Left Atrial Appendage Ligation Using the AtriClip Device: Single-Center Study of Device Safety and Efficacy.

Objective: Left atrial appendage (LAA) occlusion at the time of cardiac surgery in patients with atrial fibrillation has been shown to reduce the incidence of postoperative embolic stroke. However, the optimal method for LAA occlusion is not universally accepted. We sought to examine the safety and effectiveness of LAA occlusion with the AtriClip epicardial occlusion device. Methods: Cardiac surgical patients with atrial fibrillation who underwent LAA AtriClip placement were evaluated prospectively. Clip placement and clinical outcomes were examined after 1 year of follow-up with transesophageal echocardiography (TEE). The presence of a 10 mm or greater residual pouch, presence of flow into the LAA, or device-related thrombus (DRT) were considered failures. Results: Ninety-seven patients were analyzed. The mean CHA2DS2-VASc score was 2.4 ± 1.4. The postoperative follow-up period ranged from 366 to 1,693 days (mean 685 days or 1.87 years). Seventy-four AtriClips were placed with video-assisted thoracic surgery, whereas 23 were placed via sternotomy or thoracotomy. Successful closure was found in 96% (93 of 97) of patients at follow-up. Failure occurred in 4 patients. No clip migration or DRT was seen on 3-dimensional imaging. Of all 97 patients, 76 (78%) were on presurgical oral anticoagulation, whereas 5 (5.1%) were on postprocedure oral anticoagulation. There were no postoperative thromboembolic events at the time of the study TEE. Conclusions: The AtriClip epicardial surgical occlusion device can provide an excellent rate of successful closure of the LAA during surgical ablation procedures without DRT.

Hybrid ablation of persistent and long-standing persistent atrial fibrillation with depressed ejection fraction: A single-center observational study.

Objective: The relationship between atrial fibrillation (AF) and heart failure with depressed ejection fraction (EF) is complex. AF-related tachycardia-mediated cardiomyopathy (TMC) can lead to worsening EF and clinical heart failure. We sought to determine whether a hybrid team ablation approach (HA) can be performed safely and restore normal sinus rhythm in patients with TMC and heart failure and to delineate the effect on heart failure. Methods: We retrospectively analyzed patients with nonparoxysmal (ie, persistent and long-standing persistent) AF-related TMC with depressed left ventricular EF (LVEF ≤40%) and heart failure (New York Heart Association [NYHA] class ≥2) who underwent HA between 2013 and 2018 and had at least 1 year of follow-up. Pre-HA and post-HA echocardiograms were compared for LVEF and left atrial (LA) size. Rhythm success was defined as <30 seconds in AF/atrial flutter/atrial tachycardia without class I or III antiarrhythmic drugs. Results are expressed as mean ± SD and 95% confidence interval (CI) of the mean. Results: Forty patients met the criteria for inclusion in our analysis. The mean patient age was 67 ± 9.4 years. The majority of patients had long-standing persistent AF (26 of 40; 65%), and the remainder had persistent AF (14 of 40; 35%). All patients had NYHA class II or worse heart failure (NYHA class II, 36 of 40 [90%]; NYHA class III, 4 of 40 [10%]). The mean time in AF pre-HA was 5.6 ± 6.7 years. All patients received both HA stages. No deaths or strokes occurred within 30 days. Three new permanent pacemakers (7.5%) were placed. Rhythm success was achieved in >60% of patients during a mean 3.5 ± 1.9 years of follow-up. LVEF improved significantly by 12.0% ± 12.5% (95% CI, 7.85%-16.0%; P < .0001), and mean LA size decreased significantly by 0.40 cm ± 0.85 cm (95% CI, 0.69-0.12 cm; P < .01), with a mean of 3.0 ± 1.5 years between pre-HA and post-HA echocardiography. NYHA class improved significantly after HA (mean pre-HA NYHA class, 2.1 ± 0.3 [95% CI, 2.0-2.2]; mean post-HA NYHA class, 1.5 ± 0.6 [95% CI, 1.3-1.7]; P < .0001). Conclusions: Thoracoscopic HA of AF in selected patients with TMC heart failure is safe and can result in rhythm success with structural heart changes, including improvements in LVEF and LA size.

Systemically Administered Sindbis Virus in Combination with Immune Checkpoint Blockade Induces Curative Anti-tumor Immunity.

Oncolytic viruses represent a promising form of cancer immunotherapy. We investigated the potential of Sindbis virus (SV) for the treatment of solid tumors expressing the human cancer testis antigen NYESO-1. NYESO-1 is an immunogenic antigen frequently expressed in numerous cancers, such as ovarian cancer. We show that SV expressing the tumor-associated antigen NYESO-1 (SV-NYESO1) acts as an immunostimulatory agent, inducing systemic and rapid lymphocyte activation, leading to a pro-inflammatory environment. SV-NYESO1 treatment combined with anti-programmed death 1 (anti-PD-1) markedly augmented the anti-tumor immunity in mice over the course of treatment, resulting in an avid systemic and intratumoral immune response. This response involved reduced presence of granulocytic myeloid-derived suppressor cells in tumors and an increase in the activation of splenic and tumor-infiltrating T cells. Combined therapy also induced enhanced cytotoxic activity of T cells against NYESO-1-expressing tumors. These results were in line with an observed inverse correlation between T cell activation and tumor growth. Finally, we show that combined therapy resulted in complete clearance of NYESO-1-expressing tumors in vivo and led to long-term protection against recurrences. These findings provide a rationale for clinical studies of SV-NYESO1 combined with immune checkpoint blockade anti-PD-1 to be used in the treatment of NYESO-1-expressing tumors.

Thoracoscopic Left Atrial Appendage Clipping: A Multicenter Cohort Analysis.

OBJECTIVES: This study sought to document the closure rate, safety, and stroke rate after thoracoscopic left atrial appendage (LAA) clipping. BACKGROUND: The LAA is the main source of stroke in patients with atrial fibrillation, and thoracoscopic clipping may provide a durable and safe closure technique. METHODS: The investigators studied consecutive patients undergoing clipping as part of a thoracoscopic maze procedure in 4 referral centers (the Netherlands and the United States) from 2012 to 2016. Completeness of LAA closure was assessed by either computed tomography (n = 100) or transesophageal echocardiography (n = 122). The primary outcome was complete LAA closure (absence of residual LAA flow and pouch <10 mm). The secondary outcomes were 30-day complications; the composite of ischemic stroke, hemorrhagic stroke, or transient ischemic attack; and all-cause mortality. RESULTS: A total of 222 patients were included, with a mean age of 66 ± 9 years, and 68.5% were male. The mean CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65 to 74 years, sex category [female]) score was 2.3 ± 1.0. Complete LAA closure was achieved in 95.0% of patients. There were no intraoperative or clip-related complications, and the overall 30-day freedom from any complication rate was 96.4%. The freedom from cerebrovascular events after surgery was 99.1% after median follow-up of 20 months (interquartile range: 14 to 25 months; 369 patient-years of follow-up), and overall survival was 98.6%. The observed rate of cerebrovascular events after LAA clipping was low (0.5 per 100 patient-years). CONCLUSIONS: LAA clipping during thoracoscopic ablation is a feasible and safe technique for closure of the LAA in patients with atrial fibrillation. The lower than expected rate of cerebrovascular events after deployment was likely multifactorial, including not only LAA closure, but also the effect of oral anticoagulation and rhythm control.

Association of Calf Muscle Pump Stimulation With Sleep Quality in Adults.

Prevention of lower extremity fluid pooling (LEFP) is associated with improved sleep quality. Physical activity and compression stockings are non-invasive methods used to manage LEFP, but both are associated with low adherence. Calf muscle pump (CMP) stimulation is an alternative and more convenient approach. Convenience sampling was used to recruit 11 participants between ages 45 and 65 with poor sleep quality. A within-person single-group pre-test-post-test design was used to evaluate changes in sleep quality, daytime sleepiness, and functional outcomes sensitive to impaired sleep as measured by the Pittsburgh Sleep Quality Index (PSQI), Functional Outcomes of Sleep Questionnaire, and Epworth Sleepiness Scale after 4 weeks of CMP stimulation. Statistical analysis included effect size (ES) calculations. After daily use of CMP stimulation, participants demonstrated improvement in overall sleep quality (ES = -.97) and a large reduction in daily disturbance from poor sleep (ES = -1.25). Moderate improvements were observed in daytime sleepiness (ES = -.53) and functional outcomes sensitive to sleepiness (ES = .49). Although causality could not be determined with this study design, these results support further research to determine whether CMP stimulation can improve sleep quality. © 2016 Wiley Periodicals, Inc.

Calf muscle pump stimulation as a means to reduce symptoms of fibromyalgia syndrome.

Fibromyalgia (FM) is a debilitating chronic condition that often affects women in midlife with widespread pain that interrupts attempts to exercise. The purpose of this pilot study was to test the efficacy of calf muscle pump (CMP) stimulation as an adjuvant therapy for FM by (1) assessing the correlation of the level of symptoms, as measured by the revised Fibromyalgia Impact Questionnaire (FIQR), and blood pressure (BP), (2) measuring change in mean FIQR scores for subjects who use a CMP-stimulation device for 12 weeks, and (3) measuring the correlation of total device usage and the level of symptoms as measured by the FIQR. The 29 male and female participants (mean age = 47.3 years) were screened using the Widespread Pain Index (WPI), Symptom Severity (SS) score, and the FIQR. Participants were contacted weekly, and progress was assessed using the WPI, SS score, and the FIQR as well as general questions regarding responses to CMP stimulation. The attrition rate was high, which is not uncommon in studies of patients with FM. We found that diastolic BP was significantly inversely correlated with baseline FIQR scores during quiet sitting. Further, 12 weeks of CMP stimulation was associated with significant improvement in average FIQR scores at a rate of approximately -1.5 points per week (R (2) = .9; p ≤ .0001). Total device usage was strongly and inversely correlated with baseline FIQR scores (R (2) = .43; p = .02). These findings suggest that CMP stimulation may provide an additional treatment option for individuals with FM who are challenged to perform traditional forms of exercise.

Molecular phenotype predicts sensitivity of squamous cell carcinoma of the head and neck to epidermal growth factor receptor inhibition.

Despite nearly universal expression of the wild-type epidermal growth factor receptor (EGFR) and reproducible activity of EGFR inhibitors in patients with squamous cell carcinoma of the head and neck (SCCHN), the majority of patients will not have objective responses. The mechanisms of this intrinsic resistance are not well established. We hypothesized that sensitivity to EGFR inhibitors can be predicted based on the inhibitors' effects on downstream signaling. Cell viability assays were used to assess sensitivity to the EGFR inhibitor gefitinib (ZD1839) in 8 SCCHN cell lines. Fluorescence in-situ hybridization showed the two most sensitive lines to be highly gene-amplified for EGFR. Western blotting confirmed that phosphoEGFR was inhibited at low concentrations of gefitinib in all lines tested. Phosphorylation of downstream signaling protein AKT was inhibited in sensitive lines while inhibition of phosphoERK displayed no relationship to gefitinib efficacy. Phosphatase and tensin homolog (PTEN) expression was evident in all cell lines. Activating PIK3CA mutations were found in two resistant cell lines where pAKT was not inhibited by gefitinib. In resistant cell lines harboring PIK3CA mutations, a PI3K inhibitor, LY294002, or AKT siRNA reduced cell viability with an additive effect demonstrated in combination with gefitinib. Additionally, LY294002 alone and in combination with gefitinib, was effective at treating PIK3CA mutated tumors xenografted into nude mice. Taken together this suggests that constitutively active AKT is a mechanism of intrinsic gefitinib resistance in SCCHN. This resistance can be overcome through targeting of the PI3K/AKT pathway in combination with EGFR inhibition.

Raising stroke awareness among rural dwellers with a Facts for Action to Stroke Treatment-based educational program.

Stroke is the third leading cause of death in the United States with 780,000 new and/or recurrent strokes each year. Interventions aimed at the onset of stroke symptoms have been successful in decreasing long-term neurological deficits; however, providing the prompt medical interventions in rural areas involves unique challenges. To decrease time-to-treatment in rural areas, education about symptoms of stroke and the need for immediate medical attention are critical. The objective of this study was to measure the effectiveness of the Facts for Action to Stroke Treatment (FAST)-based educational intervention program focused on the improving knowledge about stroke of 402 rural-dwelling adults. Using a paired means t test, the participants had a significant increase in knowledge from pretest to posttest (p = .000). Of those, 215 subjects participated in 2-month follow-up testing with the paired t test showing that the increased score from pretest to 2-month follow-up remained significant (p = .000). The authors concluded that the FAST-based program was an effective tool to use when teaching recognition of stroke symptoms and the need for immediate medical intervention to rural adults.

Feasibility of treatment of lower limb edema with calf muscle pump stimulation in chronic heart failure.

BACKGROUND: Persons with chronic heart failure may exhibit a decrease in functional ability related to lower extremity edema in spite of optimal diuretic therapy and salt restrictions. AIM: The aim of this pilot prospective clinical study was to test the feasibility of using exogenous calf muscle pump stimulation to decrease lower leg edema and thus improve functional status and quality of life. METHODS: Six subjects entered into this study and agreed to use the intervention 30 min/day for one month. DXA was used to assess lower extremity composition. RESULTS: Device use averaged approximately 1 h/day and resulted in a reduction in the lean mass of the legs of 0.5 kg (range = 0.08-1.0 L; p = 0.03). Linear regression analysis of reduction of lower limb edema against daily usage suggests that increased utilization of calf muscle pump stimulation was associated with increased water losses, although this trend was not significant (R(2 = 0.4, p = 0.18). CONCLUSION: This pilot indicates that exogenous calf muscle pump stimulation could be a useful and safe addition to the patients' treatment regimes, but further studies testing a more typical population with heart failure is warranted.

Influence of seated rocking on blood pressure in the elderly: a pilot clinical study.

Patients with Alzheimer's disease (AD) who rock for 1-2 hr per day in a rocking chair demonstrate significant improvements in depression, anxiety, and balance and a decrease in pain medication usage; however, the underlying basis for their responses remains unclear. Rocking with plantar flexion uses the calf muscles, enhancing lower limb fluid return to the heart, which should increase blood pressure (BP) and may, then, also increase cerebral perfusion. Accordingly, we tested the efficacy of rocking activity for increasing BP in healthy, older persons. In a pilot laboratory study of 24 healthy, White men and women aged 55-87 years, we observed that 30 min of steady rocking led to an average 12 mmHg increase in systolic blood pressure (SBP, p < .001) and a 3.6 mmHg average increase in diastolic blood pressure (DBP, p < .001). To determine the effect of using this intervention in a nonclinical setting, we tested a similar group of 7 participants at a senior center. In this setting, we observed an average increase in SBP of 27 mmHg (p < .001) and in DBP of 2.5 mmHg (p < .001) after 30 min of rocking. In a subgroup (n = 8) of hypotensive individuals (SBP < 110 mmHg after sitting quietly for 30 min) extracted from both settings, rocking raised the average SBP from <100 mmHg to approximately 120 mmHg. These results are consistent with the hypothesis that rocking can increase BP and, therefore, may enhance cerebral perfusion. This observation may play a fundamental role in designing nursing interventions focused on improvement of symptoms associated with AD.

Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: a phase I/II study.

BACKGROUND: Epidermal growth factor receptor (EGFR) is a validated target in squamous-cell carcinoma of the head and neck, but in patients with recurrent or metastatic disease, EGFR targeting agents have displayed modest efficacy. Vascular endothelial growth factor (VEGF)-mediated angiogenesis has been implicated as a mechanism of resistance to anti-EGFR therapy. In this multi-institutional phase I/II study we combined an EGFR inhibitor, erlotinib, with an anti-VEGF antibody, bevacizumab. METHODS: Between April 15, 2003, and Jan 27, 2005, patients with recurrent or metastatic squamous-cell carcinoma of the head and neck were enrolled from seven centres in the USA and were given erlotinib (150 mg daily) and bevacizumab in escalating dose cohorts. The primary objectives in the phase I and II sections, respectively, were to establish the maximum tolerated dose and dose-limiting toxicity of bevacizumab when administered with erlotinib and to establish the proportion of objective responses and time to disease progression. Pretreatment serum and tissues were collected and analysed by enzyme-linked immunosorbent assay and immunofluorescence quantitative laser analysis, respectively. This study was registered with ClinicalTrials.gov, number NCT00055913. FINDINGS: In the phase I section of the trial, ten patients were enrolled in three successive cohorts with no dose-limiting toxic effects noted. 46 patients were enrolled in the phase II section of the trial (including three patients from the phase I section) on the highest dose of bevacizumab (15 mg/kg every 3 weeks). Two additional patients were accrued beyond the protocol-stipulated 46, leaving a total of 48 patients for the phase II assessment. The most common toxic effects of any grade were rash and diarrhoea (41 and 16 of 48 patients, respectively). Three patients had serious bleeding events of grade 3 or higher. Seven patients had a response, with four showing a complete response allowing rejection of the null hypothesis. Median time of overall survival and progression-free survival (PFS) were 7.1 months (95% CI 5.7-9.0) and 4.1 months (2.8-4.4), respectively. Higher ratios of tumour-cell phosphorylated VEGF receptor-2 (pVEGFR2) over total VEGFR2 and endothelial-cell pEGFR over total EGFR in pretreatment biopsies were associated with complete response (0.704 vs 0.386, p=0.036 and 0.949 vs 0.332, p=0.036, respectively) and tumour shrinkage (p=0.007 and p=0.008, respectively) in a subset of 11 patients with available tissue. INTERPRETATION: The combination of erlotinib and bevacizumab is well tolerated in recurrent or metastatic squamous-cell carcinoma of the head and neck. A few patients seem to derive a sustained benefit and complete responses were associated with expression of putative targets in pretreatment tumour tissue.

Ultrasonometric profiling of incidence and risk of osteoporosis in rural women.

BACKGROUND: It is estimated that over 200 million people worldwide have osteoporosis. The prevalence of osteoporosis is continuing to escalate with the increasingly aging population. The major complication of osteoporosis is an increase in fragility fractures leading to morbidity, mortality, and decreased quality of life. This investigation profiled the incidence and risk of osteoporosis in adult women from a rural setting using ultrasonic bone scanning technology. METHODS: Between 2001 and 2005, adult female subjects (n = 323) in the age range of 40-87 were drawn from an independent, community dwelling, convenience sample. Bone mineral density T-scores were evaluated using heel ultrasonometry. Demographic and risk factor data, Merck Osteoporosis Evaluation SCORE questionnaire data, and the Osteoporosis Risk Assessment questionnaire data were analyzed. RESULTS: Results of these scans indicate that 25% of the total population had a T-score < or = -1.0, implying a 1.5- to 2.0-fold increase in risk ratio of hip or spinal fracture for each standard deviational decrease. Age at menopause and weight had a positive correlation with T-scores. While the overall scores on the Merck SCORE questionnaire were inversely correlated to T-scores, no significant correlation was found between the Osteoporosis Risk Assessment questionnaire and T-score data. Additionally, women who had taken estrogen had significantly higher T-scores (p = 0.038) than those who had not. CONCLUSION: That approximately 25% of this sample has low bone mass or osteoporosis underscores the importance of early screening in order to develop preventative awareness and provide education on bone health management. This finding has particularly important ramifications, since the sample was rural women, who typically have limited access to diagnostic bone density procedures.

Reversal of lower limb edema by calf muscle pump stimulation.

BACKGROUND: Peripheral edema (PE) is commonly coupled with heart failure, restrictive cardiomyopathy, nephrotic syndrome, renal failure, and hypoproteinemia. Diuretics and/or limb elevation, although commonly prescribed to treat PE, are often insufficient to remove sufficient fluid to prevent complications. We assessed the ability of the calf muscle pump (CMP) stimulation to reverse PE. METHODS: Fluid volume was evaluated by air plethysmography in the right legs of 54 adult women (mean age 46.7 +/- 1.5 years) following venous status assessment. Change in calf volume was assessed during 30 minutes of quiet sitting, followed by 30 minutes of sitting with CMP stimulation via micromechanical stimulation of the plantar surface. RESULTS: Leg volume changes demonstrated a bimodal distribution. Leg volume decreased during quiet sitting in 56% of the study group, whereas in 44% of the group, significant lower leg fluid pooling was evident (increase in calf volume of 14.0 +/- 0.3 mL/h). CMP stimulation reversed the fluid pooling in the edematous group (-2.7 +/- 0.1 mL/h) and was able to accelerate fluid removal in the nonedematous group. CONCLUSIONS: Approximately two fifths of adult women experience substantial pooling when their lower limbs are maintained in a dependent position. Lower-extremity edema exhibited by these women may primarily be due to inadequate calf muscle tone because exogenous stimulation of the CMP was sufficient to halt and reverse fluid pooling. Whether CMP stimulation would provide a means to treat PE in individuals with edema-related health complications, such as congestive heart failure, merits further investigation.

Protein kinase C zeta mediates epidermal growth factor-induced growth of head and neck tumor cells by regulating mitogen-activated protein kinase.

Protein kinase C (PKC) zeta has been implicated as a mediator of epidermal growth factor (EGF) receptor (EGFR) signaling in certain cell types. Because EGFR is ubiquitously expressed in squamous cell carcinomas of the head and neck (SCCHN) and plays a key role in tumor progression, we determined whether PKCzeta is required for tumor cell proliferation and viability. Examination of total and phosphorylated PKCzeta expression in normal oral mucosa, dysplasia, and carcinoma as well as SCCHN tumor cell lines revealed a significant increase in activated PKCzeta expression from normal to malignant tissue. PKCzeta activity is required for EGF-induced extracellular signal-regulated kinase (ERK) activation in both normal human adult epidermal keratinocytes and five of seven SCCHN cell lines. SCCHN cells express constitutively activated EGFR family receptors, and inhibition of either EGFR or mitogen-activated protein kinase (MAPK) activity suppressed DNA synthesis. Consistent with this observation, inhibition of PKCzeta using either kinase-dead PKCzeta mutant or peptide inhibitor suppressed autocrine and EGF-induced DNA synthesis. Finally, PKCzeta inhibition enhanced the effects of both MAPK/ERK kinase (U0126) and broad spectrum PKC inhibitor (chelerythrine chloride) and decreased cell proliferation in SCCHN cell lines. The results indicate that (a) PKCzeta is associated with SCCHN progression, (b) PKCzeta mediates EGF-stimulated MAPK activation in keratinocytes and SCCHN cell lines, (c) PKCzeta mediates EGFR and MAPK-dependent proliferation in SCCHN cell lines; and (d) PKCzeta inhibitors function additively with other inhibitors that target similar or complementary signaling pathways.

Reversal of lower limb venous and lymphatic pooling by passive non-invasive calf muscle pump stimulation.

Our preliminary data indicate that exogenous plantar micromechanical stimulation at 45 Hz applied at the plantar surface can prevent tachycardia and blood pressure depression associated with immobility, consistent with improvement in venous and lymphatic fluid return delivered by increased calf muscle activity. In this study, instantaneous beat-to-beat systolic blood pressure of thirty four healthy adult women participants (n=34; age range: 35-78 years) were assessed non-invasively using servo-controlled infra-red finger arterial plethysmography, for 30 minutes in the supine position, followed by 30 minutes in the seated position without plantar stimulation, and lastly for 30 minutes in the seated position with the application of a 45 Hz plantar stimulus (50 microm, p-p). Thirty minutes of supine rest resulted in an average increase of 15 mmHg in systolic pressure. During the 30 minutes of upright sitting regimen, two distinct sub-populations were observed. One group (n=18; "hypotensives") experienced a depression of approximately 15 mmHg in systolic pressure, while the other group (n=16; "normotensives and hypertensives") experienced an elevation in the systolic pressure by approximately 8 mmHg. The subsequent 30 minute application of plantar stimulus reversed the pressure drop in hypotensives and elevated the systolic pressure by approximately 20 mmHg in all the subjects. Plantar-based exogenous micromechanical vibration may be an effective approach for reversal of blood pressure depression associated with the physical stress of immobility over a long term, consistent with enhanced venous and lymphatic fluid return delivered via improved calf muscle contractility.

Ultrasonometric profiling of incidence and risk of osteoporosis on rural women.

It is estimated that over 200 million people worldwide have osteoporosis. The prevalence of osteoporosis is continuing to escalate with the increasingly elderly population. The major complication of osteoporosis is an increase in fragility fractures leading to morbidity, mortality, and decreased quality of life. This investigation aimed at profiling the incidence and risk of osteoporosis in adult women from a rural setting using ultrasonic bone scanning technology. Peri- and postmenopausal female subjects (n=234) were drawn from a convenience sample. After a non-radiative dual X-ray absorptiometric scanning, the bone mineral density was measured from the heel of the subjects using bone ultrasonometry, and their T-scores were recorded. Results of these scans indicate that in adult women in the age range of 32 and 87, 23.5% of the population had a heel ultrasonic T-score < or =1.0, implying a 1.5 to 2.0 fold increase in risk ratio of hip or spinal fracture for each standard deviational decrease. Age at menopause was positively correlated with T-scores (p= 0.032); the higher the age at menopause, the higher the T scores. Additionally, women who had taken estrogen had significantly higher T-scores (p=0.038) than those who had not. That approximately 25% of this sample has low bone mass or osteoporosis underscores the importance of early screening in order to develop awareness and provide education on bone health management.

Phase II trial of gefitinib 250 mg daily in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

PURPOSE: An objective response rate of 11% was reported in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with 500 mg daily gefitinib although the recommended dose in lung cancer is 250 mg. This study evaluated the efficacy and toxicity of 250 mg daily gefitinib in patients with recurrent and/or metastatic SCCHN. EXPERIMENTAL DESIGN: Phase II trial with objective response rate as the primary end point. Measurements of quality of life and levels of serum vascular endothelial growth factor and transforming growth factor-alpha were assessed before and during therapy. RESULTS: In 70 patients, 1 (1.4%) partial response was observed. Median progression-free survival and overall survival were 1.8 and 5.5 months, respectively. Quality of life scores improved transiently during the first weeks of therapy before returning to baseline. Median vascular endothelial growth factor and transforming growth factor-alpha levels were above the normal range but were not predictive of outcome. Four patients experienced grade 3 drug-related adverse events. Rash of any grade was observed in 64% of subjects. Correlation between disease control (partial response + stable disease), progression-free survival, and overall survival and grade of cutaneous toxicity was observed (P = 0.001, 0.001, and 0.008 respectively). CONCLUSIONS: Gefitinib monotherapy at 250 mg in recurrent and/or metastatic SCCHN seems to have less activity than was previously observed for 500 mg daily. A dose-response relationship may exist for this agent in SCCHN and grade of cutaneous toxicity attributable to gefitinib is a clinical predictor of better outcome.