Associations of prognostic-awareness-transition patterns with emotional distress and quality of life during terminally ill cancer patients' last 6 months of life.

OBJECTIVE: Unprecedently investigate associations of prognostic-awareness-transition patterns with (changes in) depressive symptoms, anxiety symptoms, and quality of life (QOL) during cancer patients' last 6 months. METHODS: In this secondary analysis study, 334 cancer patients in their last 6 months transitioned between four prognostic-awareness states (unknown and not wanting to know, unknown but wanting to know, inaccurate awareness, and accurate awareness), thus constituting three transition patterns: maintaining-accurate-, gaining-accurate-, and maintaining-inaccurate/unknown prognostic awareness. A multivariate hierarchical linear model evaluated associations of the transition patterns with depressive symptoms, anxiety symptoms, and QOL determined at final assessment and by mean difference between the first and last assessment. RESULTS: At the last assessment before death, the gaining-accurate-prognostic-awareness group reported higher levels of depressive symptoms (estimate [95% confidence interval] = 1.59 [0.35-2.84]) and the maintaining- and gaining-accurate-prognostic-awareness groups suffered more anxiety symptoms (1.50 [0.44-2.56]; 1.42 [0.13-2.71], respectively) and poorer QOL (-7.07 [-12.61 to 1.54]; -11.06 [-17.76 to -4.35], respectively) than the maintaining-inaccurate/unknown-prognostic-awareness group. Between the first and last assessment, the maintaining- and gaining-accurate-prognostic-awareness groups' depressive symptoms (1.59 [0.33-2.85]; 3.30 [1.78-4.82], respectively) and QOL (-5.04 [-9.89 to -0.19]; -8.86 [-14.74 to -2.98], respectively) worsened more than the maintaining-inaccurate/unknown-prognostic-awareness group, and the gaining-accurate-prognostic-awareness group's depressive symptoms increased more than the maintaining-accurate-prognostic-awareness group (1.71 [0.42-3.00]). CONCLUSIONS: Unexpectedly, patients who maintained/gained accurate prognostic awareness suffered more depression, anxiety, and poorer QOL at end of life. Promoting accurate prognostic awareness earlier in the terminal-cancer trajectory should be supplemented with adequate psychological care to alleviate patients' emotional distress and enhance QOL. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01912846.

Unexpected systolic anterior motion of the mitral valve-related hypoxemia during transurethral resection of the prostate under spinal anesthesia: a case report.

BACKGROUND: Dynamic obstruction of the left ventricular outflow tract resulting from systolic anterior motion of the mitral valve can be an unexpected cause of acute and severe perioperative hypotension in noncardiac surgery. We report a patient undergoing spinal anesthesia for transurethral resection of the prostate who experienced sudden hypoxemia caused by systolic anterior motion-induced mitral regurgitation but with a clinically picture simulating fluid overload. CASE PRESENTATION: An 83-year-old man with a history of hypertension was scheduled for transurethral resection of the prostate. One hour after spinal anesthesia, he developed acute restlessness and dyspnea, with pink frothy sputum and progressive hypoxemia. Slight hypertension was noted, and an electrocardiogram showed atrial fibrillation with a rapid ventricular response. Furosemide and nitroglycerin were thus administered for suspected fluid overload or transurethral resection of the prostate syndrome; however, he then became severely hypotensive. After tracheal intubation, intraoperative transesophageal echocardiography was promptly performed, which revealed an empty hypercontractile left ventricle, significant mitral regurgitation and mosaic flow signal in the left ventricular outflow tract. Following aggressive fluid therapy, his hemodynamic changes stabilized. Repeat echocardiography in intensive care unit confirmed the presence of systolic anterior motion of the anterior mitral leaflet obstructing the left ventricular outflow tract. We speculate that pulmonary edema was induced by systolic anterior motion-associated mitral regurgitation and rapid atrial fibrillation, and the initial management had worsened his hypovolemia and provoked left ventricular outflow tract obstruction and hemodynamic instability. CONCLUSIONS: Pulmonary edema caused by systolic anterior motion of the mitral valve can be difficult to clinically differentiate from that induced by fluid overload. Therefore, bedside echocardiography is paramount for timely diagnosis and prompt initiation of appropriate therapy in the perioperative care setting.

Associations of prognostic-awareness-transition patterns with end-of-life care in cancer patients' last month.

PURPOSE: Cancer patients heterogeneously develop prognostic awareness, and end-of-life cancer care has become increasingly aggressive to the detriment of patients and healthcare sustainability. We aimed to explore the never-before-examined associations of prognostic-awareness-transition patterns with end-of-life care. METHODS: Prognostic awareness was categorized into four states: (1) unknown and not wanting to know; (2) unknown but wanting to know; (3) inaccurate awareness; and (4) accurate awareness. We examined associations of our previously identified three prognostic-awareness-transition patterns during 334 cancer patients' last 6 months (maintaining accurate prognostic awareness, gaining accurate prognostic awareness, and maintaining inaccurate/unknown prognostic awareness) and end-of-life care (cardiopulmonary resuscitation, intensive care unit care, mechanical ventilation, chemotherapy/immunotherapy, and hospice care) in cancer patients' last month by multivariate logistic regressions. RESULTS: Cancer patients in the maintaining-accurate-prognostic-awareness and gaining-accurate-prognostic-awareness groups had significantly lower odds of cardiopulmonary resuscitation (adjusted odds ratio [95% confidence interval]: 0.22 [0.06-0.78]; and 0.10 [0.01-0.97], respectively) but higher odds of hospice care (3.44 [1.64-7.24]; and 3.28 [1.32-8.13], respectively) in the last month than those in the maintaining inaccurate/unknown prognostic awareness. The maintaining-accurate-prognostic-awareness group had marginally lower odds of chemotherapy or immunotherapy received than the gaining-accurate-prognostic-awareness group (0.58 [0.31-1.10], p = .096]). No differences in intensive care unit care and mechanical ventilation among cancer patients in different prognostic-awareness-transition patterns were observed. CONCLUSION: End-of-life care received in cancer patients' last month was associated with the three distinct prognostic-awareness-transition patterns. Cancer patients' accurate prognostic awareness should be facilitated earlier to reduce their risk of receiving aggressive end-of-life care, especially for avoiding chemotherapy/immunotherapy close to death. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01912846.

Effects of Renin-Angiotensin-Aldosterone System Inhibitors on Long-Term Major Adverse Cardiovascular Events in Sepsis Survivors.

Background Sepsis is known to increase morbidity and duration of hospital stay and is a common cause of mortality worldwide. Renin-angiotensin-aldosterone system inhibitors (RAASis) are commonly used to treat hypertension but are usually discontinued during hospitalization for sepsis because of concerns about renal hypoperfusion. The aim of our study was to investigate whether RAASis should be continued after discharge in sepsis survivors and to identify the effects on the clinical outcomes. Methods and Results A total of 9188 sepsis survivors aged 20 years and older who were discharged from January 1, 2012 to December 31, 2019 were included in our analyses. We further divided sepsis survivors into RAASi users and nonusers. These groups were matched by propensity scores before the outcomes of interest, including all-cause mortality and major adverse cardiac events (MACE), were examined. After propensity score matching, 3106 RAASi users and 3106 RAASi nonusers were included in our analyses. Compared with RAASi nonusers, RAASi users had lower risks of all-cause mortality (hazard ratio [HR], 0.68; 95% CI, 0.62-0.75), MACEs (HR, 0.87; 95% CI, 0.81-0.94), ischemic stroke (HR, 0.85; 95% CI, 0.76-0.96), myocardial infarction (HR, 0.74; 95% CI, 0.61-0.90), and hospitalization for heart failure (HR, 0.84; 95% CI, 0.77-0.92). Subgroup analyses stratified by admission to the ICU and the use of inotropes showed similar results. Conclusions In our study, we found that RAASi users had reduced risks of all-cause mortality and MACEs. These findings suggested a beneficial effect of RAASi use by sepsis survivors after discharge.

Factors associated with distinct prognostic-awareness-transition patterns over cancer patients' last 6 months of life.

BACKGROUND: Cancer patients may develop prognostic awareness (PA) heterogeneously, but predictors of PA-transition patterns have never been studied. We aimed to identify transition patterns of PA and their associated factors during cancer patients' last 6 months. METHODS: For this secondary-analysis study, PA was assessed among 334 cancer patients when they were first diagnosed as terminally ill and monthly till they died. PA was categorized into four states: (a) unknown and not wanting to know; (b) unknown but wanting to know; (c) inaccurate awareness; and (d) accurate awareness. The first and last PA states estimated by hidden Markov modeling were examined to identify their change patterns. Factors associated with distinct PA-transition patterns were determined by multinomial logistic regressions focused on modifiable time-varying variables assessed in the wave before the last PA assessment to ensure a clear time sequence for associating with PA-transition patterns. RESULTS: Four PA-transition patterns were identified: maintaining accurate PA (56.3%), gaining accurate PA (20.4%), heterogeneous PA (7.8%), and still avoiding PA (15.6%). Reported physician-prognostic disclosure increased the likelihood of belonging to the maintaining-accurate-PA group than to other groups. Greater symptom distress predisposed patients to be in the still-avoiding-PA than the heterogeneous PA group. Patients with higher functional dependence and more anxiety/depressive symptoms were more and less likely to be in the heterogeneous PA group and in the still-avoiding-PA group, respectively, than in the maintaining- and gaining-accurate PA groups. CONCLUSIONS: Cancer patients heterogeneously experienced PA-transition patterns over their last 6 months. Physicians' prognostic disclosure, and patients' symptom distress, functional dependence, and anxiety/depressive symptoms, all modifiable by high-quality end-of-life care, were associated with distinct PA-transition patterns.

Evaluating if an Advance Care Planning Intervention Promotes Do-Not-Resuscitate Orders by Facilitating Accurate Prognostic Awareness.

BACKGROUND: Issuing do-not-resuscitate (DNR) orders has seldom been an outcome in randomized clinical trials of advance care planning (ACP) interventions. The aim of this study was to examine whether an ACP intervention facilitating accurate prognostic awareness (PA) for patients with advanced cancer was associated with earlier use of DNR orders. PATIENTS AND METHODS: Participants (n=460) were randomly assigned 1:1 to the experimental and control arms, with 392 deceased participants constituting the final sample of this secondary analysis study. Participants in the intervention and control arms had each received an intervention tailored to their readiness for ACP/prognostic information and symptom-management education, respectively. Effectiveness in promoting a DNR order by facilitating accurate PA was determined by intention-to-treat analysis using multivariate logistic regression with hierarchical linear modeling. RESULTS: At enrollment in the ACP intervention and before death, 9 (4.6%) and 8 (4.1%) participants and 168 (85.7%) and 164 (83.7%) participants in the experimental and control arms, respectively, had issued a DNR order, without significant between-arm differences. However, participants in the experimental arm with accurate PA were significantly more likely than participants in the control arm without accurate PA to have issued a DNR order before death (adjusted odds ratio, 2.264; 95% CI, 1.036-4.951; P=.041). Specifically, participants in the experimental arm who first reported accurate PA 31 to 90 days before death were significantly more likely than their counterparts in the control arm who reported accurate PA to have issued a DNR order in the next wave of assessment (adjusted odds ratio, 13.365; 95% CI, 1.989-89.786; P=.008). Both arms issued DNR orders close to death (median, 5-6 days before death). CONCLUSIONS: Our ACP intervention did not promote the overall presence of a DNR order. However, our intervention facilitated the issuance of NDR orders before death among patients with accurate PA, especially those who reported accurate PA 31 to 90 days before death, but it did not facilitate the issuance of DNR orders earlier than their counterparts in the control arm.ClinicalTrial.gov Identification: NCT01912846.

An Individualized, Interactive, and Advance Care Planning Intervention Promotes Transitions in Prognostic Awareness States Among Terminally Ill Cancer Patients in Their Last Six Months-A Secondary Analysis of a Randomized Controlled Trial.

CONTEXT/OBJECTIVES: To examine whether an advance care planning intervention randomized controlled trial facilitates terminally ill cancer patients' transitions to accurate prognostic awareness (PA) and the time spent in the accurate PA state in patients' last six months. METHODS: Participants (N = 460) were randomized 1:1 to experimental (interactive intervention tailored to participants' readiness for advance care planning/prognostic information) and control (symptom management education) arms with similar formats. PA was categorized into four states: 1) unknown and not wanting to know; 2) unknown but wanting to know; 3) inaccurate awareness; and 4) accurate awareness. Intervention effectiveness in the two outcomes was evaluated by intention-to-treat analysis with multistate Markov modeling (effect size ≥0.2 as minimal clinically important difference). RESULTS: The final sample constituted 188 and 184 experimental arm and control arm participants who died and were repeatedly assessed, respectively. Experimental arm participants in States 1-3 had a higher probability of shifting to accurate PA (23.0%-35.4% vs. 15.2%-26.2%) than control arm participants, and all effect sizes met the minimal clinically important difference criterion (effect sizes 0.22-0.49). In their last six months, experimental arm participants spent more time in States 3 and 4 (0.18 vs. 0.08 and 2.94 vs. 2.38 months, respectively) but less time in States 1 and 2 (2.70 vs. 3.19 and 0.18 vs. 0.36 months, respectively) (effect sizes 0.11-0.19). CONCLUSION: Our intervention meaningfully facilitated participants' transition toward accurate PA and more time spent in the accurate PA state (State 4). Our intervention can help health care professionals foster cancer patients' accurate PA earlier in the terminal illness trajectory to make informed end-of-life care decisions tailored to their readiness for prognostic information.

Advance Care Planning Improves Psychological Symptoms But Not Quality of Life and Preferred End-of-Life Care of Patients With Cancer.

BACKGROUND: This study was conducted to examine whether a longitudinal advance care planning (ACP) intervention facilitates concordance between the preferred and received life-sustaining treatments (LSTs) of terminally ill patients with cancer and improves quality of life (QoL), anxiety symptoms, and depressive symptoms during the dying process. PATIENTS AND METHODS: Of 795 terminally ill patients with cancer from a medical center in Taiwan, 460 were recruited and randomly assigned 1:1 to the experimental and control arms. The experimental arm received an interactive ACP intervention tailored to participants' readiness to engage in this process. The control arm received symptom management education. Group allocation was concealed, data collectors were blinded, and treatment fidelity was monitored. Outcome measures included 6 preferred and received LSTs, QoL, anxiety symptoms, and depressive symptoms. Intervention effectiveness was evaluated by intention-to-treat analysis. RESULTS: Participants providing data had died through December 2017. The 2 study arms did not differ significantly in concordance between the 6 preferred and received LSTs examined (odds ratios, 0.966 [95% CI, 0.653-1.428] and 1.107 [95% CI, 0.690-1.775]). Participants who received the ACP intervention had significantly fewer anxiety symptoms (ß, -0.583; 95% CI, -0.977 to -0.189; P= .004) and depressive symptoms (ß, -0.533; 95% CI, -1.036 to -0.030; P= .038) compared with those in the control arm, but QoL did not differ. CONCLUSIONS: Our ACP intervention facilitated participants' psychological adjustment to the end-of-life (EoL) care decision-making process, but neither improved QoL nor facilitated EoL care honoring their wishes. The inability of our intervention to improve concordance may have been due to the family power to override patients' wishes in deeply Confucian doctrine-influenced societies such as Taiwan. Nevertheless, our findings reassure healthcare professionals that such an ACP intervention does not harm but improves the psychological well-being of terminally ill patients with cancer, thereby encouraging physicians to discuss EoL care preferences with patients and involve family caregivers in EoL care decision-making to eventually lead to patient value-concordant EoL cancer care.

An Individualized, Interactive Intervention Promotes Terminally Ill Cancer Patients' Prognostic Awareness and Reduces Cardiopulmonary Resuscitation Received in the Last Month of Life: Secondary Analysis of a Randomized Clinical Trial.

CONTEXT/OBJECTIVE: Half of advanced cancer patients do not have accurate prognostic awareness (PA). However, few randomized clinical trials (RCTs) have focused on facilitating patients' PA to reduce their life-sustaining treatments at end of life (EOL). To address these issues, we conducted a double-blinded RCT on terminally ill cancer patients. METHODS: Experimental-arm participants received an individualized, interactive intervention tailored to their readiness for advanced care planning and prognostic information. Control-arm participants received a symptom-management educational treatment. Effectiveness of our intervention in facilitating accurate PA and reducing life-sustaining treatments received, two secondary RCT outcomes, was evaluated by intention-to-treat analysis using multivariate logistic regression. RESULTS: Participants (N = 460) were randomly assigned 1:1 to experimental and control arms, each with 215 participants in the final sample. Referring to 151-180 days before death, experimental-arm participants had significantly higher odds of accurate PA than control-arm participants 61-90, 91-120, and 121-150 days before death (adjusted odds ratio [95% CI]: 2.04 [1.16-3.61], 1.94 [1.09-3.45], and 1.93 [1.16-3.21], respectively), but not one to 60 days before death. Experimental-arm participants with accurate PA were significantly less likely than control-arm participants without accurate PA to receive cardiopulmonary resuscitation (CPR) (0.16 [0.03-0.73]), but not less likely to receive intensive care unit care and mechanical ventilation in their last month. CONCLUSION: Our intervention facilitated cancer patients' accurate PA early in their dying trajectory, reducing the risk of receiving CPR in the last month. Health care professionals should cultivate cancer patients' accurate PA early in the terminal-illness trajectory to allow them sufficient time to make informed EOL-care decisions to reduce CPR at EOL.

Accurate Prognostic Awareness Facilitates, Whereas Better Quality of Life and More Anxiety Symptoms Hinder End-of-Life Care Discussions: A Longitudinal Survey Study in Terminally Ill Cancer Patients' Last Six Months of Life.

CONTEXT: Terminally ill cancer patients do not engage in end-of-life (EOL) care discussions or do so only when death is imminent, despite guidelines for EOL care discussions early in their disease trajectory. Most studies on patient-reported EOL care discussions are cross sectional without exploring the evolution of EOL care discussions as death approaches. Cross-sectional studies cannot determine the direction of association between EOL care discussions and patients' prognostic awareness, psychological well-being, and quality of life (QOL). OBJECTIVES/METHODS: We examined the evolution and associations of accurate prognostic awareness, functional dependence, physical and psychological symptom distress, and QOL with patient-physician EOL care discussions among 256 terminally ill cancer patients in their last six months by hierarchical generalized linear modeling with logistic regression and by arranging time-varying modifiable variables and EOL care discussions in a distinct time sequence. RESULTS: The prevalence of physician-patient EOL care discussions increased as death approached (9.2%, 11.8%, and 18.3% for 91-180, 31-90, and 1-30 days before death, respectively) but only reached significance in the last month. Accurate prognostic awareness facilitated subsequent physician-patient EOL care discussions, whereas better patient-reported QOL and more anxiety symptoms hindered such discussions. The likelihood of EOL care discussions was not associated with levels of physical symptom distress, functional dependence, or depressive symptoms. CONCLUSION: Physician-patient EOL care discussions for terminally ill Taiwanese cancer patients remain uncommon even when death approaches. Physicians should facilitate EOL care discussions by cultivating patients' accurate prognostic awareness early in their cancer trajectory when they are physically and psychologically competent, with better QOL, thus promoting informed and value-based EOL care decision making.

Current status of accurate prognostic awareness in advanced/terminally ill cancer patients: Systematic review and meta-regression analysis.

BACKGROUND: No systematic meta-analysis is available on the prevalence of cancer patients' accurate prognostic awareness and differences in accurate prognostic awareness by publication year, region, assessment method, and service received. AIM: To examine the prevalence of advanced/terminal cancer patients' accurate prognostic awareness and differences in accurate prognostic awareness by publication year, region, assessment method, and service received. DESIGN: Systematic review and meta-analysis. METHODS: MEDLINE, Embase, The Cochrane Library, CINAHL, and PsycINFO were systematically searched on accurate prognostic awareness in adult patients with advanced/terminal cancer (1990-2014). Pooled prevalences were calculated for accurate prognostic awareness by a random-effects model. Differences in weighted estimates of accurate prognostic awareness were compared by meta-regression. RESULTS: In total, 34 articles were retrieved for systematic review and meta-analysis. At best, only about half of advanced/terminal cancer patients accurately understood their prognosis (49.1%; 95% confidence interval: 42.7%-55.5%; range: 5.4%-85.7%). Accurate prognostic awareness was independent of service received and publication year, but highest in Australia, followed by East Asia, North America, and southern Europe and the United Kingdom (67.7%, 60.7%, 52.8%, and 36.0%, respectively; p = 0.019). Accurate prognostic awareness was higher by clinician assessment than by patient report (63.2% vs 44.5%, p < 0.001). CONCLUSION: Less than half of advanced/terminal cancer patients accurately understood their prognosis, with significant variations by region and assessment method. Healthcare professionals should thoroughly assess advanced/terminal cancer patients' preferences for prognostic information and engage them in prognostic discussion early in the cancer trajectory, thus facilitating their accurate prognostic awareness and the quality of end-of-life care decision-making.

The Implications of Tobacco Smoking on Acute Postoperative Pain: A Prospective Observational Study.

Background. The clinical importance of cigarette smoking on acute postoperative pain perception is not fully understood. Methods. To determine whether smokers who underwent major surgery need more postoperative opiate than do nonsmokers. We prospectively enrolled 407 male and 441 female participants who underwent in-hospital surgery. Current-smokers were compared with nonsmokers and past-smokers about opiate use during the first 72 h after surgery. Results. A greater proportion of males had more smoking history than females. The average age of male current-smokers is smaller than both nonsmokers and past-smokers. The surgical type (upper abdomen, lower abdomen, extremities, spine, and others) and duration of surgery have no differences between current-smokers, past-smokers, and nonsmokers. Statistically, the male current-smokers required more opiate analgesics during the first 72 h following surgery compared with the male nonsmokers and past-smokers; furthermore, the male current-smokers reported higher pain intensity when moving and at rest on day 1 after surgery. Conclusions. In this study, the male current-smokers required more morphine in the first 72 h after surgery than did the nonsmokers and past-smokers. Furthermore, smoking was more prevalent among the males than the females. Health care providers must be aware of the potential for increased narcotic requirements in male current-smokers.

Attenuation of Isoflurane Preconditioning-Induced Acute Cardioprotection in Hypertensive Hypertrophied Hearts.

OBJECTIVES: To evaluate the efficiency of isoflurane-induced anesthetic preconditioning and the role of mitochondrial manganese superoxide dismutase (MnSOD) in hypertensive hypertrophied hearts. DESIGN: A prospective animal investigation. SETTING: Medical center hospital research laboratory. PARTICIPANTS: Male spontaneously hypertensive rats (SHRs) and normotensive control Wistar-Kyoto (WKY) rats. INTERVENTIONS: All pentobarbital-anesthetized open-chest rats were subjected to a 45-minute left coronary artery occlusion followed by a 120-minute reperfusion. Before ischemia, both SHR and WKY rats were assigned randomly to receive a 30-minute exposure to 0.9% saline or 1.0 minimum alveolar concentration isoflurane. MEASUREMENTS AND MAIN RESULTS: The myocardial infarct size, assessed as a percentage of the area at risk, was significantly greater in the hypertrophied SHRs than in the WKY rats (65.3%±8.7% v 51.8%±7.2%, p<0.05). Isoflurane preconditioning appreciably reduced the infarct size in the WKY hearts (30.9%±10.5%, p<0.05) but not in the SHR hearts. MnSOD protein expression and enzymatic activity were increased drastically in response to isoflurane exposure in the hearts of the WKY rats (p<0.05) but not in the SHRs. CONCLUSIONS: Isoflurane-induced anesthetic preconditioning is attenuated in hypertensive hypertrophied hearts. This impairment may be associated with the loss of MnSOD augmentation during ischemia and reperfusion.

Role of nitric oxide synthase uncoupling at rostral ventrolateral medulla in redox-sensitive hypertension associated with metabolic syndrome.

Metabolic syndrome (MetS), which is rapidly becoming prevalent worldwide, is long known to be associated with hypertension and recently with oxidative stress. Of note is that oxidative stress in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons reside, contributes to sympathoexcitation and hypertension. This study sought to identify the source of tissue oxidative stress in RVLM and their roles in neural mechanism of hypertension associated with MetS. Adult normotensive rats subjected to a high-fructose diet for 8 weeks developed metabolic traits of MetS, alongside increases in sympathetic vasomotor activity and blood pressure. In RVLM of these MetS rats, the tissue level of reactive oxygen species was increased, nitric oxide (NO) was decreased, and mitochondrial electron transport capacity was reduced. Whereas the protein expression of neuronal NO synthase (nNOS) or protein inhibitor of nNOS was increased, the ratio of nNOS dimer/monomer was significantly decreased. Oral intake of pioglitazone or intracisternal infusion of tempol or coenzyme Q10 significantly abrogated all those molecular events in high-fructose diet-fed rats and ameliorated sympathoexcitation and hypertension. Gene silencing of protein inhibitor of nNOS mRNA in RVLM using lentivirus carrying small hairpin RNA inhibited protein inhibitor of nNOS expression, increased the ratio of nNOS dimer/monomer, restored NO content, and alleviated oxidative stress in RVLM of high-fructose diet-fed rats, alongside significantly reduced sympathoexcitation and hypertension. These results suggest that redox-sensitive and protein inhibitor of nNOS-mediated nNOS uncoupling is engaged in a vicious cycle that sustains the production of reactive oxygen species in RVLM, resulting in sympathoexcitation and hypertension associated with MetS.

Determinants of preference for home death among terminally ill patients with cancer in Taiwan: a cross-sectional survey study.

BACKGROUND: Studies worldwide have shown that most patients with cancer prefer to die at home. Few studies have directly explored the determinants of preference for home death in patients with cancer living in Asia, and none has been conducted in Taiwan. OBJECTIVES: This study was designed to identify determinants of home-death preference among terminally ill patients with cancer in Taiwan. METHODS: A convenience sample of 2,188 terminally ill patients with cancer from 24 hospitals nationwide was surveyed. This study used multivariate logistic regression analysis to identify the determinants of preference for home death in the realms of patient demographics and disease characteristics, awareness of prognosis, and family support. RESULTS: Slightly more than half of the participants expressed the preference to die at home (n = 1,114, 54.7%). The adjusted odds of preferring to die at home were greater for participants described by one or more of the following: (1) family members knew the participant's preference for place of death (p < .001), (2) participant knew his or her prognosis (p = .032), (3) participant had greater functional dependency (p < .001), (4) participant was diagnosed with either liver/pancreatic (p = .028) or head/neck (p = .012) cancer, and (5) participant had less than a junior high school education (p < .001). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study supports the argument that most terminally ill patients with cancer in Taiwan prefer to die at home. To achieve patient preferences for home death, healthcare professionals should provide prognostic information and initiate end-of-life care discussions among patients and their family to facilitate family understanding of their ill relative's place-of-death preference. Developing clinical interventions to alleviate physical symptoms and providing hospice homecare services for terminally ill patients with cancer, especially those with lung cancer and greater functional dependency, may facilitate a preference for and actualization of home death.

Nontranscriptional activation of PI3K/Akt signaling mediates hypotensive effect following activation of estrogen receptor ß in the rostral ventrolateral medulla of rats.

BACKGROUND: Estrogen acts on the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons are located, to elicit vasodepressor effects via an estrogen receptor (ER)ß-dependent mechanism. We investigated in the present study nontranscriptional mechanism on cardiovascular effects following activation of ERß in the RVLM, and delineated the involvement of phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (Akt) signaling pathway in the effects. METHODS: In male Sprague-Dawley rats maintained under propofol anesthesia, changes in arterial pressure, heart rate and sympathetic neurogenic vasomotor tone were examined after microinjection bilaterally into RVLM of 17ß-estradiol (E2ß) or a selective ERα or ERß agonist. Involvement of ER subtypes and PI3K/Akt signaling pathway in the induced cardiovascular effects were studied using pharmacological tools of antagonists or inhibitors, gene manipulation with antisense oligonucleotide (ASON) or adenovirus-mediated gene transfection. RESULTS: Similar to E2ß (1 pmol), microinjection of ERß agonist, diarylpropionitrile (DPN, 1, 2 or 5 pmol), into bilateral RVLM evoked dose-dependent hypotension and reduction in sympathetic neurogenic vasomotor tone. These vasodepressive effects of DPN (2 pmol) were inhibited by ERß antagonist, R,R-tetrahydrochrysene (50 pmol), ASON against ERß mRNA (250 pmol), PI3K inhibitor LY294002 (5 pmol), or Akt inhibitor (250 pmol), but not by ERα inhibitor, methyl-piperidino-pyrazole (1 nmol), or transcription inhibitor, actinomycin D (5 or 10 nmol). Gene transfer by microinjection into bilateral RVLM of adenovirus encoding phosphatase and tensin homologues deleted on chromosome 10 (5 × 10(8) pfu) reversed the vasodepressive effects of DPN. CONCLUSIONS: Our results indicate that vasodepressive effects following activation of ERß in RVLM are mediated by nongenomic activation of PI3K/Akt signaling pathway. This study provides new insight in the intracellular signaling cascades involved in central vasodepressive functions of estrogen.

Meta-analysis of cultural differences in Western and Asian patient-perceived barriers to managing cancer pain.

PURPOSE: barriers to managing cancer pain contribute to cancer patients' reluctance to report pain and use prescribed analgesics, resulting in inadequate pain control. Patients' perceived barriers to managing cancer pain may be influenced by culture. This meta-analysis compared differences in Western and Asian patient-perceived barriers to managing cancer pain. METHODS: the literature was systematically reviewed to compare pain barriers in Western and Asian cancer patients in 22 studies that used Ward's Barrier Questionnaire. Differences in weighted barrier scores were compared by meta-regression analysis. RESULTS: Asian cancer patients had higher barrier scores than Western patients, except for barriers of 'good patient', 'side effects', 'distract physician', 'fear of injections', and 'addiction'. Meta-regression analysis indicated that Asian patients' perceived pain barriers differed significantly from those of Western patients for disease progression (weighted mean difference [WMD] = 1.32; 95% confidence interval [CI] 0.80, 1.84, p < 0.0001), tolerance (WMD = 1.63; 95% CI 0.91, 2.36, p < 0.0001), fatalism (WMD = 0.89; 95% CI 0.28, 1.52, p = 0.004), and total score (WMD = 0.82; 95% CI 0.36, 1.28, p < 0.0001). CONCLUSION: Asian patients' perceived barriers to managing cancer pain were significantly higher than those for Western patients (especially for concerns about disease progression, tolerance, and fatalism). Asian cancer patients need to be assessed and carefully treated for perceived barriers to optimize cancer pain management.

Successful reversal of bupivacaine and lidocaine-induced severe junctional bradycardia by lipid emulsion following infraclavicular brachial plexus block in a uremic patient.

Cardiac toxicity of bupivacaine has long been documented and it could be potentiated in certain circumstances, such as preexisting cardiac conduction abnormality or uremic status. The concept that lipid emulsion acts as a rescue of bupivacaine's toxicity has prevailed pending universal recognition. Herein, we report the successful use of lipid to resuscitate a female uremic patient who sustained junctional bradycardia while she was receiving ultrasound-guided infraclavicular brachial plexus block with the dose of local anesthetics far below the currently recommended maximum one. The possible mechanisms for the occurrence of cardiotoxicity in this case are discussed and the role of lipid emulsion as a treatment is reviewed.

Bedside ultrasonic detection of massive hemothorax due to superior vena cava perforation after hemodialysis catheter insertion.

Hemothorax resulting from perforation of a great vessel is an uncommon but life-threatening complication which may occur during central venous insertion of a hemodialysis catheter. We describe a 78-year-old uremic female who developed unexplained and refractory shock on the completion of percutaneous placement of a hemodialysis catheter in the right subclavian vein under general anesthesia. Bedside transthoracic ultrasound revealed a large anechoic area above the right hemidiaphragm, suggestive of the presence of extensive hemothorax. The diagnosis was further confirmed by prompt drainage of fresh blood from the right thoracostomy tube. Emergent thoracotomy was performed and perforation of the superior vena cava was identified. Hemodynamic stability was restored after surgical repair of the injured vessel, aggressive volume resuscitation and inotropic/vasopressor treatment. This case suggests that portable ultrasonography is an invaluable bedside tool which allows anesthesiologists to made reliable and prompt diagnosis of potentially fatal complications, such as perforation of great central vein due to inadvertent cannulation.

Nitric oxide triggers delayed anesthetic preconditioning-induced cardiac protection via activation of nuclear factor-kappaB and upregulation of inducible nitric oxide synthase.

Nitric oxide (NO) plays a pivotal role both in triggering and mediating delayed protection against myocardial I/R injury during anesthetic-induced preconditioning (APC). However, the signaling mechanisms that underlie this phenomenon remain unclear. Using isoflurane as a representative anesthetic, the present study tested the hypothesis that NO released after anesthetic-induced preconditioning initiates delayed cardioprotection via activation of nuclear transcription factor-kappaB (NF-kappaB), leading to myocardial adaptation by upregulation of iNOS and increase in production of NO. Sprague-Dawley rats that received open-chest surgery under pentobarbital anesthesia were subject to 30 min of left coronary artery occlusion, followed by 120 min of reperfusion. Exposure to 60 min of 2.1% isoflurane inhalation with oxygen 24 h before ischemia significantly reduced I/R-induced myocardial infarct size that was associated with overexpression of iNOS protein and increased NO content in the heart. These protective effects were abolished by pretreatment with a NOS inhibitor, N-nitro-L-arginine methyl ester, an NF-kappaB blocker, diethyldithiocarbamate, before isoflurane, or a selective iNOS inhibitor, S-methylisothiourea, before left coronary artery occlusion. Isoflurane exposure also evoked a robust increase in myocardial NO content, followed by nucleus-bound translocation of p65 or p50 subunit of NF-kappaB and increase in NF-kappaB DNA-binding activity in heart tissues. These molecular events after isoflurane exposure were blocked by pretreatment with N-nitro-L-arginine methyl ester. We conclude that NO generated immediately after isoflurane exposure triggers downstream activation of NF-kappaB, resulting in subsequent upregulation of iNOS expression and NO synthesis that mediate APC-induced delayed cardioprotection.