Stroke volume index (SVI) predicts all-cause mortality following transcatheter aortic valve replacement (TAVR).

BACKGROUND: Left ventricular systolic dysfunction in patients with severe aortic stenosis (AS) may result in low transvalvular gradients and underestimation of AS severity. A low-flow state may occur with reduced LVEF. Little is known about the implications of low compared to normal flow in patients with reduced LVEF undergoing transcatheter aortic valve replacement (TAVR). OBJECTIVES: We compared survival rates with degree of flow across stenosed aortic valves and left ventricular dysfunction. We hypothesized that the stroke volume index (SVI) offers essential information regarding survival following TAVR. METHODS: We retrospectively reviewed patients with LVEF <50 % undergoing TAVR at the Gates Vascular Institute in Buffalo, New York, from 2012 to 2017. We performed Receiver Operator Characteristics to examine the value of SVI in predicting the postoperative outcome of patients. Kaplan-Meier and Cox regression analyses were used to investigate the effect of a low-flow state on five-year survival in patients with systolic dysfunction undergoing TAVR. RESULTS: Five-year survival following TAVR was decreased in patients with low-flow AS (SVI <35 mL/m2) compared to patients with normal flow. Seventy-four percent (n = 50) of patients with low-flow compared to 43 % (n = 22) of patients with normal flow were deceased five years post-TAVR (p ≤0.001). ROC curve indicated SVI to be a clinical predictor of five year survival (AUC 0.732, 95 % CI: 0.641-0.823, p < 0.001). CONCLUSION: Patients with systolic dysfunction and low transvalvular flow AS had increased mortality five years following TAVR. These findings highlight a better prognosis in patients with normal flow and LV systolic dysfunction. CONDENSED ABSTRACT: Low-flow aortic stenosis can occur with reduced left ventricular function. We compared survival rates of patients with known reduced left ventricular function in low-flow and normal flow aortic stenosis. This retrospective single-center study examined mortality rates following transcatheter aortic valve replacement. The mean gradient was not a predictor of mortality. This study shows patients with low-flow aortic stenosis have decreased five-year survival following valve replacement.

Do Intrathecal Opioids Improve Surgical Outcomes After Coronary Artery Bypass Grafting? A Systematic Review and Analysis.

BACKGROUND: Intrathecal opioids have long been used as analgesia for intractable cancer pain or as part of spinal anesthesia during obstetric operations. More recently, they have been used preoperatively as a pain management adjuvant for open cardiac and thoracic procedures. OBJECTIVE: This study aims to analyze the impact of administering intrathecal opioids before cardiac and thoracic surgeries on postoperative pain and mechanical ventilation. STUDY DESIGN: Systematic review and meta-analysis. SETTING: University, School of Medicine, and several university-affiliated hospitals. METHODS: Five outcomes were studied, including the primary outcome of time to extubation, secondary outcomes of analgesia requirements at 24 and 48 hours, resting pain scores at 1 and 24 hours post-extubation, ICU length of stay in hours, and hospital length of stay in days. A search of multiple databases provided 28 studies reporting 4,000 total patients. Outcomes were measured using continuous mean difference with a 95% confidence interval, and the studies were examined for heterogeneity and sensitivity analysis. RESULTS: The primary outcome analysis suggested that time to extubation was 42 minutes shorter in the intrathecal opioid group (ranging from 82 to 1 minute, P = 0.04). There was also a decrease in postoperative analgesia requirements at both 24 hours (mean difference (MD) = -8.95 mg morphine equivalent doses (MED) [-9.4, -8.5], P < 0.001) and 48 hours (MD = -17.7 mg MED [-23.1, -12.4], P < 0.001) with I2 of 94% and 85% respectively, an improvement of pain scores at both 1 hour (MD = -2.24 [-3.16, -1.32], P < 0.001) and 24-hours (MD = -1.64 [-2.48, -0.80], P =< 0.001) I2 of 94% and 85%, no change in both ICU length of stay (MD = -0.27 hours [-0.55, 0.01], P = 0.06) I2 = 77% and hospital length of stay (MD = -0.30 days [-0.66, 0.06], P = 0.11) I2 = 32%. LIMITATIONS: The major limitation of this meta-analysis was the inconsistent dosages of intrathecal opioids utilized. Some used the same dose for each patient, while other studies used weight-based doses. The differences in the outcomes observed may then be a result of the different amounts of opioids administered rather than the technique itself. Another limitation was the inconsistent timing of reports for pain scores and postoperative analgesic requirements. Further studies were analyzed at the 2 time periods for both secondary outcomes, making it difficult to attribute the 2 effects solely to the intervention. CONCLUSIONS: We conclude that preoperative injection of intrathecal opioids is significantly associated with decreased time to extubation, decreased postoperative analgesia requirement, and improved pain scores. In controlled conditions with adequate staff education, this method of analgesia may make it possible to extubate the patients after the surgery in the operating room and fast-track their discharge from the hospital.

Theranostic chimeric antigen receptor (CAR)-T cells: Insight into recent trends and challenges in solid tumors.

Cell therapy has reached significant milestones in various life-threatening diseases, including cancer. Cell therapy using fluorescent and radiolabeled chimeric antigen receptor (CAR)-T cell is a successful strategy for diagnosing or treating malignancies. Since cell therapy approaches have different results in cancers, the success of hematological cancers has yet to transfer to solid tumor therapy, leading to more casualties. Therefore, there are many areas for improvement in the cell therapy platform. Understanding the therapeutic barriers associated with solid cancers through cell tracking and molecular imaging may provide a platform for effectively delivering CAR-T cells into solid tumors. This review describes CAR-T cells' role in treating solid and non-solid tumors and recent advances. Furthermore, we discuss the main obstacles, mechanism of action, novel strategies and solutions to overcome the challenges from molecular imaging and cell tracking perspectives.

Carotid artery stenting prior to coronary artery bypass grafting in patients with carotid stenosis: Clinical outcomes.

OBJECTIVES: Management of patients undergoing coronary artery bypass grafting (CABG) with obstructive disease of the carotid arteries is still a matter of debate. We compared the results of staged carotid artery stenting (CAS) before CABG in patients with carotid lesions. MATERIALS AND METHOD: Patients with significant carotid artery disease who were deemed to simultaneously suffer from an obstructive coronary artery disease requiring CABG from 2008 to 2018 were screened and enrolled in this study. We performed a staged CAS in cases with ≥60% stenosis and neurological symptoms or asymptomatic patients with ≥80% carotid artery stenosis. Patients with bilateral carotid lesions received sequential CAS within three weeks. Six weeks after the CAS procedure, all patients underwent CABG. RESULTS: A total of 142 patients were included. Eighty-five of these had neurological symptoms, while the remaining 40% were asymptomatic. Thirty-one patients underwent sequential CAS for bilateral lesions. The cerebrovascular event (CVE) following CAS (3 patients) and CABG (3 patients) was 4.2%. There was only a single case of mortality in this cohort. Although it was not statistically significant, CVE after CABG was more frequent in patients with bilateral carotid disease. CONCLUSIONS: Our results showed that staged CAS could be performed with minimal adverse outcomes in patients suffering from a simultaneous occlusive disease of carotids and coronary arteries before CABG. Bilateral CAS will further decrease cerebrovascular events and could be performed consequently or concomitantly.

Pseudohyponatremia Secondary to Hypercholesterolemia in the Setting of Intrahepatic Cholestasis due to Metastatic Liver Disease: A Case Report and Review of the Literature.

OBJECTIVE: We describe a rare case of pseudohyponatremia in the setting of hypercholesterolemia caused by cholestasis due to metastatic liver disease and provide a review of the published cases in the literature. CASE REPORT: We report a case of pseudohyponatremia in a 60-year-old man with rectal cancer with extensive metastasis to the liver. While assessing the patient for hyponatremia, extremely elevated serum cholesterol with normal serum osmolality was detected leading to the diagnosis of pseudohyponatremia. This is one of very few reports of pseudohyponatremia in patients with elevated cholesterol in cholestatic liver disease. CONCLUSION: Hypercholesterolemia is an exceedingly rare cause for pseudohyponatremia. Although pseudohyponatremia per se does not carry a risk to the patient, the delay in diagnosis and treatment plans may pose additional risks. Pseudohyponatremia needs to be considered in patients with low sodium and co-existing cholestasis from metastatic liver disease.

Targeting mitochondria in cancer therapy: Insight into photodynamic and photothermal therapies.

Mitochondria are critical multifunctional organelles in cells that generate power, produce reactive oxygen species, and regulate cell survival. Mitochondria that are dysfunctional are eliminated via mitophagy as a way to protect cells under moderate stress and physiological conditions. However, mitophagy is a double-edged sword and can trigger cell death under severe stresses. By targeting mitochondria, photodynamic (PD) and photothermal (PT) therapies may play a role in treating cancer. These therapeutic modalities alter mitochondrial membrane potential, thereby affecting respiratory chain function and generation of reactive oxygen species promotes signaling pathways for cell death. In this regard, PDT, PTT, various mitochondrion-targeting agents and therapeutic methods could have exploited the vital role of mitochondria as the doorway to regulated cell death. Targeted mitochondrial therapies would provide an excellent opportunity for effective mitochondrial injury and accurate tumor erosion. Herein, we summarize the recent progress on the roles of PD and PT treatments in regulating cancerous cell death in relation to mitochondrial targeting and the signaling pathways involved.

Photothermal therapy-mediated autophagy in breast cancer treatment: Progress and trends.

Breast cancer (BC) has different clinical manifestations due to its diverse mechanism of action that has created many challenges to choosing appropriate treatment. Recent findings of the biology of breast cancer including the mechanisms of survival and metastasis, understanding the effective signaling pathways in tumor formation and modeling of cancer cell responses to the therapeutic approaches provided significant advances in BC treatment. In this regard, the use of phototherapy-based approaches such as photothermal therapy (PTT) would be an encouraging alternative for tumor suppression through activating autophagy or suppressing cell signaling that influences the cell cycle to induce cell death. Since autophagy has a dual opposite role consisting of pro-survival and growth inhibition in breast cancer microenvironments, the regulation of autophagy would be playing promising roles in the treatment of BC using PTT. This review updates the molecular mechanisms that PTT could evoke autophagic cell death in breast cancer. Moreover, this article provides insights into the biological effects of autophagy-targeted-PTT as a promising strategy for breast cancer therapy.

A review on targeting tumor microenvironment: The main paradigm shift in the mAb-based immunotherapy of solid tumors.

Monoclonal antibodies (mAbs) as biological macromolecules have been remarked the large and growing pipline of the pharmaceutical market and also the most promising tool in modern medicine for cancer therapy. These therapeutic entities, which consist of whole mAbs, armed mAbs (i.e., antibody-toxin conjugates, antibody-drug conjugates, and antibody-radionuclide conjugates), and antibody fragments, mostly target tumor cells. However, due to intrinsic heterogeneity of cancer diseases, tumor cells targeting mAb have been encountered with difficulties in their unpredictable efficacy as well as variability in remission and durable clinical benefits among cancer patients. To address these pitfalls, the area has undergone two major evolutions with the intent of minimizing anti-drug responses and addressing limitations experienced with tumor cell-targeted therapies. As a novel hallmark of cancer, the tumor microenvironment (TME) is becoming the great importance of attention to develop innovative strategies based on therapeutic mAbs. Here, we underscore innovative strategies targeting TME by mAbs which destroy tumor cells indirectly through targeting vasculature system (e.g., anti-angiogenesis), immune system modulation (i.e., stimulation, suppression, and depletion), the targeting and blocking of stroma-based growth signals (e.g., cancer-associated fibroblasts), and targeting cancer stem cells, as well as, their effector mechanisms, clinical uses, and relevant mechanisms of resistance.

Evaluation of Adding Dexmedetomidine to Ropivacaine in Pediatric Caudal Epidural Block: A Randomized, Double-blinded Clinical Trial.

BACKGROUND: Caudal block is one of the methods of pain management performed following lower abdominal surgery, though having its own limitations. OBJECTIVES: In the present study, the effects and side effects of adding dexmedetomidine to ropivacaine in the caudal epidural block were investigated in children after lower abdominal surgery. METHODS: In this randomized, double-blinded clinical trial, 46 children aged three to six years were divided into two groups to perform a caudal block following lower abdominal surgery under general anesthesia. The injectable solution contained ropivacaine in the R group (1 mL/kg ropivacaine 0.2%), as the control group, and dexmedetomidine (2 µg/kg) and ropivacaine 0.2% (1 mL/kg) in the DR group. The pain score (modified CHEOPS score), duration of analgesia, amount of analgesia consumed (i.v. paracetamol), hemodynamic changes, and possible adverse effects were assessed at one, two, and six hours in both groups. RESULTS: The pain score at one and two hours showed no significant difference between the two study groups (P > 0.05). In the DR group, however, the pain score at the sixth hour was significantly lower, and the duration of analgesia was longer (P = 0.001). The amount of analgesic consumption was also lower in the DR group (P = 0.001). However, there was no significant difference in systolic blood pressure and heart rate (P < 0.05), in the case of diastolic blood pressure, a significant difference (P < 0.05) was seen (DR group lower than the R group). There was no statistically significant difference between the study groups in the duration of surgery, recovery time, and side effects (P < 0.05). CONCLUSIONS: In the present study, the addition of dexmedetomidine to ropivacaine in the caudal epidural blockade improved postoperative analgesia without significant adverse effects in pediatric patients.

Evaluating the radioprotective effect of Cimetidine, IMOD, and hybrid radioprotectors agents: An in-vitro study.

INTRODUCTION: There are various radioprotective agents with different mechanisms that help to decrease ionizing radiation side effects. The radioprotective effect of Cimetidine and IMOD was assessed individually and compared with the hybrid radioprotectors agents (HRPAs-IMOD and Cimetidine) on human lymphocyte cells. METHODS: Twenty healthy volunteers (ten men and ten women) participated in the present study. About 75 mL peripheral blood lymphocytes from each individual were collected, and they were divided into 36 groups. Briefly, the blood samples were treated with different concentrations of Cimetidine (12.6 and 25.2 µg/mL) and IMOD (0.04, 0.08, and 0.12 mg/mL), and also a combination of these agents, namely hybrid radioprotectors agents (HRPAs). Besides, the irradiated groups were exposed to 2 and 4 Gy of Co-60 gamma irradiation. The amount of cellular damage was assessed using the micronucleus assay. The repeated measurements and paired T-test statistical analysis were used to compare the micronucleus frequencies in different groups. RESULTS: The micronucleus frequencies were significantly reduced (p < 0.05) in irradiated groups when the non-toxic concentrations of Cimetidine, IMOD, and HRPAs have been used. The reduction in micronucleus frequency was obtained 5-29% for Cimetidine and 40-51% for IMOD in peripheral blood lymphocytes irradiated with 2 Gy. This reduction in 4 Gy irradiation was 8-17% for Cimetidine and 27-37% for IMOD. The HRPAs resulted in a higher radioprotective effect, in a way that they cause up to 58% and 43% micronucleus frequency reduction in 2 and 4 Gy, respectively. CONCLUSION: In conclusion, the HRPAs showed the highest level of radioprotective. In addition, IMOD was remarkably higher radioprotective than Cimetidine, which may be related to its greater non-toxic concentrations.

A clinical trial of volume- versus pressure-controlled intraoperative ventilation during laparoscopic bariatric surgeries.

BACKGROUND: Intra-operative ventilation is often challenging in patients with morbid obesity undergoing bariatric surgery. OBJECTIVES: To test the noninferiority of pressure-controlled ventilation (PCV) to volume-controlled ventilation (VCV) in respiratory mechanics. SETTING: Bariatric Surgery Center, Iran. METHODS: In a randomized open-labeled clinical trial, 66 individuals with morbid obesity undergoing laparoscopic bariatric surgeries underwent intraoperative ventilation with either PCV or VCV. The measurements taken were peak and mean airway pressures (H2O), partial pressure of arterial oxygen (PaO2), partial pressure of arterial carbon dioxide (PaCO2) and end-tidal carbon dioxide (CO2). We additionally collected pulse-oximetric oxygen saturation, inspiratory concentration of oxygen (FiO2), and hemodynamic variables. Data were analyzed with repeated measures over the time of intubation, after peritoneal insufflation, and every 15 minutes, thereafter up to one hour. RESULTS: PCV mode was successful to sustain adequate ventilation in 97% of the patients, which was similar to the 94% success rate of the VCV mode. Peak airway pressure increased 6 cmH2O and end-tidal CO2 rose by 5 mm Hg after abdominal insufflation in both groups (P = .850 and .376). Alveolar-arterial oxygen gradient similarly increased within 30 minutes after tracheal intubation both in PCV and VCV groups, with small trend of being higher in the VCV group. The ratio of dead space to tidal volumes (VD/VT) did not have a meaningful change (P = .724). CONCLUSION: PCV was noninferior to VCV during laparoscopic bariatric surgery. Either mode of ventilation could be alternatively used during the anesthesia care of these patients.

Corneal collagen cross-linking in pediatric keratoconus with three protocols: a systematic review and meta-analysis.

BACKGROUND: Keratoconus is a bilateral progressive noninflammatory degenerative disease of the cornea characterized by corneal thinning, irregular astigmatism, and subsequent visual impairment. It has an aggressive course in children. This systematic review evaluates the efficacy of available corneal collagen cross-linking (CXL) protocols for stabilizing the cornea in pediatric patients with keratoconus. METHODS: We searched all peer-reviewed publications from 2000 to 2019 indexed in PubMed, Google Scholars, Web of Science, and Cochrane's Database for the terms keratoconus and cross-linking. The following data were extracted from eligible studies: study design, type of intervention, number of the eyes and mean age of patients for each study, duration of follow-up period, mean pre- and postoperative uncorrected and corrected visual acuity, keratometric and aberrometric indices, were analyzed with RevMan 5.3 software. Intra-and intergroup post hoc analyses of outcome variables were performed using t tests. RESULTS: A total of 28 studies, including 1,300 eyes, were reviewed. In conventional and accelerated epithelium-off techniques, there was a significant improvement in uncorrected and corrected visual acuities. Similarly, the keratometric indices improved significantly after CXL. Uncorrected visual acuity did not alter after CXL using transepithelial method. CONCLUSIONS: Both conventional and accelerated collagen CXL of the cornea are effective therapeutic options in management of keratoconus in children.

The Evaluation of Factors Affecting Hemodynamic Variability in Mechanically-Ventilated Patients After Cardiac Surgery.

BACKGROUND: Optimizing cardiac preload is usually the first step in patients with unstable hemodynamic. However, it should be remembered that an unnecessary volume expansion may exacerbate the hemodynamic. In mechanically ventilated patients, the ventilatory induced hemodynamic variations (VIHV) can be used to predict the fluid requirement. These variations (called dynamic indices of cardiac filling pressure), are superior to static indices (central venous and pulmonary artery occlusion pressure) in diagnosing any volume requirement. We theorized that some conditions other than hypovolemia might affect these hemodynamic variations. OBJECTIVES: The current study aimed to discover these conditions in adult patients admitted to post-cardiac surgery ICU. METHODS: This antegrade cross-sectional study was conducted on 304 adult patients who were admitted to ICU after elective cardiac surgery in a teaching hospital (Tabriz-Iran). During the first 3 hours of the admission, the systolic (ΔSBP), diastolic (ΔDBP), mean (ΔMAP), and arterial blood pulse pressures (ΔPP) were invasively monitored and calculated in percent value. Because of the return of spontaneous breathing in most of the patients, the calculations were done only during the first 3-hour. All patients with spontaneous breathing, irregular cardiac rhythm, or re-admission to OR in this period were excluded from the study. We recorded demographic and surgical characteristics, perioperative hemodynamic and echocardiographic, and complications data and surveyed the correlation between VIHV and perioperative data. RESULTS: Two hundred and ninety two patients met the inclusion criteria. Coronary artery bypass grafting (CABG) was the most common surgery (64.4 %). Cardiopulmonary bypass (CPB) was used in 95.55% of the surgeries. In the first 24-hour, 51 patients required re-operation because of sternum closure, bleeding control, cardiac tamponade, and coronary artery revascularization. Mortality and morbidity occurred in 2 (0.68%) and 50 (17.12%) patients, respectively. Among VIHVs, the ΔPP had the most significant value. Thus, mean ΔPP was calculated and the correlation between its severity (≤ 20% vs. > 20%) and other values surveyed. It was high in patients with cardiac dysfunction and tamponade (P value < 0.001). No significant correlation was found between mean ΔPP severity and hemorrhage rate, fluid balance, need to vasoactive agents, blood products, or bleeding control, redo CABG or sternum closure surgery, time to tracheal extubation, ICU stay, and postoperative complications. Patients with closed sternum were the same as those with the unclosed sternum. CONCLUSIONS: The ΔPP was the most sensitive VIHV parameter. Cardiac dysfunction and tamponade increased ΔPP. Unclosed sternum did not affect its value. ΔPP value did not affect postoperative complications rate, time to tracheal extubation, or ICU stay.

High plateletcrit is associated with early loss of patency after open and endovascular interventions for chronic limb ischemia.

OBJECTIVE: Plateletcrit (PCT) reflects the total platelet mass in blood and can be calculated from a complete blood count. We examined the effect of PCT on outcomes of endovascular and open interventions for chronic limb ischemia. METHODS: Patients who underwent revascularization for chronic limb ischemia (Rutherford categories 3-6) between June 2001 and December 2014 were retrospectively identified. PCT on admission was recorded. Patients and limbs were divided into tertiles of low (0.046-0.211), medium (0.212-0.271), and high (0.272-0.842) PCT. Patency, limb salvage, major adverse limb events, major adverse cardiac events, and survival rates were calculated using Kaplan-Meier analysis and compared with log-rank test. Cox regression analysis was used for multivariate analysis. RESULTS: A total of 1431 limbs (1210 patients) were identified and divided into low PCT (477 limbs in 407 patients), medium PCT (477 limbs in 407 patients), and high PCT (477 limbs in 396 patients) groups. The patients in the high tertile were 2 years older that the patients in the other two tertiles (P = .009). Five-year primary patency was 65% ± 3% in the low-PCT group compared with 55% ± 3% and 51% ± 3% in the medium and high PCT groups, respectively (P = .004). Five-year secondary patency was 81% ± 2% in the low PCT group compared with 82% ± 2% and 72% ± 3% in the medium and high PCT groups, respectively (P = .02). Five-year limb salvage rate was 86% ± 2% in the low PCT group compared with 79% ± 3% and 74% ± 3% in the medium PCT and high PCT groups, respectively (P = .004). Multivariate regression analysis showed that low PCT was independently associated with primary patency after endovascular interventions (hazard ratio, 0.67 [0.47-0.95]; P = .02) but not after open interventions (hazard ratio, 0.72 [0.43-1.21]; P = .21). CONCLUSIONS: High PCT is associated with poor patency and limb salvage rates after interventions for lower extremity chronic limb ischemia. Multivariate regression analysis confirmed association of low PCT with improved primary patency after endovascular interventions but not after open interventions. High PCT may be a marker of increased platelet reactivity and could be used to identify patients at high risk for early thrombosis and failure after interventions.