European Society of Cardiology quality indicators for the prevention and management of cancer therapy-related cardiovascular toxicity in cancer treatment.

AIMS: To develop quality indicators (QIs) for the evaluation of the prevention and management of cancer therapy-related cardiovascular toxicity. METHODS AND RESULTS: We followed the European Society of Cardiology (ESC) methodology for QI development which comprises (i) identifying the key domains of care for the prevention and management of cancer therapy-related cardiovascular toxicity in patients on cancer treatment, (ii) performing a systematic review of the literature to develop candidate QIs, and (iii) selecting of the final set of QIs using a modified Delphi process. Work was undertaken in parallel with the writing of the 2022 ESC Guidelines on Cardio-Oncology and in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. In total, 5 main and 9 secondary QIs were selected across five domains of care: (i) Structural framework, (ii) Baseline cardiovascular risk assessment, (iii) Cancer therapy related cardiovascular toxicity, (iv) Predictors of outcomes, and (v) Monitoring of cardiovascular complications during cancer therapy. CONCLUSION: We present the ESC Cardio-Oncology QIs with their development process and provide an overview of the scientific rationale for their selection. These indicators are aimed at quantifying and improving the adherence to guideline-recommended clinical practice and improving patient outcomes.

Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations.

Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short- and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.

A pilot investigation on impact of participation in a long-term follow-up clinic (LTFU) on breast cancer and cardiovascular screening among women who received chest radiation for Hodgkin lymphoma.

BACKGROUND: Women treated with chest radiation for Hodgkin lymphoma (HL) are at significantly increased risk of breast cancer and cardiovascular disease. HL survivors are recommended to have annual dual screening with mammogram (MMG) and breast magnetic resonance imaging (MRI). They are also recommended to undergo echocardiogram (echo) 5 years after completion of radiation. We performed a pilot study to characterize the women who are and are not receiving proper dual screening for breast cancer and baseline echo, and to examine the impact of a LTFU clinic consultation on screening. METHODS: A retrospective chart review of 114 women treated for HL at University of Minnesota (UMN) between 1993 and 2009 was performed. Demographics, disease and treatment history (age at diagnosis, stage, radiation dose and field, chemotherapy, recurrence) were assessed, as well as screening practices (MMG, MRI, both and echo), participation in LTFU clinic, and recommendations from providers. Data was summated in yes/no (y/n) format; statistical analysis was performed using chi-squared and Fisher's exact tests. Breast cancer and cardiovascular screening outcomes were compared by participation in the LTFU clinic (y/n) using Fisher's exact tests. P values < 0.05 were considered statistically significant. RESULTS: Forty-one of 114 women met inclusion criteria and had follow-up data for analysis. Median age at diagnosis was 29 years; 67.6% were diagnosed at stage IIa. Median dose of radiation was 3570 cGy. 56.1% participated in the LTFU clinic at the UMN. 36.6% had dual screening with both MMG and MRI, 41.5% had screening with only MMG, and 19.5% had no screening performed. Women were more likely to have dual screening if they were seen in LTFU clinic vs not seen in LTFU clinic (52.2 vs 16.7%, p = 0.02). 67.5% of women were screened with echo; women were also more likely to have screening with echo if seen in LTFU clinic vs not seen (86.4 vs 44.4%, p = 0.007). CONCLUSION: Many women are not getting the proper dual screening for breast cancer despite their increased risk, with only 36.6% of our study sample getting dual screening. Having a consultation in a LTFU clinic increases dual screening for breast cancer and echo screening for cardiovascular disease. Proper screening allows for detection of secondary breast cancer at earlier stages where treatment can be local therapy. Diagnosing CV disease early could allow for proper preventative treatment or intervention.

Characterizing axillary web syndrome: ultrasonographic efficacy.

The aim of this study was to determine if ultrasound could successfully characterize axillary web syndrome (AWS) and clarify the pathophysiologic basis of AWS as a vascular or lymphatic abnormality, or an abnormal tissue structure. This prospective study evaluated women who developed AWS following breast cancer surgery. Using an 18 MHz ultrasound transducer, images were taken of the AWS cord and compared to mirror images on the contralateral side. A blinded radiologist assessed the ultrasound characteristics of and structural changes in the skin and subcutaneous tissue and formulated an opinion as to the side in which AWS was located. Seventeen subjects participated in the study. No structure or abnormality consistent with AWS could be identified by ultrasound. There were no statistical differences between the ipsilateral and contralateral side in skin thickness; subcutaneous reflector thickness, number or disorganization; or subcutaneous tissue echodensity (p>0.05). The radiologist correctly identified the side with AWS in 12 of 17 subjects (=0.41). A distinct ultrasonographic structure or abnormality could not be identified in subjects with AWS using 18 MHz ultrasound. The inability to identify a specific structure excludes the possibility that AWS is associated with vein thrombosis or a fascial abnormality, and supports the theory that AWS may be pathology that is not visible with 18 MHz ultrasound, such as microlymphatic stasis or binding of fibrin or other proteins in the interstitial space.

Screening, prevention and management of osteoporosis and bone loss in adult and pediatric hematopoietic cell transplant recipients.

Long-term survivors of hematopoietic cell transplantation (HCT) are at risk for loss of bone mineral density (BMD) and subsequent osteoporosis. There is a lack of clear guidelines for the screening, prevention and treatment of bone loss after HCT. We reviewed the prevailing literature and provide guidelines developed by our center for the screening and management of this complication. Bone loss occurs predominantly within the first 6-12 months after autologous and allogeneic HCT. Recovery first occurs in the lumbar spine and is followed by a slower recovery of BMD in the femoral neck. BMD may not return to baseline levels in patients with continuing exposure to corticosteroids and calcineurin inhibitors. All HCT recipients should be advised general interventions to reduce fracture risk including adequate intake of calcium and vitamin D. We recommend screening all adult allogeneic and autologous HCT recipients with dual-energy X-ray absorptiometry 1 year after transplantation. Patients at high risk for bone loss (for example, patients receiving ≥ 5 mg of prednisone equivalent daily for > 3 months) can be screened earlier (for example, 3-6 months after HCT). Where indicated, bisphosphonates or other anti-resorptive agents (for example, calcitonin) can be used for prevention or treatment of osteoporosis in adult HCT recipients. Pediatric HCT recipients should be referred to a pediatric endocrinologist for evaluation and treatment of bone loss. There remain several areas of uncertainty that need further research in adult and pediatric HCT recipients, such as the optimal timing and frequency of screening for loss of bone mineral density, relationship of bone loss with risk of fractures, selection of appropriate patients for pharmacologic therapy, and optimal dosing schedule and duration of therapy with anti-resorptive agents.

Post-transplant lymphoproliferative disorders in lung transplant recipients: 20-yr experience at the University of Minnesota.

Post-transplant lymphoproliferative disorders (PTLD) are potentially fatal complications of solid organ transplantation. The natural history of PTLD varies considerably among the different types of organs transplanted. While lung transplant recipients are highly susceptible to PTLD, there are only a few small studies that detail PTLD in this setting. We undertook this study to better describe the characteristics and treatment response in PTLD after lung transplantation. We conducted a retrospective chart review of lung and heart/lung-transplant recipients between 1985 and 2008. A total of 32 cases (5%) of PTLD were identified in 639 patients. The median interval after transplantation to the diagnosis was 40 (3-242) months. Eight patients (25%) were diagnosed within one yr of transplantation and had PTLD predominantly within the thorax and allograft. Twenty-four patients (75%) were diagnosed more than one yr after transplantation and their tumors mainly affected the gastrointestinal tract. Monomorphic PTLD, diffuse large B-cell lymphoma, was diagnosed in 91%. Treatment of PTLD varied according to stage and clinical circumstances. Twenty-four patients (75%) have died. The median overall survival was 10 (0-108) months. PTLD after lung transplantation remains a challenge as a result of its frequency, complexity and disappointing outcome.

Malassezia: is it a pulmonary pathogen in the stem cell transplant population?

Malassezia furfur is a yeast that can cause a variety of infections, most commonly in normal hosts, and also in immunocompromised hosts. This yeast typically colonizes the skin, and is the causative agent of tinea versicolor. However, in immunocompromised hosts, it can more commonly cause catheter-related fungemia or folliculitis. Pulmonary infections from Malassezia have not been commonly recognized. Unlike many other common opportunistic fungal infections in immunocompromised hosts, neutropenia and the use of broad-spectrum antibiotics do not appear to be significant risk factors for Malassezia infections in the stem cell transplant (SCT) population. Additionally, disseminated infection, despite fungemia, is uncommon. A series of patients who underwent SCT at the University of Minnesota between 2004 and 2006 were reviewed for the occurrence of suspected Malassezia infections in the post-transplant period. Four cases of possible pulmonary M. furfur infection were identified in our SCT recipients. The clinical characteristics of these patients, the infections, treatment, and outcome are described. In addition, we discuss the possible pathogenicity of this yeast in the pulmonary setting.

The effect of postsurgical antibiotics on the healing of intrabony defects following treatment with enamel matrix proteins.

BACKGROUND: Regenerative treatment with enamel matrix proteins has been shown to promote healing in intrabony defects. However, up to now various postoperative antibiotic regimens have been used in combination with enamel matrix proteins and therefore it cannot be excluded that the results may also be attributable to the effect of the antibiotic treatment. The aim of this randomized, controlled, blinded, clinical investigation was to determine the effect of postsurgical administration of antibiotics on the healing of intrabony periodontal defects treated with enamel matrix proteins. METHODS: Thirty-four patients each of whom exhibited one deep intrabony defect were randomly treated with either enamel matrix proteins plus antibiotics (test: EMD + AB) or with enamel matrix proteins alone (control: EMD). The antibiotic regimen consisted of a combination of 3 x 375 mg amoxicillin and 3 x 250 mg metronidazole daily for 7 days. The following parameters were recorded at baseline and at 1 year by the same calibrated and blinded investigator: plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), gingival recession (GR), and clinical attachment level (CAL). Power analysis to determine superiority of antibiotic treatment showed that the available sample size would yield 85% power to detect a 1 mm difference. RESULTS: No statistically significant differences in any of the investigated parameters between the 2 groups were observed at baseline. No serious adverse events such as allergic reactions or abscesses after any of the treatments were observed during the entire study period. The results have shown that in the EMD + AB group the PD decreased from 9.1 +/- 1.5 mm to 4.5 +/- 1.1 mm (P<0.0001) and the CAL changed from 11.0 +/- 1.6 mm to 7.5 +/- 1.4 mm (P<0.0001). In the EMD group the PD decreased from 9.0 +/- 1.7 mm to 4.3 +/- 1.7 mm (P <0.0001) and the CAL changed from 10.6 +/- 1.6 mm to 7.3 +/- 1.5 mm (P <0.0001). There were no significant differences in any of the investigated parameters between the 2 groups. CONCLUSIONS: It can be concluded that the systemic administration of amoxicillin and metronidazole adjacent to the use of EMD for the surgical treatment of intrabony periodontal defects does not produce statistically superior PD reduction and CAL gain when compared to treatment with EMD alone. Hence, the present results do not support the routine administration of amoxicillin and metronidazole following regenerative treatment with EMD.

Comparison of enamel matrix proteins and bioabsorbable membranes in the treatment of intrabony periodontal defects. A split-mouth study.

BACKGROUND: Enamel matrix proteins (EMP) have recently been introduced as a new modality for regenerative periodontal treatment. However, limited information is available concerning the comparison of the treatment of intrabony periodontal defects with enamel matrix proteins and other regenerative treatment alternatives. METHODS: The aim of the present controlled clinical trial was to compare the treatment of deep intrabony periodontal defects with EMP to that with guided tissue regeneration (GTR) with bioabsorbable membranes. Sixteen patients, each of whom displayed one pair of intrabony defects located contralaterally in the same jaw, were randomly treated with EMP or with a bioabsorbable membrane. Prior to surgery and 8 months later the following parameters were evaluated by a blinded examiner: Plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), gingival recession (GR), and clinical attachment level (CAL). Antibiotics (amoxicillin and metronidazole) were given during the first 10 days after surgery. No statistical significant differences in any of the investigated parameters between the 2 groups were observed at baseline. RESULTS: No serious adverse events (e.g., allergic reactions or abscesses) after any of the treatments were noted during the entire observation period. Membrane exposure occurred in 7 out of the 16 GTR treated sites. Clinical examination was performed again 8 months postoperatively. Sites treated with EMP demonstrated a reduction of PD from 8.1+/-1.7 mm to 4.3+/-1.2 mm (P <0.001) and a change in CAL from 10.3+/-1.8 mm to 7.2+/-1.2 mm (P <0.001). The sites treated with GTR showed a reduction of PD from 8.3+/-1.7 mm to 4.3+/-0.7 mm (P <0.001) and a change of CAL from 10.1+/-1.9 mm to 7.1+/-1.7 mm (P <0.001). Both treatment procedures led to significant improvements of PD and CAL. However, no statistically significant differences in any of the investigated parameters were observed between the test and control group. CONCLUSIONS: It may be concluded that both therapies led to shortterm improvements of the investigated clinical parameters. Further studies of much higher power are needed to support equivalence.