Impact of Delusions and Hallucinations on Clinical Insight Dimensions in Schizophrenia Spectrum Disorders.

INTRODUCTION: Insight in psychosis has been conceptualized as a continuous, dynamic, and multidimensional phenomenon. This study aims to determine the impact of delusions and hallucinations in different dimensions of clinical insight in schizophrenia spectrum disorders. METHODS: Cross-sectional multicenter study including 516 patients (336 men) diagnosed with schizophrenia spectrum disorders. Based on dichotomized scores of Positive and Negative Syndrome Scale (PANSS) items P1 (delusions) and P3 (hallucinations), patients were assigned to four groups according to current clear presence of delusions (scores 4 or above 4 in PANSS item P1) and/or hallucinations (scores 4 or above 4 in PANNS item P3). Insight was assessed using the three main dimensions of the Scale of Unawareness of Mental Disorder (SUMD). RESULTS: Around 40% of patients showed unawareness of illness; 30% unawareness of the need for treatment; and 45% unawareness of the social consequences of the disorder. Patients with current clear presence of delusions had higher overall lack of awareness, regardless of current clear presence of hallucinations. Similarly, the clear presence of delusions showed a greater predictive value on insight than the presence of hallucinations, although the implication of both in the prediction was modest. CONCLUSIONS: Our results confirm that lack of insight is highly prevalent in schizophrenia spectrum disorders, particularly when patients experience delusions. This study adds insight-related data to the growing symptom-based research, where specific types of psychotic experiences such as hallucinations and delusions could form different psychopathological patterns, linking the phenomenology of delusions to a lack of clinical insight.

Feasibility and Short-Term SpO2/FiO2 Changes in Hospitalized Adults with COVID-19 Pneumonia after Chest Physiotherapy with Threshold PEP Valve: A Cross-Sectional Study.

BACKGROUND: One of the main features of COVID-19 pneumonia is hypoxemic acute respiratory failure (ARF), often requiring ventilatory support. The influence of chest physiotherapy in patients with ARF is not extensively studied. The aim of the study was to analyze the short-time effects of chest physiotherapy using a 10 cm H2O threshold valve in patients with COVID-19 and ARF. Methods; Quasi-experimental cross-sectional study, in hospitalized patients from March to May 2020. The fractions of inspired oxygen, oxygen saturation, heart rate, respiratory rate and dyspnea were collected before and after the starting session (day 1) and after the 5th day of therapy. RESULTS: The final sample size included 125 patients. Significant differences (p < 0.01) were found in the pre-post intervention SpO2/FiO2 ratio (250 ± 88.4 vs. 275.6 ± 97.5, p < 0.001), reaching 354.4 ± 110.2 after 5 days of therapy (p < 0.001 with respect to the baseline). The respiratory and heart rate dyspnea level did not change during the intervention. In patients needing FiO2 > 0.4, the SpO2/FiO2 ratio improvement was higher than in patients with milder severity (46.85 ± 77.69, p < 0.01). CONCLUSIONS: Chest physiotherapy with a 10 cm H2O threshold valve seems to be a safe and tolerated intervention with short-term improvement in oxygenation in patients with COVID-19 pneumonia.

Real-World Outcomes in Patients with Metastatic Colorectal Cancer in Spain: The RWD-ACROSS Study.

The retrospective, observational RWD-ACROSS study analyzed disease characteristics, systemic treatment, and survival in patients with metastatic colorectal cancer (mCRC) in Spain. In total, 2002 patients were enrolled (mean age 65.3 years; 62.7% male). Overall median overall survival (OS) was 26.72 months, and was longer in patients with left-sided tumors (28.85 vs. 21.04 months (right-sided tumors); p < 0.0001) and in patients receiving first-line anti-epidermal growth factor receptor (EGFR) treatment (31.21 vs. 26.75 (anti-vascular endothelial growth factor (VEGF) treatment) and 24.45 months (chemotherapy); p = 0.002). Overall median progression-free survival (PFS) was 10.72 months and was longer in patients with left-sided tumors (11.24 vs. 9.31 months (right-sided tumors); p < 0.0001), and in patients receiving either first-line anti-EGFR or anti-VEGF (12.13 and 12.00 vs. 8.98 months (chemotherapy); p < 0.001). PFS was longer with anti-VEGF treatment in patients with right-sided tumors and wild-type RAS (11.24 vs. 8.78 (anti-EGFR) and 7.83 months (chemotherapy); p = 0.025). Both anti-EGFR and anti-VEGF produced longer PFS in patients with left-sided tumors and wild-type RAS than chemotherapy alone (12.39 and 13.14 vs. 9.83 months; p = 0.011). In patients with left-sided tumors and mutant RAS, anti-VEGF produced a longer PFS than chemotherapy alone (12.36 vs. 9.34 months; p = 0.001). In Spain, wild-type RAS or left-sided mCRC tumors are predictive of longer survival times.

The Effects of Accompaniment on Maternal Anxiety During Elective Cesarean Delivery: A Quasi-experimental Study.

BACKGROUND: In Spain, allowing women to be accompanied by their partners during cesarean deliveries is a poorly consolidated practice. Going through this experience alone, not only deprives women from the opportunity of sharing the birth with their partners, but also, forces them to face, on their own, one of the most stressful experiences during pregnancy. OBJECTIVE: To analyze whether significant differences exist in levels of anxiety of women who receive an elective cesarean delivery, according to whether they are allowed to be accompanied by their partners. DESIGN: Quasi-experimental, longitudinal, prospective study, comparing a group of 31 women receiving elective cesarean deliveries, without the presence of their partners, with a group of 33 women with elective cesarean deliveries who were accompanied by their partners. Anxiety levels were assessed using the STAI-State/Trait scale. Participants were given a questionnaire to assess their level of satisfaction with the care received. RESULTS: Anxiety measured via total scores on the STAI-S scale was significantly lower (p < 0.004) among the women who were accompanied by their partners during the elective cesarean delivery (median = 25), compared to the group who were not (median = 50). The differences were also significant (p < 0.003) considering the impact of accompaniment upon the group with high scores in the STAI-S (> 31) and continue to be significant when using the cut-off point of very high scores on the STAI-S (> 45). CONCLUSIONS: Presence of partners during elective cesareans is a key factor for decreasing the anxiety caused by the surgery and for improving the overall experience of cesarean deliveries.

What is already known on this subject? Cesarean deliveries are one of the most stressful life experiences. Allowing women to be accompanied by their partners during cesarean deliveries is a poorly consolidated practice in some countries. Otherwise relevant international institutions recommend allowing an accompanying adult, present with the mother in the operating room during the entire process.What this study adds? Presence of partners during elective cesareans is a key factor for decreasing deliveries' anxiety, improving the overall experience, but it needs a mentality change in the obstetric and surgical team. These results could change the services organization in a more humane delivery, with overall positive impact in the patients' care.

The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer.

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. MATERIALS AND METHODS: Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. RESULTS: The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). CONCLUSION: These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.

Role of Extracellular Vesicles Produced by Stem Cells in Tissue Repair.

The purpose of this Special Issue is to emphasize the great potential of the translational applications of extracellular vesicles (EVs) produced by stem cells (mesenchymal stem cells, induced pluripotent stem cells, etc [...].

An Exploratory Analysis on the 2D:4D Digit Ratio and Its Relationship with Social Responsiveness in Adults with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a genetic disorder produced by a lack of expression of paternally derived genes in the 15q11-13 region. Research has generally focused on its genetic and behavioral expression, but only a few studies have examined epigenetic influences. Prenatal testosterone or the maternal testosterone-to-estradiol ratio (MaTtEr) has been suggested to play an important role in the development of the 'social brain' during pregnancy. Some studies propose the 2D:4D digit ratio of the hand as an indirect MaTtEr measure. The relationship between social performance and MaTtEr has been studied in other neurodevelopmental conditions such as Autism Spectrum Disorder (ASD), but to our best knowledge, it has never been studied in PWS. Therefore, our study aims to clarify the possible existence of a relationship between social performance-as measured using the Social Responsiveness Scale (SRS)-and MaTtEr levels using the 2D:4D ratio. We found that, as a group, PWS individuals have shorter index and ring fingers than the control group, but no significant difference in the 2D:4D ratios. The 2D:4D ratio showed a correlation only with Restricted Interests and Repetitive Behavior Subscale, where a positive correlation only for male individuals with PWS was found. Considering only PWS with previous GH treatment during childhood/adolescence (PWS-GH), index and ring fingers did not show differences in length with the control group, but the 2D:4D ratio was significantly higher in the right or dominant hand compared to controls.

Thrombospondin-1 induction and VEGF reduction by proteasome inhibition.

The present study focuses on investigating the expression of thrombospondin-1 (TSP-1), a natural inhibitor of neovascularization. Immunofluorescent staining was used to detect the expression of TSP-1 in rabbit corneal tissue with vascularization induced by limbectomy. TSP-1 was detected in healthy and Cultured Autologous Oral Mucosal Epithelial Cell Sheet (CAOMECS) grafted rabbit corneas. TSP-1 was not detected in diseased corneas. Rabbit and human primary oral mucosal and corneal epithelial cells were cultured and treated with proteasome inhibitor (PI) in vitro. Changes in the expression of TSP-1, HIF-1 alpha and 2 alpha, VEGF-A, and VEGF receptor were analyzed by Western blotting. Neovascularization developed in rabbits' corneas as early as 1 month after limbectomy and was stable for at least 3 months. HIF-1 alpha and VEGF-A expression was reduced in CAOMECS grafted corneas, as compared to sham corneas. While TSP-1 expression was decreased in injured corneas, it was expressed in CAOMECS grafted corneas, but still less expressed compared to healthy corneas. PI treatment, of human oral mucosal and corneal epithelial cells increased TSP-1 expression and reduced VEGF-A expression. The results showed that TSP-1 expression was lost in injured corneal surface and that CAOMECS grafting restored TSP-1 expression to certain extent. Proteasome inhibition treatment increased TSP-1 and decreased VEGF-A expression in human oral mucosal and corneal epithelial cells. The result suggests that corneal neovascularization could be managed with the inhibition of the proteasome after CAOMECS grafting and increase corneal transparency.

An adapted scale to evaluate insight in Prader-Willi Syndrome

ObjectiveTo develop an insight scale for Prader-Willi Syndrome (PWS), a genetically determined neurodevelopmental disorder with different psychopathological and behavioural problems.MethodologyA sample of 36 PWS patients (58.3% women) attended at the Endocrinological Department of the Corporació Sanitària Parc Taulí (Sabadell, Barcelona) was evaluated. Insight was assessed by means of an adapted version of the Scale of Unawareness of Mental Disorder (SUMD), including three general insight dimensions: awareness of having a PWS, awareness of the effects of psychopharmacological medication and awareness of the social consequences, as well as three items that assess awareness of each particular symptom of the disease (obesity/overweight, excessive appetite and excessive food intake).ResultsThe final Scale included six items and demonstrated an adequate internal consistency (Cronbach Alfa of 0.857 for Caregivers and 0.798 for Clinicians) but a high inter-rate variability. External validation using an Analytical-Visual Insight Scale was adequate.ConclusionsThe Adapted version for Prader-Willi patients of the Scale of Unawareness of Mental Disorder (APW-SUD) showed adequate psychometric properties and it is an easy to administer means to assess insight in this population. (AU)

ObjetivoDesarrollar una escala de insight para el síndrome de Prader-Willi (PWS), un trastorno del desarrollo genéticamente determinado, con diferentes problemas psicopatológicos y conductuales.MetodologíaEvaluamos una muestra de 36 PWS (58,3% mujeres), atendidos en el Departamento de Endocrinología de la Corporació Sanitària Parc Taulí (Sabadell, Barcelona). El insight fue valorado mediante una versión adaptada de la Scale of Unawareness of Mental Disorder, incluyendo tres dimensiones generales: conciencia de tener PWS, conciencia de los efectos de la medicación psicofarmacológica, y conciencia de las consecuencias sociales, así como tres ítems que valoran el insight de cada síntoma particular de la enfermedad (obesidad/sobrepeso, excesivo apetito y exceso de ingesta).ResultadosLa escala final incluye seis ítems y ha demostrado una adecuada consistencia interna (alfa de Cronbach de 0,857 para cuidadores y de 0,798 para clínicos), pero una alta variabilidad interobservador. La validación externa usando una escala analítico-visual de insight fue adecuada.ConclusionesLa versión adaptada para pacientes con PWS de la Scale of Unawareness of Mental Disorder muestra adecuadas propiedades psicométricas y es una vía fácil de administrar para evaluar el insight en esta población. (AU)

Posology and Serum-/Xeno-Free Engineered Adipose Stromal Cells Cell Sheets.

Well-characterized adipose stem cells and chemically defined culture media are important factors that control the production of the cell sheet, used in translational medicine. In this study, we have developed and engineered multilayer adipose stem cell cell sheets (ASCCSs) using chemically defined/serum-free culture media: undifferentiated or differentiated into osteoblasts and chondrocytes. In addition, using the cell sheet transmittance, we estimated the number of cells per cell sheet. Undifferentiated ASCCSs were engineered in 10 days, using serum-free/xeno-free culture media. They were CD29+, CD73+, CD90+, CD105+, HLA-A+, and HLA-DR-. ASCCSs differentiated into chondrocytes and osteoblasts were also engineered using chemically defined and animal-free culture media, in only 14 days. The addition of an ROCK inhibitor improved the chondrocyte cell sheet engineering. The decrease in the cell sheet transmittance rate was higher for the osteoblast cell sheets due to the intracellular Ca2+ accumulation. The estimation of cell number per cell sheet was carried out with the transmittance, which will provide important information for cell sheet posology. In conclusion, three types of ASCCSs were engineered using serum-free, xeno-free culture media, expressing their specific markers. Their transmittance measurement allowed estimating the number of cells per cell sheet, with a non-invasive methodology.

Social Responsiveness and Psychosocial Functioning in Adults with Prader-Willi Syndrome.

Although various studies have investigated symptoms of autism spectrum disorder (ASD) in Prader−Willi syndrome (PWS), little is known about the consequences of these symptoms, especially in psychosocial function. We aimed to explore ASD symptoms in adults with PWS with special attention to psychosocial functionality. This cross-sectional study included 26 adults (15 women) with PWS who attended a reference unit for rare diseases. Participants' primary caregivers completed the Social Responsiveness Scale (SRS), and clinicians assessed multidimensional functioning with the Personal and Social Performance Scale (PSP). Impaired social responsiveness was identified in 20 (76.9%) participants, and manifest to marked difficulties in social functioning were identified in 13 (50%). Participants with impaired social responsiveness (SRS ≥ 60) had significantly worse scores in functionality measured with the PSP (U = 12.5; p = 0.009) and with three of the four PSP main areas. Moreover, scores for the Social Cognition domain of the SRS correlated positively with the Socially useful activities (p < 0.05) and Personal and social relationships (p < 0.01) main areas of the PSP. These results suggest that difficulties in social skills should be assessed in all psychosocial evaluations of patients with PWS.

An adapted scale to evaluate insight in Prader-Willi Syndrome.

OBJECTIVE: To develop an insight scale for Prader-Willi Syndrome (PWS), a genetically determined neurodevelopmental disorder with different psychopathological and behavioural problems. METHODOLOGY: A sample of 36 PWS patients (58.3% women) attended at the Endocrinological Department of the Corporació Sanitària Parc Taulí (Sabadell, Barcelona) was evaluated. Insight was assessed by means of an adapted version of the Scale of Unawareness of Mental Disorder (SUMD), including three general insight dimensions: awareness of having a PWS, awareness of the effects of psychopharmacological medication and awareness of the social consequences, as well as three items that assess awareness of each particular symptom of the disease (obesity/overweight, excessive appetite and excessive food intake). RESULTS: The final Scale included six items and demonstrated an adequate internal consistency (Cronbach Alfa of 0.857 for Caregivers and 0.798 for Clinicians) but a high inter-rate variability. External validation using an Analytical-Visual Insight Scale was adequate. CONCLUSIONS: The Adapted version for Prader-Willi patients of the Scale of Unawareness of Mental Disorder (APW-SUD) showed adequate psychometric properties and it is an easy to administer means to assess insight in this population.

Tracking temporal response dynamics in the ventral striatum during social feedback in anorexia nervosa: A functional magnetic resonance imaging exploratory study.

OBJECTIVE: Research suggests abnormalities in reward-based processes in anorexia nervosa (AN). However, few studies have explored if such alterations might be associated with different temporal activation patterns. This study aims to characterize alterations in time-dependent processes in the ventral striatum (VS) during social feedback in AN using functional magnetic resonance imaging (fMRI). METHOD: Twenty women with restrictive-subtype AN and 20 age-matched healthy controls (HC) underwent a social judgment experimental fMRI task. Temporal VS hemodynamic responses were extracted in SPM for each participant and each social condition (acceptance/rejection). RESULTS: Compared with age-matched HC, patients with AN showed a significant time by group interaction of peak VS response throughout the task, with a progressive blunting of peak activation responses, accompanied by a progressive increase in baseline activity levels over time. DISCUSSION: The results suggest an attenuated response pattern to repetitive social rejection in the VS in patients with AN, together with a difficulty in returning to baseline. The information obtained from this study will guide future, design-specific studies to further explore alterations temporal dynamics.

Measurement of the Adipose Stem Cells Cell Sheets Transmittance.

In the field of cell therapy, the interest in cell sheet technology is increasing. To determine the cell sheet harvesting time requires experience and practice, and different factors could change the harvesting time (variability among donors and culture media, between cell culture dishes, initial cell seeding density). We have developed a device that can measure the transmittance of the multilayer cell sheets, using a light emitting diode and a light detector, to estimate the harvesting time. The transmittance of the adipose stromal cells cell sheets (ASCCS) was measured every other day as soon as the cells were confluent, up to 12 days. The ASCCS, from three different initial seeding densities, were harvested at 8, 10, and 12 days after seeding. Real-time PCR and immunostaining confirmed the expression of specific cell markers (CD29, CD73, CD90, CD105, HLA-A, HLA-DR), but less than the isolated adipose stromal cells. The number of cells per cell sheets, the average thickness per cell sheet, and the corresponding transmittance showed no correlation. Decrease of the transmittance seems to be correlated with the cell sheet maturation. For the first time, we are reporting the success development of a device to estimate ASCCS harvesting time based on their transmittance.

Efficacy of Low-Dose versus High-Dose Continuous Cyclic Azithromycin Therapy for Preventing Acute Exacerbations of COPD.

BACKGROUND: Long-term azithromycin therapy significantly reduces the frequency of COPD exacerbations (ECOPD). However, previous studies have used different dosing regimens, and the efficacy of these regimens has not been compared. OBJECTIVE: Compare the efficacy of low-dose with high-dose continuous cyclic azithromycin (CC-A) in severe COPD. METHODS: Patients with severe COPD and repeated exacerbations (ECOPD ≥4 or ≥3 with at least 1 hospital admission in the previous year) were prospectively recruited (January 2017 to December 2019) as a multicenter cohort (from 3 university hospitals in the Barcelona area) and treated with low-dose CC-A: 250 mg 3 times per week (250-CC-A group). This cohort was compared with a historical (January 2007 to December 2013) single-center cohort of severe COPD with frequent ECOPD treated with high-dose CC-A: 500 mg 3 times per week (500-CC-A group). To assess differences in ECOPD prevention according to the administration of low-dose or high-dose CC-A, moderate-to-severe ECOPD was evaluated during the 12-month period before and after starting CC-A therapy. RESULTS: Fifty-eight patients with severe COPD were evaluated: 37 in the low-dose group and 21 in the high-dose group. The 250-CC-A therapy group achieved a mean reduction in moderate-to-severe ECOPD of 65.6% at 12 months after starting CC-A therapy (with a 61.5% reduction in hospitalizations), while the 500-CC-A group achieved a reduction of 60.5% (with a 44.8% reduction in hospitalizations). No significant differences between 250-CC-A and 500-CC-A dosages were observed in the mean annual reduction of moderate-to-severe ECOPD (p = 0.55) or hospitalizations (p = 0.07) with respect to the year prior to starting CC-A. CONCLUSIONS: Low-dose 250-CC-A therapy over a 1-year period is similar to high-dose 500-CC-A in reducing exacerbation frequency in severe COPD patients with frequent ECOPD despite maximal medical therapy.

Multidimensional Evaluation of Awareness in Prader-Willi Syndrome.

There are no studies about insight or awareness of illness in patients with Prader-Willi Syndrome (PWS). The objective of this study was to explore the level of awareness of the disorder, of the need for medication, and of the social consequences of the disease, as well as of its main symptoms in PWS. We also aimed to explore relationships between awareness and sociodemographic and clinical characteristics, and to compare all data with a matched sample of patients with psychosis. Insight was assessed by an Adapted version of the Scale of Unawareness of Mental Disorder in a cross-sectional pilot study at a University Hospital. Thirty-six individuals with PWS (58.3% women) were included. Results showed that PWS patients had a good awareness of the illness and of the effects of medication, in contrast to a lack of awareness of illness' social consequences. Awareness of obesity/overweight was excellent, as was the awareness of excessive appetite. Awareness of excessive food intake was only mild. Insight correlated with age and functionality, but not with BMI. PWS patients showed a better insight into the illness but a similar awareness of the effects of the medication and of the social consequences of the disease as compared to schizophrenia-spectrum patients. This profile of insight may have relevant clinical implications.

Association of Calcitriol Supplementation with Reduced COVID-19 Mortality in Patients with Chronic Kidney Disease: A Population-Based Study.

Treatment with calcitriol, the hormonal form of vitamin D, has shown beneficial effects in experimental models of acute lung injury. In this study, we aimed to analyze the associations between calcitriol supplementation and the risk of SARS-CoV2 infection or COVID-19 mortality. Individuals ≥18 years old living in Catalonia and supplemented with calcitriol from April 2019 to February 2020 were compared with propensity score matched controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality. Associations between calcitriol supplementation and outcome variables were analyzed using multivariable Cox proportional regression. A total of 8076 patients were identified as being on calcitriol treatment. Advanced chronic kidney disease and hypoparathyroidism were the most frequent reasons for calcitriol supplementation in our population. Calcitriol use was associated with reduced risk of SARS-CoV2 infection (HR 0.78 [CI 95% 0.64-0.94], p = 0.010), reduced risk of severe COVID-19 and reduced COVID-19 mortality (HR 0.57 (CI 95% 0.41-0.80), p = 0.001) in patients with advanced chronic kidney disease. In addition, an inverse association between mean daily calcitriol dose and COVID-19 severity or mortality was observed in treated patients, independently of renal function. Our findings point out that patients with advanced chronic kidney disease could benefit from calcitriol supplementation during the COVID-19 pandemic.

Prognostic value of lymphocyte-to-monocyte ratio previously determined to surgery in patients with non-metastatic renal cell carcinoma: A systematic review and a prisma-compliant meta-analysis.

BACKGROUND: The prognostic value of pretreatment lymphocyte to monocyte ratio in patients with renal cell carcinoma and, especially, in non-metastatic patients remains controversial. METHODS: We conducted a PRISMA-compliant meta-analysis to systematically assess the prognostic value of LMR in patients with non-metastatic RCC. Overall survival, cancer-specific survival, and disease-free survival were analyzed. Pooled hazard ratios and 95% confidence intervals were calculated. RESULTS: Seven studies comprising 4666 patients were included in the analysis. Unlike those observed in a previous meta-analysis, a lower lymphocyte to monocyte ratio was associated with poorer cancer-specific survival (fix-effect model, hazard ratio 3.04, 95% confidence intervals 2.05-4.51, P < .05). Heterogeneity Chi-squared value Q exp = 0. (P = .82) (I2 = 0%). However, the association between a low lymphocyte to monocyte ratio and overall survival or disease-free survival did not obtain significance. CONCLUSION: A lower lymphocyte to monocyte ratio implied poor cancer-specific survival in patients with non-metastatic renal cell carcinoma. Prospective studies are required to confirm our findings. REGISTRATION NUMBER: ClinicalTrials.gov (identifier: NCT04213664).

Volume Infusion Markedly Increases Femoral dP/dtmax in Fluid-Responsive Patients Only.

OBJECTIVES: To evaluate the preload dependence of femoral maximal change in pressure over time (dP/dtmax) during volume expansion in preload dependent and independent critically ill patients. DESIGN: Retrospective database analysis. SETTING: Two adult polyvalent ICUs. PATIENTS: Twenty-five critically ill patients with acute circulatory failure. INTERVENTIONS: Thirty-five fluid infusions of 500 mL normal saline. MEASUREMENTS AND MAIN RESULTS: Changes in femoral dP/dtmax, systolic, diastolic, and pulse femoral arterial pressure were obtained from the pressure waveform analysis using the PiCCO2 system (Pulsion Medical Systems, Feldkirchen, Germany). Stroke volume index was obtained by transpulmonary thermodilution. Statistical analysis was performed comparing results before and after volume expansion and according to the presence or absence of preload dependence (increases in stroke volume index ≥ 15%). Femoral dP/dtmax increased by 46% after fluid infusion in preload-dependent cases (mean change = 510.6 mm Hg·s; p = 0.005) and remained stable in preload-independent ones (mean change = 49.2 mm Hg·s; p = 0.114). Fluid-induced changes in femoral dP/dtmax correlated with fluid-induced changes in stroke volume index in preload-dependent cases (r = 0.618; p = 0.032), but not in preload-independent ones. Femoral dP/dtmax strongly correlated with pulse and systolic arterial pressures and with total arterial stiffness, regardless of the preload dependence status (r > 0.9 and p < 0.001 in all cases). CONCLUSIONS: Femoral dP/dtmax increased with volume expansion in case of preload dependence but not in case of preload independence and was strongly related to pulse pressure and total arterial stiffness regardless of preload dependence status. Therefore, femoral dP/dtmax is not a load-independent marker of left ventricular contractility and should be not used to track contractility in critically ill patients.