Purpose

Clinicians anecdotally noted that elderly patients who suffered from traumatic injuries (falls or other injuries) often re-present and are readmitted with fall injuries. Herein, we hypothesized that fall injuries and fall-related deaths and readmissions are increasing over time, and assessed whether the overall rates of death, hospital admission, and 30-day readmission due to falls increased from 2010 to 2014 in the elderly population (≥65) in the US.

Patients and methods

The WHO mortality database and the National Readmission Database (NRD) were queried to assess rates of deaths and hospital admissions and 30-day readmissions associated with fall injuries in the elderly population that presented with trauma. Descriptive statistics were obtained. The generalized linear mixed modeling (GLMM) framework was utilized to examine the relationship between fixed-effect predictor variables and the dichotomous outcome, indicating readmission within 30 days of previous discharge while accounting for hospital clustering with a random intercept.

Results

Fall-related death increased by 1.4% from 2010 to 2014. Similarly, the hospital admission rate increased by 2% and was mainly associated with increased admission of elderly 65-74 years old. Approximately 55% of the fall patients were placed in nursing facilities in 2010, and this rate increased by 3% from 2010 to 2014. Thirty-day readmission rates for fall and trauma patients remained stable from 2010 to 2014. However, the rate of fall patients readmitted within 30 days for a subsequent fall increased from 15.6% to 17.4% between 2010 and 2014.

Conclusion

Our data indicate a steady increase in deaths and admissions for fall injuries in the elderly population. Strikingly, the incidence of readmission for a subsequent fall is increasing. With the aging population, this trend is likely to continue and highlights the need for elderly social support systems and fall prevention programs.

Hidradenitis suppurativa (HS), a chronic disease of the apocrine bearing skin causing induration, pain, draining sinuses, and subcutaneous abscesses, significantly impairs patients quality of life (QOL). Full-thickness excision followed by skin grafting of the involved area can be curative. Herein, we evaluated the impact of this surgical treatment on QOL and depression symptomatology. Adult patients (≥18 years) who consented to participate filled out the dermatology quality of life (DLQI) and the Patient History Questionnaire (PHQ-9) at consent and at 1, 6, and 12 months post-initial evaluation and surgery. Demographics, HS, admission, and operative information were collected. Sixteen patients were included. Subjects were mainly white (81.3 %) and female (56.3%) with a median age of 38.2 (Interquartile range: 34.2-54.5); 62.5% were obese (BMI= 39.7 [28.4-50.6]). Half of the subjects presented with HS in 2 or more areas. Six patients were still undergoing surgeries at 6 months. One-, six-, and 12-month follow-up surveys were obtained from 14, 11, and 8 subjects for DQLI and from 14, 9, and 5 subjects for PHQ9. DLQI scores significantly decreased at 6 months compared to baseline, which indicates QOL improvement (10 [4-20] vs 15.5 [12-21.8], P = .036). Although not significant, PHQ9 scores tended to decrease. For those with the worst disease, DLQI significantly decreased at both 6 (P = .049) and 12 months (P = .047) compared to baseline. Despite a small sample size, our data suggest that aggressive surgical treatment improves the QOL of HS patients. Further studies are warranted to confirm our findings.

Background

Elderly (65 and older) fall-related injuries are a significant cause of morbidity and mortality. Although frailty predicts poor outcomes in geriatric trauma, literature comparing frailty scoring systems remains limited. Herein, we evaluated which frailty scoring system best predicts falls over time in the elderly.

Materials and methods

Acute surgical patients 65 y and older were enrolled and prospectively observed. Demographics and frailty, assessed using the FRAIL Scale, Trauma Specific Frailty Index (TSFI), and Canadian Frailty Scale (CSHA-CFS), were collected at enrollment and 3 mo intervals following discharge for 1 y. Surveys queried the total number and timing of falls. Changes in frailty over time were assessed by logistic regression and area under the curve (AUC).

Results

Fifty-eight patients were enrolled. FRAIL Scale and CSHA-CFS scores did not change over time, but TSFI scores did (P ≤ 0.01). Worsening frailty was observed using TSFI at 6 (P ≤ 0.01) and 12 mo (P ≤ 0.01) relative to baseline. Mortality did not differ based on frailty using any frailty score. Increasing frailty scores and time postdischarge was associated with increased odds of a fall. AUC estimates with 95% CI were 0.72 [0.64, 0.80], 0.81 [0.74, 0.88], and 0.76 [0.68, 0.84] for the FRAIL Scale, TSFI, and CSHA-CFS, respectively.

Conclusions

The risk of falls postdischarge were associated with increased age, time postdischarge, and frailty in our population. No scale appeared to significantly outperform the other by AUC estimation. Further study on the longitudinal effects of frailty is warranted.

Background

Race and socioeconomic status influence outcomes for adult and pediatric burn patients, yet the impact of these factors on elderly patients (Medicare eligible, 65 years of age) remains unknown.

Methods

Data pooled from three verified burn centers from 2004 to 2014 were reviewed retrospectively. Age, race, gender, percent total body surface area (%TBSA) burn, mortality, length of stay (LOS), LOS per %TBSA burn, and zip code which provided Census data on race, poverty, and education levels within a community were collected. Data were analyzed using logistic and generalized linear models in SAS version 9.4 (SAS Institute, Cary, NC, USA).

Results

Our population was mainly Caucasian (63%), African American (18%), Hispanic (7.6%), and Asian (3.5%). Mean age was 76.3 ± 8.3 years, 52.5% were male. Mean %TBSA was 9 ± 13.8%; 15% of the patients sustained an inhalation injury. The mortality rate was 14.4%. Inhalation injury was significantly associated with mortality and discharge to a skilled nursing facility (SNF) (p < 0.05). Race was significantly associated with socioeconomic disparities and affected LOS/TBSA, but not discharge to SNF or mortality on univariate analysis. Poverty level, education level, and insurance status (others vs. public) independently predicted SNF discharge, while median income and insurance type independently predicted LOS/TBSA.

Conclusion

In this elderly cohort, race did not predict standard markers of burn outcome (mortality and discharge to SNF). Socioeconomic status independently predicted LOS and discharge to SNF, suggesting a relationship between socioeconomic status and recovery from a burn injury. Better understanding of racial and socioeconomic disparities is necessary to provide equitable treatment of all patients.

We previously reported that a 4- to 6-week low-fat fish oil (LFFO) diet did not affect serum insulin-like growth factor (IGF)-1 levels (primary outcome) but resulted in lower omega-6 to omega-3 fatty acid ratios in prostate tissue and lower prostate cancer proliferation (Ki67) as compared with a Western diet. In this post hoc analysis, the effect of the LFFO intervention on serum pro-inflammatory eicosanoids, leukotriene B4 (LTB4) and 15-S-hydroxyeicosatetraenoic acid [15(S)-HETE], and the cell-cycle progression (CCP) score were investigated. Serum fatty acids and eicosanoids were measured by gas chromatography and ELISA. CCP score was determined by quantitative real-time reverse transcriptase PCR (RT-PCR). Associations between serum eicosanoids, Ki67, and CCP score were evaluated using partial correlation analyses. BLT1 (LTB4 receptor) expression was determined in prostate cancer cell lines and prostatectomy specimens. Serum omega-6 fatty acids and 15(S)-HETE levels were significantly reduced, and serum omega-3 levels were increased in the LFFO group relative to the Western diet group, whereas there was no change in LTB4 levels. The CCP score was significantly lower in the LFFO compared with the Western diet group. The 15(S)-HETE change correlated with tissue Ki67 (R = 0.48; P < 0.01) but not with CCP score. The LTB4 change correlated with the CCP score (r = 0.4; P = 0.02) but not with Ki67. The LTB4 receptor BLT1 was detected in prostate cancer cell lines and human prostate cancer specimens. In conclusion, an LFFO diet resulted in decreased 15(S)-HETE levels and lower CCP score relative to a Western diet. Further studies are warranted to determine whether the LFFO diet antiproliferative effects are mediated through the LTB4/BLT1 and 15(S)-HETE pathways.

Background

Obesity is associated with poorly differentiated and advanced prostate cancer and increased mortality. In preclinical models, caloric restriction delays prostate cancer progression and prolongs survival. We sought to determine if weight loss (WL) in men with prostate cancer prior to radical prostatectomy affects tumor apoptosis and proliferation, and if WL effects other metabolic biomarkers.

Methods

In this Phase II prospective trial, overweight and obese men scheduled for radical prostatectomy were randomized to a 5-8 week WL program consisting of standard structured energy-restricted meal plans (1200-1500 Kcal/day) and physical activity or to a control group. The primary endpoint was apoptotic index in the radical prostatectomy malignant epithelium. Secondary endpoints were proliferation (Ki67) in the radical prostatectomy tissue, body weight, body mass index (BMI), waist to hip ratio, body composition, and serum PSA, insulin, triglyceride, cholesterol, testosterone, estradiol, leptin, adiponectin, interleukin 6, interleukin 8, insulin-like growth factor 1, and IGF binding protein 1.

Results

In total 23 patients were randomized to the WL intervention and 21 patients to the control group. Subjects in the intervention group had significantly more weight loss (WL:-3.7 ± 0.5 kg; Control:-1.6 ± 0.5 kg; p = 0.007) than the control group and total fat mass was significantly reduced (WL:-2.1 ± 0.4; Control: 0.1 ± 0.3; p = 0.015). There was no significant difference in apoptotic or proliferation index between the groups. Among the other biomarkers, triglyceride, and insulin levels were significantly decreased in the WL compared with the control group.

Conclusions

In summary, this short-term WL program prior to radical prostatectomy resulted in significantly more WL in the intervention vs. the control group and was accompanied by significant reductions in body fat mass, circulating triglycerides, and insulin. However, no significant changes were observed in malignant epithelium apoptosis or proliferation. Future studies should consider a longer term or more intensive weight loss intervention.

Calorie restriction (CR) inhibits prostate cancer progression, partially through modulation of the IGF axis. IGF-1 receptor (IGF-1R) blockade reduces prostate cancer xenograft growth. We hypothesized that combining calorie restriction with IGF-1R blockade would have an additive effect on prostate cancer growth. Severe combined immunodeficient mice were subcutaneously injected with 22Rv1 cells and randomized to: (1) Ad libitum feeding/intraperitoneal saline (Ad-lib); (2) Ad-lib/20 mg/kg twice weekly, intraperitoneal ganitumab [anti-IGF-1R antibody (Ad-lib/Ab)]; (3) 40% calorie restriction/intraperitoneal saline (CR); (4) CR/ intraperitoneal ganitumab, (CR/Ab). CR and ganitumab treatment were initiated one week after tumor injection. Euthanasia occurred 19 days post treatment. Results showed that CR alone decreased final tumor weight, plasma insulin and IGF-1 levels, and increased apoptosis. Ganitumab therapy alone reduced tumor growth but had no effect on final tumor weight. The combination therapy (CR/Ab) further decreased final tumor weight and proliferation, increased apoptosis in comparison to the Ad-lib group, and lowered plasma insulin levels relative to the Ad-lib and Ad-lib/Ab groups. Tumor AKT activation directly correlated with plasma IGF-1 levels. In conclusion, whereas ganitumab therapy modestly affected 22Rv1 tumor growth, combining IGF-1R blockade with calorie restriction resulted in a significant decrease in final tumor weight and improved metabolic profile.

Background

Benign human prostate tubule-initiating cells (TIC) and aggressive prostate cancer display common traits, including tolerance of low androgen levels, resistance to apoptosis, and microenvironment interactions that drive epithelial budding and outgrowth. TIC can be distinguished from epithelial and stromal cells that comprise prostate tissue via cell sorting based upon Epcam, CD44, and CD49f antigenic profiles. Fetal prostate epithelial cells (FC) possess a similar antigenic profile to adult TIC and are capable of inducing tubule formation. To identify the TIC niche in human prostate tissue, differential keratin (KRT) expression was evaluated.

Results

Gene expression data generated from Affymetrix Gene Chip human U133 Plus 2.0 array of sorted adult and fetal epithelial cells revealed KRT13 to be significantly enriched in FC and TIC compared to basal cells (BC) and luminal cells (LC) (p<0.001). Enriched KRT13 expression was confirmed by RT-PCR and cytospin immunostaining. Immunohistochemical analysis of KRT13 expression revealed rare KRT13+ epithelia throughout prostatic ducts/acini in adult tissue specimens and differentiated tubules in 24-week recombinant grafts, In contrast, abundant KRT13 expression was observed in developing ducts/acini in fetal prostate and cord-like structures composing 8-week recombinant grafts. Immunostaining of a prostate tissue microarray revealed KRT13+ tumor foci in approximately 9% of cases, and this subset displayed significantly shorter time to recurrence (p = 0.031), metastases (p = 0.032), and decreased overall survival (p = 0.004). Diagnostic prostate needle biopsies (PNBX) from untreated patients with concurrent bone metastases (clinical stage M1) displayed KRT13+ tumor foci, as did bone metastatic foci.

Conclusions

The expression profile of KRT13 in benign fetal and adult prostate tissue and in recombinant grafts, as well as the frequency of KRT13 expression in primary and metastatic prostate cancer indicates that it may be a marker of a stem/progenitor-like cell state that is co-opted in aggressive tumor cells. KRT13 is enriched in benign stem-like cells that display androgen-resistance, apoptosis-resistance, and branching morphogenesis properties. Collectively our data demonstrate that KRT13 expression is associated with poor prognosis at multiple stages of disease progression and may represent an important biomarker of adverse outcome in patients with prostate cancer.

Objectives

To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19.

Design

Retrospective observational study.

Setting

Multicenter, international COVID-19 registry.

Subjects

Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021.

Interventions

None.

Measurements and main results

Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001).

Conclusions

Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients.