Limited English proficiency, cardiovascular risk factors, cardiovascular disease, and in-hospital COVID-19 outcomes.

OBJECTIVES: Cardiovascular risk factors and history of cardiovascular disease are associated with greater morbidity and mortality in patients hospitalized with COVID-19. Limited English proficiency (LEP) has also been associated with worse outcomes in this setting, including requiring intensive care unit (ICU) level of care and in-hospital death. Whether non-English-language preference (NELP) modifies the association between cardiovascular risk factors or disease and outcomes in patients hospitalized with COVID-19 is unknown. STUDY DESIGN: Retrospective cohort study of adult patients admitted to a large New England health system between March 1 and December 31, 2020, who tested positive for COVID-19. NELP was defined as having a preferred language that was not English noted in the electronic health record. METHODS: Cardiovascular risk factors, history of cardiovascular disease, and NELP were related to the primary composite clinical outcome-death or ICU admission-using multivariable binary logistic regression adjusted for demographic and clinical characteristics. Interaction terms for NELP and model covariates were evaluated. RESULTS: Of 3582 patients hospitalized with COVID-19, 1024 (28.6%) had NELP; 812 (79.3%) of the patients with NELP received interpreter services. Death or ICU admission occurred in 794 (22.2%) of the hospitalized patients. NELP was not significantly associated with the primary composite outcome in unadjusted or adjusted analyses. In the adjusted analyses, only male gender, coronary artery disease, pulmonary circulatory disease, and liver disease significantly predicted the primary outcome. NELP did not modify the effect of these associations. CONCLUSIONS: NELP was not significantly associated with odds of death or ICU admission, nor did it modify the association between cardiovascular risk factors or history of cardiovascular disease and this composite outcome. Because most patients with NELP received interpreter services, these findings may support the role of such services in ensuring equitable outcomes.

Impact of Prior COVID-19 Infections on Cardiac Rehabilitation Completion Rates and Outcomes.

PURPOSE: This is a retrospective cohort study designed to evaluate the impact of having a prior COVID-19 infection on cardiac rehabilitation (CR) completion rates and outcomes. METHODS: Participants enrolled into the CR program from June 1, 2020, to March 30, 2022. They completed both physical and mental health assessments prior to enrollment and upon completion of the program. The cohort was divided into (-) COVID and (+) COVID based on whether they self-reported a prior COVID-19 infection. Outcome measures included General Anxiety Disorder-7, Patient Health Questionnaire-9, Mental Composite Score (Short Form Health Survey-36), Physical Composite Score (Short Form Health Survey-36), and exercise capacity (reported in METs). Program completion rates and outcome measures were compared between (-) COVID and (+) COVID cohorts. RESULTS: A total of 806 participants were enrolled in the study. Program completion rates were 58.7% in the (-) COVID group and 67.2% in the (+) COVID group ( P = .072). African Americans ( P = .017), diabetics ( P = .017), and current smokers ( P = .003) were less likely to complete the program. Both (-) COVID and (+) COVID groups showed significant improvement in all outcome measures after completing the CR program. However, there was no difference in outcomes between groups. CONCLUSIONS: Having a prior COVID-19 infection did not negatively impact the mental and physical health benefits obtained by completing the CR program, regardless of the American Association of Cardiovascular and Pulmonary Rehabilitation risk category.

Incidence and Predictors of New-Onset Atrial Fibrillation After Transcatheter Edge-to-Edge Repair of the Mitral Valve (from the Nationwide Readmissions Database).

Patients who underwent transcatheter edge-to-edge repair (TEER) for mitral regurgitation with atrial fibrillation (AF) at baseline have higher mortality than those without AF. Data on new-onset AF (NOAF) after TEER are limited. Using the 2016 to 2018 Nationwide Readmissions Database, we identified a cohort of patients who underwent TEER and classified them into 3 groups based on AF presence during the study period. The primary end point was the incidence and timing of NOAF up to 6 months after TEER. Logistic regression modeling identified independent predictors of NOAF at readmission. Of the 6,861patients that underwent TEER, 4,134 (59.9%) had AF at baseline, and 239 (3.5%) developed NOAF. Median time-to-NOAF admission was 47 days (interquartile range 16 to 113), and 37% of patients with NOAF presented within 30 days after TEER. Patients with NOAF experienced costlier and longer index-TEER hospitalization and had more co-morbidities. Chronic kidney disease (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.03 to 2.20), fluid and electrolyte disorders (OR 1.59, 95% CI 1.01 to 2.52), and heart failure (OR 1.86, 95% CI 1.01 to 3.44) were identified as independent predictors of NOAF. Hypertensive complications and heart failure were the leading causes of readmission. In conclusion, those patients that developed NOAF after TEER tended to be an overall sicker group at baseline compared with the remainder of the study cohort. These data, obtained from a nationally representative cohort, highlight a particular group of patients subject to developing NOAF and their association with increased rehospitalization in the post-TEER setting. Predictors of NOAF can be screened for during TEER workup to identify patients at increased risk.

Cardiac Tamponade Associated with Pembrolizumab Therapy in Patient with Pneumonectomy for Lung Cancer.

A 57-year-old man with a history of right pneumonectomy for squamous cell lung cancer who presented with dyspnea and hypotension, was found to have pericardial effusion complicated by cardiac tamponade, associated with pembrolizumab therapy. Pericardiocentesis could not be safely attempted due to presence of right-sided mediastinal tissue shift in the setting of previous right pneumonectomy. The patient improved significantly with surgical placement of pericardial window. Analysis of the pericardial fluid was negative for malignancy and was consistent with acute inflammation. Pembrolizumab and other immune checkpoint inhibitors are associated with cardiovascular toxicity, including pericardial effusion and in rare cases, cardiac tamponade. Treatment of cardiac tamponade in post-pneumonectomy patients may be subject to anatomical limitations precluding percutaneous pericardiocentesis and requires early recognition as well as availability of surgical intervention.

Associations between cumulative social risk, psychosocial risk, and ideal cardiovascular health: Insights from the HeartSCORE study.

Background: Limited studies have assessed the effects of psychosocial risk factors on achievement of ideal cardiovascular health (CVH). Methods: Using the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) cohort, we examined the cross-sectional associations of cumulative social risk (CSR) and three psychosocial factors (depression, stress, perceived discrimination) with ideal CVH. CSR was calculated by assigning one point for each of: low family income, low education level, minority race (Black), and single-living status. Ideal CVH was calculated by assigning one point for ideal levels of each factor in American Heart Association's Life's Simple 7. Ideal CVH was dichotomized into fewer versus higher by combining participants achieving <3 versus ≥3 factors. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of having fewer ideal CVH factors. Psychosocial factors were assessed as mediators of the association between CSR and ideal CVH. Results: We included 2000 participants (mean age 59.1 [7.5] years, 34.6% male, 42.7% Black, and 29.1% with low income), among whom 60.6% had <3 ideal CVH factors. The odds of having fewer ideal CVH factors increased significantly with increasing CSR scores from 1 to 2, to ≥3 compared to individuals with CSR score of zero, after adjusting for age and sex (OR [95% CIs]: 1.77 [1.41 - 2.22]; 2.09 [1.62 - 2.69] 2.67 [1.97 - 3.62], respectively). Taking the components of ideal CVH separately, higher CSR was directly associated with odds of being in 'non-ideal' category for six of the seven factors, but was inversely associated with probability of being in 'non-ideal' category for cholesterol. The association was modestly attenuated after adjusting for depression, stress, and perceived discrimination (corresponding OR [95% CI]: 1.69 [1.34 - 2.12], 1.96 [1.51 - 2.55], 2.34 [1.71 - 3.20]). The psychosocial factors appeared to mediate between 10% and 20% of relationship between CSR and ideal CVH. Conclusions: Increased CSR was associated with lower probability of achieving ideal CVH factors. A modest amount of the effect of CSR on ideal CVH appeared to be mediated by depression, stress and perceived discrimination. Public health strategies aimed at improving ideal cardiovascular health may benefit from including interventions targeting social and psychosocial risk factors.

Long-term Cardiovascular Manifestations and Complications of COVID-19: Spectrum and Approach to Diagnosis and Management.

Survivors of coronavirus disease 2019 (COVID-19) may experience persistent symptoms, abnormal diagnostic test findings, incident disease in specific organ systems, or progression of existing disease. Post-acute COVID-19 syndrome (PACS) is defined by persistent, recurrent, or new symptoms, findings, or diagnoses beyond four weeks after the initial infection. PACS has been characterized as a multi-organ syndrome, often with cardiopulmonary symptoms that include fatigue, dyspnea, chest pain, and palpitations. Cardiovascular pathologies in PACS include new-onset arrhythmia, myocarditis, unmasked coronary artery disease, and diastolic dysfunction as well as abnormal findings on electrocardiogram, troponin testing, and cardiac magnetic resonance imaging. In this review, we discuss the cardiovascular symptoms, pathophysiology, clinical investigation, and management strategies for cardiopulmonary symptoms of PACS. We offer a treatment algorithm for primary care clinicians encountering patients with cardiopulmonary PACS and discuss ongoing research on this topic.

Maternal Outcomes in Women with Peripartum Cardiomyopathy versus Age and Race-Matched Peers in an Urban US Community.

Peripartum cardiomyopathy (PPCM) is idiopathic systolic congestive heart failure around pregnancy. Comparisons with matched controls are lacking. We investigated maternal characteristics and outcomes up to 12 months in a cohort admitted to Montefiore Health System in Bronx, New York 1999−2015 (n = 53 cases and n = 92 age and race-matched controls, >80% Black or Hispanic/Latina). Compared to peers, women with PPCM had more chronic hypertension (24.5% vs. 8.8%, p = 0.001), prior gestational hypertension (20.8% vs. 5.4%, p = 0.001), prior preeclampsia (17.0% vs. 3.3%, p = 0.001), familial dilated cardiomyopathy (5.7% vs. 0.0%, p = 0.04), smoking (15.1% vs. 2.2%, p = 0.001), lower summary socioeconomic scores (−4.12 (IQR −6.81, −2.13) vs. −1.62 (IQR −4.20, −0.74), p < 0.001), public insurance (67.9% vs. 29.3% p = 0.001), and frequent depressive symptoms. Women with PPCM were often admitted antepartum (34.0% vs. 18.5%, p = 0.001) and underwent Cesarean section (65.4% vs. 30.4%, p = 0.001), but had less preterm labor (27.3% vs. 51.1%, p = 0.001). Women were rarely treated with bromocriptine (3.8%), frequently underwent left ventricular assist device placement (9.4% and n = 2 with menorrhagia requiring transfusion and progesterone) or heart transplantation (3.8%), but there were no in-hospital deaths. In sum, women with PPCM had worse socioeconomic disadvantage and baseline health than matched peers. Programs addressing social determinants of health may be important for women at high risk of PPCM.

Personalized, Electronic Health Record-Integrated Decision Aid for Stroke Prevention in Atrial Fibrillation: A Small Cluster Randomized Trial and Qualitative Analysis of Efficacy and Acceptability.

BACKGROUND: Shared decision-making in cardiology is increasingly recommended to improve patient-centeredness of care. Decision aids can improve patient knowledge and decisional quality but are infrequently used in real-world practice. This mixed-methods study tests the efficacy and acceptability of a decision aid integrated into the electronic health record (Integrated Decision Aid [IDeA]) and delivered by clinicians for patients with atrial fibrillation considering options to reduce stroke risk. We aimed to determine whether the IDeA improves patient knowledge, reduces decisional conflict, and is seen as acceptable by clinicians and patients. METHODS: A small cluster randomized trial included 6 cardiovascular clinicians and 66 patients randomized either to the IDeA (HealthDecision) or usual care (clinician discretion) during a clinical encounter when stroke prevention treatment options were discussed. The primary outcome was patient knowledge of personalized stroke risk. Exploratory outcomes included decisional conflict, values concordance, trust, the presence of a shared decision-making process, and patient knowledge related to time spent using the IDeA. Additionally, we conducted semistructured interviews with clinicians and patients who used the IDeA were conducted to assess acceptability and predictions of future use. RESULTS: The IDeA significantly increased patients' knowledge of their stroke risk (odds ratio, 3.88 [95% CI, 1.39-10.78]; P<0.01]). Patients had less uncertainty about their final decision (P=0.04). There were no significant differences in values concordance, trust in clinician or shared decision-making. Despite training, each clinician used the IDeA differently. Qualitative analysis revealed patients prefer using the IDeA earlier in their diagnosis. Clinicians were satisfied with the IDeA, yet varied in the contexts in which they planned to use it in the future. CONCLUSIONS: Using an Integrated Decision Aid, or IDeA, increases patient knowledge and lessens uncertainty for decision-making around stroke prevention in atrial fibrillation. Qualitative data provide insight into potential implementation strategies in real-world practice.

Persistence of abnormal global longitudinal strain in women with peripartum cardiomyopathy.

OBJECTIVES: Data regarding the longitudinal relationship of global longitudinal strain (GLS) and echocardiographic parameters are lacking in peripartum cardiomyopathy (PPCM). We evaluated GLS and its correlation with change (∆) in left ventricular ejection fraction (LVEF). METHODS: We retrospectively identified women age ≥16 years hospitalized at Montefiore Medical Center in Bronx, NY from 1999-2015 with International Statistical Classification of Diseases and Related Health Problems, 9th revision codes for PPCM or an occurrence of unexplained heart failure during or up to 5 months postpartum. N = 195 charts were reviewed for inclusion/exclusion criteria, n = 53 patients met criteria for PPCM, and of those, n = 13 had a baseline and follow-up echocardiogram suitable for GLS analysis. RESULTS: Of those eligible for strain analysis, the mean age was 30 ± 6 years, 46.2% identified as Black and 38.5% as Hispanic/Latina. Baseline LVEF was 30 (25, 35)%, GLS was -13.2 (-14, -7.6)%. At a mean follow-up time of 1.2 ± 0.7 years, 11/13 had persistently mild -15.6 (-16.3, -12.7)%, and 2/13 severely abnormal GLS -7.05 (-7.1, -7.0)%. There was no correlation between baseline GLS and ∆LVEF (r = .014, P = .965). CONCLUSIONS: Global longitudinal strain is a sensitive method to identify subclinical myocardial dysfunction. In this series of women with PPCM, GLS remained persistently abnormal over time, even if LVEF improved. Future studies should examine the implication of persistently abnormal GLS in PPCM.

The development of incorpoRATE: A measure of physicians' willingness to incorporate shared decision making into practice.

OBJECTIVES: To develop 'incorpoRATE', a brief and broadly applicable measure of physicians' willingness to incorporate shared decision making (SDM) into practice. METHODS: incorpoRATE was developed across three phases: 1) A review of relevant literature to inform candidate domain and item development, 2) Cognitive interviews with US physicians to iteratively refine the measure, and 3) Pilot testing of the measure across a larger sample of US physicians to explore item and measure performance. RESULTS: The final measure consists of seven items that assess physician perspectives on various components of SDM use that may present as barriers in practice. During pilot testing, the majority of physicians expressed positive opinions about the overall concept of SDM, yet were less comfortable acting on informed patient choices when there was known incongruence with their own recommendations. CONCLUSIONS: incorpoRATE is a novel physician-reported measure that assesses physicians' willingness to incorporate SDM in practice. PRACTICE IMPLICATIONS: incorpoRATE has the potential to help us further understand the limited adoption of SDM and areas of focus for improving the use of SDM in the future. We recommend that incorpoRATE be subject to further psychometric, real-world testing, in order to explore its performance across different samples of physicians and organizations.

Hyperglycaemia, adverse outcomes and impact of intravenous insulin therapy in patients presenting with acute ST-elevation myocardial infarction in a socioeconomically disadvantaged urban setting: The Montefiore STEMI Registry.

BACKGROUND: Hyperglycaemia occurs frequently in ST-elevation myocardial infarction (STEMI) and is associated with poor outcomes, for which continuous insulin infusion therapy (CIIT) may be beneficial. Information is limited regarding hyperglycaemia in acute STEMI affecting urban minority populations, or how CIIT fares in such real-world settings. METHODS AND RESULTS: We assembled an acute STEMI registry at an inner-city health system, focusing on patients with initial blood glucose ≥180 mg/dL to determine the impact of CIIT vs usual care. Clinical and outcomes data were added through linkage to electronic records. Inverse-probability-of-treatment weighting using propensity scores (PS) was used to compare CIIT vs no CIIT. The 1067 patients included were mostly Hispanic or African American; 356 had blood glucose ≥180 mg/dL. Such pronounced hyperglycaemia was related to female sex, minority race-ethnicity and lower socioeconomic score, and associated with increased death and death or CVD readmission. CIIT was preferentially used in patients with marked hyperglycaemia and was associated with in-hospital hypoglycaemia (21% vs 11%, P = .019) and, after PS weighting, with increased in-hospital (RR 3.23, 95% CI 0.94, 11.06) and 1-year (RR 2.26, 95% CI 1.02, 4.98) mortality. No significant differences were observed for death at 30 days or throughout follow-up, or death and readmission at any time point. CONCLUSIONS: Pronounced hyperglycaemia was common and associated with adverse prognosis in this urban population. CIIT met with selective use and was associated with hypoglycaemia, together with increased mortality at specific time points. Given the burden of metabolic disease, particularly among race-ethnic minorities, assessing the benefits of CIIT is a prerogative that requires evaluation in large-scale randomized trials.

The impact and utility of encounter patient decision aids: Systematic review, meta-analysis and narrative synthesis.

OBJECTIVE: To determine the effect of encounter patient decision aids (PDAs) as evaluated in randomized controlled trials (RCTs) and conduct a narrative synthesis of non-randomized studies assessing feasibility, utility and their integration into clinical workflows. METHODS: Databases were systematically searched for RCTs of encounter PDAs to enable the conduct of a meta-analysis. We used a framework analysis approach to conduct a narrative synthesis of non-randomized studies. RESULTS: We included 23 RCTs and 30 non-randomized studies. Encounter PDAs significantly increased knowledge (SMD = 0.42; 95% CI 0.30, 0.55), lowered decisional conflict (SMD= -0.33; 95% CI -0.56, -0.09), increased observational-based assessment of shared decision making (SMD = 0.94; 95% CI 0.40, 1.48) and satisfaction with the decision-making process (OR = 1.78; 95% CI 1.19, 2.66) without increasing visit durations (SMD= -0.06; 95% CI -0.29, 0.16). The narrative synthesis showed that encounter tools have high utility for patients and clinicians, yet important barriers to implementation exist (i.e. time constraints) at the clinical and organizational level. CONCLUSION: Encounter PDAs have a positive impact on patient-clinician collaboration, despite facing implementation barriers. PRACTICAL IMPLICATIONS: The potential utility of encounter PDAs requires addressing the systemic and structural barriers that prevent adoption in clinical practice.

Differential effects of cognitive load on subjective versus motor responses to ambiguously valenced facial expressions.

Valence is a principal dimension by which we understand emotional experiences, but oftentimes events are not easily classified as strictly positive or negative. Inevitably, individuals vary in how they tend to interpret the valence of ambiguous situations. Surprised facial expressions are one example of a well-defined, ambiguous affective event that induces trait-like differences in the propensity to form a positive or negative interpretation. To investigate the nature of this affective bias, we asked participants to organize emotional facial expressions (surprised, happy, sad) into positive/negative categories while recording their hand-movement trajectories en route to each response choice. We found that positivity-negativity bias resulted in differential hand movements for modal versus nonmodal response trajectories, such that when an individual categorized a surprised face according to his or her nonmodal interpretation (e.g., a negatively biased individual selecting a positive interpretation), the hand showed an enhanced spatial attraction to the alternative, modal response option (e.g., negative) in the opposite corner of the computer screen (Experiment 1). Critically, we also demonstrate that this asymmetry between modal versus nonmodal response trajectories is mitigated when the valence interpretations are made under a cognitive load, although the frequency of modal interpretations is unaffected by the load (Experiment 2). These data inform a body of seemingly disparate findings regarding the effect of cognitive effort on affective responses, by showing within a single paradigm that varying cognitive load selectively alters the dynamic motor movements involved in indicating affective interpretations, whereas the subjective interpretations themselves remain consistent across variable cognitive loads. (PsycINFO Database Record

An expanded composite scale of MRI-defined disease severity in multiple sclerosis: MRDSS2.

The objective of this study was to test a new version of the Magnetic Resonance Disease Severity Scale (MRDSS2), incorporating cerebral gray matter (GM) and spinal cord involvement from 3 T MRI, in modeling the relationship between MRI and physical disability or cognitive status in multiple sclerosis (MS). Fifty-five MS patients and 30 normal controls underwent high-resolution 3 T MRI. The patients had an Expanded Disability Status Scale score of 1.6±1.7 (mean±SD). The cerebral normalized GM fraction (GMF), the T2 lesion volume (T2LV), and the ratio of T1 hypointense LV to T2LV (T1/T2) were derived from brain images. Upper cervical spinal cord area (UCCA) was obtained from spinal cord images. A within-subject d-score (difference of MS from normal control) for each MRI component was calculated, equally weighted, and summed to form MRDSS2. With regard to the relationship between physical disability and MRDSS2 or its individual components, MRI-Expanded Disability Status Scale correlations were significant for MRDSS2 (r=0.33, P=0.013) and UCCA (r=-0.33, P=0.015), but not for GMF (P=0.198), T2LV (P=0.707), and T1/T2 (P=0.240). The inclusion of UCCA appeared to drive this MRI-disability relationship in MRDSS2. With regard to cognition, MRDSS2 showed a larger effect size (P=0.035) than its individual components [GMF (P=0.081), T2LV (P=0. 179), T1/T2 (P=0.043), and UCCA (P=0.818)] in comparing cognitively impaired with cognitively preserved patients (defined by the Minimal Assessment of Cognitive Function in MS). Both cerebral lesions (T1/T2) and atrophy (GMF) appeared to drive this relationship. We describe a new version of the MRDSS, which has been expanded to include cerebral GM and spinal cord involvement. MRDSS2 has concurrent validity with clinical status.

Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy.

Chemoresistance to platinum therapy is a major obstacle that needs to be overcome in the treatment of ovarian cancer patients. The high rates and patterns of therapeutic failure seen in patients are consistent with a steady accumulation of drug-resistant cancer stem cells (CSCs). This study demonstrates that the Notch signaling pathway and Notch3 in particular are critical for the regulation of CSCs and tumor resistance to platinum. We show that Notch3 overexpression in tumor cells results in expansion of CSCs and increased platinum chemoresistance. In contrast, γ-secretase inhibitor (GSI), a Notch pathway inhibitor, depletes CSCs and increases tumor sensitivity to platinum. Similarly, a Notch3 siRNA knockdown increases the response to platinum therapy, further demonstrating that modulation of tumor chemosensitivity by GSI is Notch specific. Most importantly, the cisplatin/GSI combination is the only treatment that effectively eliminates both CSCs and the bulk of tumor cells, indicating that a dual combination targeting both populations is needed for tumor eradication. In addition, we found that the cisplatin/GSI combination therapy has a synergistic cytotoxic effect in Notch-dependent tumor cells by enhancing the DNA-damage response, G(2)/M cell-cycle arrest, and apoptosis. Based on these results, we conclude that targeting the Notch pathway could significantly increase tumor sensitivity to platinum therapy. Our study suggests important clinical applications for targeting Notch as part of novel treatment strategies upon diagnosis of ovarian cancer and at recurrence. Both platinum-resistant and platinum-sensitive relapses may benefit from such an approach as clinical data suggest that all relapses after platinum therapy are increasingly platinum resistant.

Harnessing structure-activity relationship to engineer a cisplatin nanoparticle for enhanced antitumor efficacy.

Cisplatin is a first line chemotherapy for most types of cancer. However, its use is dose-limited due to severe nephrotoxicity. Here we report the rational engineering of a novel nanoplatinate inspired by the mechanisms underlying cisplatin bioactivation. We engineered a novel polymer, glucosamine-functionalized polyisobutylene-maleic acid, where platinum (Pt) can be complexed to the monomeric units using a monocarboxylato and an O --> Pt coordinate bond. We show that at a unique platinum to polymer ratio, this complex self-assembles into a nanoparticle, which releases cisplatin in a pH-dependent manner. The nanoparticles are rapidly internalized into the endolysosomal compartment of cancer cells, and exhibit an IC50 (4.25 +/- 0.16 microM) comparable to that of free cisplatin (3.87 +/- 0.37 microM), and superior to carboplatin (14.75 +/- 0.38 microM). The nanoparticles exhibited significantly improved antitumor efficacy in terms of tumor growth delay in breast and lung cancers and tumor regression in a K-ras(LSL/+)/Pten(fl/fl) ovarian cancer model. Furthermore, the nanoparticle treatment resulted in reduced systemic and nephrotoxicity, validated by decreased biodistribution of platinum to the kidney as quantified using inductively coupled plasma spectroscopy. Given the universal need for a better platinate, we anticipate this coupling of nanotechnology and structure-activity relationship to rationally reengineer cisplatin could have a major impact globally in the clinical treatment of cancer.