The histone deacetylases (HDACs) occur in 11 different isoforms, and these enzymes regulate the activity of a large number of proteins involved in cancer initiation and progression. The discovery of isoform selective HDAC inhibitors (HDACIs) is desirable, as it is likely that such compounds would avoid some of the undesirable side effects found with the first generation inhibitors. A series of HDACIs previously reported by us were found to display some selectivity for HDAC6 and to induce cell cycle arrest and apoptosis in pancreatic cancer cells. In the present work, we show that structural modification of these isoxazole-based inhibitors leads to high potency and selectivity for HDAC6 over HDAC1-3 and HDAC10, while unexpectedly abolishing their ability to block cell growth. Three inhibitors with lower HDAC6 selectivity inhibit the growth of cell lines BxPC3 and L3.6pl, and they only induce apoptosis in L3.6pl. We conclude that HDAC6 inhibition alone is insufficient for disruption of cell growth, and that some degree of class 1 HDAC inhibition is required. Moreover, the highly selective HDAC6Is reported herein that are weakly cytotoxic may find use in cancer immune system reactivation.

Lead poisoning remains one of the most prevalent and preventable environmental health hazards affecting children. Low-level lead exposure has been shown to significantly increase the risk of learning disabilities, behavioral problems, and developmental delay. It also has substantial social implications as lead toxicity disproportionately affects children from low-income, ethnic minority households. Early Intervention (EI) is a state-based federal program (Part C of the Federal Individuals with Disabilities Education Act) created to support the development of children from birth to age 3 years who are experiencing or who are at risk for developmental delay. In 2016, an Illinois EI and Lead Workgroup was established to address the best practice of offering EI services to children who have been exposed to lead. This work serves as a template for advocates and health providers in other states to establish automatic eligibility for EI services at low levels of lead exposure, while also demonstrating the capacity to serve these children without overwhelming the state's EI system. [ Pediatr Ann. 2018;47(10):e413–e418.]

INTRODUCTION AND OBJECTIVES: Payers are increasingly focusing on preventable complications and hospital readmissions as they seek greater value for healthcare dollars. Many renal cancer patients are older, have multiple comorbidities, and are at increased risk for such complications. Measures of patient frailty have been validated in other fields as useful tools that simply and objectively identify patients at risk for complications and readmissions. This study evaluated the predictive value of a frailty index in identifying renal cancer patients at risk for postoperative Clavien III, IV or V complications.METHODS: We identified all patients diagnosed with renal cancer after undergoing open or minimally invasive radical or partial nephrectomy between 2005 and 2013 in the National Surgical Quality Improvement Program database. The modified frailty index (mFI) was calculated for each patient by scoring the presence /absence of comorbid conditions (Table 1). Univariate and multivariable regression analyses were performed to determine whether mFI and other clinical variables could independently predict serious complications.RESULTS: N¼11,755 patients underwent renal cancer surgery and 35.4% had mFI score ¼ 0, 52.5% had mFI¼1, 9.1% had mFI¼2, 2% had mFI¼3, and 0.7% had mFI4. Univariate analysis showed that higher mFI scores were associated with four-fold increased risk of sustaining a Clavien III, IV or V complication (p<0.0001). Higher mFI also predicted for suffering more than one of the 12 measured Clavien 3 complications (p <0.0001). Multivariable regression (Table 2) showed that patients with a frailty index of 1, 2, 3 and 4 had a monotonically increasing odds of suffering a Clavien 3 complication. Prolonged OR time, lower preoperative serum albumin and older age also predicted for increased risk of serious complications and readmissions.CONCLUSIONS: The modified Frailty Index is a simple and objective measure that independently predicts Clavien 3 complications and readmissions in renal cancer patients undergoing open or minimally invasive surgery.

INTRODUCTION AND OBJECTIVES: Payers are increasingly focusing on preventable complications and readmissions as they seek greater healthcare value. Benign prostate hyperplasia (BPH) with lower urinary tract symptoms occurs in almost 90% of men over 80, and many of these elderly men with multiple comorbidities eventually undergo surgery for poor urinary quality of life or frank urinary retention. Measures of patient frailty are potentially useful to identify such elderly men at risk for complications, thus we evaluated the predictive value of a frailty index in identifying BPH patients at risk for Clavien III, IV or V postoperative complications.METHODS: We identified all patients who underwent BPH surgery (TURP, laser coagulation, enucleation and vaporization) between 2005 and 2013 in the National Surgical Quality Improvement Program database. The modified frailty index (mFI) was calculated for each patient by scoring the presence/absence of comorbid conditions (Table 1). Univariate and multivariate analyses were performed to determine whether mFI and other clinical variables could independently predict serious complications.RESULTS: N¼18,827 patients (mean 71.7, SD¼ 9.3 years) underwent BPH surgery and 34.7% had mF¼0, 47% had mFI¼1, 12.3% had mFI¼2, 4.1% had mFI¼3, and 1.8% had mFI 4. Univariate analysis showed that higher mFI was associated with 2-fold increased risk of any complication (p<0.01) overall, but when stratified only for men over age 70, a 5-fold increased risk (p <0.0001) was noted. Multivariate regression (Table 2) showed that among men under 70, only those with mFI 4 were at risk for complications whereas among men aged 70, mFI 1, 2, 3 and 4 had monotonically increasing odds of suffering a Clavien 3 complication. Lower preop albumin but not older age and BMI also predicted for increased risk of serious complications and readmissions.CONCLUSIONS: The frailty index is a simple and objective measure that independently predicts Clavien 3 complications in BPH patients undergoing transurethral resection or laser surgery. This index has greater predictive value in men 70.

Rosa's (Note: All names have been changed to protect privacy) daughter was 8 years old when she told her mother, “I'm not going to stay one more day in this house.” For years, Rosa and her two daughters were subjected to domestic abuse. Shortly after her daughter said that very statement, Rosa realized they would never be safe until she left her husband's home. Rosa packed her daughters' things and left that morning.