Comparison of 2 different inhaled epoprostenol dosing strategies for acute respiratory distress syndrome in critically ill adults: Weight-based vs fixed-dose administration.

PURPOSE: Inhaled epoprostenol (iEPO) is a viable, temporizing option for acute respiratory distress syndrome (ARDS), although the optimal iEPO dosing strategy remains inconclusive. The purpose of this study was to evaluate oxygenation and ventilation parameters in a comparison of weight-based and fixed-dose iEPO in adult patients with moderate-to-severe ARDS. METHODS: A retrospective cohort study was conducted at 2 academic medical centers in adult intensive care unit (ICU) patients administered either fixed-dose or weight-based iEPO for moderate-to-severe ARDS. The primary endpoint was the highest recorded change in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) within 4 hours of baseline. Secondary analyses compared responder rates within 4 hours of initiation, oxygenation and ventilation parameters, in-hospital mortality rates, mechanical ventilation duration, length of stay (ICU and hospital), and tracheostomy rates between the study groups. RESULTS: A total of 294 patients were included, n = 194 with 100 (34.0%) and 194 (66.0%) in the weight-based and fixed-dose iEPO groups, respectively. The mean (SD) change in the highest recorded PaO2/FiO2 value from baseline up to 4 hours after initiation in the fixed-dose and weight-based groups was 81.1 (106.0) and 41.0 (72.5) mm Hg, respectively (P = 0.0015). The responder rate at 4 hours after iEPO initiation was significantly higher in the fixed-dose group (69.9%) than in the weight-based group (30.1%) (P = 0.02). The only predictor of response was fixed-dose administration (odds ratio, 3.28; 95% confidence interval, 1.6-6.7; P = 0.0012). Clinical outcomes were comparable between the groups. CONCLUSION: Fixed-dose iEPO was associated with significantly higher response rates then weight-based iEPO during the first 4 hours of therapy. Fixed-dose iEPO is a more convenient strategy than weight-based approaches.

Impact of the COVID pandemic on vascular access creation for haemodialysis in 16 Spanish haemodialysis centres.

Background: The coronavirus disease (COVID) pandemic has resulted in a major disruption in healthcare that has affected several medical and surgical specialties. European and American Vascular Societies have proposed deferring the creation of an elective vascular access (VA) [autologous or prosthetic arteriovenous fistula (AVF) or arteriovenous graft (AVG)] in incident patients on haemodialysis (HD) in the era of the COVID pandemic. The aim of this study is to examine the impact of the COVID pandemic on VA creation and the central venous catheter (CVC)-related hospitalizations and complications in HD patients dialyzed in 16 Spanish HD units of three different regions. Methods: We compared retrospectively two periods of time: the pre-COVID (1 January 2019-11 March 2020) and the COVID era (12 March 2020-30 June 2021) in all HD patients (prevalent and incident) dialyzed in our 16 HD centres. The variables analysed were type of VA (CVC, AVF and AVG) created, percentage of CVC in incident and prevalent HD patients, CVC-related hospitalizations and complications (infection, extrusion, disfunction, catheter removal) and percentage of CVC HD sessions that did not reach the goal of Kt (>45) as a marker of HD adequacy. Results: A total of 1791 VAs for HD were created and 905 patients started HD during the study period. Patients who underwent vascular access surgery during the COVID period compared with pre-COVID period were significantly younger, with a significant decrease in surgical activity to create AVFs and AVGs in older HD patients (>75 and >85 years of age). There was a significant increase in CVC placement (from 59.7% to 69.5%; P < 0.001) from the pre-COVID to the COVID period. During the COVID pandemic, a significantly higher number of patients started HD through a CVC (80.3% versus 69.1%; P < 0.001). The percentage of CVC in prevalent HD patients has not decreased in the 19 months since the start of the pandemic [414 CVC/1058 prevalent patients (39.4%)]. No significant changes were detected in CVC-related hospitalizations between the pre-COVID and COVID periods. In the COVID period, a significant increase in catheter replacement and the percentage of HD session that did not reach the HD dose objective (Kt > 45) was observed. Conclusions: COVID has presented a public health system crisis that has influenced VA for HD, with an increase in CVCs relative to AVFs. A decrease in HD sessions that did not reach the HD dose objective was observed in the COVID period compared with a pre-COVID period.

Rapid decline of anti-SARS-CoV-2 antibodies in patients on haemodialysis: the COVID-FRIAT study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients on haemodialysis (HD) have high mortality. We investigated the value of reverse transcription polymerase chain reaction (RT-PCR) and the dynamic changes of antibodies (enzyme-linked immunosorbent assay immunoglobulin M (IgM) + IgA and/or IgG) in a large HD cohort. METHODS: We conducted a prospective observational study in 10 Madrid HD centres. Infection rate, anti-SARS-CoV-2 antibody dynamics and the incidence of asymptomatic SARS-CoV-2 infection (defined by positive RT-PCR, IgM + IgA and/or IgG) were assessed. RESULTS: From 1 March to 15 April 2020, 136 of 808 (16.8%) HD patients were diagnosed with symptomatic COVID-19 by RT-PCR of nasopharyngeal swabs and 42/136 (31%) died. In the second fortnight of April, RT-PCR and anti-SARS-CoV-2 antibodies were assessed in 763 of the surviving patients. At this point, 69/91 (75.8%) symptomatic COVID-19 patients had anti-SARS-CoV-2 antibodies. Four weeks later, 15.4% (10/65) of initially antibody-positive patients had become negative. Among patients without prior symptomatic COVID-19, 9/672 (1.3%) were RT-PCR positive and 101/672 patients (15.0%) were antibody positive. Four weeks later, 62/86 (72.1%) of initially antibody-positive patients had become negative. Considering only IgG titres, serology remained positive after 4 weeks in 90% (54/60) of patients with symptomatic COVID-19 and in 52.5% (21/40) of asymptomatic patients. The probability of an adequate serologic response (defined as the development of anti-SARS-CoV-2 antibodies that persisted at 4 weeks) was higher in patients who had symptomatic COVID-19 than in asymptomatic SARS-CoV-2 infection {odds ratio [OR) 4.04 [95% confidence interval (CI) 2.04-7.99]} corrected for age, Charlson comorbidity index score and time on HD. Living in a nursing home [OR 5.9 (95% CI 2.3-15.1)] was the main risk factor for SARS-CoV-2 infection. CONCLUSIONS: The anti-SARS-CoV-2 antibody immune response in HD patients depends on clinical presentation. The antibody titres decay earlier than previously reported for the general population. This inadequate immune response raises questions about the efficacy of future vaccines.

Utilidad del MAPA y bioimpedancia para el tratamiento y control de la HTA en pacientes en hemodiálisis crónica / Usefulness of ABPM and bioimpedance for the treatment and control of hypertension in patients on chronic haemodialysis

INTRODUCCIÓN: La hipertensión arterial (HTA) en los pacientes en hemodiálisis (HD) es muy frecuente y se asocia a un aumento de la morbimortalidad. Los objetivos de nuestro trabajo han sido: 1. Conocer la tensión arterial (TA) en la sesión de HD. 2. Estudiar la TA, en el periodo interdialítico, mediante monitorización ambulatoria de presión arterial (MAPA) de 44 horas. 3. Conocer la concordancia entre la TA en la sesión de HD y MAPA. 4. Valorar los cambios de tratamiento después de la realización del MAPA. 5. Realizar una bioimpedancia espectroscópica (BIS) a todos los pacientes y en los hiperhidratados e hipertensos, según MAPA, valorar cambios en la TA después de ajustar el peso seco (PS). 6. Conocer factores asociados a la TA sistólica (TAS) y TA diastólica (TAD) promedio del MAPA. MATERIAL Y MÉTODOS: Estudio prospectivo observacional, que incluyó a 100 pacientes de nuestra unidad de diálisis. Se han recogido las tensiones pre y post-HD, durante dos semanas y, posteriormente, colocamos a los pacientes un aparato de MAPA a mitad de semana, durante 44 horas. Previo a comenzar la siguiente sesión de diálisis, realizamos una BIS. A aquellos pacientes hiperhidratados e hipertensos, según MAPA, se les realizó un segundo MAPA para valorar cambios en los valores de TA. RESULTADOS: Según MAPA, el 65% de pacientes presentaron una TA diurna > 135/85 mmHg, 90% TA nocturna > 120/70 mmHg y 76% TA promedio > 130/80 mmHg. El 11% presentó un patrón dipper, 51% no dipper y 38% riser. Las TAS y TAD promedio fueron 4,7 mmHg (3,8%) y 1,1 mmHg (1,64%) más altas el segundo día. En el 6% de pacientes fue necesario bajar la dosis de antihipertensivos, 9% suspenderlos, 28% aumentar dosis y 17% añadir un nuevo fármaco. La TAD pre-HD es la que mejor concordancia presenta con el MAPA. Después de realizar BIS y ajustar PS hubo un descenso significativo en todas las cifras de TA. El análisis univariante mostró que la TAS promedio fue más alta en pacientes con baño alto en calcio, mayor cantidad de fármacos antihipertensivos y mayores dosis de eritropoyetina (EPO). El análisis multivariante mostró asociación significativa para EPO y número de fármacos (p < 0,01). La TAD promedio fue más alta en pacientes más jóvenes, con Charlson más bajos, menor índice de masa corporal (IMC), menos diuresis, no diabéticos y con mayores dosis de EPO. El estudio de regresión lineal mostró como variables significativas la edad (p < 0,005), IMC (p < 0,03) y EPO (p < 0,03). CONCLUSIONES: Nuestro estudio muestra: 1. La variabilidad de criterio de HTA, según utilicemos cifras de TA durante la sesión de HD o MAPA. 2. La variabilidad de TA en el periodo interdiálisis. 3. La TAD prediálisis es la que mejor concordancia presenta con el MAPA. 4. La utilización conjunta de la BIS y el MAPA mejora el control de la TA. 5. La dosis de EPO es el factor más importante asociado a la HTA en nuestros pacientes

INTRODUCTION: Hypertension is very common in haemodialysis (HD) patients, and is associated with increased morbidity and mortality rates. The goals of our research were to: 1. Measure blood pressure (BP) during HD sessions; 2. Study BP in between HD sessions with 44-hour Ambulatory Blood Pressure Monitoring (ABPM); 3. Identify differences between the BP recorded during HD and with the ABPM; 4. Evaluate changes in treatment after the ABPM; 5. Perform bioimpedance spectroscopy (BIS) on all patients and, in those hyper-hydrated or hypertensive according to ABPM, assess for changes in BP after adjusting the dry weight; 6. Identify factors associated with average systolic and diastolic BP measured by ABPM. MATERIAL AND METHODS: Prospective observational study, which included 100 patients from our dialysis unit. We measured BP before and after the HD sessions for two weeks and then, mid-week, we attached the ABPM device to the patients for 44 hours. Before starting the following dialysis session, we performed BIS. A second ABPM was performed on hyper-hydrated patients and patients hypertensive according to ABPM to evaluate changes in BP values. RESULTS: According to the ABPM, 65% of patients had daytime BP > 135/85 mmHg, 90% night-time BP > 120/70 mmHg and 76% average BP > 130/80 mmHg; 11% had a dipper pattern, 51% non-dipper and 38% riser. The average systolic and diastolic BP readings were 4.7 mmHg (3.8%) and 1.1 mmHg (1.64%) higher on the second day. The dose of antihypertensive medication had to be lowered in 6% of patients, 9% had to stop taking it, 28% needed increased doses and 17% had to add a new drug. The pre-HD diastolic BP best matched the ABPM. After performing the bioimpedance and adjusting dry weight, there was a statistically significant decrease in all BP values. The univariate analysis showed that the average systolic BP was higher in patients with a high-calcium dialysis bath, more antihypertensive drugs and higher doses of EPO. The multivariate analysis showed significant association for EPO and number of drugs (p < 0.01). The average diastolic BP was higher in younger patients and patients with lower Charlson index, lower body mass index and less diuresis, those on higher doses of EPO and non-diabetics. The linear regression study showed age (p < 0.005), body mass index (p < 0.03) and EPO (p < 0.03) as significant variables. CONCLUSIONS: Our study shows: 1. The variability of hypertension criteria according to use of BP values from during the HD session or ABPM; 2. The variability of BP in the interdialysis period; 3. That the pre-dialysis diastolic BP best corresponds with the ABPM. 4. That the use of both BIS and ABPM improves the control of BP; 5. That the dose of EPO is the most important factor associated with hypertension in our patients

Usefulness of ABPM and bioimpedance for the treatment and control of hypertension in patients on chronic haemodialysis.

INTRODUCTION: Hypertension is very common in haemodialysis (HD) patients, and is associated with increased morbidity and mortality rates. The goals of our research were to: 1. Measure blood pressure (BP) during HD sessions; 2. Study BP in between HD sessions with 44-h Ambulatory Blood Pressure Monitoring (ABPM); 3. Evaluate changes in treatment after the ABPM; 4. Perform bioimpedance spectroscopy (BIS) on all patients and, in those hyper-hydrated or hypertensive according to ABPM, assess for changes in BP after adjusting the dry weight; 5. Identify factors associated with average systolic and diastolic BP measured by ABPM. MATERIAL AND METHODS: Prospective observational study, which included 100 patients from our dialysis unit. We measured BP before and after the HD sessions for two weeks and then, mid-week, we attached the ABPM device to the patients for 44 h. Before starting the following dialysis session, we performed BIS. A second ABPM was performed on hyper-hydrated patients and patients hypertensive according to ABPM to evaluate changes in BP values. RESULTS: According to the ABPM, 65% of patients had daytime BP > 135/85 mmHg, 90% night-time BP > 120/70 mmHg and 76% average BP > 130/80 mmHg; 11% had a dipper pattern, 51% non-dipper and 38% riser. The average systolic and diastolic BP readings were 4.7 mmHg (3.8%) and 1.1 mmHg (1.64%) higher on the second day. The dose of antihypertensive medication had to be lowered in 6% of patients, 9% had to stop taking it, 28% needed increased doses and 17% had to add a new drug. The pre-HD diastolic BP best matched the ABPM. After performing the bioimpedance and adjusting dry weight, there was a statistically significant decrease in all BP values. The univariate analysis showed that the average systolic BP was higher in patients with a high-calcium dialysis bath, more antihypertensive drugs and higher doses of EPO. The multivariate analysis showed significant association for EPO and number of drugs (p < 0.01). The average diastolic BP was higher in younger patients and patients with lower Charlson index, lower body mass index and less diuresis, those on higher doses of EPO and non-diabetics. The linear regression study showed age (p < 0.005), body mass index (p < 0.03) and EPO (p < 0.03) as significant variables. CONCLUSIONS: Our study shows: 1. The variability of hypertension criteria according to use of BP values from during the HD session or ABPM; 2. The variability of BP in the interdialysis period; 3. That the pre-dialysis diastolic BP best corresponds with the ABPM. 4. That the use of both BIS and ABPM improves the control of BP; 5. That the dose of EPO is the most important factor associated with hypertension in our patients.

Usefulness of ABPM and bioimpedance for the treatment and control of hypertension in patients on chronic haemodialysis. / Utilidad del MAPA y bioimpedancia para el tratamiento y control de la HTA en pacientes en hemodiálisis crónica.

INTRODUCTION: Hypertension is very common in haemodialysis (HD) patients, and is associated with increased morbidity and mortality rates. The goals of our research were to: 1. Measure blood pressure (BP) during HD sessions; 2. Study BP in between HD sessions with 44-hour Ambulatory Blood Pressure Monitoring (ABPM); 3. Identify differences between the BP recorded during HD and with the ABPM; 4. Evaluate changes in treatment after the ABPM; 5. Perform bioimpedance spectroscopy (BIS) on all patients and, in those hyper-hydrated or hypertensive according to ABPM, assess for changes in BP after adjusting the dry weight; 6. Identify factors associated with average systolic and diastolic BP measured by ABPM. MATERIAL AND METHODS: Prospective observational study, which included 100 patients from our dialysis unit. We measured BP before and after the HD sessions for two weeks and then, mid-week, we attached the ABPM device to the patients for 44 hours. Before starting the following dialysis session, we performed BIS. A second ABPM was performed on hyper-hydrated patients and patients hypertensive according to ABPM to evaluate changes in BP values. RESULTS: According to the ABPM, 65% of patients had daytime BP > 135/85 mmHg, 90% night-time BP > 120/70 mmHg and 76% average BP > 130/80 mmHg; 11% had a dipper pattern, 51% non-dipper and 38% riser. The average systolic and diastolic BP readings were 4.7 mmHg (3.8%) and 1.1 mmHg (1.64%) higher on the second day. The dose of antihypertensive medication had to be lowered in 6% of patients, 9% had to stop taking it, 28% needed increased doses and 17% had to add a new drug. The pre-HD diastolic BP best matched the ABPM. After performing the bioimpedance and adjusting dry weight, there was a statistically significant decrease in all BP values. The univariate analysis showed that the average systolic BP was higher in patients with a high-calcium dialysis bath, more antihypertensive drugs and higher doses of EPO. The multivariate analysis showed significant association for EPO and number of drugs (p < 0.01). The average diastolic BP was higher in younger patients and patients with lower Charlson index, lower body mass index and less diuresis, those on higher doses of EPO and non-diabetics. The linear regression study showed age (p < 0.005), body mass index (p < 0.03) and EPO (p < 0.03) as significant variables. CONCLUSIONS: Our study shows: 1. The variability of hypertension criteria according to use of BP values from during the HD session or ABPM; 2. The variability of BP in the interdialysis period; 3. That the pre-dialysis diastolic BP best corresponds with the ABPM. 4. That the use of both BIS and ABPM improves the control of BP; 5. That the dose of EPO is the most important factor associated with hypertension in our patients.

Esteatocistoma solitario de cuero cabelludo / Solitary steatocystoma of the scalp

El esteatocistoma es un hamartoma quístico de la porción media de las unidades folículo sebáceas que afecta principalmente el ducto sebáceo. Comúnmente se encuentra de manera múltiple y se transmite en forma autosómica dominante; en algunos casos se presenta en un contexto no familiar y en otros puede ser solitario. La primera descripción del esteatocistoma múltiple (EM) muy probablemente corresponde a Jamieson en 1873. La forma solitaria de esteatocistoma fue descrito por primera vez en 1982 por Brownstein y existen pocos casos descritos en la literatura Presentamos un caso clínico de paciente varón joven con tumoración solitaria en cuero cabelludo que fue extirpado cuyo resultado histopatológico fue de esteatocistoma solitario.

Steatocystoma is a cystic hamartoma of the middle portion of the sebaceous follicular units that mainly affects the sebaceous duct. It commonly presents in multiple forms and is transmitted in an autosomal dominant manner; in some cases, it occurs in a non-familial context and in others it may be solitary. The first description of steatocystoma multiplex (MS) is most likely by Jamieson in 1873. The solitary form of steatocystoma was first described in 1982 by Brownstein and there are few cases described in the literature. We present a clinical case of a young male patient with a solitary tumor on the scalp that was excised and whose histopathological result was solitary steatocystoma.

Human adipose mesenchymal stem cells modulate myeloid cells toward an anti-inflammatory and reparative phenotype: role of IL-6 and PGE2.

BACKGROUND: Mesenchymal stem cells (MSCs) activate the endogenous immune regulatory system, inducing a therapeutic effect in recipients. MSCs have demonstrated the ability to modulate the differentiation of myeloid cells toward a phagocytic and anti-inflammatory profile. Allogeneic, adipose-derived MSCs (ASCs) have been investigated for the management of complex perianal fistula, with darvadstrocel being the first ASC therapy approved in Europe in March 2018. Additionally, ASCs are being explored as a potential treatment in other indications. Yet, despite these clinical advances, their mechanism of action is only partially understood. METHODS: Freshly isolated human monocytes from the peripheral blood were differentiated in vitro toward M0 non-polarized macrophages (Mphs), M1 pro-inflammatory Mphs, M2 anti-inflammatory Mphs, or mature dendritic cells (mDCs) in the presence or absence of ASCs, in non-contact conditions. The phenotype and function of the differentiated myeloid populations were determined by flow cytometry, and their secretome was analyzed by OLINK technology. We also investigated the capacity of ASCs to modulate the phenotype and function of terminally differentiated M1 Mphs. The role of soluble factors interleukin (IL)-6 and prostaglandin E2 (PGE2) on the ability of ASCs to modulate myeloid cells was assessed using neutralization assays, CRISPR/Cas9 knock-down of cyclooxygenase 2 (COX-2), and ASC-conditioned medium assays using pro-inflammatory stimulus. RESULTS: Co-culture of monocytes in the presence of ASCs resulted in the polarization of Mphs and mDCs toward an anti-inflammatory and phagocytic phenotype. This was characterized by an increase in phagocytic receptors on the cell surface of Mphs (M0, M1, and M2) and mDCs, as well as modulation of chemokine receptors and reduced expression of pro-inflammatory, co-stimulatory molecules. ASCs also modulated the secretome of Mphs and mDCs, demonstrated by reduced expression of pro-inflammatory factors and increased expression of anti-inflammatory and reparative factors. Chemical inhibition of PGE2 with indomethacin abolished this modulatory effect, whereas treatment with a neutralizing anti-IL-6 antibody resulted in a partial abolishment. The knock-down of COX-2 in ASCs and the use of IL-1ß-activated ASC-conditioned media confirmed the key role of PGE2 in ASC-mediated myeloid modulation. In our in vitro experimental settings, ASCs failed to modulate the phenotype and function of terminally polarized M1 Mphs. CONCLUSIONS: The results demonstrate that ASCs are able to modulate the in vitro differentiation of myeloid cells toward an anti-inflammatory and reparative profile. This modulatory effect was mediated mainly by PGE2 and, to a lesser extent, IL-6.

How far should we go in optimal cytoreductive surgery for ovarian cancer?

The treatment of ovarian cancer should be appropriate, since clinical and surgical decisions may affect the prognosis; the surgery must be performed by an expert oncological surgeon or gynecological oncologist, it's fundamental roles are cancer staging and cytoreduction. The concept of staging surgery in early stages has its justification in the fact that up to 11% of "early ovarian cancers" will have metastasis in different sites of the peritoneal cavity at the time of diagnosis. In advanced stages of epithelial ovarian cancer, the goal is the complete cytoreduction of all visible macroscopic disease, since this variable is the most strongly associated with increased overall survival and disease-free period. The ideal time for cytoreductive surgery in relation to chemotherapy (before or after) is still under debate. In 2010 a randomized trial (EORTC) was published, comparing 310 patients initially operated (followed by adjuvant chemotherapy) versus 322 patients initially treated with neoadjuvant chemotherapy (followed by cytoreductive surgery); no significant differences in overall survival between groups were found. Another important factor playing a role in survival and in the probability of surgical cytoreductive success is tumor biology; there has been described a clear difference between serous and mucinous tumors, but some groups advocate that maximal surgical effort in mucinous tumors may compensate morbidity with an increase in survival. The extension of resection in cytoreduction is still controversial; some authors have confirmed that the most important factor is the residual disease and that radical surgery is superior to non-radical surgery in terms of overall survival. The need and extent of lymphadenectomy in advanced cancer will be treated in another chapter of this issue. Undoubtedly, an important factor is to perform procedures in specialized centers.

Dissecting Allo-Sensitization After Local Administration of Human Allogeneic Adipose Mesenchymal Stem Cells in Perianal Fistulas of Crohn's Disease Patients.

Adipose mesenchymal stem cells (ASC) are considered minimally immunogenic. This is due to the low expression of human leukocyte antigens I (HLA-I), lack of HLA-II expression and low expression of co-stimulatory molecules such as CD40 and CD80. The low rate of observed immunological rejection as well as the immunomodulatory qualities, position ASC as a promising cell-based therapy for the treatment of a variety of inflammatory indications. Yet, few studies have addressed relevant aspects of immunogenicity such as ASC donor-to-patient HLA histocompatibility or assessment of immune response triggered by ASC administration, particularly in the cases of presensitization. The present study aims to assess allo-immune responses in a cohort of Crohn's disease patients administered with allogeneic ASC (darvadstrocel formerly Cx601) for the treatment of complex perianal fistulas. We identified donor-specific antibodies (DSA) generation in a proportion of patients and observed that patients showing preexisting immunity were prone to generating DSA after allogeneic therapy. Noteworthy, naïve patients generating DSA at week 12 (W12) showed a significant reduction in DSA titer at week 52 (W52), whereas DSA titer was reduced in pre-sensitized patients only with no specificities against the donor administered. Remarkably, we did not observe any correlation of DSA generation with ASC therapeutic efficacy. In vitro complement-dependent cytotoxicity (CDC) studies have revealed limited cytotoxic levels based upon HLA-I expression and binding capacity even in pro-inflammatory conditions. We sought to identify CDC coping mechanisms contributing to the limited cytotoxic killing observed in ASC in vitro. We found that ASC express membrane-bound complement regulatory proteins (mCRPs) CD55, CD46, and CD59 at basal levels, with CD46 more actively expressed in pro-inflammatory conditions. We demonstrated that CD46 is a main driver of CDC signaling; its depletion significantly enhances sensitivity of ASC to CDC. In summary, despite relatively high clearance, DSA generation may represent a major challenge for allogeneic cell therapy management. Sensitization may be a significant concern when evaluating re-treatment or multi-donor trials. It is still unknown whether DSA generation could potentially be the consequence of donor-to-patient interaction and, therefore, subsequently link to efficacy or biological activity. Lastly, we propose that CDC modulators such as CD46 could be used to ultimately link CDC specificity with allogeneic cell therapy efficacy.

Left ventricular endocardial pacing in the real world: Five years of experience at a single center.

BACKGROUND: A left ventricular (LV) endocardial lead implant to achieve cardiac resynchronization therapy (CRT) is feasible when a conventional implant failed due to anatomical or technical issues or when the venous implant was performed but the patient did not respond to the therapy. METHODS: Data about the implantation procedure (age, sex, clinical characteristics, anticoagulant use, and previous devices), patient characteristics (indication, technique used, lead model, complications), and follow-up (clinical and echocardiographic outcome, LV lead electrical measurements) were analyzed for all CRT systems implanted using LV endocardial lead, due to failed conventional implant or nonresponse, between April 2011 and November 2016. RESULTS: Thirty-five patients were implanted with an active fixation LV endocardial lead during the study period, without significant complications. There were no dislodgements or severe complications related to the implant procedure in the follow-up period (36 ± 20 months) and a high percentage of patients responded to therapy, as assessed by several indicators. CONCLUSIONS: An LV endocardial lead implant was feasible when the conventional technique had previously failed or was not effective. A high rate of response was achieved without any significant complications.

Laryngeal chondrosarcoma, case report and literature review.

INTRODUCTION: Chondrosarcoma constitutes 0.2% of all malignant tumors of the larynx. Many surgeons treat it with total laryngectomy due to the limited experience with this neoplasm because its rarity, and although several conservative approaches have been proposed, the data of these techniques are limited and based on retrospective series. PRESENTATION OF CASE: A 52-year-old male with a transglottic submucosal tumor and glottic stenosis in fiberoptic examination showed by tomography a laryngeal tumor that infiltrates vocal cords, glottis, cricoid and thyroid cartilage of 3 × 2.7 × 4 cm. Patient was submitted to total laryngectomy with selective bilateral neck dissection because obstructive tumor. Pathology reported a cricoid cartilage tumor consistent with grade 2 chondrosarcoma. DISCUSSION: Biopsy by laryngoscopy is considered the standard procedure for the diagnosis of laryngeal tumors, however the need for general anesthesia and the difficulty in intubation in some patients with large tumors make difficult to obtain an adequate biopsy in some cases with submucosal tumor. Conservative surgeries should be individualized based on the size and location of the tumor as well as on the patient's general conditions. Radical treatment is recommended for high-grade and large tumors in which conservative surgery would destabilize the cricoid ring. CONCLUSION: There is no diagnostic and treatment approach established for laryngeal chondrosarcoma, we believe that percutaneous biopsy would be the diagnostic test of choice because it is less invasive and has a high sensitivity and specificity; it could also identify patients who are candidates for conservative surgeries.

Transfemoral access when superior venous approach is not feasible equals overall success of permanent pacemaker implantation. Ten-year series.

BACKGROUND: When permanent pacemaker implantation is not possible or advisable via superior venous access (i.e., axillary or subclavian veins), safe and feasible surgical alternatives are required. The femoral approach is relatively unknown and seldom studied. This single-center study analyzed 10-year outcomes of a femoral implantation approach. METHODS: Data about the implantation procedure (indication, approach, lead and pacemaker models, complications), patient characteristics (age, sex, medications, comorbidities), and follow-up were analyzed for all permanent pacemaker implantations using the femoral approach between June 2001 and June 2011. RESULTS: A permanent pacemaker was implanted with the femoral approach in 50 patients (mean age, 76 years [range: 45-96], 31 [61%] men). The most frequent indication was atrioventricular block, associated with sinus rhythm in 30 patients and with atrial fibrillation in eight patients. Overall, 20 patients (40%) were treated with oral anticoagulants postimplantation. Mean implantation time was 64 minutes (range: 20-210) and mean fluoroscopy time was 6.7 minutes (range: 0.2-50). Minimum follow-up window was 1 year (June 2012), with a mean of 50 months [range: 1-113]). No deaths, septic episodes, or severe complications were associated with the procedure, acute or long-term. Follow-up data were available for 46 patients, of who 21 (46%) died during follow-up (mean age, 87 years [range: 73-101]). No cause of death was associated with the femoral technique. CONCLUSION: Permanent pacemaker implantation through femoral access is not difficult for an experienced implant surgeon. Outcomes were comparable to systems implanted by superior venous approach, and no severe complications were observed at 10-year follow-up.

Optoelectronic tweezers under arbitrary illumination patterns: theoretical simulations and comparison to experiment.

Photovoltaic tweezers are a promising tool to place and move particles on the surface of a photovoltaic material in a controlled way. To exploit this new technique it is necessary to accurately know the electric field created by a specific illumination on the surface of the crystal and above it. This paper describes a numerical algorithm to obtain this electric field generated by several relevant light patterns, and uses them to calculate the dielectrophoretic potential acting over neutral, polarizable particles in the proximity of the crystal. The results are compared to experiments carried out in LiNbO3with good overall agreement.

Lower incidence of venous thrombosis with temporary active-fixation lead implantation in mobile patients.

AIMS: Temporary transfemoral cardiac pacing is widely accepted, but is associated with high incidence of asymptomatic deep vein thrombosis (DVT), which in turn is associated with restricted patient mobility. The passive-fixation lead typically used in this procedure restricts patient mobility during implantation. METHODS AND RESULTS: An active-fixation lead allowing normal ambulation was prospectively assessed in 47 consecutive patients. Prior to explantation, venous duplex ultrasound was performed to determine DVT incidence, with the contralateral leg as control. To reduce possible false negatives, ventilation/perfusion scintigraphy was also performed (n = 42). Patient mobility during implantation was classified as high (n = 29), moderate (n = 6), or low (n = 12). Anticoagulants were limited to cases meeting standard guidelines. Asymptomatic DVT was diagnosed in three patients (6.4%), compared with 25-39% reported using standard passive-fixation leads. Furthermore, all of these patients had low mobility during the implantation period. No post-implantation lung scan showed high probability of pulmonary embolism. CONCLUSION: In the 75% of patients with moderate or high mobility, there were no DVT cases. The 6.4% DVT incidence was limited to patients with low mobility and was significantly lower than the norm for this procedure. A larger, randomized study is needed to confirm the benefits of the mobility allowed by an active-fixation lead.

La investigación experimental y la experiencia clínica con las superficies de los implantes dentales (II) / No disponible

Actualmente, la investigación en las superficies de los implantes es un importante campo de la implantología oral. La superficie tratada con láser puede incrementar la adhesión osteoblástica e impulsar la oseointegración. El zirconio es un nuevo material cerámico para los implantes dentales. Las superficies rugosas por chorreado y/o grabado ácido pueden ser bioactivadas con diferentes sustancias (factores de crecimiento, PGRF; fluoruros; proteínas morfogenéticas, BMP-2; melatonina; estatinas) que constituyen otras formas de mejorar la oseointegración. Más recientemente, la tecnología de las nano estructuras ha comenzado en la implantología oral con el desarrollo de superficies nanoporosas que manifiestan una mejor respuesta osteogénica e incrementa la unión mecánica hueso-titanio. La incorporación de nuevos materiales y procesos técnicos en la investigación sobre superficies de implantes ofrecen nuevas posibilidades de mejorar su respuesta tisular y su potencial regenerativo óseo (AU)

Today, implant surface research is a very important field of implant dentistry. Surface treated with laser may increase osteoblast adhesion and enhance osseointegration. Zirconia is a new ceramic material for dental implants. Blasted and acid roughened implant surfaces may be bioactived with different substances (growth factors, PRGF; fluoride; morphogenetic proteins, BMP-2; melatonin, statines) that constitute another ways of improve the osseointegration. Mostrecently, nanostructuring technology begins in implant dentistry with the development of nanoporous surfaces that manifest better osteogenic response and increase bone-titanium mechanical interlocking. The introduction of new materials and new technical process in dental surfaces research offering new possibilities for better tissue response and bone regenerative potential (AU)

The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1.

Neurons are known to have a lower glycolytic rate than astrocytes and when stressed they are unable to upregulate glycolysis because of low Pfkfb3 (6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase-3) activity. This enzyme generates fructose-2,6-bisphosphate (F2,6P(2)), the most potent activator of 6-phosphofructo-1-kinase (Pfk1; ref. 4), a master regulator of glycolysis. Here, we show that Pfkfb3 is absent from neurons in the brain cortex and that Pfkfb3 in neurons is constantly subject to proteasomal degradation by the action of the E3 ubiquitin ligase, anaphase-promoting complex/cyclosome (APC/C)-Cdh1. By contrast, astrocytes have low APC/C-Cdh1 activity and therefore Pfkfb3 is present in these cells. Upregulation of Pfkfb3 by either inhibition of Cdh1 or overexpression of Pfkfb3 in neurons resulted in the activation of glycolysis. This, however, was accompanied by a marked decrease in the oxidation of glucose through the pentose phosphate pathway (a metabolic route involved in the regeneration of reduced glutathione) resulting in oxidative stress and apoptotic death. Thus, by actively downregulating glycolysis by APC/C-Cdh1, neurons use glucose to maintain their antioxidant status at the expense of its utilization for bioenergetic purposes.

Regulation of glycolysis and pentose-phosphate pathway by nitric oxide: impact on neuronal survival.

Besides its essential role at regulating neural functions through cyclic GMP, nitric oxide is emerging as an endogenous physiological modulator of energy conservation for the brain. Thus, nitric oxide inhibits cytochrome c oxidase activity in neurones and glia, resulting in down-regulation of mitochondrial energy production. The subsequent increase in AMP facilitates the activation of 5'-AMP-dependent protein kinase, which rapidly triggers the activation of 6-phosphofructo-1-kinase--the master regulator of the glycolytic pathway--and Glut1 and Glut3--the main glucose transporters in the brain. In addition, nitric oxide activates glucose-6-phosphate dehydrogenase, the first and rate-limiting step of the pentose-phosphate pathway. Here, we review recent evidences suggesting that nitric oxide exerts a fine control of neuronal energy metabolism by tuning the balance of glucose-6-phosphate consumption between glycolysis and pentose-phosphate pathway. This may have important implications for our understanding of the mechanisms controlling neuronal survival during oxidative stress and bioenergetic crisis.