Improving the palliative-procedure decision-making process for patients with peritoneal carcinomatosis: A secondary analysis.

BACKGROUND: Peritoneal carcinomatosis (PC) is common in patients with advanced gynecologic and gastrointestinal cancers. Frequently, patients with PC undergo palliative surgery or procedures to manage disease-related complications and side effects. However, there are limited data regarding patients' and family caregivers' decision-making processes about these procedures. Thus, we sought to describe the decision-making experiences of patients with PC who elect to pursue palliative surgical procedures and their family caregivers. METHODS: We conducted a secondary analysis of qualitative data collected during a pilot randomized controlled trial of BOLSTER, a nurse-led telehealth intervention for patients with PC and their caregivers after an acute hospitalization and palliative procedure. Participants in both study arms described their experiences in semi-structured interviews. We re-analyzed coded qualitative data with a focus on understanding decision-making experiences surrounding palliative surgery and procedures using conventional content analysis. RESULTS: Interviews from 32 participants, 23 patients and 9 caregivers, were analyzed. Participants reported their decision-making was complicated by illness uncertainty and a desire for clear, effective communication with surgical and medical oncology teams. Participants requested more information about the impact of palliative procedures on their daily life. Several also noted that, without improved understanding, a misalignment between patient and family caregiver goals and palliative procedures may inadvertently increase suffering. CONCLUSION: Discussions related to patients' goals and preferences can improve the quality of treatment decision-making in patients with PC and their caregivers. Future research should test interventions to improve advanced cancer patients' illness understanding and decision-making surrounding palliative surgery and procedures.

Feasibility and acceptability of a nurse-led telehealth intervention (BOLSTER) to support patients with peritoneal carcinomatosis and their caregivers: A pilot randomized clinical trial.

OBJECTIVE: Patients with advanced gynecologic (GYN) and gastrointestinal (GI) cancers frequently develop peritoneal carcinomatosis (PC), which limits prognosis and diminishes health-related quality of life (HRQoL). Palliative procedures may improve PC symptoms, yet patients and caregivers report feeling unprepared to manage ostomies, catheters, and other complex needs. Our objectives were to (1) assess the feasibility of an efficacy trial of a nurse-led telehealth intervention (BOLSTER) for patients with PC and their caregivers; and (2) assess BOLSTER's acceptability, potential to improve patients' HRQoL and self-efficacy, and potential impact on advance care planning (ACP). METHODS: Pilot feasibility RCT. Recently hospitalized adults with advanced GYN and GI cancers, PC, and a new complex care need and their caregivers were randomized 1:1 to BOLSTER or enhanced discharge planning (EDP). We defined feasibility as a ≥ 50% approach-to-consent ratio and acceptability as ≥70% satisfaction with BOLSTER. We assessed patients' HRQoL and self-efficacy at baseline and six weeks, then compared the proportion experiencing meaningful improvements by arm. ACP documentation was identified using natural language processing. RESULTS: We consented 77% of approached patients. In the BOLSTER arm, 91.0% of patients and 100.0% of caregivers were satisfied. Compared to EDP, more patients receiving BOLSTER experienced improvements in HRQoL (68.4% vs. 40.0%) and self-efficacy for managing symptoms (78.9% vs. 35.0%) and treatment (52.9% vs. 42.9%). The BOLSTER arm had more ACP documentation. CONCLUSIONS: BOLSTER is a feasible and acceptable intervention with the potential to improve patients' HRQoL and promote ACP. An efficacy trial comparing BOLSTER to usual care is underway. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03367247; PI: Wright.

RETINA EXPANSION TECHNIQUE FOR MACULAR HOLE APPOSITION REPORT 2: Efficacy, Closure Rate, and Risks of a Macular Detachment Technique to Close Large Full-Thickness Macular Holes.

PURPOSE: To describe the safety and efficacy of a technique to close large thickness macular holes. METHODS: A consecutive retrospective interventional case series of 16 patients with macular holes greater than 650 microns in "aperture" diameter were included. The technique involves vitrectomy, followed by internal limiting membrane peeling. The macula is detached using subretinal injection of saline. Fluid-air exchange is performed to promote detachment and stretch of the retina. After this, the standard fluid-air exchange is performed and perfluoropropane gas is injected. Face-down posturing is advised. Adverse effects, preoperative, and postoperative visual acuities were recorded. Optical coherence tomography scans were also taken. RESULTS: The mean hole size was 739 microns (SD: 62 microns; mean base diameter: 1,311 microns). Eighty-three percent (14 of 16) of eyes had successful hole closure after the procedure. At 12-month follow-up, no worsening in visual acuity was reported, and improvement in visual acuity was noted in 14 of 16 eyes. No patients lost vision because of the procedure. CONCLUSION: It is possible to achieve anatomical closure of large macular holes using RETMA. No patients experienced visual loss. The level of visual improvement is likely limited because of the size and chronicity of these holes.

Dynamic cell-cell and cell-ECM interactions in the heart.

Recent studies have placed an increasing amount of emphasis on the cardiovascular system and understanding how the heart and its vasculature can be regenerated following pathological stresses, such as hypertension and myocardial infarction. The remodeling process involves the permanent cellular constituents of the heart including myocytes, fibroblasts, endothelial cells, pericytes, smooth muscle cells and stem cells. It also includes transient cell populations, such as immune cells (e.g. lymphocytes, mast cells and macrophages) and circulating stem cells. Following injury, there are dramatic shifts in the various cardiac cell populations that can affect cell-cell and cell-extracellular matrix interactions and cardiac function. Cardiac fibroblasts are a key component in normal heart function, as well as during the remodeling process through dynamic cell-cell interactions and synthesis and degradation of the extracellular matrix. Fibroblasts dynamically interact with the various cardiac cell populations through mechanical, chemical (autocrine and/or paracrine) and electrophysiological means to alter gene and protein expression, cellular processes and ultimately cardiac function. Better understanding these cell-cell and cell-extracellular matrix interactions and their biological consequences should provide novel therapeutic targets for the treatment of heart disease. In this review we discuss the nature of these interactions and the importance of these interactions in maintaining normal heart function, as well as their role in the cardiac remodeling process. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium."

Real-world management of abnormal scarring using topical silicone gel: expert consensus and case series from the Asian SCARS Expert Group.

Preventing abnormal scar formation and correcting non-aesthetic mature scars are important to prevent physical and psychosocial consequences of abnormal scarring. Evidence-based guidelines for scar management in Asian patients recommend first-line silicone-based products. Dermatix®* Ultra and Dermatix Ultra Kids are topical silicone gels containing a vitamin C ester that helps lighten scar tissue. Herein, we report a case series including patients with hypertrophic and keloid scars treated with Dermatix, showing that Dermatix is effective for scar treatment and prevention, as well as expert consensus supporting the safe and effective use of Dermatix.

Renal functional responses to selective intrarenal renin inhibition in Cyp1a1-Ren2 transgenic rats with ANG II-dependent malignant hypertension.

Angiotensin (ANG) II-dependent hypertension is characterized by increases in intrarenal ANG II levels, derangement in renal hemodynamics, and augmented tubular sodium reabsorptive capability. Increased nephron expression of renin-angiotensin system components, such as angiotensinogen by proximal tubule cells and renin by collecting duct principal cells, has been associated with an augmented ability of the kidney to form ANG II in hypertensive states. However, the contribution of de novo intrarenal ANG II production to the development and maintenance of ANG II-dependent hypertension remains unclear. The present study was performed to determine the effects of selective intrarenal renin inhibition on whole kidney hemodynamics and renal excretory function in Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension in the absence of the confounding influence of associated reductions in mean arterial pressure (MAP). Male Cyp1a1-Ren2 transgenic rats were induced to develop malignant hypertension, anesthetized, and surgically prepared for intrarenal administration of the direct renin inhibitor aliskiren (0.01 mg/kg). Following acute aliskiren treatment, urine flow and sodium excretion increased (10.5 ± 1.1 to 15.9 ± 1.9 µl/min, P < 0.001; 550 ± 160 to 1,370 ± 320 neq/min, P < 0.001, respectively) and ANG II excretion decreased (120 ± 30 to 63 ± 17 fmol/h, P < 0.05). There were no significant changes in MAP, glomerular filtration rate, estimated renal plasma flow, plasma ANG II levels, or protein excretion. The present findings demonstrate that selective renal renin inhibition elicits diuretic and natriuretic responses in Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension. Elevated intraluminal ANG II levels likely act to augment tubular reabsorptive function and, thereby, contribute to the elevated blood pressure in Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension.

Granulocyte macrophage colony-stimulating factor--secreting allogeneic cellular immunotherapy for hormone-refractory prostate cancer.

PURPOSE: This trial evaluated the safety, clinical activity, and immunogenicity of an allogeneic cellular immunotherapy in 55 chemotherapy-naïve patients with hormone-refractory prostate cancer (HRPC). The immunotherapy, based on the GVAX platform, is a combination of two prostate carcinoma cell lines modified with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene. EXPERIMENTAL DESIGN: HRPC patients with radiologic metastases (n = 34) or rising prostate-specific antigen (PSA) only (n = 21) received a prime dose of 500 million cells and 12 boost doses of either 100 million cells (low dose) or 300 million cells (high dose) biweekly for 6 months. End points were changes in PSA, time to progression, and survival. RESULTS: Median survival was 26.2 months (95% confidence interval, 17, 36) in the radiologic group: 34.9 months (8, 57) after treatment with the high dose (n = 10) of immunotherapy and 24.0 months (11, 35) with the low dose (n = 24). The median time to bone scan progression in the radiologic group was 5.0 months (2.6, 11.6) with the high dose and 2.8 months (2.8, 5.7) with the low dose. In the rising-PSA group (n = 21) receiving the low dose, the median time to bone scan progression was 5.9 months (5.6, not reached), and median survival was 37.5 months (29, 56). No dose-limiting or autoimmune toxicities were seen; the most common adverse events were injection site reaction and fatigue. CONCLUSIONS: These results suggest that this GM-CSF-secreting, allogeneic cellular immunotherapy is well tolerated and may have clinical activity in patients with metastatic HRPC. Phase 3 trials to confirm these results are under way.

The influence of dilution on the offline measurement of exhaled nitric oxide.

OBJECTIVE: Measurement of fractional exhaled nitric oxide (FeNO) is used to determine the presence and severity of eosinophilic airway inflammation in asthma and other wheezing illnesses. The gold standard of online measurement during a single prolonged exhalation is not suitable for use in young children. The international guidelines for offline measurements recommend collection of exhaled gas in an appropriate reservoir for later analysis in young children. The apparatus required for gas collection, however, creates dead space within the system, which may result in sample dilution and hence inaccuracy. Our objective was to investigate the effect such dilution might have on the accuracy of offline FeNO by comparing the results to online results. APPROACH: Thirty-five adult subjects without respiratory disease underwent online measurement of FeNO and, thereafter, undertook offline FeNO measurements via exhalation into a collection reservoir using one, five or ten inhalation-exhalation cycles. Fifteen of the subjects also exhaled using the five-breath technique via apparatus with additional dead space. An equation incorporating dead space volume and the number of breaths was used to predict the degree of dilution; the predicted results were compared to the measured results. MAIN RESULTS: The median (IQR) FeNO from a one-breath technique (22 (15-28) ppb was not significantly different to online values (19 (12-27) ppb, p = 1.00), but the results from the five-breath technique (11 (4-19) ppb, p < 0.0001), the ten-breath technique (6 (4-15) ppb, p < 0.0001) and the additional dead space experiment (6 (3-8) ppb, p = 0.0006) were significantly lower than online FeNO. Measured values were consistently significantly different to those predicted by the dilution equation, even when incorporating the exact exhaled volume of gas. SIGNIFICANCE: Offline FeNO results may be inaccurate when subjects are unable to fill the collection reservoir with a single exhalation, thus the technique may not be suitable for preschool children.

Novel technique for removal of persistent subretinal fluid following nondrain retinal detachment surgery.

This manuscript describes a case of successful reattachment of a macular-off retinal detachment following optical coherence tomography-guided internal drainage of retained subretinal fluid following a nondrain method. To date, there has not been any documented treatment option for this common phenomenon. This novel technique describes a method to remove such fluid and successfully appose the retina to the retinal pigment epithelial layer.

Chronic direct renin inhibition with aliskiren prevents the development of hypertension in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent hypertension.

INTRODUCTION: This study was performed to determine whether chronic direct renin inhibition can prevent the development of slowly progressive angiotensin (ANG) II-dependent hypertension and the associated derangements in renal function in Cyplal-Ren2 transgenic rats with inducible expression of the Ren2 gene. METHODS: Male Cyplal-Ren2 rats (n = 6) were fed a normal diet containing 0.15% indole-3-carbinol (I3C) for 16 days to induce slowly progressive ANG II-dependent hypertension. Conscious systolic blood pressure was measured daily using tail-cuff plethysmography. The rats were then anesthetized with pentobarbital sodium and surgically prepared for the measurement of mean arterial pressure (MAP) and renal hemodynamics and excretory function. RESULTS: In rats induced with I3C, systolic blood pressure increased by day 3 (130 ± 7-160 ± 5 mm Hg, P < 0.01) and continued to increase to 191 ± 6 mm Hg (P < 0.001) by day 16. In a separate group of rats (n = 6), chronic administration of the direct renin inhibitor, aliskiren (30 mg/kg/d, sc), prevented the development of hypertension (113 ± 5 versus 114 ± 5 mm Hg, not significant). Rats treated with aliskiren exhibited significantly lower mean arterial pressure (138 ± 4 versus 201 ± 6 mm Hg, P < 0.001), renal vascular resistance (23 ± 4 versus 38 ± 3 mm Hg/mL/min · g, P < 0.01), urine flow (17.6 ± 1.4 versus 25.1 ± 2.9 µL/min, P < 0.05) and urinary sodium excretion (1.11 ± 0.32 versus 2.35 ± 0.28 µEq/min, P < 0.05) and higher renal plasma flow (4.22 ± 0.23 versus 2.56 ± 0.21 mL/min · g, P < 0.01) and glomerular filtration rate (1.19 ± 0.07 versus 0.78 ± 0.08 mL/min · g, P< 0.01), compared with induced rats not treated chronically with aliskiren. CONCLUSIONS: The present findings demonstrate that chronic direct renin inhibition with aliskiren prevents the development of ANG II-dependent hypertension and the associated derangements in renal hemodynamics and excretory function in Cyplal-Ren2 transgenic rats.

Direct renin inhibition with aliskiren normalizes blood pressure in Cyp1a1-Ren2 transgenic rats with inducible angiotensin ii-dependent malignant hypertension.

INTRODUCTION: Cyp1a1-Ren2 transgenic rats [strain name: TGR(Cyp1a1Ren2)], administered indole-3-carbinol (I3C) develop angiotensin (ANG) II-dependent hypertension due to hepatic expression of the Ren2 renin gene. Although AT1 receptor blockade prevents the development of hypertension and normalizes the elevated arterial blood pressure of Cyp1-Ren2 rats, little information is available regarding the blood pressure and renal functional responses to direct inhibition of renin in this high circulating renin model of ANG II-dependent hypertension. This study was performed to determine the effects of acute direct renin inhibition with aliskiren on blood pressure and renal hemodynamics in Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension. METHODS: Mean arterial pressure (MAP) and renal hemodynamics were measured in pentobarbital-anesthetized male Cyp1a1-Ren2 rats during control conditions and after administration of the renin inhibitor, aliskiren (10 mg/kg, intravenous). RESULTS: Rats induced with I3C had higher MAP (194 ± 7 versus 141 ± 2 mm Hg, P < 0.001), lower renal plasma flow (RPF; 2.47 ± 0.23 versus 4.17 ± 0.35 mL/min/g, P < 0.001) and lower glomerular filtration rate (GFR; 1.01 ± 0.07 versus 1.34 ± 0.06 mL/min/g, P = 0.01) than noninduced Cyp1a1-Ren2 rats (n = 5). Aliskiren administration decreased MAP (194 ± 7 to 136 ± 2 mm Hg, P < 0.001) and increased RPF (2.47 ± 0.23 versus 4.31 ± 0.20 mL/min/g, P < 0.001) in hypertensive but not in normotensive rats, without altering GFR. CONCLUSIONS: Acute renin inhibition with aliskiren normalizes MAP and RPF in Cyp1a1-Ren2 rats with malignant hypertension. The normalization of MAP and RPF after acute renin inhibition indicates that renin generated by expression of the Ren2 gene is responsible for the maintenance of malignant hypertension and the associated reduction in renal hemodynamic function in Cyp1a1-Ren2 rats.

Transient induction of ANG II-dependent malignant hypertension causes sustained elevation of blood pressure and augmentation of the pressor response to ANG II in CYP1A1-REN2 transgenic rats.

INTRODUCTION: Transgenic rats with inducible expression of the mouse Ren2 renin gene [strain name: TGR(Cyp1a1Ren2)] allow induction of various degrees of ANG II-dependent hypertension. Dietary administration of the aryl hydrocarbon indole-3-carbinol (I3C) at a dose of 0.15% induces a slowly developing form of ANG II-dependent hypertension, whereas dietary administration of a higher dose (0.3%) of I3C results in the development of ANG II-dependent malignant hypertension. Cessation of administration of 0.15% I3C results in the normalization of blood pressure, indicating the reversibility of hypertension induced by this dose of I3C. The present study was performed to determine if ANG II-dependent malignant hypertension is similarly reversible following cessation of dietary administration of 0.3% I3C. METHODS: Cyp1a1-Ren2 rats (n = 6) were fed a normal diet containing 0.3% I3C for 11 days to induce malignant hypertension. RESULTS: Cyp1a1-Ren2 rats induced with I3C exhibited pronounced increases in systolic blood pressure (SBP) (132 +/- 3-229 +/- 11 mm Hg, P < 0.001) and marked decreases in body weight (303 +/- 4-222 +/- 2 g, P < 0.001). When I3C administration was terminated, SBP decreased to 167 +/- 4 mm Hg (P < 0.01) and body weight increased to normal levels (309 +/- 2 g, P < 0.01) within 12 days. However, SBP remained significantly elevated (172 +/- 1 mm Hg, P < 0.01) for up to 3 weeks after termination of dietary administration of 0.3% I3C. In addition, the magnitude of the blood pressure response to intravenous bolus administration of 50 ng of ANG II (50 microL in volume) 3 weeks after cessation of dietary I3C administration was substantially higher than that observed in normotensive control rats (134 +/- 1 mm Hg, n = 6) not previously induced with 0.3% I3C (53 +/- 2 versus 38 +/- 3 mm Hg, P < 0.05). CONCLUSIONS: The present findings demonstrate that transient induction of ANG II-dependent malignant hypertension results in prolonged elevations of arterial blood pressure and marked augmentation of the magnitude of the pressor response to ANG II in Cyp1a1-Ren2 transgenic rats.