A study on the effect of flow unsteadiness on the yield of a chemical reaction in a t micro-reactor

Despite the very simple geometry and the laminar flow, T-shaped microreactors have been found to be characterized by different and complex steady and unsteady flow regimes, depending on the Reynolds number. In particular, flow unsteadiness modifies strongly the mixing process; however, little is known on how this change may affect the yield of a chemical reaction. In the present work, experiments and 3-dimensional numerical simulations are carried out jointly to analyze mixing and reaction in a T-shaped microreactor with the ultimate goal to investigate how flow unsteadiness affects the reaction yield. The onset of the unsteady asymmetric regime enhances the reaction yield by more than 30%; however, a strong decrease of the yield back to values typical of the vortex regime is observed when the flow undergoes a transition to the unsteady symmetric regime

Mixing Improvement in a T-Shaped Micro-Junction through Small Rectangular Cavities

The T-shaped micro-junction is among the most used geometry in microfluidic applications, and many design modifications of the channel walls have been proposed to enhance mixing. In this work, we investigate through numerical simulations the introduction of one pair of small rectangular cavities in the lateral walls of the mixing channel just downstream of the confluence region. The aim is to preserve the simple geometry that has contributed to spread the practical use of the T-shaped micro-junction while suggesting a modification that should, in principle, work jointly with the vortical structures present in the mixing channel, further enhancing their efficiency in mixing without significant additional pressure drops. The performance is analyzed in the different flow regimes occurring by increasing the Reynolds number. The cavities are effective in the two highly-mixed flow regimes, viz., the steady engulfment and the periodic asymmetric regimes. This presence does not interfere with the formation of the vortical structures that promote mixing by convection in these two regimes, but it further enhances the mixing of the inlet streams in the near-wall region of the mixing channel without any additional cost, leading to better performance than the classical configuration

Prognostic Role of Bacterial and Fungal Infections in Patients with Liver Cirrhosis with and without Acute-on-Chronic Liver Failure: A Prospective 2-Center Study

Background. Bacterial and fungal infections (BFIs) are frequent in patients with cirrhosis and often trigger acute-on-chronic liver failure (ACLF). This prospective observational study aims to describe the interactions between BFI and ACLF in terms of mortality and related risk factors. Methods. We performed a 2-center prospective observational study enrolling hospitalized patients with cirrhosis admitted for acute decompensation. Data were recorded at admission and during hospitalization. Survival was recorded up to 1 year. Results. Among the 516 patients enrolled, 108 (21%) were infected at admission, while an additional 61 patients (12%) developed an infection during hospital stay. In the absence of ACLF, the 1-year mortality rate of patients with BFI did not differ from that of patients without BFI (33% vs 31%; P = .553). In contrast, those with ACLF triggered or complicated by BFI had a significantly higher mortality rate than those who remained free from BFI (75% vs 54%; P = .011). Competing risk analysis showed that the negative impact of ACLF-related BFI on long-term prognosis was independent from Model for End-stage Liver Disease (MELD) incorporating serum sodium concentration score, comorbidity, and basal C-reactive protein level. Finally, multivariable logistic regression showed that higher MELD score (P < .001), QuickSOFA score ≥2 points (P = .007), and secondary bloodstream (P = .022) and multidrug-resistant pathogen isolation (P = .030) were independently associated with ACLF in patients with BFI. Conclusions. This large prospective study indicated that the adverse impact of BFI on long-term survival in decompensated cirrhosis is not universal but is limited to those patients who also develop ACLF. Both disease severity and microbiological factors predispose infected decompensated patients to ACLF

Multiorgan Metastasis of Human HER-2+ Breast Cancer in Rag2−/−;Il2rg−/− Mice and Treatment with PI3K Inhibitor

In vivo studies of the metastatic process are severely hampered by the fact that most human tumor cell lines derived from highly metastatic tumors fail to consistently metastasize in immunodeficient mice like nude mice. We describe a model system based on a highly immunodeficient double knockout mouse, Rag2−/−;Il2rg−/−, which lacks T, B and NK cell activity. In this model human metastatic HER-2+ breast cancer cells displayed their full multiorgan metastatic potential, without the need for selections or additional manipulations of the system. Human HER-2+ breast cancer cell lines MDA-MB-453 and BT-474 injected into Rag2−/−;Il2rg−/− mice faithfully reproduced human cancer dissemination, with multiple metastatic sites that included lungs, bones, brain, liver, ovaries, and others. Multiorgan metastatic spread was obtained both from local tumors, growing orthotopically or subcutaneously, and from cells injected intravenously. The problem of brain recurrencies is acutely felt in HER-2+ breast cancer, because monoclonal antibodies against HER-2 penetrate poorly the blood-brain barrier. We studied whether a novel oral small molecule inhibitor of downstream PI3K, selected for its penetration of the blood-brain barrier, could affect multiorgan metastatic spread in Rag2−/−; Il2rg−/− mice. NVP-BKM120 effectively controlled metastatic growth in multiple organs, and resulted in a significant proportion of mice free from brain and bone metastases. Human HER-2+ human breast cancer cells in Rag2−/−;Il2rg−/− mice faithfully reproduced the multiorgan metastatic pattern observed in patients, thus allowing the investigation of metastatic mechanisms and the preclinical study of novel antimetastatic agents

Raltitrexed plus oxaliplatin (TOMOX) as first-line chemotherapy for metastatic colorectal cancer. A phase ii study of the italian group for the study of gastrointestinal tract carcinomas (GISCAD)

Background: To evaluate the safety and efficacy of the novel raltitrexed/oxaliplatin combination (TOMOX) as first-line chemotherapy for patients with advanced colorectal cancer. Materials and methods: Previously untreated patients with metastatic colorectal cancer received raltitrexed 3 mg/m2 plus oxaliplatin 100 mg/m2, both intravenously, on day 1 every 3 weeks. Patients were re-evaluated after every third cycle and chemotherapy was continued up to tolerance or disease progression. Results: Fifty-eight patients from 13 Italian Group for the Study of Gastrointestinal Tract Carcinomas (GISCAD) centers were accrued from September 1999 to November 2000. According to the intention-to-treat analysis from 58 patients, the overall response rate was 50% [95% confidence interval (CI) 38% to 62%], with three complete responses and 26 partial responses. The median overall survival (44 patients currently alive) was >9 months and the median time to disease progression was 6.5 months (range 1-15 months). The main hematological toxicity was grade III/IV neutropenia, which occurred in 17% of patients, while anemia and thrombocytopenia were uncommon. Grade III/IV non-hematological toxicities were transient transaminitis (17% of patients); asthenia (16% of patients); neurotoxicity (10% of patients) and diarrhea (7% of patients). No toxic death was observed, one patient with grade IV asthenia after the first cycle refused chemotherapy. Conclusions: The results of this study suggest that the TOMOX combination is an effective and well tolerated regimen for the treatment of advanced colorectal cancer. Its ease of administration and patient tolerance warrant further investigation as an alternative to fluoropyrimidine-based regimens with repeated and prolonged fluorouracil infusions

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Background & Aims: Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF. Methods: A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded. Results: Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC). Conclusions: Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. ClinicalTrials.gov number: NCT03056612. Lay summary: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death – termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD – patients in this group rarely require hospital admission and have a much lower 1-year mortality risk

Usefulness of bronchoalveolar lavage in suspect COVID-19 repeatedly negative swab test and interstitial lung disease

The diagnosis of coronavirus disease 2019 (COVID-19) relies on nasopharyngeal swab, which shows a 20–30% risk of false negativity [1]. Bronchoalveolar lavage (BAL) is reported to be useful in patients with pulmonary interstitial infiltrates on high-resolution computed tomography (HRCT). We investigated the usefulness of BAL in symptomatic patients with positive HRCT and a repeatedly negative swab test (‘grey zone’)

Assessing the accuracy of patient report of the 5As (ask, assess, advise, assist, and arrange) for smoking cessation counseling

Objective: The 5As framework (ask, advise, assess, assist, arrange) is a recommended strategy for smoking cessation counseling in primary care. This study compares patient report with direct observation to assess the degree of recall bias for each of the 5As. Methods: Primary care visits by 107 adult smokers and 16 physicians were audio-recorded. Within 48 hours after the visit, patients completed a survey assessing whether or not smoking was discussed and items specific to each of the 5As. The audio recordings were evaluated to assess the presence of each A. The sensitivity, specificity, positive predictive value, and negative predictive value of patient report versus direct observation were computed. Results: The frequency of the 5As based on evaluation of the audio recording ranged from 13% (arrange) to 98% (ask). The sensitivity and specificity of patient report were 92% and not applicable for ask, 90% and 50% for assess, 94% and 33% for advise, 90% and 50% for assist, and 85% and 67% for arrange follow-up. Positive predictive values ranged from 28% to 98%; negative predictive values ranged from 0% to 97%. Conclusion: Compared with the gold standard of direct observation, patient report of each of the 5As is reasonably sensitive but not specific. Patients overreport the occurrence of each of the 5As

What is my heart rate right now? Comparing data from different devices

The extraordinary development of wearable devices and Internet of Things (IoT) technologies has substantially expanded the opportunities offered to remote healthcare systems, allowing to monitor physiological parameters out of clinical settings. One of the most important parameters is surely a subject's heart rate (HR). A key point in the design of a reliable remote healthcare solution is the proper selection of the devices: here, the focus is on the accuracy of HR data collected by wearable devices, which is still debatable, since rigorous validations are rarely applied. This paper aims at comparing the HR values obtained by different devices, namely smartwatches, chest-strap, pulse-oximeter, and by different methods, like the oscillometric-based one and the palpatory one, using an electrocardiogram as the reference measurement instrument. Results show different accuracy and precision values included in the ranges [-1, 3] bpm and [4], [12] bpm, respectively, thus confirming the importance that manufacturers make these figures available, for a better device selection depending on the target application