Effects of Sacubitril-Valsartan in Patients With Various Types of Heart Failure: A Meta-analysis.

ABSTRACT: We performed a meta-analysis investigating the efficacy and adverse effects of sacubitril-valsartan in various types of heart failure including more recent studies and a larger sample size. We conducted an electronic search through Cochrane, Web of Science, PubMed, and Embase. Included studies were randomized controlled trials analyzing the efficacy of sacubitril-valsartan compared with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) in patients with heart failure. Fourteen trials were included. Pooled estimates were analyzed using RevMan 5.4.1. The odds ratio (OR) of hospitalization from worsening heart failure that compared sacubitril-valsartan with control was 0.70 (95% CI, 0.51-0.97; P = 0.03) in patients with heart failure with reduced ejection fraction (HFrEF) with a relative risk reduction (RRR) of 24.3% and absolute risk reduction (ARR) of 3.4%. In patients with heart failure with midrange (HFmEF) and preserved (HFpEF) ejection fraction, the OR was 0.80 (95% CI, 0.71-0.90; P = 0.0001) with RRR of 14.5% and ARR of 3.3%. There was a significant reduction in cardiovascular deaths (OR = 0.79; 95% CI, 0.70-0.89; P = <0.0001) and all-cause mortality (OR = 0.84; 95% CI, 0.75-0.94; P = 0.002) in patients with HFrEF, with no significant differences in patients with HFmEF and HFpEF. Hospitalization rate was significantly reduced in patients taking sacubitril-valsartan across all analyzed cohorts. Sacubitril-valsartan significantly reduced the risk of all-cause mortality and cardiovascular death in patients with HFrEF but not in patients with HFmEF/HFpEF. These findings support sacubitril-valsartan use in reducing hospitalization of patients with HFmEF and HFpEF. More studies should be performed to further analyze the efficacy of sacubitril-valsartan in patients with HFmEF/HFpEF.

The METREPOL criteria-are they still relevant?

The medical management of radiation accidents manual on the acute radiation syndrome proposed a successful strategic approach to diagnosing and treating acute radiation syndrome: the response category concept. Based on clinical and laboratory parameters, this approach aimed to assess damage to critical organ systems as a function of time, categorising different therapeutical approaches. After 20 years of its publication, the following paper attempts to provide a broad overview of this important document and tries to respond if proposed criteria are still relevant for the medical management of radiation-induced injuries. In addition, a critical analysis of its limitations and perspectives is proposed.

Cutaneous and local radiation injuries.

The threat of a large-scale radiological or nuclear (R/N) incident looms in the present-day climate, as noted most recently in an editorial in Scientific American (March 2021). These large-scale incidents are infrequent but affect large numbers of people. Smaller-scale R/N incidents occur more often, affecting smaller numbers of people. There is more awareness of acute radiation syndrome (ARS) in the medical community; however, ionising radiation-induced injuries to the skin are much less understood. This article will provide an overview of radiation-induced injuries to the skin, deeper tissues, and organs. The history and nomenclature; types and causes of injuries; pathophysiology; evaluation and diagnosis; current medical management; and current research of the evaluation and management are presented. Cutaneous radiation injuries (CRI) or local radiation injuries (LRI) may lead to cutaneous radiation syndrome, a sub-syndrome of ARS. These injuries may occur from exposure to radioactive particles suspended in the environment (air, soil, water) after a nuclear detonation or an improvised nuclear detonation (IND), a nuclear power plant incident, or an encounter with a radioactive dispersal or exposure device. These incidents may also result in a radiation-combined injury; a chemical, thermal, or traumatic injury, with radiation exposure. Skin injuries from medical diagnostic and therapeutic imaging, medical misadministration of nuclear medicine or radiotherapy, occupational exposures (including research) to radioactive sources are more common but are not the focus of this manuscript. Diagnosis and evaluation of injuries are based on the scenario, clinical picture, and dosimetry, and may be assisted through advanced imaging techniques. Research-based multidisciplinary therapies, both in the laboratory and clinical trial environments, hold promise for future medical management. Great progress is being made in recognising the extent of injuries, understanding their pathophysiology, as well as diagnosis and management; however, research gaps still exist.

Basic concepts of radiation emergency medicine.

Nuclear and radiological accidents are not frequent but may lead to major consequences in the population. For the health systems, the need to handle a large number of victims will probably remain as an exception. However, a high number of affected victims can be expected in some terrorist scenarios. In addition, medical accidents in radiotherapy, fluoroscopy and diagnostic radiology have increased the number of patients with severe radiation injuries considerably, especially in developed countries. Given the increased use of ionising radiation for industrial and medical purposes and new technological applications emerging, the number of accidents may increase in the future. Consequently, the early identification and adequate management of these emergencies is a priority, as well as the need for medical preparedness, requiring knowledge about various emergency scenarios and planning appropriate responses to them before they occur. Unfortunately, medical professionals have a substantial knowledge gap in identifying and treating injured persons affected by ionising radiation. As managing radiation accidents is a very challenging process, exercises must be carried out to organise a well-trained multidisciplinary group of professionals to manage any radiation accident properly. Efforts on a continuously updated guidance system should be developed. In addition, new approaches to foster sustainable interdisciplinary and international cooperative networks on radiation injuries are necessary. Lessons learned from past nuclear and radiological emergencies have significantly contributed to strengthening scientific knowledge and increasing the available medical information on the effects of ionising radiation in the human body. In this context, radiation emergency medicine has emerged as a discipline that contributes to the diagnosis, treatment, medical follow-up and prognosis of persons affected by radiation injuries in a nuclear or a radiological emergency. In this paper, we review some relevant concepts related to the medical preparedness and multidisciplinary response required to attend to persons affected by these emergencies.

Luminescent and Photoconductive Layered Lead Halide Perovskite Compounds Comprising Mixtures of Cesium and Guanidinium Cations.

Interest in hybrid organic-inorganic lead halide compounds with perovskite-like two-dimensional crystal structures is growing due to the unique electronic and optoelectronic properties of these compounds. Herein, we demonstrate the synthesis, thermal and optical properties, and calculations of the electronic band structures for one- and two-layer compounds comprising both cesium and guanidinium cations: Cs[C(NH2)3]PbI4 (I), Cs[C(NH2)3]PbBr4 (II), and Cs2[C(NH2)3]Pb2Br7 (III). Compounds I and II exhibit intense photoluminescence at low temperatures, whereas compound III is emissive at room temperature. All of the obtained substances are stable in air and do not thermally decompose until 300 °C. Since Cs+ and C(NH2)3+ are increasingly utilized in precursor solutions for depositing polycrystalline lead halide perovskite thin films for photovoltaics, exploring possible compounds within this compositional space is of high practical relevance to understanding the photophysics and atomistic chemical nature of such films.

Chikungunya: Molecular Aspects, Clinical Outcomes and Pathogenesis.

The alarming worldwide emergence of the chikungunya virus began in the last decade. Since the first autochthonous transmission in Mexico in November of 2014, the virus has spread throughout the country, resulted in multiple outbreaks. This virus produces an acute and self-limiting disease characterized by fever, polyarthralgia, myalgia, exanthema, and general malaise. It is transmitted to humans by the bite of Aedes aegypti and A. albopictus mosquitoes. The fact that the clinical presentation is similar to that produced by other arboviruses complicates its clinical diagnosis. The chronic stage of the disease can cause severe consequences lasting months or years, from local arthralgia to rheumatoid arthritis. In this review, we emphasize the public health threat posed by this highly disabling emerging disease, the clinical outcomes, and its possible physiopathological process. We outline the diagnosis and the impact that this virus has had in Mexico since its introduction.

Prediction model for early biochemical recurrence after radical prostatectomy based on the Cancer of the Prostate Risk Assessment score and the presence of secondary circulating prostate cells.

OBJECTIVE: To establish a prediction model for early biochemical recurrence based on the Cancer of the Prostate Risk Assessment (CAPRA) score and the presence of secondary circulating prostate cells (CPCs). PATIENTS AND METHODS: We conducted a prospective single-centre study of men who underwent radical prostatectomy as monotherapy for prostate cancer. Clinicopathological findings were used to calculate the CAPRA score. At 90 days after surgery, blood was taken for CPC detection, mononuclear cells were obtained using differential gel centrifugation, and CPCs were identified using immunocytochemistry. A CPC was defined as a cell expressing prostate-specific antigen (PSA) but not CD45. The CPC test results were defined as positive or negative. Patients were followed up for up to 5 years and biochemical recurrence was defined as a PSA level >0.2 ng/mL. The validity of the CAPRA score was calibrated using partial validation, and Cox proportional hazard regression to build three models: a CAPRA score model, a CPC model and a CAPRA/CPC combined model. RESULTS: A total of 321 men, with a mean age of 65.5 years, participated in the study. After 5 years of follow-up the biochemical recurrence-free survival rate was 98.55%. For the model that included CAPRA score there was a hazard ratio (HR) of 7.66, for the CPC model there was an HR of 34.52 and for the combined model there were HRs of 2.60 for CAPRA score and 22.5 for CPC. Using the combined model, 23% of men changed from the low-risk to the high-risk category, or vice versa. CONCLUSION: The incorporation of CPC detection significantly improved the model's discriminative ability in establishing the probability of biochemical recurrence; patients in the high-risk group according to CAPRA score who are negative for CPCs have a much better prognosis. The addition of CPC detection gives clinically significant information to aid the decision on who may be eligible for adjuvant therapy.

Crystal structure and electronic properties of Y3AlC3.

A novel ternary aluminum carbide, Y(3)AlC(3), has been synthesized under application of a lithium metal flux at high temperature (1523 K). Single-crystal structure determination of this compound revealed a new structure type with the Wyckoff sequence 2j3e and remarkable structural features at the border between Zintl and intermetallic phases. The puzzling bonding structure of Y(3)AlC(3) is analyzed with the aid of electronic structure calculations (energy bands and the electron localization function).

YAlC: A Bonding Chameleon with Heteropolyacetylene Features.

YAlC was prepared by a flux method. It crystallizes as a partially filled-up TlI structure, showing remarkable structural aspects at the border between Zintl phases and intermetallics. This novel ternary aluminide-carbide exhibits a unique one-dimensional multi-center bond and a polyacetylene-related aluminum carbide substructure. The different functionalities of aluminum and of yttrium are quite remarkable. While the latter behaves more like a trivalent ion, aluminum contributes considerably to covalent bonding with carbon. Still yttrium d states contribute, but hardly in a directed manner.

Elimination of primary circulating prostate cells after radical prostatectomy for prostate cancer decreases the risk of future biochemical failure.

OBJECTIVES: Primary CPCs are those detected in the blood of prostate cancer patients before radical treatment; secondary CPCs are those detected afterwards. Although primary CPCs are frequently found, it has been suggested that only a few will survive and go on to form metastasis. We evaluate the frequency of primary and secondary CPC detection and the association with biochemical failure, relation with clinical-pathological parameters and clinical implications in men treated by radical prostatectomy (RP) for prostate cancer. METHODS: Serial blood samples were taken before surgery and during follow up after RP. Mononuclear cells were obtained by differential gel centrifugation, and CPCs were identified using standard immunocytochemistry using anti-PSA monoclonal antibodies. Age, pathological stage (organ confined, non organ confined), pathological grade, margin status (positive, negative), extracapsular extension, perineural, vascular, and lymphatic infiltration (positive, negative) were compared with the presence/absence of CPCs in patients with and without biochemical failure. Kaplan Meier method was used to compare the unadjusted biochemical failure free survival of patients with and without CPCs. RESULTS: 138 of 423 (32.6%) men undergoing prostate biopsy for an elevated serum PSA were diagnosed of prostate cancer. Of these men 15 (10.9%) were CPC negative. 95 CPC positive men underwent RP. There was no relation between primary CPC detection and clinical-pathological parameters; however, secondary CPCs were associated both with clinical-pathological parameters and biochemical failure. CONCLUSIONS: Primary CPCs are frequently detected in men with prostate cancer, but they are not associated with biochemical failure, so that they may be useful for prostate cancer detection but not for prognosis. The persistence of CPCs after surgery is associated with increased biochemical failure.

Secondary circulating prostate cells predict biochemical failure in prostate cancer patients after radical prostatectomy and without evidence of disease.

INTRODUCTION: Although 90% of prostate cancer is considered to be localized, 20%-30% of patients will experience biochemical failure (BF), defined as serum PSA >0.2 ng/mL, after radical prostatectomy (RP). The presence of circulating prostate cells (CPCs) in men without evidence of BF may be useful to predict patients at risk for BF. We describe the frequency of CPCs detected after RP, relation with clinicopathological parameters, and association with biochemical failure. METHODS AND PATIENTS: Serial blood samples were taken during followup after RP, mononuclear cells were obtained by differential gel centrifugation, and CPCs identified using standard immunocytochemistry using anti-PSA monoclonal antibodies. Age, pathological stage (organ confined, nonorgan confined), pathological grade, margin status (positive, negative), extracapsular extension, perineural, vascular, and lymphatic infiltration (positive, negative) were compared with the presence/absence of CPCs and with and without biochemical failure. Kaplan Meier methods were used to compare the unadjusted biochemical failure free survival of patients with and without CPCs. RESULTS: 114 men participated, and secondary CPCs were detected more frequently in patients with positive margins, extracapsular extension, and vascular and lymphatic infiltration and were associated with biochemical failure independent of these clinicopathological variables, and with a shorter time to BF. CONCLUSIONS: Secondary CPCs are an independent risk factor associated with increased BF in men with a PSA <0.2 ng/mL after radical prostatectomy, but do not determine if the recurrence is due to local or systemic disease. These results warrant larger studies to confirm the findings.

Cost-Benefit of incorporating the detection of circulating prostate cells in a screening programme for prostate cancer.

OBJECTIVES: Prostate cancer is the second most common cancer in men after skin cancer, screening is used to detect early stage cancer using serum prostate specific antigen(PSA). A level of PSA 〉 4.0ng/m as a cut-off point or abnormal digital rectal examination (DRE) are used to indicate a prostate biopsy. Nevertheless, non-malignant pathologies can increase serum PSA level so that 70% of biopsies are negative for cancer, and thus potentially unnecessary, causing anxiety, costly clinical tests and prolonged follow-up. Thus the search for new biomarkers is important. Circulating primary prostate cells (CPCs) may be such a marker. We analyze a cohort of patients using CPCs to detect prostate cancer in men with a serum PSA 〉4.0ng/ml or abnormal DRE in terms of cost-benefit. METHODS: A cohort of 263 patients with a PSA 〉4.0 ng/ml and a test to detect CPCs who underwent prostate biopsy were analyzed. The results of both tests were compared with biopsy results; sensibility, specificity, and predictive values were calculated. Costs of each test, process, drug costs and complications were determined as well as indirect costs. RESULTS: Of the 263 patients, 77 (28.6%) had prostate cancer detected, for the test using CPCs there was a sensibility of 85.7%, specificity of 90.3% and negative predictive value of 93.9%. Thus men CPC negative may not need a prostate biopsy. Potential savings for the 263 patients were between €32,068 in a public health service and €69,253 for inpatient private health insurance patients. Follow up cost were higher in false-positive CPC patients but, as there were fewer false positive patients, total costs were lower. CONCLUSIONS: The use of primary CPC detection as a complementary test in men with a serum PSA 〉4.0ng/ml to indicate prostate biopsy is a specific, cost effective test, eliminating approximately 70% of prostate biopsies. This results in a significant health care saving both in direct and indirect costs, in the costs of complications. Implementation costs were minimal as equipment and reagents are part of the routine clinical laboratory. The method deserves further investigation to confirm the results.

[Soy beverages and women's health: evidence review and experts opinion]. / Bebidas de soja y salud femenina. Revisión de la evidencia y opinión de expertos.

Introduction: Soy drinks are an increasingly consumed option within the Western diet. However, there are concerns about potential endocrine disruptor effects and possible impact on women's reproductive health. This review evaluates scientific documents in gynecology and obstetrics under an evidence-based medicine approach. All methods adhered to PRISMA 2020 declaration guidelines. The evaluated studies do not support a positive association between soy intake and early puberty or breast cancer; instead, a protective effect against such neoplasm was observed. Transplacental passage of soy isoflavones and their presence in breast milk has been reported without any maternal-fetal complications nor congenital malformations. Exposure to soy-derived products appears to have a neutral effect on body weight and bone health. Studies performed in adults indicate that soy may promote a minimal increase in thyrotropin (TSH) in subjects with subclinical hypothyroidism. The impact of soy-based foods on gut microbiota appears favorable, especially when consuming fermented products. Many of the human studies have been conducted with isoflavones supplements, isolated or textured soy proteins. Therefore, the results and conclusions should be interpreted cautiously, as these are not entirely applicable to commercial soy beverages.

Introducción: Las bebidas vegetales de soja constituyen una alternativa dentro de la dieta habitual. Sin embargo, existe la preocupación de potenciales efectos en la salud reproductiva de la mujer por mecanismos de disrupción endócrina. En esta revisión se evalúan documentos científicos en el área de la Ginecología y la Obstetricia bajo el tamiz de la medicina basada en la evidencia, respondiendo preguntas estructuradas. La metodología se apegó a las guías establecidas por la declaración PRISMA 2020. Los estudios evaluados descartan un riesgo incrementado de pubertad precoz o cáncer de mama; incluso se aprecia un efecto protector frente a dicha neoplasia. Se ha reportado el paso transplacentario de isoflavonas de soja y su presencia en la leche materna, sin que ello implique una relación con complicaciones materno-fetales o malformaciones congénitas. La exposición a productos de soja no parece influir sobre el peso corporal y la salud ósea de la mujer. Los estudios en adultos indican que la soja favorece un mínimo incremento de tirotropina (TSH) en personas con antecedente de hipotiroidismo subclínico. El impacto de los alimentos basados en soja sobre la microbiota intestinal parece ser favorable para su diversidad, particularmente al consumir productos fermentados. Muchos de los estudios en humanos han sido realizados con suplementos de isoflavonas o con productos que contienen proteínas aisladas o texturizadas de soja. Por tanto, los resultados y las conclusiones deben interpretarse con cautela ya que no son totalmente extrapolables a las bebidas comerciales de soja.

Increasing Immune Dysfunction is Associated with Increasing Matrix-Metalloproteinase-2 Expression and Predicts Biochemical Failure in Men with Bone Marrow Micro-Metastasis Positive Localized Prostate Cancer.

INTRODUCTION: To determine if there was an association of the ALC (absolute lymphocyte count) and LCP (lymphocytopenia) with the expression of MMP-2 in bone marrow micro-metastasis, the changes occurring during follow-up and association with biochemical failure. METHODS AND PATIENTS: One month after surgery blood and bone marrow samples were taken to determine the presence of micro-metastasis, the presence of circulating prostate cells (CPCs) and ALC. CPCs and micro-metastasis were detected using immunocytochemistry and MMP-2 expression determined in micro-metastasis. Only men positive for micro-metastasis participated in the study. At end follow blood was taken for serum PSA, ALC and CPCs, if the ALC decreased by more than 10% bone marrow sampling was repeated and MMP-2 expression determined, similarly for men with BF. Men who had stable ALCs had an end of study evaluation of the bone marrow. RESULTS: 402 men underwent radical prostatectomy, one month post surgery 79 men were positive for only bone marrow micro-metastasis and formed the study group; of whom 36/79 (45%) underwent BF. Clinical pathological findings were not significantly different between men with or without BF. In men with BF the ALC was significantly lower one-month post surgery. The 5 and 10 year Kaplan-Meier survival was 100% at 5-years and 65% at 10-years for the whole cohort. Men without BF had stable ALCs. A decrease of >10% in the ALC was associated with increasing MMP-2 expression in the micro-metastasis and surrounding stromal tissue, the appearance of CPCs 6-12 months later and BF. CONCLUSIONS: the immune host-tumour cell interaction in the microenvironment is dynamic and changes with time. A decreasing ALC may be a valuable marker in identifying men with high risk of BF and changes in immune mediated dormancy before the PSA rises.

The CAPRA-S Score and Immune Dysfunction as a Guide to Outcome in Men Treated with Prostatectomy Radical as Mono-Therapy for Prostate Cancer.

OBJECTIVE: Incorporate the immune function as determined by the absolute lymphocyte count (ALC) into the CAPRA-S risk stratification score to determine if predictive values could be improved. MATERIALS AND METHODS: The clinical pathological findings in the surgical specimen and total PSA were used to define the three CAPRA-S risk groups. One month after surgery and at each follow up total PSA and the ALC were determined, until biochemical failure (BF) or the end of the study period. A cut off value of <1,000 lymphocytes/mm3 was used to define lymphocytopenia (LCP). Each CAPRA-S group was sub-divided based on the presence or absence of LCP. Kaplan-Meier biochemical failure free survival (BFFS) curves and restricted mean biochemical failure free survival times were calculated for each group. RESULTS: 404 patients participated of whom 103 (25.5%) underwent BF. 270 men were CAPRA-S low risk (LR), 89 intermediate risk (IR) and 45 high risk (HR), of whom LCP was found in 22 (8%) of low risk, 24 (27%) of intermediate risk and 17 (38%) of high risk men. LCP was significantly associated with a higher PSA, higher Gleason and CAPRA-S scores and BF. HRs were 1.76 for IR, 2.49 for HR and 1.29 for LCP. Five-year BFFS for men without LCP, LR 93.5%, IR 61% and HR 36%, for those with LCP, LR 55%, IR 25% and HR 6%. All patients with LCP and IR or HR scores relapsed within 6 years. 10 year BFFS for men without LCP were 71% LR, 43% IR and 23% HR, LR with LCP 16%. Men with BF had increasing LCP approximately 18 months before BF. CONCLUSIONS: The incorporation of the ALC taken one month after surgery with the CAPRA-S improves risk stratification; decreases in the ALC suggest that BF is occuring. These results need to be confirmed with larger studies.

Work-family enrichment: A potential buffer of inflammation among black adults?

Background: Inflammation plays a known role in the development of cardiovascular disease (CVD), the leading cause of death in the United States and a condition that disproportionately affects Blacks. Although social stressors are frequently studied, the role of positive experiences in inflammation and its potential for CVD remains understudied. To address this gap, we examined the relationship between work family enrichment and inflammation in a population-based sample of working adults. Methods: Participants were 447 working adults from Refresher Cohort of the National Study of Midlife Development in the United States (MIDUS) and the oversample of Blacks from the Milwaukee, WI. Serum concentration of pro-inflammatory biomarkers (IL-6/sIL-6r; CPR; Fibrinogen) were obtained via blood draw. Family-to-work enrichment (FtoWE) and work-to-family enrichment (WtoFE) were each assessed with four established survey questions. Results: Blacks had higher concentrations of IL-6, CRP and Fibrinogen, and lower levels of sIL-6r than whites. A significant inverse relationship was observed between WtoFE and systemic inflammation as well as WtoFE and serum IL-6 concentration. Conclusions: Individuals who perceived a stronger enhancing effect from work onto family showed lower levels of systemic inflammation and decreased concentrations of the pro-inflammatory cytokine IL-6; highlighting the potential work-family enrichment or other positive experiences may have in buffering the negative cardiovascular effects of inflammation. However, variation between racial groups remain undetermined.

Megathrust reflectivity reveals the updip limit of the 2014 Iquique earthquake rupture.

The updip limit of seismic rupture during a megathrust earthquake exerts a major control on the size of the resulting tsunami. Offshore Northern Chile, the 2014 Mw 8.1 Iquique earthquake ruptured the plate boundary between 19.5° and 21°S. Rupture terminated under the mid-continental slope and did not propagate updip to the trench. Here, we use state-of-the-art seismic reflection data to investigate the tectonic setting associated with the apparent updip arrest of rupture propagation at 15 km depth during the Iquique earthquake. We document a spatial correspondence between the rupture area and the seismic reflectivity of the plate boundary. North and updip of the rupture area, a coherent, highly reflective plate boundary indicates excess fluid pressure, which may prevent the accumulation of elastic strain. In contrast, the rupture area is characterized by the absence of plate boundary reflectivity, which suggests low fluid pressure that results in stress accumulation and thus controls the extent of earthquake rupture. Generalizing these results, seismic reflection data can provide insights into the physical state of the shallow plate boundary and help to assess the potential for future shallow rupture in the absence of direct measurements of interplate deformation from most outermost forearc slopes.

Tunable and Compartmentalized Multimaterial Bioprinting for Complex Living Tissue Constructs.

Recapitulating inherent heterogeneity and complex microarchitectures within confined print volumes for developing implantable constructs that could maintain their structure in vivo has remained challenging. Here, we present a combinational multimaterial and embedded bioprinting approach to fabricate complex tissue constructs that can be implanted postprinting and retain their three-dimensional (3D) shape in vivo. The microfluidics-based single nozzle printhead with computer-controlled pneumatic pressure valves enables laminar flow-based voxelation of up to seven individual bioinks with rapid switching between various bioinks that can solve alignment issues generated during switching multiple nozzles. To improve the spatial organization of various bioinks, printing fidelity with the z-direction, and printing speed, self-healing and biodegradable colloidal gels as support baths are introduced to build complex geometries. Furthermore, the colloidal gels provide suitable microenvironments like native extracellular matrices (ECMs) for achieving cell growths and fast host cell invasion via interconnected microporous networks in vitro and in vivo. Multicompartment microfibers (i.e., solid, core-shell, or donut shape), composed of two different bioink fractions with various lengths or their intravolume space filled by two, four, and six bioink fractions, are successfully printed in the ECM-like support bath. We also print various acellular complex geometries such as pyramids, spirals, and perfusable branched/linear vessels. Successful fabrication of vascularized liver and skeletal muscle tissue constructs show albumin secretion and bundled muscle mimic fibers, respectively. The interconnected microporous networks of colloidal gels result in maintaining printed complex geometries while enabling rapid cell infiltration, in vivo.

Mortality in patients with septic shock correlates with anti-inflammatory but not proinflammatory immunomodulatory molecules.

BACKGROUND: Mortality in patients with septic shock remains unacceptably high and the attempts to antagonize certain proinflammatory cytokines based on the results of animal model studies have failed to improve survival rates. The objective of this article is to examine the pro-/anti-inflammatory cytokine balance in patients with septic shock and its connection with mortality. METHODS: Serum levels of proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin 1ß [IL-1ß], interferonγ [IFN-γ], and IL-6) and soluble cytokine antagonists (soluble TNF receptor I [sTNF-RI], sTNF-RII, and IL-1Ra) were determined on admission to the intensive care unit (ICU) and 3, 7, 14, and 28 days later in 52 patients with septic shock and in 36 healthy controls. Specific sandwich enzyme-linked immunosorbent assay (ELISA) was used for all determinations. RESULTS: Serum levels of most of the pro- and anti-inflammatory molecules examined (TNF-α, IL-6, sTNF-RI, sTNF-RII, and IL-1 receptor agonist [IL-1Ra]) were significantly elevated on admission and during the 28-day observation period in patients when compared to controls. Notably, the anti-inflammatory mediators sTNF-RI, sTNF-RII, and IL-1Ra were better predictors of mortality. Receiver-operating characteristic (ROC) analysis revealed that sTNF-RI or sTNF-RII concentrations over 2767 or 4619 pg/mL, respectively, determined a high risk of death (sensitivity: 100%-100%, specificity: 57.1%-71.4%, area under the curve [AUC] 0.759-0.841, respectively), whereas IL-1Ra concentrations below 7033 pg/mL determined a high probability of survival (sensitivity: 60%, specificity: 100%, AUC 0.724). In addition, IFN-γ levels were significantly higher in survivors than in controls during the initial 2 weeks of observation. CONCLUSIONS: Our data show that serum cytokine disturbance patterns have prognostic significance in patients with septic shock admitted to the ICU. The pattern, defined by an early response to continuously elevated anti-inflammatory cytokine serum levels, is associated with an enhanced risk of a fatal outcome for patients.

[The transvaginal approach in acute appendicitis]. / El abordaje transvaginal en la apendicitis aguda.

INTRODUCTION: The purpose of this work is to present 8 minilaparoscopic-assisted transvaginal appendectomies using rigid instruments in patients with acute appendicitis. MATERIAL AND METHODS: Eight minilaparoscopic-assisted transvaginal appendectomies were performed from the 10th of August 2009 to the 30th of June 2010. The inclusion criteria were women between 18 and 65 years of age with a diagnosis of acute appendicitis. The exclusion criteria were palpable masses, appendicular abscesses, ASA III and IV; morbid obesity (BMI > 35); gynaecological infections; virgin patients and pregnant women. The surgical intervention was performed with rigid instruments. Surgical time, the need for post-operative analgesics, and post-surgical complications. RESULTS: The age range varied between 18 and 42 years, with a mean of 29.6 years. The mean surgical time was 48.3 minutes (37-75). Analgesics were given to 2 patients after surgery (1 parenteral and 1 oral). Five patients were discharged before 24 hours and 3 at 48 hours. There were no post-operative complications. CONCLUSIONS: Minilaparoscopic-assisted transvaginal appendectomy with rigid instruments, in selected women is a feasible and safe method, and with better aesthetic results than laparoscopic appendectomy, but future studies will be required that can demonstrate its advantages.