by 18 F-florbetapir PET/CT and to identify mechanistic pathways mediating its association with outcomes. Methods: Eighty-one participants with newly-diagnosed systemic AL amyloidosis were prospectively enrolled and underwent 18 F-florbetapir PET/CT. LV amyloid burden was quantified using 18 F-florbetapir LV percent injected dose (%ID). Mayo AL stage was determined using troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and difference between involved and uninvolved free light chain levels. Major adverse cardiac events (MACE) were defined as all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months. Results: Among participants (median age 61 years, 57% males), 36% experienced MACE. Incidence of MACE increased across tertiles of LV amyloid burden from 7% to 63% (p<0.001). LV amyloid burden was significantly associated with MACE in univariable analysis (hazard ratio 1.45, 95% confidence interval 1.15-1.82, p=0.002). However, this association became non-significant in multivariable analyses adjusted for Mayo AL stage. Mediation analysis showed that the association between 18 F-florbetapir LV %ID and MACE was primarily mediated by NT-proBNP (p<0.001), a marker of cardiomyocyte stretch and component of Mayo AL stage. Conclusion: In this first study to link cardiac 18 F-florbetapir uptake to subsequent outcomes, LV amyloid burden estimated by LV %ID predicted MACE in AL amyloidosis. But this effect was not independent of Mayo AL stage. LV amyloid burden was associated with MACE primarily via NT-pro-BNP, a marker of cardiomyocyte stretch and component of Mayo AL stage. These findings provide novel insights into the mechanism through which myocardial AL amyloid leads to MACE. Clinical Perspective: In systemic light-chain (AL) amyloidosis, cardiac involvement is the key determinant of adverse outcomes. Usually, prognosis is based on the Mayo AL stage, determined by troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the difference between involved and uninvolved immunoglobulin free light chain levels (dFLC). Cardiac amyloid burden is not considered in this staging. In the present study, we used the amyloid-specific radiotracer 18 F-florbetapir to quantify left ventricular (LV) amyloid burden in 81 participants with newly-diagnosed AL amyloidosis and evaluated its prognostic value on major adverse outcomes (MACE: all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months). We found that higher LV amyloid burden by 18 F-florbetapir positron emission tomography/computed tomography (PET/CT) was strongly associated with MACE. However, this association became non-significant after adjustment for the Mayo AL stage. Mediation analysis offered novel pathophysiological insights, implying that LV amyloid burden leads to MACE predominantly through cardiomyocyte stretch and light chain toxicity (by NT-proBNP), rather than through myocardial injury (by troponin T), also considering the severity of plasma cell dyscrasia (by dFLC). This mediation by NT-proBNP may explain why the association with outcomes was non-significant with adjustment for Mayo AL stage. Together, these results establish quantitative 18 F-florbetapir PET/CT as a valid method to predict adverse outcomes in AL amyloidosis. These results support the use of 18 F-florbetapir PET/CT to measure the effects of novel fibril-depleting therapies, in addition to plasma cell therapy, to improve outcomes in systemic AL amyloidosis.

Point-of-care hemoglobin A1c margin of error alters resident management of Type 2 diabetes when near glycemic target.

AIMS: Point-of-care (POC) HbA1c is frequently used as a surrogate for serum HbA1c. We aimed to determine if resident management of type 2 diabetes changed after accounting for the + 0.5% margin of error associated with POC HbA1c devices. METHODS: Residents were surveyed in an outpatient clinic regarding two of their patients with type 2 diabetes for which they had obtained a POC HbA1c. For one patient, the resident was asked if management would change if the POC HbA1c were 0.5% higher (called the positive case), and for another if management would change if POC HbA1c were 0.5% lower (negative case). RESULTS: Twelve of 58 (21%) cases had a change in management. Of the 27 cases where POC HbA1c was near the glycemic target (defined as POC HbA1c ≥6.0% and <8.0%), 11 (41%) resulted in a change in management while one (3%) of the 31 cases outside that interval had a change in management. CONCLUSION: POC HbA1c testing is well-suited for patients with poorly controlled type 2 diabetes while serum HbA1c testing may be more appropriate when near a patient's personalized HbA1c target since small changes in HbA1c can lead to differences in medical management.

Dermatomyositis: a debilitating paraneoplastic phenomenon following a diagnosis of localised squamous cell carcinoma of the cervix.

This case report describes the management of a patient, recently diagnosed with Stage IIIC cervical cancer, presenting with significant proximal muscle weakness, dysphagia and cutaneous changes over the hands, knees and outer thighs bilaterally. Following multiple investigations, this clinical presentation was proven to be dermatomyositis as a paraneoplastic phenomenon, a rare diagnosis with cervical cancer.Improvement of the presenting symptoms followed commencement of radical chemoradiation to the primary tumour plus administration of high dose steroids and intravenous immunoglobulins.As demonstrated in this case, and accompanying literature review, dermatomyositis is a rare complication of cervical cancer but should be considered as urgent treatment of the underlying malignancy is imperative. Involving members of the multidisciplinary team, including dieticians and physiotherapists, is of utmost importance to optimise the patient's recovery from such a debilitating diagnosis.

Additional Burden Averted in the United States From Use of MF59-Adjuvanted Seasonal Influenza Vaccine Compared With Standard Seasonal Influenza Vaccine Among Adults ≥65 Years.

Background: The MF59-adjuvanted trivalent inactivated influenza vaccine (aIIV3) is designed to overcome immunosenescence and enhance vaccine responses in older adults. We expanded on the Centers for Disease Control and Prevention (CDC) modeling method to estimate the number of additional influenza-related outcomes averted with aIIV3 versus generic quadrivalent inactivated influenza vaccine (IIV4) in adults ≥65 years over 3 influenza seasons (2017-2018 to 2019-2020) in the United States. Methods: A static compartmental model was developed based on an existing CDC model with 2 previously recommended calculation methods that increased the accuracy of the model in providing estimates of burden averted. Model inputs included vaccine effectiveness, vaccine coverage, population counts, and disease burden estimates. Additional burden averted (symptomatic cases, outpatient visits, hospitalizations, intensive care unit [ICU] admissions, and deaths) was expressed as total incremental cases averted between the vaccines. Sensitivity analyses tested the resilience of the model results to uncertainties in model inputs. Results: The model estimated that vaccination with aIIV3 versus IIV4 would avert 2.24 times as many symptomatic cases, outpatient visits, hospitalizations, ICU stays, and deaths during 2017-2018; the burden averted in 2018-2019 and 2019-2020 with aIIV3 would be 3.44 and 1.72 times that averted with IIV4, respectively. Disease burden estimates and relative vaccine effectiveness of aIIV3 had the greatest impact on model estimates. Conclusions: Over 3 influenza seasons, the model estimated that aIIV3 was more effective than IIV4 in averting influenza-related outcomes, preventing 1.72 to 3.44 times as many influenza illnesses with proportionate decreases in related healthcare use and complications.

Beyond the Knife in Renal Cell Carcinoma: A Systematic Review-To Ablate or Not to Ablate?

Intensified systemic therapy in metastatic renal cell carcinoma (mRCC) has led to improved patient outcomes. Patients commonly require local control of one or a few metastases. The aim was to evaluate metastasis-directed ablative therapies in extracranial mRCC. Two databases and one registry were searched, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach, for all prospective and matched-pair case-control mRCC studies of radiofrequency ablation (RFA), cryotherapy, microwave ablation (MWA), and stereotactic body radiotherapy (SBRT). Eighteen studies were identified. Fourteen investigated SBRT in 424 patients. Four thermal ablation studies were identified: two cryotherapy (56 patients) and two RFA studies (90 patients). The median participant number was 30 (range 12-69). The combined median follow-up was 17.3 months (range 8-52). Four SBRT studies reported local control (LC) at 12 months, median 84.4% (range 82.5-93). Seven studies (six SBRT and one cryotherapy) reported an LC rate of median 87% (79-100%). Median overall survival (OS) was reported in eight studies (five SBRT, two cryotherapy, and one RFA) with a median of 22.7 months (range 6.7-not reached). Median progression-free survival was reported in seven studies (five SBRT, one cryotherapy, and one RFA); the median was 9.3 months (range 3.0-22.7 months). Grade ≥ 3 toxicity ranged from 1.7% to 10%. SBRT has excellent local control outcomes and acceptable toxicity. Only four eligible thermal ablative studies were identified and could not be compared with SBRT. Translationally rich definitive studies are warranted.

European Society of Gynaecological Oncology Guidelines for the Management of Patients with Vulvar Cancer - Update 2023.

BACKGROUND: As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) first published in 2017 evidence-based guidelines for the management of patients with vulvar cancer. OBJECTIVE: To update the ESGO guidelines based on the new evidence addressing the management of vulvar cancer and to cover new topics in order to provide comprehensive guidelines on all relevant issues of diagnosis and treatment of vulvar cancer. METHODS: The ESGO Council nominated an international development group comprised of practicing clinicians who provide care to vulvar cancer patients and have demonstrated leadership through their expertize in clinical care and research, national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (18 experts across Europe). To ensure that the statements were evidence-based, new data identified from a systematic search were reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 206 international practitioners in cancer care delivery and patient representatives. RESULTS: The updated guidelines cover comprehensively diagnosis and referral, staging, pathology, pre-operative investigations, surgical management (local treatment, groin treatment, sentinel lymph node procedure, reconstructive surgery), (chemo)radiotherapy, systemic treatment, treatment of recurrent disease (vulvar, inguinal, pelvic, and distant recurrences), and follow-up. Management algorithms are also defined.