Hypotension prediction index guided goal-directed therapy to reduce postoperative acute kidney injury during major abdominal surgery: study protocol for a multicenter randomized controlled clinical trial.

BACKGROUND: Acute kidney injury (AKI) is a significant postoperative complication associated with increased mortality and hospital costs. Hemodynamic strategies, such as goal-directed therapy, might reduce AKI risk. Predicting and proactively managing intraoperative hypotension may be helpful. This trial aims to investigate if a preemptive hemodynamic strategy guided by the hypotension prediction index (HPI) can decrease the incidence of moderate-to-severe AKI within 30 days following major elective abdominal surgery. METHODS: This is an open-label, controlled, multicenter, randomized clinical trial that involves daily patient follow-up until hospital discharge. Inclusion criteria are patients aged over 65 and/or categorized as ASA III or IV physical status, undergoing major elective abdominal surgery (general, urological, or gynecological procedures) via laparoscopic or open approach under general or combined anesthesia. INTERVENTION: In the intervention group, hemodynamic management will be based on the HPI and the advanced functional hemodynamic variables provided by the Hemosphere platform and the AcumenIQ® sensor (Edwards Lifesciences). The primary outcome is the incidence of moderate-to-severe AKI within 7 days post-surgery. Secondary outcomes include postoperative complications and 30-day mortality. DISCUSSION: This study explores the potential of HPI-guided hemodynamic management in reducing AKI after major elective abdominal surgery, with implications for postoperative outcomes and patient care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05569265. Registered on October 6, 2022.

Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia.

Blinatumomab is a BiTE® (bispecific T-cell engager) molecule that redirects CD3+ T-cells to engage and lyse CD19+ target cells. Here we demonstrate that subcutaneous (SC) blinatumomab can provide high efficacy and greater convenience of administration. In the expansion phase of a multi-institutional phase 1b trial (ClinicalTrials.gov, NCT04521231), heavily pretreated adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) received SC blinatumomab at two doses: (1) 250 µg once daily (QD) for week 1 and 500 µg three times weekly (TIW) thereafter (250 µg/500 µg) or (2) 500 µg QD for week 1 and 1000 µg TIW thereafter (500 µg/1000 µg). The primary endpoint was complete remission/complete remission with partial hematologic recovery (CR/CRh) within two cycles. At the data cutoff of September 15, 2023, 29 patients were treated: 14 at the 250 µg/500 µg dose and 13 at 500 µg/1000 µg dose. Data from two ineligible patients were excluded. At the end of two cycles, 12 of 14 patients (85.7%) from the 250 µg/500 µg dose achieved CR/CRh of which nine patients (75.0%) were negative for measurable residual disease (MRD; <10-4 leukemic blasts). At the 500 µg/1000 µg dose, 12 of 13 patients (92.3%) achieved CR/CRh; all 12 patients (100.0%) were MRD-negative. No treatment-related grade 4 cytokine release syndrome (CRS) or neurologic events (NEs) were reported. SC injections were well tolerated and all treatment-related grade 3 CRS and NEs responded to standard-of-care management, interruption, or discontinuation. Treatment with SC blinatumomab resulted in high efficacy, with high MRD-negativity rates and acceptable safety profile in heavily pretreated adults with R/R B-ALL.

Clinical outcomes after CPX-351 in patients with high-risk acute myeloid leukemia: A comparison with a matched cohort from the Spanish PETHEMA registry.

BACKGROUND: CPX-351 is approved for the treatment of therapy related acute myeloid leukemia (t-AML) and AML with myelodysplastic related changes (MRC-AML). The benefits of this treatment over standard chemotherapy has not been addressed in well matched cohorts of real-life patients. METHODS: Retrospective analysis of AML patients treated with CPX-351 as per routine practice. A propensity score matching (PSM) was used to compare their main outcomes with those observed in a matched cohort among 765 historical patients receiving intensive chemotherapy (IC), all of them reported to the PETHEMA epidemiologic registry. RESULTS: Median age of 79 patients treated with CPX-351 was 67 years old (interquartile range 62-71), 53 were MRC-AML. The complete remission (CR) rate or CR without recovery (CRi) after 1 or 2 cycles of CPX-351 was 52%, 60-days mortality 18%, measurable residual disease <0.1% in 54% (12 out of 22) of them. Stem cell transplant (SCT) was performed in 27 patients (34%), median OS was 10.3 months, and 3-year relapse incidence was 50%. Using PSM, we obtained two comparable cohorts treated with CPX-351 (n = 52) or IC (n = 99), without significant differences in CR/CRi (60% vs. 54%) and median OS (10.3 months vs. 9.1 months), although more patients were bridged to SCT in the CPX-351 group (35% vs. 12%). The results were confirmed when only 3 + 7 patients were included in the historical cohort. In multivariable analyses, SCT was associated with better OS (HR 0.33 95% CI: 0.18-0.59), p < 0.001. CONCLUSION: Larger post-authorization studies may provide evidence of the clinical benefits of CPX-351 for AML in the real-life setting.

Nitrogen recovery from sludge centrate by membrane contactor: Influence of operating parameters and cleaning conditions.

In urban wastewater treatment, the sludge generated is treated by anaerobic digestion, to be subsequently dehydrated by centrifuges. Currently, the liquid fraction obtained in this dehydration process is recirculated at the head of the treatment plant. However, its high nitrogen and phosphorus content makes it an effluent with high added value. The recovery of these nutrients could be an excellent alternative for the production of fertilizers or other industrial applications. In this study, the use of a liquid-liquid phase membrane contactor is presented as a favorable solution for the recovery of ammoniacal nitrogen from sludge centrated. The polypropylene hollow fiber membrane was evaluated considering its ammonia removal and recovery capacity. For this, different parameters were evaluated: the influence of the type and concentration of the acid solution, the wastewater pH, the flow rates of feeding and the acid stripping solution, and the contact time. Results showed that with a contact time of 65 min, ammonia removal and recovery percentages of the order of 90% were achieved. The flow rates of the stripping and feed solutions together with the acid concentration did not have a significant influence on the removal but on the recovery. Concerning used acid, sulphuric and phosphoric acid solutions achieved better results than nitric acid solution. The most critical parameter was the pH, obtaining the highest removal and recovery of ammonium at the highest pH. Finally, a stable cleaning protocol was obtained, between preventive and moderate cleanings to avoid severe cleanings, keeping the membrane at its maximum capacity.

Co-designing a behavioural intervention for reducing the impact of chemotherapy-induced peripheral neuropathy symptoms: An evidence- and theory-driven approach.

OBJECTIVE: This study aims to co-design an evidence- and theory-based behavioural intervention to reduce the impact of chemotherapy-induced peripheral neuropathy (CIPN) symptoms on patients' quality of life. METHODS: Guided by the Medical Research Council Framework for developing and evaluating complex interventions, our intervention development process was guided by (a) findings of systematic reviews, (b) inductive analysis of 39 h of observational fieldwork, 12 patient and 11 clinician interviews, (c) deductive analysis using the Common-Sense Model to develop a Self-Regulation Model of CIPN and (d) 17 patients and 18 clinicians co-designing the intervention. RESULTS: CIPN perception and coping behaviours were highlighted as processes to target when co-designing an intervention. The processes targeted in our intervention are CIPN perception and coping behaviours, namely, (a) self-monitoring of symptoms, (b) communicating and early reporting of symptoms to clinicians, (c) participating in making chemotherapy dose reduction decisions with their clinicians and (d) engaging in self-management and safety strategies to reduce impact of CIPN symptoms. To address these, a behavioural intervention was deemed suitable. CONCLUSION: We developed a self-regulation model of CIPN and a logic model for documenting the proposed mechanism of action of our co-designed behavioural intervention for reducing impact of CIPN symptoms.

Co-designing a cancer care intervention: reflections of participants and a doctoral researcher on roles and contributions.

BACKGROUND: Patient and Public Involvement is most usually framed in the context of designing, conducting and/or disseminating research. Participatory methods such as Experience-Based Co-Design (EBCD) further allow service users to directly engage in developing, testing and implementing interventions and services alongside healthcare staff. This paper aims to explore how participants in an EBCD project came-over time-to perceive their role and involvement in co-designing a cancer care intervention. METHODS: The findings are based on our reflections, a research diary, email correspondence and fieldnotes from co-design events. Co-design participants who attended most of the ten co-design events took part through written reflections or audio-recorded video calls. Ten reflective pieces were collected from clinicians (n = 4), PPI group members/patient participants (n = 4), a doctoral researcher (n = 1) and a visual illustrator (n = 1). Inductive data analysis of participant reflections was carried out using reflexive thematic analysis. Meeting fieldnotes, email correspondence and the researcher's diary were deductively analysed using the initial themes generated from this inductive analysis. RESULTS: Five main themes were identified: (1) changing perception of roles during the co-design process, (2) defining a 'co-designer', (3) engagement and ownership, (4) role of the research facilitator in maintaining momentum, and (5) perceived benefits of involvement. CONCLUSION: Our findings show the changing perceptions of roles and contributions among participants over time. Patients typically described their role as co-designers in terms simply of sharing their experiences. In contrast, clinicians perceived themselves as co-designers because they were working with patients who were actively involved in decision-making. Levels of engagement were affected by several factors such as time and facilitation, but most participants came to view themselves as co-owners of the intervention. Overall, participants perceived their involvement as a positive experience with clinicians also reporting wider positive impacts on their clinical practice.

Experience-Based Co-Design is a method for helping patients and clinicians work together to improve healthcare services. Studies of participant experiences in projects which use this method and how they perceive the co-designer role are rare. Our study explores how we­patients and clinicians­saw our role and participation as co-designers over time. Our findings are based on our written and verbal reflections of participating in a co-design project aimed at developing an information resource booklet and film for use in cancer care. We also analysed meeting records, email messages between participants and a reflective diary kept by the researcher who was coordinating the project. Our findings show that views of our roles and contributions as co-design participants changed over time. Patients tended to see themselves as 'co-designers' simply because they shared their experiences throughout the co-design process. In contrast, clinicians saw themselves as 'co-designers' because they were working together with patients and making decisions with them. Factors such as time demands, and the skill of the facilitator affected the commitment of participants to co-design activities. Most participants regard the ownership of the newly developed information resources as being shared. Overall, we viewed our participation in the co-design project as a positive experience with results that will benefit clinical practice.

Radical cancer treatment is safe during COVID-19: the real-world experience of a large London-based Comprehensive Cancer Centre during the first wave.

BACKGROUND: During the COVID pandemic, there was a paucity of data to support clinical decision-making for anticancer treatments. We evaluated the safety of radical treatments which were delivered whilst mitigating the risks of concurrent COVID-19 infection. METHODS: Using descriptive statistics, we report on the characteristics and short-term clinical outcomes of patients undergoing radical cancer treatment during the first COVID-19 wave compared to a similar pre-pandemic period. RESULTS: Compared to 2019, the number of patients undergoing radical treatment in 2020 reduced by: 28% for surgery; 18% for SACT; and 10% for RT. Within SACT, 36% received combination therapy, 35% systemic chemotherapy, 23% targeted treatments, 5% immunotherapy and 2% biological therapy. A similar proportion of RT was delivered in 2019 and 2020 (53% vs. 52%). Oncological outcomes were also similar to pre-COVID-19. The COVID-19 infection rates were low: 12 patients were positive pre surgery (1%), 7 post surgery (<1%), 17 SACT patients (2%) and 3 RT patients (<1%). No COVID-19-related deaths were reported. CONCLUSIONS: Whilst there were fewer patients receiving radical anticancer treatments, those who did receive treatment were treated in a safe environment. Overall, cancer patients should have the confidence to attend hospitals and be reassured of the safety measures implemented.

Post-Transplantation Cyclophosphamide After HLA Identical Compared to Haploidentical Donor Transplant in Acute Myeloid Leukemia: A Study on Behalf of GETH-TC.

Post-transplantation cyclophosphamide (PTCY) effectively prevents graft-versus-host disease (GVHD) after unmanipulated HLA-haploidentical hematopoietic stem cell transplantation (HSCT) and achieves low rates of GVHD in HLA-identical transplantation. To compare the outcomes of haploidentical versus HLA identical HSCT in patients undergoing HSCT for acute myeloid leukemia (AML) using PTCY. We conducted a retrospective study of 229 patients undergoing first HSCT for AML using PTCY with additional immunosuppression, 99 from matched sibling or unrelated donor (MSD/MUD) performed in 3 hospitals and 130 from haploidentical donors (haplo group) performed in 20 hospitals within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cellular Therapy. Peripheral blood stem cells were used as graft in 89% of patients; myeloablative conditioning was used in 56%. There were significantly more patients with active disease (5% versus 20%, P = .001), high/very high disease risk index (DRI) (32% versus 67%, P = .000) and prior auto-HSCT (2% versus 11%, P = .010) in the haplo group. Median follow-up was 27 and 62.5 months for MSD/MUD and haplo, respectively. At 2 years, no significant differences were observed in overall survival (OS) (72% versus 62%, P = .07), event-free survival (EFS) (70% versus 54%, P = .055), cumulative incidence of relapse (19% versus 25%, P = .13), non-relapse mortality (14% versus 19%, P = .145), and the composite endpoint of GVHD and relapse-free survival (49% versus 42%, P = .249). Multivariate analysis identified only age and active disease as significant risk factors for OS and EFS; reduced-intensity conditioning, high/very high DRI, and haplo donor were nearly statistically significant for these outcomes. Grade II-IV acute GVHD was lower in MSD/MUD (14% versus 47%, P = .000). Cumulative incidences of grade III-IV acute GVHD (4% versus 9%, P = .14) and moderate-severe chronic GVHD (22% versus 19%, P = .28) were similar. Limitations of our study include limited sample size, differences between haplo and MSD/MUD groups and heterogeneous additional immunosuppression and PTCY timing in MSD/MUD. The use of an HLA-identical donor with PTCY in patients with AML showed lower incidence of clinically significant grade II-IV acute GVHD compared to haplo donors. Further studies with larger sample sizes should be performed to establish a possible benefit of HLA-identical donor on survival. © 2022 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The Impact of COVID-19 on the Delivery of Systemic Anti-Cancer Treatment at Guy's Cancer Centre.

BACKGROUND: This study aimed to assess the outcome of cancer patients undergoing systemic anti-cancer treatment (SACT) at our centre to help inform future clinical decision-making around SACT during the COVID-19 pandemic. METHODS: Patients receiving at least one episode of SACT for solid tumours at Guy's Cancer Centre between 1 March and 31 May 2020 and the same period in 2019 were included in the study. Data were collected on demographics, tumour type/stage, treatment type (chemotherapy, immunotherapy, biological-targeted) and SARS-CoV2 infection. RESULTS: A total of 2120 patients received SACT in 2020, compared to 2449 in 2019 (13% decrease). From 2019 to 2020, there was an increase in stage IV disease (62% vs. 72%), decrease in chemotherapy (42% vs. 34%), increase in immunotherapy (6% vs. 10%), but similar rates of biologically targeted treatments (37% vs. 38%). There was a significant increase in 1st and 2nd line treatments in 2020 (68% vs. 81%; p < 0.0001) and reduction in 3rd and subsequent lines (26% vs. 15%; p = 0.004) compared to 2019. Of the 2020 cohort, 2% patients developed SARS-CoV2 infections. CONCLUSIONS: These real-world data from a tertiary Cancer Centre suggest that despite the challenges faced due to the COVID-19 pandemic, SACT was able to be continued without any significant effects on the mortality of solid-tumour patients. There was a low rate (2%) of SARS-CoV-2 infection which is comparable to the 1.4%-point prevalence in our total cancer population.

Five-year outcomes after intravitreal bevacizumab of treatment-naive eyes with macular edema secondary to CRVO in routine clinical practice: Results of the Pan-American Collaborative Retina Study (PACORES) group.

PURPOSE: The purpose of this study was to report the 5-year outcomes of treatment-naive eyes with cystoid macular edema secondary to central retinal vein occlusion treated with intravitreal bevacizumab in routine clinical practice. METHODS: We conducted multicenter retrospective non-comparative case series of 102 eyes. The main outcome measured was the change in best-corrected visual acuity (BCVA) at 5 years. Secondary outcomes included the number of injections and the change in CMT at 5 years. RESULTS: At 5 years, the mean BCVA improved from 1.22 ± 0.58 (Snellen 20/428) at baseline to 1.00 ± 0.68 logMAR (Snellen 20/200; p < 0.0001). At 5 years, 48 (47%) eyes had a gain of ≥ 3 lines, 41 (40.2%) eyes remained within 3 lines and 13 (12.7%) eyes had a loss of ≥ 3 lines of BCVA. The CMT improved from 740 ± 243 to 322 ± 179 µm (p < 0.0001). At 5 years, 59 (57.8%) eyes had a completely dry SD-OCT. Patients received a total of 10.6 ± 6.1 (range 6-27) injections. Baseline BCVA (p < 0.0001) and the duration of symptoms prior to initial anti-VEGF injection (p = 0.0274) were the only predictive factors for BCVA at 5 years. CONCLUSIONS: After 5 years with an average of 10.6 injections, there was a mean gain of 0.22 logMAR. In addition, more eyes achieved a BCVA of ≥ 20/40, gained ≥ 3 lines and less patients had a BCVA ≤ 20/200. Eyes with a better baseline BCVA and a shorter duration of symptoms were more likely to achieve better BCVA at 5 years.

Incidencia de complicaciones intra y posoperatorias en pacientes geriátricos durante la cirugía abdominal mayor electiva / Incidence of intraoperative and postoperative complications in geriatric patients during major elective abdominal surgery

Introducción: El aumento de la expectativa de vida determina un incremento en la incidencia de enfermedades con indicación quirúrgica. El avance en las técnicas quirúrgicas, los cuidados intensivos y el conocimiento más profundo del proceso de envejecimiento tiende a favorecer la disminución de la morbimortalidad perioperatoria del paciente geriátrico. Objetivo: Determinar la incidencia de complicaciones intra y posoperatorias en pacientes geriátricos durante la cirugía abdominal mayor electiva. Métodos: Se realizó un estudio observacional descriptivo, de corte transversal a 373 pacientes geriátricos programados para intervención quirúrgica abdominal mayor desde enero de 2017 hasta diciembre de 2019 en el Hospital Clínico Quirúrgico Dr. Miguel Enríquez. Se registró la incidencia de complicaciones perioperatorias relacionándolas con las variables de estudio. Resultados: Las complicaciones más frecuentes fueron las cardiovasculares. La mortalidad fue escasa. Conclusiones: Las complicaciones perioperatorias detectadas en los pacientes geriátricos estudiados, se relacionan con las enfermedades previas, el tipo y la envergadura de la cirugía y con el tiempo quirúrgico(AU)

Introduction: The increase in life expectancy determines an increase in the incidence of diseases with surgical indication. Advances in surgical techniques, intensive care and deeper understanding of the aging process tend to favor the reduction of perioperative morbidity and mortality among geriatric patients. Objective: To determine the incidence of intraoperative and postoperative complications among geriatric patients during elective major abdominal surgery. Methods: A descriptive, cross-sectional and observational study was carried out with 373 geriatric patients scheduled for major abdominal surgery from January 2017 to December 2019 at Dr. Miguel Enríquez Clinical-Surgical Hospital. The incidence of perioperative complications was recorded, relating them to the study variables. Results: The most frequent complications were the cardiovascular ones. Mortality was low. Conclusions: The perioperative complications identified among the geriatric patients studied are related with previous diseases, with the type and extent of surgery, and with the surgical time(AU)

Utilidad del ondansetrón vs dexametasona como profilaxis antiemética posoperatoria durante la cirugía mayor ginecológica / Usefulness of ondansetron versus dexamethasone as postoperative antiemetic prophylaxis during major gynecologic surgery

Introducción: Las náuseas y vómitos posoperatorios son una secuela no deseada durante la etapa de recuperación anestésica. Objetivo: Evaluar la utilidad de la dexametasona en comparación con el ondansetrón para la prevención de las náuseas y vómitos posoperatorios después de procedimientos quirúrgicos ginecológicos mayores, bajo anestesia general orotraqueal. Método: Se realizó un estudio observacional analítico, prospectivo, en 84 pacientes mayores de 19 años, en el Hospital Clínico Quirúrgico Miguel Enríquez desde octubre de 2018 hasta septiembre de 2019, divididas de forma secuencial, en orden de llegada a la unidad quirúrgica, en dos grupos. Al grupo 1 se le administró dexametasona (4 mg endovenosa); al grupo 2 (4 mg de ondansetrón), 30 min antes de finalizar la cirugía. Resultados: Predominó de forma significativa el riesgo medio de náuseas y vómitos posoperatorios en los pacientes con edades comprendidas entre 41 y 50 años. Predominó la condición de excelente y buena (pgt;0,05) en cuanto a la efectividad del tratamiento profiláctico. La cefalea prevaleció de forma significativa en el grupo 2. La mayor parte de las pacientes no presentó eventos adversos. Conclusiones: El ondansetrón y la dexametasona son útiles para la profilaxis de las náuseas y vómitos posoperatorios en pacientes intervenidas de cirugía mayor ginecológica, bajo anestesia general orotraqueal por lo que se considera un tratamiento seguro, con eventos adversos leves y de fácil control(AU)

Introduction: Postoperative nausea and vomiting are an unwanted sequel during the anesthetic recovery stage. Objective: To evaluate the usefulness of dexamethasone compared with ondansetron for the prevention of postoperative nausea and vomiting after major gynecological surgical procedures, under general orotracheal anesthesia. Method: A prospective, analytical and observational study was carried out with 84 patients older than 19 years of age, at Miguel Enríquez Hospital Clinical-Surgical Hospital, from October 2018 to September 2019, divided sequentially, in order of arrival at the surgical unit, into two groups. The group 1 was administered dexamethasone (4 mg intravenously), and the group 2 was administered ondansetron (4 mg), 30 min before the end of the surgery. Results: The average risk of postoperative nausea and vomiting prevailed significantly among patients aged 41-50 years. Excellent and good conditions predominated (pgt;0.05) in terms of effectiveness of prophylactic treatment. Headache prevailed significantly in the group 2. Most of the patients did not present adverse events. Conclusions: Ondansetron and dexamethasone are useful for postoperative nausea and vomiting prophylaxis among patients who received major gynecological surgery, under general orotracheal anesthesia, a reason why it is considered a safe treatment, with mild adverse events and easy control(AU)

Strategy for identification of a potential inherited leukemia predisposition in a 299 patient's cohort with tumor-only sequencing data.

Myeloid neoplasms (MN) are usually sporadic late-onset cancers; nevertheless, growing evidence suggests that ∼5% of the cases could emerge as a consequence of inherited predisposition. Distinguishing somatic from germline variants is of vital importance, in order to establish an appropriate individualized management and counsel the patients and their relatives. Since many of the genes associated with myeloid neoplasm germline predisposition (MNGP) are also affected in sporadic MN, we intended to design a strategy to identify potentially inherited variants in a tumor only NGS panel in a cohort of 299 patients with a variety of MN. We considered as indicative of potential inherited origin, variants detected in BM sample at a ∼50% VAF classified as pathogenic, likely pathogenic or of unknown significance detected in MNGP-related genes. A total of 104 suspicious variants from 90 patients were filtered-in in tumor samples. Mutational patterns, follow-up data, and sequencing of a range of non-myeloid tissues were used for narrowing down the list of suspicious variants, and ultimately discriminate their nature. Our data supports the importance of considering variants found upon tumor-only sequencing as potentially of germline origin, and we offer a pipeline to define the nature of the variants.

Non-contact wide-angled visualization with chandelier-assisted scleral buckling for primary uncomplicated rhegmatogenous retinal detachment.

PURPOSE: To report our experience in non-contact wide-angled visualization with chandelier-assisted scleral buckling (SB) in uncomplicated primary rhegmatogenous retinal detachments (RRD). METHODS: Retrospective case series of 282 eyes that underwent non-contact wide-angled visualization with chandelier-assisted SB and were followed for a mean of 13.5 months. RESULTS: There were 160 male patients. The average age was 42.6 years old. There were 262 eyes that were phakic, 18 pseudophakic, and 2 aphakic. Two-thirds of eyes presented with the macula detached. Eyes had an average of 1.6 breaks. The single operation anatomic success rate was 85.1% (240/282). The pre-op visual acuity improved from 1.21 to 0.76 logMAR at 6 months (p < 0.0001). Complications included a case of scleral laceration, choroidal hemorrhage, 3 epiretinal membranes, 1 macular fold, and 4 eyes with buckle exposure. CONCLUSION: Non-contact wide-angled visualization with chandelier-assisted SB compares favorably with conventional SB for primary uncomplicated primary RRD.

Changes in the process performance and microbial community by addition of the metabolic uncoupler 3,3',4',5-tetrachlorosalicylanilide in sequencing batch reactors.

A complete study about the effects of 3,3',4',5-tetrachlorosalicylanilide (TCS) on organic matter elimination performance, sludge production and on the microbial community of a biological wastewater treatment process has been performed. For this purpose two sequencing batch reactors (SBR) worked in parallel for 43 days with 0.8 mg·L-1 of TCS (SBR-1) and without this metabolic uncoupler (SBR-2). Results indicated that 63.3% of sludge reduction was achieved in SBR-1. However, COD removal efficiency was maintained in similar values in both reactors (89.1% and 92.1% in SBR-1 and SBR-2, respectively). The exhaustive mixed liquor characterization led to know deeply the action mechanism of TCS. In this way, a 69% of adenosine triphosphate (ATP) reduction was observed in SBR-1 in comparison with values measured in SBR-2. On the contrary, an increase in soluble microbial products (SMP) and DNA concentrations occurred as a consequence of TCS addition. Thus, it could be concluded that sludge reduction due to TCS addition was due to both uncoupling effect and cellular lysis. Also, increase in all microbial hydrolytic enzymatic activities measured was observed, which explained the stable performance achieved in SBR-1 despite to the results explained above. It should be highlighted that this uncoupler should not be used in biological treatments that require nitrogen elimination because nitrifying bacteria were affected by its addition (Nitrosomonas and Nitrospira). Finally, the 16S rRNA gene amplicon sequencing informed that an important reduction of bacterial diversity resulted in SBR-1 due to TCS addition.

Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1α but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients.

Epidemiological associations linking between obstructive sleep apnea and poorer solid malignant tumor outcomes have recently emerged. Putative pathways proposed to explain that these associations have included enhanced hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) cell expression in the tumor and altered immune functions via intermittent hypoxia (IH). Here, we examined relationships between HIF-1α and VEGF expression and nocturnal IH in cutaneous melanoma (CM) tumor samples. Prospectively recruited patients with CM tumor samples were included and underwent overnight polygraphy. General clinical features, apnea-hypopnea index (AHI), desaturation index (DI4%), and CM characteristics were recorded. Histochemical assessments of VEGF and HIF-1α were performed, and the percentage of positive cells (0, <25, 25-50, 51-75, >75%) was blindly tabulated for VEGF expression, and as 0, 0-5.9, 6.0-10.0, >10.0% for HIF-1α expression, respectively. Cases with HIF-1α expression >6% (high expression) were compared with those <6%, and VEGF expression >75% of cells was compared with those with <75%. 376 patients were included. High expression of VEGF and HIF-1α were seen in 88.8 and 4.2% of samples, respectively. High expression of VEGF was only associated with increasing age. However, high expression of HIF-1α was significantly associated with age, Breslow index, AHI, and DI4%. Logistic regression showed that DI4% [OR 1.03 (95% CI: 1.01-1.06)] and Breslow index [OR 1.28 (95% CI: 1.18-1.46)], but not AHI, remained independently associated with the presence of high HIF-1α expression. Thus, IH emerges as an independent risk factor for higher HIF-1α expression in CM tumors and is inferentially linked to worse clinical CM prognostic indicators.

Yellow (577 nm) micropulse laser versus half-dose verteporfin photodynamic therapy in eyes with chronic central serous chorioretinopathy: results of the Pan-American Collaborative Retina Study (PACORES) Group.

PURPOSE: To compare the functional and anatomical outcomes of eyes with chronic central serous chorioretinopathy treated with yellow micropulse (MP) laser versus half-dose verteporfin photodynamic therapy (PDT). METHODS: This is a multicentre, retrospective comparative study of 92 eyes treated with yellow MP laser (duty cycle of 5%, zero spacing between spots, spot size varied from 100 to 200 µm, power varied from 320 to 660 mW, and the pulse burst duration was 200 ms) and 67 eyes treated with PDT (half-dose verteporfin (3 mg/m2) infused over 10 min), followed by laser activation for 83 s. Spot sizes varied from 400 to 2000 µm. RESULTS: In the MP group, at 12 months of follow-up, the mean best corrected visual acuity (BCVA) improved from the logarithm of the minimum angle of resolution (logMAR) of 0.41±0.27 at baseline to 0.21±0.26 (P<0.0001), 48.9% (45/92) of eyes had an improvement of ≥3 lines of BCVA from baseline, 48.9% (45/92) of eyes remained within 2 lines of baseline BCVA, and only 2.2% (2/92) of eyes lost ≥3 lines of BCVA from baseline. In the PDT group, at 12 months of follow-up, the mean BCVA changed from logMAR of 0.50±0.34 at baseline to 0.47±0.34 (P=0.89), 19% (13/67) of eyes had an improvement of ≥3 lines of BCVA from baseline, 73% (49/67) of eyes remained within 2 lines of baseline BCVA, and 7% (5/67) of eyes lost ≥3 lines of BCVA from baseline. There were no adverse events attributable to the yellow MP laser treatment. One eye in the PDT group developed choroidal neovascularisation, which was treated with three intravitreal bevacizumab injections. CONCLUSIONS: Both PDT and MP are effective in restoring the macular anatomy. In places where PDT is not available, yellow MP laser may be an adequate treatment alternative.

A prospective multicenter cohort study of cutaneous melanoma: clinical staging and potential associations with HIF-1α and VEGF expressions.

Melanoma is a highly prevalent cancer that is associated with substantial mortality. Although clinical staging procedures can serve as relatively robust prognostic indicators, we aimed to determine whether assessments of the abundance of hypoxia inducible factor-1α (HIF-1α) or vascular endothelial growth factor (VEGF) in postexcisional melanoma tumor tissues may enable more accurate determination of tumor aggressiveness. We carried out a multicenter prospective study, in which we systematically evaluated 376 consecutive patients diagnosed with melanoma, and performed histochemical assessments for both HIF-1α and VEGF immunoreactivity in the tumor biopsies. Multivariate analyses showed that higher HIF-1α expression, but not high VEGF, were associated significantly and independently with increased tumor aggressiveness as derived from several well-established aggressiveness criteria. A limitation of this study was that this was a descriptive prospective study lacking a post-hoc verification arm. Thus, the presence of increased numbers of positively labeled HIF-1α cells in melanoma tumors may potentially serve as an indicator of tumor phenotype and prognosis, and accordingly guide therapy.

Un-explained visual loss following silicone oil removal: results of the Pan American Collaborative Retina Study (PACORES) Group.

PURPOSE: To report the incidence and clinical features of patients that experienced un-explained visual loss following silicone oil (SO) removal. METHODS: Multicenter retrospective study of patients that underwent SO removal during 2000-2012. Visual loss of ≥2 lines was considered significant. RESULTS: A total of 324 eyes of 324 patients underwent SO removal during the study period. Forty two (13%) eyes suffered a significant visual loss following SO removal. Twenty three (7.1%) of these eyes lost vision secondary to known causes. In the remaining 19 (5.9%) eyes, the loss of vision was not explained by any other pathology. Eleven of these 19 patients (57.9%) were male. The mean age of this group was 49.2 ± 16.4 years. Eyes that had an un-explained visual loss had a mean IOP while the eye was filled with SO of 19.6 ± 6.9 mm Hg. The length of time that the eye was filled with SO was 14.8 ± 4.4 months. In comparison, eyes that did not experience visual loss had a mean IOP of 14 ± 7.3 mm Hg (p < 0.0002) and a mean tamponade duration of 9.3 ± 10.9 months (p < 0.0001). CONCLUSIONS: An un-explained visual loss after SO removal was observed in 5.9% of eyes. Factors associated with this phenomenon included a higher IOP and longer SO tamponade duration.

Hybrid Intelligent System to Perform Fault Detection on BIS Sensor During Surgeries.

This paper presents a new fault detection system in hypnotic sensors used for general anesthesia during surgery. Drug infusion during surgery is based on information received from patient monitoring devices; accordingly, faults in sensor devices can put patient safety at risk. Our research offers a solution to cope with these undesirable scenarios. We focus on the anesthesia process using intravenous propofol as the hypnotic drug and employing a Bispectral Index (BISTM) monitor to estimate the patient's unconsciousness level. The method developed identifies BIS episodes affected by disturbances during surgery with null clinical value. Thus, the clinician-or the automatic controller-will not take those measures into account to calculate the drug dose. Our method compares the measured BIS signal with expected behavior predicted by the propofol dose provider and the electromyogram (EMG) signal. For the prediction of the BIS signal, a model based on a hybrid intelligent system architecture has been created. The model uses clustering combined with regression techniques. To validate its accuracy, a dataset taken during surgeries with general anesthesia was used. The proposed fault detection method for BIS sensor measures has also been verified using data from real cases. The obtained results prove the method's effectiveness.