The cross-sectional association of frailty with chronic past and current use of benzodiazepine drugs.

BACKGROUND: Frailty, a clinical syndrome characterized by vulnerability to stressors resulting from multisystemic loss of physiological reserve. The use of benzodiazepines in older adults has been associated with confusion, sedation, and cognitive impairment, which in turn may lead to frailty. AIMS: The purpose of this study was to determine the cross-sectional association between frailty and chronic past or current use of benzodiazepine drugs among older US Veterans. METHODS/DESIGN: This is a cross-sectional study of community-dwelling older Veterans who had determinations of frailty. Benzodiazepine prescription data were obtained via EHR. A 31-item VA Frailty Index (VA-FI) was generated at the time of the assessment. We categorized Veterans into robust (FI ≤ 0.10), pre-frail (FI 0.10-0.21), and Frail (FI ≥ 0.21). After adjusting for sociodemographic characteristics, we calculated ORs and 95% CIs using a binomial logistic regression (BLR) model to assess the cross-sectional association between benzodiazepine use and frailty. RESULTS: Population sample consisted of 17,423 Veterans, mean age 75.53 (SD = 8.03) years, 70.80% Caucasian, 97.34% male, 14,545 (83.50%) patients were non-users of benzodiazepine drugs, 2408 (13.80%) had a past use, and 470 (2.70%) were current users. In BLR, individuals with past (OR 2.51, 95% CI 2.30-2.74, p < .001) or current (OR 2.36, 95% CI 1.96-2.83, p < .001) use showed a higher association with frailty as compared to individuals who were non-users. CONCLUSIONS: The use of benzodiazepine was cross-sectionally associated with frailty in older Veterans. These results suggest that screening for frailty in patients with past or current exposure to benzodiazepine medications may be necessary for proper management.

Follicular mucinosis in patients with hematologic malignancies other than mycosis fungoides: A clinicopathologic study.

BACKGROUND: Follicular mucinosis (FM), which is defined by mucin accumulation within follicular epithelium, may occur in mycosis fungoides (MF). FM without MF is occasionally reported in systemic hematologic malignancies and may be diagnostically challenging. OBJECTIVE: To describe clinicopathologic characteristics of FM in patients with hematologic malignancies other than MF. METHODS: Clinical data and histopathology features were analyzed in patients with FM and hematologic malignancies diagnosed between 1994 and 2017. RESULTS: A total of 18 patients with FM and systemic hematologic malignancies without cutaneous T-cell lymphoma (CTCL) were identified; 9 of them were discovered after hematopoietic stem cell transplantation. No patients with non-CTCL-associated FM (n = 46 [37 biopsy specimens]) developed CTCL during a mean follow-up of 4.3 years. Of the cases of CTCL associated with FM (n = 44 [31 biopsy specimens]), MF was the most common subtype (n = 38), although other CTCLs were identified. FM in patients with non-CTCL hematologic malignancies differed clinically from those with MF-associated FM, presenting most frequently with erythematous papules (P < .0001), without plaques (P <.0001), without alopecia (P = .001), and without histopathologically identified epidermal exocytosis (P = .013). LIMITATIONS: A retrospective study in a single cancer center. CONCLUSIONS: FM can present in systemic hematologic malignancies, including after hematopoietic stem cell transplantation. Papular lesional morphologic and histopathologic features may help to distinguish these cases from MF.

The association of a frailty index from laboratory tests and vital signs with clinical outcomes in hospitalized older adults.

BACKGROUND: Frailty, a state of vulnerability to stressors resulting from loss of physiological reserve due to multisystemic dysfunction, is common among hospitalized older adults. Hospital clinicians need objective and practical instruments that identify older adults with frailty. The FI-LAB is based on laboratory values and vital signs and may capture biological changes of frailty that predispose hospitalized older adults to complications. The study's aim was to assess the association of the FI-LAB versus VA-FI with hospital and post-hospital clinical outcomes in older adults. METHODS: Retrospective cohort study was conducted on Veterans aged ≥60 admitted to a VA hospital. We identified acute hospitalizations January 2011-December-2014 with 1-year follow-up. A 31-item FI-LAB was created from blood laboratory tests and vital signs collected within the first 48 h of admission and scores were categorized as low (<0.25), moderate (0.25-0.40), and high (>0.40). For each FI-LAB group, we obtained odds ratio (OR) and confidence intervals (CI) for hospital and post-hospital outcomes using multivariate binomial logistic regression. Additionally, we calculated hazard ratios (HR) and CI for all-cause in-hospital mortality comparing the high and moderate FI-LAB group with the low group. RESULTS: Patients were 1407 Veterans, mean age 72.7 (SD = 9.0), 67.8% Caucasian, 96.1% males, 47.0% (n = 661), 41.0% (n = 577), and 12.0% (n = 169) were in the low, moderate, and high FI-LAB groups, respectively. Moderate and high scores were associated with prolonged LOS, OR:1.62 (95% CI:1.29-2.03); and 3.36 (95% CI:2.27-4.99), ICU admission, OR:1.40 (95% CI:1.03-1.90); and OR:2.00 (95% CI:1.33-3.02), nursing home placement OR:2.36 (95% CI:1.26-4.44); and 5.99 (95% CI:2.83-12.70), 30-day readmissions OR:1.74 (95% CI:1.20-2.52); and 2.20 (95% CI:1.30-3.74), 30-day mortality OR: 2.51 (95% CI:1.01-6.23); and 8.97 (95% CI:3.42-23.53), 6-month mortality OR:3.00 (95% CI:1.90-4.74); and 6.16 (95% CI:3.55-10.71), and 1-year mortality OR: 2.66 (95% CI:1.87-3.79); and 4.76 (95% CI:3.00-7.54) respectively. The high FI-LAB group showed higher risk of in-hospital mortality, HR:18.17 (95% CI:4.01-80.52) with an area-under-the-curve of 0.843 (95% CI:0.75-0.93). CONCLUSIONS: High and moderate FI-LAB scores were associated with worse in-hospital and post-hospital outcomes. The FI-LAB may identify hospitalized older patients with frailty at higher risk and assist clinicians in implementing strategies to improve outcomes.

Concurrent Validity of Pictorial Fit-Frail Scale (PFFS) in Older Adult Male Veterans with Different Levels of Health Literacy.

Introduction: Frailty is a state of vulnerability characterized by multisystemic physiological decline. The Pictorial Fit Frail Scale (PFFS) is a practical, image-based assessment that may facilitate the assessment of frailty in individuals with inadequate health literacy (HL). Objective: Determine the concurrent validity and feasibility of the PFFS in older Veterans with different levels of HL and cognition. Methods: Cross-sectional study in a geriatric clinic at a Veteran Health Administration (VHA) medical center. Veterans ≥65 years old completed a HL evaluation, PFFS, FRAIL scale and cognitive screening. We assessed the associations between PFFS, FRAIL scale, and VA-Frailty Index (VA-FI), and compared PFFS and FRAIL scale accuracy with a Receiver Operating Characteristic curve, Area Under the Curve (AUC) analysis, using the VA-FI as reference. Results: Eighty-three Veterans, mean age 76.20 (SD = 6.02) years, 65.1% Caucasian, 69.9% had inadequate HL, 57.8% were frail and 20.5% had cognitive impairment. All participants completed the 43 PFFS items. There were positive correlations between PFFS and VA-FI, r = .55 (95% CI: 0.365-0.735, p < .001), and FRAIL scale, r = .673 (95% CI: 0.509-0.836, p < .001). Compared to the VA-FI, the PFFS (AUC = 0.737; 95% CI: 0.629-0.844) and FRAIL scale (AUC = 0.724;95% CI: 0.615-0.824; p < .001) showed satisfactory diagnostic accuracy. Conclusions: The PFFS is valid and feasible in evaluating frailty in older Veterans with different levels of HL and cognition.

Cryopreservation and recovery of human endometrial epithelial cells with high viability, purity, and functional fidelity.

OBJECTIVE: To develop a protocol for cryopreservation and recovery of human endometrial epithelial cells (eECs) retaining molecular and functional characteristics of endometrial epithelium in vivo. DESIGN: In vitro study using human endometrial cells. SETTING: University research laboratory. PATIENT(S): Endometrial biopsies were obtained from premenopausal women undergoing benign gynecologic procedures. INTERVENTION(S): Primary eECs were cryopreserved in 1% fetal bovine serum/10% dimethylsulfoxide in Defined Keratinocyte Serum-Free Medium (KSFM). Recovered cells were observed for endometrial stromal fibroblast (eSF) contamination and subsequently evaluated for morphology, gene expression, and functional characteristics of freshly cultured eECs and in vivo endometrial epithelium. MAIN OUTCOME MEASURE(S): Analysis of eEC morphology and the absence of eSF contamination; evaluation of epithelial-specific gene and protein expression; assessment of epithelial polarity. RESULT(S): Endometrial epithelial cells recovered after cryopreservation (n = 5) displayed epithelial morphology and expressed E-cadherin (CDH1), occludin (OCLN), claudin1 (CLDN1), and keratin18 (KRT18). Compared with eSF, recovered eECs displayed increased (P<.05) expression of epithelial-specific genes AREG, CDH1, DEFB4A, MMP7, and WNT7A, while exhibiting low-to-undetectable (P<.05) stromal-specific genes COL6A3, HOXA11, MMP2, PDGFRB, and WNT5A. Recovered eECs secreted levels of cytokines and growth factors similarly to freshly cultured eECs. Recovered eECs could form a polarized monolayer with high transepithelial electrical resistance (TER) and impermeability to small molecules, and expressed apical/basolateral localization of CDH1 and apical localization of OCLN. CONCLUSION(S): We have developed a protocol for cryopreservation of eECs in which recovered cells after thawing demonstrate morphologic, transcriptomic, and functional characteristics of human endometrial epithelium in vivo.