Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most frequent cause of progressive dementia in senior adults. It is characterized by memory loss and cognitive impairment secondary to cholinergic dysfunction and N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed of amyloid-ß (Aß), and selective neurodegeneration are the anatomopathological hallmarks of this disease. The dysregulation of calcium may be present in all the stages of AD, and it is associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, and chronic neuroinflammation. Although the cytosolic calcium alterations in AD are not completely elucidated, some calcium-permeable channels, transporters, pumps, and receptors have been shown to be involved at the neuronal and glial levels. In particular, the relationship between glutamatergic NMDA receptor (NMDAR) activity and amyloidosis has been widely documented. Other pathophysiological mechanisms involved in calcium dyshomeostasis include the activation of L-type voltage-dependent calcium channels, transient receptor potential channels, and ryanodine receptors, among many others. This review aims to update the calcium-dysregulation mechanisms in AD and discuss targets and molecules with therapeutic potential based on their modulation.

Thermodynamic Analysis of the Solubility of Isoniazid in (PEG 200 + Water) Cosolvent Mixtures from 278.15 K to 318.15 K.

The solubility of drugs in cosolvent systems of pharmaceutical interest is of great importance for understanding and optimizing a large number of processes. Here, we report the solubility of isoniazid in nine (PEG 200 + water) cosolvent mixtures at nine temperatures (278.15, 283.15, 288.15, 293.15, 298.15, 303.15, 308.15, and 318.15 K) determined by UV-vis spectrophotometry. From the solubility data, the thermodynamic solution, mixing, and transfer functions were calculated in addition to performing the enthalpy-entropy compensation analysis. The solubility of isoniazid depends on the concentration of PEG 200 (positive cosolvent effect) and temperature (endothermic process) reaching its maximum solubility in pure PEG 200 at 318.15 K and the lowest solubility in pure water at 278.15 K. The solution process is favored by the solution entropy and according to the enthalpy-entropy compensation analysis it is driven by entropy in mixtures rich in water and by enthalpy in mixtures rich in PEG 200.

Type III Kounis Syndrome Secondary to Ciprofloxacin-Induced Hypersensitivity.

Kounis syndrome (KS) is a rare syndrome characterized by the co-occurrence of acute coronary syndromes in the setting of mast cell and platelet activation in response to hypersensitivity reactions. It can be manifested as coronary vasospasms, acute myocardial infarction, or stent thrombosis triggered by drugs, vaccines, foods, coronary stents, and insect bites. It is a life-threatening condition that needs to be adequately recognized for early diagnosis and appropriate treatment. In this case report, we present a 71-year-old patient with a history of arterial hypertension and non-ST elevation myocardial infarction six months earlier that was treated percutaneously with angioplasty plus stent implantation in the circumflex artery, who subsequently presented to the emergency department due to generalized itching associated with tongue swelling, dyspnea, and chest pain after ingestion of ciprofloxacin for the treatment of a urogenital infection. An electrocardiogram showed ST elevation in II, III, and aVF leads, and positive troponin; thus, a coronary arteriography was performed that showed complete thrombotic stent occlusion in the circumflex artery. Consequently, diagnosis of type 4b inferolateral acute myocardial infarction secondary to ciprofloxacin-triggered type III Kounis syndrome was made. The aim of this report is to understand the relationship between the allergic reaction to ciprofloxacin and the acute coronary syndrome, and to create awareness of the importance of early diagnosis and treatment of this potentially fatal syndrome.

Graphene oxide-silver nanoparticle hybrid material: an integrated nanosafety study in zebrafish embryos.

This work reports an integrated nanosafety study including the synthesis and characterization of the graphene oxide-silver nanoparticle hybrid material (GO-AgNPs) and its nano-ecotoxicity evaluation in the zebrafish embryo model. The influences of natural organic matter (NOM) and a chorion embryo membrane were considered in this study, looking towards more environmentally realistic scenarios and standardized nanotoxicity testing. The nanohybrid was successfully synthesized using the NaBH4 aqueous method, and AgNPs (~ 5.8 nm) were evenly distributed over the GO surface. GO-AgNPs showed a dose-response acute toxicity: the LC50 was 1.5 mg L-1 for chorionated embryos. The removal of chorion, however, increased this toxic effect by 50%. Furthermore, the presence of NOM mitigated mortality, and LC50 for GO-AgNPs changed respectively from 2.3 to 1.2 mg L-1 for chorionated and de-chorionated embryos. Raman spectroscopy confirmed the ingestion of GO by embryos; but without displaying acute toxicity up to 100 mg L-1, indicating that the silver drove toxicity down. Additionally, it was observed that silver nanoparticle dissolution has a minimal effect on these observed toxicity results. Finally, understanding the influence of chorion membranes and NOM is a critical step towards the standardization of testing for zebrafish embryo toxicity in safety assessments and regulatory issues.

Genetic and Molecular Aspects of Drug-Induced QT Interval Prolongation.

Long QT syndromes can be either acquired or congenital. Drugs are one of the many etiologies that may induce acquired long QT syndrome. In fact, many drugs frequently used in the clinical setting are a known risk factor for a prolonged QT interval, thus increasing the chances of developing torsade de pointes. The molecular mechanisms involved in the prolongation of the QT interval are common to most medications. However, there is considerable inter-individual variability in drug response, thus making the application of personalized medicine a relevant aspect in long QT syndrome, in order to evaluate the risk of every individual from a pharmacogenetic standpoint.

Effect of Combined Diclofenac and B Vitamins (Thiamine, Pyridoxine, and Cyanocobalamin) for Low Back Pain Management: Systematic Review and Meta-analysis.

BACKGROUND: Cumulative evidence suggests an analgesic effect of thiamine, pyridoxine, and cyanocobalamin (TPC) in monotherapy, and also when combined with nonsteroidal anti-inflammatory drugs (NSAIDs), particularly diclofenac, in a synergistic manner. The aim of this review was to determine the effects of diclofenac combined with TPC compared with diclofenac monotherapy for low back pain (LBP) management. METHODS: We searched for randomized clinical trials on the MEDLINE, EMBASE, LILACS, and Cochrane databases of records of clinical trials, among other sources. We evaluated the risk of bias regarding randomization, allocation concealment, blinding, incomplete outcome data, selective reporting, and other biases. A random-effects meta-analysis to examine patients with acute LBP (N = 1,108 adults) was performed, along with a subsequent sensitivity analysis. RESULTS: Five studies in patients with LBP were included in the qualitative synthesis. Four of these studies in acute LBP were included in the first meta-analysis. A sensitivity test based on risk of bias (three moderate- to high-quality studies) found that the combination therapy of diclofenac plus TPC was associated with a significant reduction in the duration of treatment (around 50%) compared with diclofenac monotherapy (odds ratio = 2.23, 95% confidence interval = 1.59 to 3.13, P < 0.00001). We found no differences in the safety profile and patient satisfaction. CONCLUSIONS: This meta-analysis demonstrated that combination therapy of diclofenac with TPC might have an analgesic superiority compared with diclofenac monotherapy in acute LBP. However, there is not enough evidence to recommend this therapy in other types of pain due to the scarcity of high-quality studies.

Proton Pump Inhibitors and Dementia: Physiopathological Mechanisms and Clinical Consequences.

Alzheimer's disease (AD) is the most common type of dementia, mainly encompassing cognitive decline in subjects aged ≥65 years. Further, AD is characterized by selective synaptic and neuronal degeneration, vascular dysfunction, and two histopathological features: extracellular amyloid plaques composed of amyloid beta peptide (Aß) and neurofibrillary tangles formed by hyperphosphorylated tau protein. Dementia and AD are chronic neurodegenerative conditions with a complex physiopathology involving both genetic and environmental factors. Recent clinical studies have shown that proton pump inhibitors (PPIs) are associated with risk of dementia, including AD. However, a recent case-control study reported decreased risk of dementia. PPIs are a widely indicated class of drugs for gastric acid-related disorders, although most older adult users are not treated for the correct indication. Although neurological side effects secondary to PPIs are rare, several preclinical reports indicate that PPIs might increase Aß levels, interact with tau protein, and affect the neuronal microenvironment through several mechanisms. Considering the controversy between PPI use and dementia risk, as well as both cognitive and neuroprotective effects, the aim of this review is to examine the relationship between PPI use and brain effects from a neurobiological and clinical perspective.

Characterization of adverse drug reactions causing admission to an intensive care unit.

AIMS: This study aimed to determine the occurrence of adverse drug reactions (ADRs) that caused admission to the intensive care unit (ICU) of a university hospital. METHODS: Clinical records were reviewed for patients meeting the inclusion criteria who were admitted to the ICU between September and December 2012. Suspected cases of ADRs were documented. Nine researchers later evaluated causality using the Naranjo Algorithm, preventability using the Schumock and Thornton criteria, and clinical classification based on the dose-time-susceptibility system. RESULTS: In total, 96 patients presented 108 cases of ADR (13.8%, 95% confidence interval 11.2-16.4%) as the cause of admission. The most frequent ADRs were bradyarrhythmias and upper gastrointestinal bleeding (12%). Therapeutic failure accounted for 20%. The most commonly associated medications were acetylsalicylic acid (16%) and losartan (10%). Forty-six cases were categorized as possible, and only one as definite. According to the dose-time-susceptibility classification, in 82% of the cases, the dosage was collateral (within the therapeutic range), and 90% were independent of time; the factors most associated with susceptibility to ADRs were comorbidities (42%) and age (49%). Forty-four percent of the ADRs were considered possibly preventable. CONCLUSIONS: ADRs contribute significantly to ICU admissions, and a significant number of ADRs are preventable. National studies are needed to assess their incidence and to establish classification standards to reduce their clinical impact.

Efficient multicolor tunability of ultrasmall ternary-doped LaF3 nanoparticles: energy conversion and magnetic behavior.

Luminescence-tunable multicolored LaF3:xCe3+,xGd3+,yEu3+ (x = 5; y = 1, 5, 10, and 15 mol%) nanoparticles have been synthesized via a low cost polyol method. Powder X-ray diffraction and high-resolution transmission electron microscopy studies confirm the hexagonal phase of the LaF3:xCe3+,xGd3+,yEu3+ nanophosphors with average sizes (oval shape) ranging from 5 to 7 nm. Energy-dispersive X-ray spectroscopy analyses show the uniform distribution of Ce3+, Gd3+, and Eu3+ dopants in the LaF3 host matrix. The photoluminescence spectra and electron paramagnetic resonance measurements guarantee the presence of Eu2+, corroborated through DC susceptibility measurements of the samples displaying paramagnetic behavior at 300 K, whereas weak ferromagnetic ordering is shown at 2 K. The non-radiative energy transfer processes from the 4f(2F5/2) → 5d state (Ce3+) to the intraconfigurational 4f excited levels of rare earth ions and simultaneous emissions in the visible region from the 4f65d1 (Eu2+) and 5D0 (Eu3+) emitting levels, leading to overlapped broad and narrow emission bands, have been proclaimed. The energy transfer mechanism proposes involvement of the Gd3+ ion sub-lattice as the bridge and finally trapping by Eu2+/3+, upon excitation of the Ce3+ ion. The calculation of experimental intensity parameters (Ω2,4) has been discussed and the highest emission quantum efficiency (η = 85%) of the Eu3+ ion for the y = 10 mol% sample is reported. The advantageous existence of the Eu2+/Eu3+ ratio along with variously doped nanomaterials described in this work, results in tunable emission color in the blue-white-red regions, highlighting the potential application of the samples in solid-state lighting devices, scintillation devices, and multiplex detection.

Predictors of Outcome in Modern Surgery for Lung Abscess.

Background Surgery for lung abscess is a challenging task. Timing and indications for surgery are not well established. Identification of predictors of outcome could help to clarify the role of surgery. Methods Patients who underwent major thoracic surgery for infectious lung abscess were identified at six centers for general thoracic surgery in Germany, Spain, the United Kingdom, and the United States. Study period was 2000 to 2016. Results There were 91 patients. Pulmonary sepsis (48), pleural empyema (43), persistent air leakage (25), acute renal failure (12), and respiratory failure with mechanical ventilation (25) were already preoperatively present. The mean Charlson index of comorbidity was 3.0 (median: 2.0; interquartile range: 3). Procedures were segmentectomy (18), lobectomy (58), and pneumonectomy (15). The 30-day mortality following surgery was 13/91.Preoperative sepsis (odds ratio [OR]: 13.69; 95% confidence interval [CI]: 1.86-610.53; p < 0.01), preoperative persistent air leak (OR: 13.46, 95% CI: 3.00-85.37, p < 0.01), respiratory failure (OR: 5.60; 95% CI: 1.41-24.84; p < 0.01), acute renal failure (OR: 6.15 ; 95% CI: 1.24-29.56 ; p = 0.01), and Charlson index of comorbidity ≥ 3 (OR: 7.19 ; 95% CI: 1.43-71.21 ; p < 0.01) are associated with higher mortality, whereas age > 70 years (p = 0.46) and the extent of pulmonary resection (segmentectomy, lobectomy, pneumonectomy) have no significant influence on mortality. Patients with fatal outcome have significantly higher Charlson index of comorbidity (p < 0.01). Conclusions Delayed referral for surgery is common. Significant predictors for fatal outcome are pulmonary sepsis, septic complications (air leak, pleural empyema), septic organ failure (respiratory, acute renal failure), and preexisting comorbidity (Charlson index of comorbidity ≥ 3). The extent of surgical resection shows no significant influence.

A phased genome assembly of a Colombian Trypanosoma cruzi TcI strain and the evolution of gene families.

Chagas is an endemic disease in tropical regions of Latin America, caused by the parasite Trypanosoma cruzi. High intraspecies variability and genome complexity have been challenges to assemble high quality genomes needed for studies in evolution, population genomics, diagnosis and drug development. Here we present a chromosome-level phased assembly of a TcI T. cruzi strain (Dm25). While 29 chromosomes show a large collinearity with the assembly of the Brazil A4 strain, three chromosomes show both large heterozygosity and large divergence, compared to previous assemblies of TcI T. cruzi strains. Nucleotide and protein evolution statistics indicate that T. cruzi Marinkellei separated before the diversification of T. cruzi in the known DTUs. Interchromosomal paralogs of dispersed gene families and histones appeared before but at the same time have a more strict purifying selection, compared to other repeat families. Previously unreported large tandem arrays of protein kinases and histones were identified in this assembly. Over one million variants obtained from Illumina reads aligned to the primary assembly clearly separate the main DTUs. We expect that this new assembly will be a valuable resource for further studies on evolution and functional genomics of Trypanosomatids.

Enhancing Trypanosomatid Identification and Genotyping with Oxford Nanopore Sequencing: Development and Validation of an 18S rRNA Amplicon-Based Method.

Trypanosomatids, including Trypanosoma and Leishmania species, present significant medical and veterinary challenges, causing substantial economic losses, health complications, and even fatalities. Diagnosing and genotyping these species and their genotypes is often complex, involving multiple steps. This study aimed to develop an amplicon-based sequencing (ABS) method using Oxford Nanopore long-read sequencing to enhance Trypanosomatid detection and genotyping. The 18S rDNA gene was targeted for its inter-species conservation. The Trypanosomatid-ABS method effectively distinguished between 11 Trypanosoma species (including Trypanosoma evansi, Trypanosoma theileri, Trypanosoma vivax, and Trypanosoma rangeli) and 6 Trypanosoma cruzi discrete typing units (TcI to TcVI and TcBat), showing strong concordance with conventional methods (κ index of 0.729, P < 0.001). It detected co-infections between Trypanosomatid genera and T. cruzi, with a limit of detection of one parasite per mL. The method was successfully applied to human, animal, and triatomine samples. Notably, TcI predominated in chronic Chagas samples, whereas TcII and TcIV were found in the acute stage. Triatomine vectors exhibited diverse Trypanosomatid infections, with Triatoma dimidiata mainly infected with TcI and occasional TcBat co-infections, and Rhodnius prolixus showing TcI and TcII infections, along with T. rangeli co-infections and mixed TcII infections. Animals were infected with T. vivax, T. theileri, and T. evansi. The ABS method's high resolution, sensitivity, and accuracy make it a valuable tool for understanding Trypanosomatid dynamics, enhancing disease control strategies, and enabling targeted interventions.

The polygenic implication of clopidogrel responsiveness: Insights from platelet reactivity analysis and next-generation sequencing.

Clopidogrel is widely used worldwide as an antiplatelet therapy in patients with acute coronary disease. Genetic factors influence interindividual variability in response. Some studies have explored the polygenic contributions in the drug response, generating pharmacogenomic risk scores (PgxPRS). Importantly, these factors are less explored in underrepresented populations, such as Latin-American countries. Identifying patients at risk of high-on-treatment platelet reactivity (HTPR) is highly valuable in translational medicine. In this study we used a custom next-generation sequencing (NGS) panel composed of 91 single nucleotide polymorphisms (SNPs) and 28 genes related to clopidogrel metabolism, to analyze 70 patients with platelet reactivity values, assessed through closure time (CT). Our results demonstrated the association of SNPs with HTPR and non-HTPR, revealing the strongest associations with rs2286823 (OR: 5,0; 95% CI: 1,02-24,48; p: 0,03), rs2032582 (OR: 4,41; 95% CI: 1,20-16,12; p: 0,019), and rs1045642 (OR: 3,38; 95% CI: 0,96-11,9; p: 0,05). Bivariate regression analysis demonstrated the significant association of several SNPs with the CT value, a "surrogate" biomarker of clopidogrel response. Exploratory results from the LASSO regression model showed a high discriminatory capacity between HTPR and non-HTPR patients (AUC: 0,955), and the generated PgxPRS demonstrated a significant negative association between the risk score, CT value, and the condition of HTPR and non-HTPR. To our knowledge, our study addresses for the first time the analysis of the polygenic contribution in platelet reactivity using NGS and establishes PgxPRS derived from the LASSO model. Our results demonstrate the polygenic implication of clopidogrel response and offer insights applicable to the translational medicine of antiplatelet therapy in an understudied population.

Prospective study on the treatment of lower-extremity chronic venous and mixed ulcers using tissue-engineered skin substitute made by the self-assembly approach.

BACKGROUND: Despite present optimal standard treatment of lower-extremity ulceration, a high incidence of recurrence and treatment failure is observed. The objective of this project was to evaluate the effect of a self-assembled skin substitute (SASS) made by tissue engineering as a temporary cutaneous dressing in the treatment of hard-to-heal chronic ulcers. PATIENTS AND METHODS: The prospective uncontrolled case study includes patients suffering from venous or mixed ulcers lasting more than 6 months and unresponsive to compression therapy, with an Ankle Brachial Index greater than 0.5. Compression therapy was combined with the weekly application of SASS, produced from the patient's own skin cells, until healing. A weekly follow-up recorded wound size, skin aspect, pain, drainage, and percentage of wound healing. Photographs were also taken to assess ulcer evolution. RESULTS: Fourteen ulcers present on 5 patients were treated. A mean of 6.7 SASS depositions by ulcer was required for healing. Two ulcers developed a minor wound infection, which was treated with oral antibiotics; another 2 ulcers recurred, and 1 healed with a second course of treatment, whereas 1 ulcer had a small recurrence treated with local wound care. CONCLUSION: The authors' study suggests that the SASS used as a biological dressing is a promising treatment for hard-to-heal chronic venous and mixed ulcers that are unresponsive to compression therapy.

Making Sense of Composite Endpoints in Clinical Research.

Multiple drugs currently used in clinical practice have been approved by regulatory agencies based on studies that utilize composite endpoints. Composite endpoints are appealing because they reduce sample size requirements, follow-up periods, and costs. However, interpreting composite endpoints can be challenging, and their misuse is not uncommon. Incorrect interpretation of composite outcomes can lead to misleading conclusions that impact patient care. To correctly interpret composite outcomes, several important questions should be considered. Are the individual components of the composite outcome equally important to patients? Did the more and less important endpoints occur with similar frequency? Do the component endpoints exhibit similar relative risk reductions? If these questions receive affirmative answers, the use and interpretation of the composite endpoint would be appropriate. However, if any component of the composite endpoint fails to satisfy the aforementioned criteria, interpretation can become difficult, necessitating additional steps. Regulatory agencies acknowledge these challenges and have specific considerations when approving drugs based on studies employing composite endpoints. In conclusion, composite endpoints are valuable tools for evaluating the efficacy and net clinical benefit of interventions; however, cautious interpretation is advised.

Development of Antiepileptic Drugs throughout History: From Serendipity to Artificial Intelligence.

This article provides a comprehensive narrative review of the history of antiepileptic drugs (AEDs) and their development over time. Firstly, it explores the significant role of serendipity in the discovery of essential AEDs that continue to be used today, such as phenobarbital and valproic acid. Subsequently, it delves into the historical progression of crucial preclinical models employed in the development of novel AEDs, including the maximal electroshock stimulation test, pentylenetetrazol-induced test, kindling models, and other animal models. Moving forward, a concise overview of the clinical advancement of major AEDs is provided, highlighting the initial milestones and the subsequent refinement of this process in recent decades, in line with the emergence of evidence-based medicine and the implementation of increasingly rigorous controlled clinical trials. Lastly, the article explores the contributions of artificial intelligence, while also offering recommendations and discussing future perspectives for the development of new AEDs.

A Latin American consensus meeting on the essentials of mixed pain.

OBJECTIVES: The term "mixed pain" has been established when a mixture of different pain components (e.g. nociceptive, neuropathic, and nociplastic) are present. It has gained more and more acceptance amongst pain experts worldwide, but many questions around the concept of mixed pain are still unsolved. The sensation of pain is very personal. Cultural, social, personal experiences, idiomatic, and taxonomic differences should be taken into account during pain assessment. Therefore, a Latin American consensus committee was formed to further elaborate the essentials of mixed pain, focusing on the specific characteristics of the Latin American population. METHODS: The current approach was based on a systematic literature search and review carried out in Medline. Eight topics about the definition, diagnosis, and treatment of mixed pain were discussed and voted for by a Latin American consensus committee and recommendations were expressed. RESULTS: At the end of the meeting a total of 14 voting sheets were collected. The full consensus was obtained for 21 of 25 recommendations (15 strong agreement and 6 unanimous agreement) formulated for the above described 8 topics (7 of the 8 topics had for all questions at least a strong agreement - 1 topic had no agreement for all 4 questions). CONCLUSION: In a subject as complex as mixed pain, a consensus has been reached among Latin American specialists on points related to the definition and essence of this pain, its diagnosis and treatment. Recommendations for diagnosis and treatment of mixed pain in Latin America were raised.

Pharmacogenomic profile of actionable molecular variants related to drugs commonly used in anesthesia: WES analysis reveals new mutations.

Background: Genetic interindividual variability is associated with adverse drug reactions (ADRs) and affects the response to common drugs used in anesthesia. Despite their importance, these variants remain largely underexplored in Latin-American countries. This study describes rare and common variants found in genes related to metabolism of analgesic and anaesthetic drug in the Colombian population. Methods: We conducted a study that included 625 Colombian healthy individuals. We generated a subset of 14 genes implicated in metabolic pathways of common medications used in anesthesia and assessed them by whole-exome sequencing (WES). Variants were filtered using two pipelines: A) novel or rare (minor allele frequency-MAF <1%) variants including missense, loss-of-function (LoF, e.g., frameshift, nonsense), and splice site variants with potential deleterious effect and B) clinically validated variants described in the PharmGKB (categories 1, 2 and 3) and/or ClinVar databases. For rare and novel missense variants, we applied an optimized prediction framework (OPF) to assess the functional impact of pharmacogenetic variants. Allelic, genotypic frequencies and Hardy-Weinberg equilibrium were calculated. We compare our allelic frequencies with these from populations described in the gnomAD database. Results: Our study identified 148 molecular variants potentially related to variability in the therapeutic response to 14 drugs commonly used in anesthesiology. 83.1% of them correspond to rare and novel missense variants classified as pathogenic according to the pharmacogenetic optimized prediction framework, 5.4% were loss-of-function (LoF), 2.7% led to potential splicing alterations and 8.8% were assigned as actionable or informative pharmacogenetic variants. Novel variants were confirmed by Sanger sequencing. Allelic frequency comparison showed that the Colombian population has a unique pharmacogenomic profile for anesthesia drugs with some allele frequencies different from other populations. Conclusion: Our results demonstrated high allelic heterogeneity among the analyzed sampled, enriched by rare (91.2%) variants in pharmacogenes related to common drugs used in anesthesia. The clinical implications of these results highlight the importance of implementation of next-generation sequencing data into pharmacogenomic approaches and personalized medicine.

Use of extracorporeal membrane oxygenation in non-elective major thoracic surgery for infectious lung abscess.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) support for elective cardiothoracic surgery is well established. In contrast, there are not much data regarding the usefulness and outcome of ECMO in non-elective major lung resections for infectious lung abscess. METHODS: All patients undergoing non-elective major lung surgery for infectious lung abscess at 5 centres in Germany, UK and Spain were enrolled in a prospective database. Malignant disorders and intrathoracic complications of other procedures were excluded. RESULTS: There were 127 patients. The median age was 59 years (interquartile range 18.75). The mean Charlson index of comorbidity was 2.83 (standard deviation 2.57). Surgical procedures were lobectomy (89), pneumectomy (20) and segmentectomy (18). ECMO was used for 10 patients (pneumectomy 2, lobectomy 8) and several more received pre-ECMO treatment. Mortality was 17/127. Intraoperatively no ECMO-associated complications were encountered. EMCO [1/10 vs 16/117; odds ratio (OR): 0.70, 95% confidence interval (CI) 0.08-5.91, P = 0.74] and the extent of pulmonary resection were not associated with higher mortality. Preoperative sepsis (OR: 17.84, 95% CI 2.29-139.28, P < 0.01), preoperative air leak (OR: 13.12, 95% CI 4.10-42.07, P < 0.001), acute renal failure (OR: 7.00, 95% CI 2.19-22.43, P < 0.01) and Charlson index of comorbidity ≥3 (OR: 10.83, 95% CI 2.36-49.71, P < 0.01) were associated with significantly higher mortality. CONCLUSIONS: The application of ECMO is widening the possibilities for successful surgical management of infectious, non-malignant lung abscesses. Particularly, patients with marginal functional operability benefit from the availability and readiness to use ECMO. Mortality is determined by the burden of pre-existent comorbidity, severe sepsis and septic shock.

Fast and efficient electrochemical thinning of ultra-large supported and free-standing MoS2 layers on gold surfaces.

Molybdenum disulfide (MoS2) is a very promising layered material for electrical, optical, and electrochemical applications because of its unique and outstanding properties. To unlock its full potential, among different preparation routes, electrochemistry has gain interest due to its simple, fast, scalable and simple instrumentation. However, obtaining large-area monolayer MoS2 that will enable the fabrication of novel electronic and electrochemical devices is still challenging. In this work, we reported a simple and fast electrochemical thinning process that results in ultra-large MoS2 down to monolayer on Au surfaces. The high affinity of MoS2 by Au surfaces enables the removal of bulk layers while preserving the first layer attached to the electrode. With a proper choice of the applied potential, more than 90% of the bulk regions can be removed from large-area MoS2 crystals, as confirmed by atomic force microscopy, photoluminescence, and Raman spectroscopy. We further address a set of contributions that are helpful to elucidate the features of MoS2, namely, the hyphenation of electrochemistry and optical microscopy for real-time observation of the thinning process that was revealed to occur from the edges to the center of the flake, an image treatment to estimate the thinning area and thinning rate, and the preparation of free-standing MoS2 layers by electrochemically thinning bulk flakes on microhole-structured Ni/Au meshes.