Current Management Algorithms Research Articles

Dynamic Assessment of Drain Fluid Amylase Estimates the Risk of CR-POPF Following Pancreatoduodenectomy.

To evaluate whether drain fluid amylase levels on day-1 (DFA1) and day-3 (DFA3) can reliably estimate the risk of clinically relevant-postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) compared to either value alone or in combination with clinicopathologic variables. CR-POPF is a major source of morbidity and mortality following PD. Current drain management algorithms are variable and are mostly dependent on DFA1, while the DFA3 is seldom utilized to guide clinical decision making. Between 2015-2020, patients who underwent PD at two high-volume pancreas centers and had intraoperative drain placement with measurement of DFA1 and DFA3 were retrospectively reviewed. Models to predict CR-POPF were constructed using DFA1, DFA3, fistula risk score (FRS) and other patient or treatment-related parameters. The fittest and more parsimonious model was used to construct a CR-POPF risk calculator. Nine-hundred-twenty-three patients were included in the analysis. The FRS was high in 100(10.9%), intermediate in 524(57.3%), low in 211(23.1%) and negligible in 79(8.6%) patients. The overall rate of CR-POPF was 9.2%. Five logistic regression models were constructed using variables known to be implicated in CR-POPF. A model based solely on DFA1 and DFA3 with a cross-validated area under the curve of 0.846 was selected. A calculator using DFA1 and DFA3 was created based on this model to estimate the risk of CR-POPF. Risk of CR-POPF following pancreatoduodenectomy can be accurately estimated based on measurement of DFA1 and DFA3. Our CR-POPF kinetics calculator can facilitate postoperative risk stratification and guide drain management algorithms.

The Acute Coronary Syndrome Risk in Medically Managed Subjects with Type 2 Diabetes Mellitus - Is the ASCVD Risk Score Failing Here?

Type 2 Diabetics have elevated risk for acute coronary syndrome (ACS). The current management algorithm focuses on atherosclerotic cardiovascular (ASCVD) risk score to stratify this risk. However, in medically managed subjects, this algorithm may not be accurate. This study compares the ASCVD risk score in an Indian population with T2DM under medical supervision and the actual incidence of ACS. It also compared the ASCVD risk scores in cases with T2DM who developed ACS to controls and tried to estimate whether the ASCVD risk score is different in the two subsets, evaluating the utility of the ASCVD risk score in predicting ACS. This is an electronic medical record (EMR) based case-control study. Only records of subjects with T2DM where details of age, sex, body mass index, blood pressure, duration of diabetes, family history of ACS, lipid profile, renal and liver function tests were included. The incidence of ACS was calculated in the selected records, and the records of subjects with ACS were compared with age and sex-matched subjects without ACS. Data are summarized as median and interquartile range (IQR). Wilcoxon rank-sum test was used for checking differences in continuous variables and Pearson's Chi-squared test for categorical data. Univariate and multivariate logistic regression analyses were used to check the effect of ASCVD scores and other variables on the occurrence of ACS.Statistical data analyses were performed using JASP, version 0.16.4 (JASP Team [2022]) for MS Windows. Of the 1226 EMRs included in the analysis, 207 had ACS. The actual incidence of ACS was 16.85% in 6 years, higher than the mean predicted 10-year incidence of 14.56 percent (p <0.05). The cases were age and sex-matched with controls and the ASCVD incidence was estimated in the two groups. The mean ASCVD score in the cases was 14.565 ± 8.709 (Min: 1.5, Max: 38.3) and controls 13.114 ± 8.247 (Min: 1.4, Max: 45). The chance of development of ACS increases with elevated systolic blood pressure (per mmHg rise OR: 1.04, 95% CI: 1.03, 1.06; p <0.001), positive family history (OR: 5.70, 95% CI: 3.41, 9.77; p <0.001), statin use (OR: 2.26, 95% CI: 1.46, 3.52; p <0.001), and longer duration of diabetes (for every year increase OR: 1.19, 95% CI: 1.13, 1.25; p <0.001). The ASCVD risk score underestimates the ACS risk in subjects with T2DM under medical supervision and may not differ in those who developed and did not develop ACS. We also conclude that factors like a negative family history (30% less risk), longer duration of diabetes, and higher SBP are relevant in those who developed ACS.

Use of negative pressure wound therapy with instillation to salvage infected breast reconstruction implant pockets: a retrospective review of cases

"Introduction: Periprosthetic breast implant infections are a well-known but devastating complication of breast reconstruction, occurring in up to 35 per cent of patients postoperatively. Historically, surgical washout and explantation was common practice to control infection, often sacrificing the reconstruction. Methods: After successfully using negative-pressure wound therapy with instillation (Veraflo, Intermed, Auckland) on lower leg wounds, we transferred the use of this technology to infected breast pockets. Results: In the first year using NPWTi, our department managed seven patients (8 breast reconstructions) presenting with breast device infection at an average of 15.3 days postoperatively. The average length of stay for treatment was 7.4 days with 2.5 operations over this period. Four patients had attempted salvage of their reconstructive pocket and all were discharged with a breast expander in situ. Conclusion: Attempted salvage using negative-pressure wound therapy with instillation may improve rates of reconstruction salvage after periprosthetic infection. We present our current management algorithm for periprosthetic infections."

Lymphocele Complication After Kidney Transplant: Current Literature Review and Management Algorithm.

Kidney transplant is the best treatment option for patients with end-stage renal disease. It reduces mortality and improves the quality of life. However, kidney transplant presents medical and surgical complications, and one of the most common is the posttransplant lymphocele. Lymphocele complication has an incidence of up to 20% and presents with variable clinical symptoms, which are directly associated with the size and compression effect on the adjacent organs. There are reported risk factors that favor the appearance of lymphocele. Despite known factors, there are more relevant factors (male sex, deceased donor, and corticosteroids) to carry out a stricter follow-up. The treatment of lymphoceles can vary according to the severity of the symptoms, characteristics of the collection, and the patient's clinical status. Despite the high recurrence, percutaneous intervention is the initial approach in this condition. If percutaneous aspiration, drainage, and sclerotherapy are unsuccessful, then open or laparoscopic fenestration can be performed; laparoscopy is the standard of treatment since it is highly effective and has few adverse effects.

Mavacamten: a first-in-class myosin inhibitor for obstructive hypertrophic cardiomyopathy.

Mavacamten is a first-in-class, targeted, cardiac-specific myosin inhibitor approved by the US Food and Drug Administration for the treatment of adults with symptomatic New York Heart Association Classes II and III obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten was developed to target the hyper-contractile phenotype, which plays a critical role in the pathophysiology of the disease. In Phase 2 and 3 clinical trials, mavacamten was well tolerated, reduced left ventricular outflow tract gradients, improved exercise capacity and symptoms, and was associated with improvements in other clinically relevant parameters, such as patient-reported outcomes and circulating biomarkers. In addition, treatment with mavacamten was associated with evidence of favourable cardiac remodelling in multi-modality imaging studies. Mavacamten substantially reduced guideline eligibility for septal reduction therapy candidates with oHCM and drug-refractory symptoms. In this article, the available efficacy and safety data from completed and ongoing clinical studies of mavacamten in patients with symptomatic oHCM are reviewed. Longer term extension studies may help address questions related to the positioning of mavacamten in current oHCM management algorithms, interactions with background therapy, as well as the potential for disease modification beyond symptomatic relief of left ventricular outflow tract obstruction.

Expert Consensus on Comprehensive Early Rhythm Control in Addition to Guideline-Based Care for Atrial Fibrillation: A Modified Delphi Survey

Atrial fibrillation (AF) practice guidelines recommend a rhythm-control strategy to improve symptoms and quality of life, noting the side effects of antiarrhythmic drugs and catheter ablation. Emerging evidence indicates that comprehensive early rhythm control with antiarrhythmic drugs or catheter ablation is associated with a lower risk of adverse cardiovascular outcomes versus the usual care. Using an online modified Delphi survey approach, perspectives and expert consensus among electrophysiologists were examined through a series of ranking and likelihood questions around treatment decision-making on (1) the use of comprehensive early rhythm-control strategies in patients with AF based on guidelines and emerging research and (2) treatment selection factors. A panel of 17 electrophysiologists reached a consensus on using early rhythm control (median 90, interquartile range 14) based on the view that early intervention improved cardiovascular outcomes (mean rank 1.6 of 3, 82% within 1 SD) and symptoms (1.8 of 3, 41%). AF-related symptoms were identified as the most important in making a treatment initiation decision (1.1 of 7, 88%), followed by AF type (2.5 of 7, 82%). Participants were most likely to initiate treatment at AF symptom onset (median 80; interquartile range 6). In making treatment selection decisions, participants ranked short-term/long-term safety (1.9 of 7, 88%) and efficacy (1.8 of 7, 53%) as the top 2 considerations. In conclusion, experts were in favor of early rhythm control; however, additional research is needed to address the role that early rhythm-control strategies play in current AF treatment management algorithms.

Nivolumab in the treatment of thoracic cancer — new possibilities

Immune checkpoint inhibitors have significantly changed the treatment of patients with advanced non-small cell lung cancer in recent years. The value of nivolumab was initially assessed in patients previously treated with systemic therapy. The association of nivolumab with ipilimumab and the interaction of these antibodies on different immune checkpoints have proven effective in solid tumors (melanoma and renal cell carcinoma). The CheckMate-9LA study assessed the value of dual immunotherapy combined with platinum-based chemotherapy in the first-line treatment of advanced non-small cell lung cancer. A clinical benefit – prolonged overall survival in patients receiving combination therapy – was documented. The results of the CheckMate743 trial for patients with pleural mesothelioma provide a basis for changing the current management algorithm for patients with this diagnosis. Patients diagnosed with mesothelioma of a non-epithelioid type particularly benefit from two-drug immunotherapy compared to chemotherapy. Maintaining the safety of treatment using immunotherapy targeting two immune checkpoints remains the challenge.

Socioeconomic Status as a Determinant of Delayed Diagnosis of Sickle Cell Disease - A Case Report of Newly Diagnosed Sickle Cell Disease in a 52-Year-Old Woman

A look into socioeconomic status (SES) associations with delayed diagnosis of sickle cell disease (SCD) is necessary to improve societal norms, governmental health policies, and strategies. A person's social standing in a society is generally governed by the combination of his education, profession, and income, which is regarded as his SES. Considerable evidence establishes the likelihood of individuals from low SES suffering from the disease, cognitive problems, and increased mortality (Lubeck et al., 2019, National Research, 2004). Sickle cell disease (SCD) is one of the most common severe genetic hemoglobinopathies recognized by the World Health Organization as a global public health problem. Socioeconomic status (SES) is an individual's social or economic standing and measures an individual's or family's financial position or rank in a social group. Current guidelines and management algorithms of SCD do not factor in the effect of SES on patients with SCD. There needs to be more literature regarding the role of SES and its impact on clinical outcomes and characteristics of SCD. Studies have shown that lower SES is linked to disproportionate access to health care in many diseases, and of all the factors that measure SES, income was the most indicative.

Clinical Impact and Outcomes of Socioeconomic Status on Patients with Sickle Cell Disease: A Pilot Study and Literature Review

Sickle cell disease (SCD) is one of the most common severe genetic hemoglobinopathies that has been recognized by the World Health Organization as a global public health problem. Socioeconomic status (SES) is defined as an individual's social or economic standing and is a measure of an individual's or family's economic position or rank in a social group. Current guidelines and management algorithms of SCD do not factor in the effect of SES on patients with SCD. There is a paucity of literature regarding the role of SES and its effect on clinical outcomes and characteristics of SCD. Studies have shown that lower SES is linked to disproportionate access to health care in many diseases and of all the factors that measure SES, income was the most indicative. We conducted an anonymous online survey of 1339 patients with sickle cell disease over two (2) years (2021-2023). The questionnaire inquired about how many years the patient had SCD, whether they were being seen by a hematologist, what the average household income was, what the highest level of education in the household was, number of hospitalizations in the past year, insurance status, payment plan discussions, appointments missed due to cost, and the main factor in the delay of treatment. Using data analysis software, results showed that patients with lower SES had statistically significant higher number of missed appointments and statistically significant higher number of hospitalizations when compared to patients with higher SES. Our literature review showed that patients and families of patients with SCD were of predominantly low SES corresponding to lower household incomes and lower educational levels when compared to healthy patients/families. In the setting of SCD, lower SES has been shown to result in increased prevalence of disease, greater occurrence of possible complications, increased number of in-hospital admissions, increased mortality, increased healthcare utilization costs, and decreased health-related quality of life (HRQoL) for patients and families. The impact of SES on patients with SCD is a national health problem and increased advocacy is needed for the implementation of SES in the management of SCD moving forward to achieve decreased healthcare utilization costs while increasing health-related quality of life and access to healthcare for patients and families.

Review Article on Epithelial Ovarian Cancer with Peritoneal Metastasis

Introduction: Many advances have emerged in the management of peritoneal metastases of ovarian cancer origin, widely known as the most common gynaecological malignancy. This review is an update of the current management algorithm of peritoneal carcinomatosis of ovarian cancer, including screening methods, biomarkers and surgical techniques, in an effort to shed some light into this difficult to treat malignancy. Objective: To assess awareness in the management of epithelial ovarian cancer (EOC) with peritoneal metastasis with updated therapeutic standpoints.

Neonatal Myocardial Infarction: A Proposed Algorithm for Coronary Arterial Thrombus Management.

Neonatal myocardial infarction is rare and is associated with a high mortality of 40% to 50%. We report our experience with neonatal myocardial infarction, including presentation, management, outcomes, and our current patient management algorithm. We reviewed all infants admitted with a diagnosis of coronary artery thrombosis, coronary ischemia, or myocardial infarction between January 2015 and May 2021. We identified 21 patients (median age, 1 [interquartile range (IQR), 0.25-9.00] day; weight, 3.2 [IQR, 2.9-3.7] kg). Presentation included respiratory distress (16), shock (3), and murmur (2). Regional wall motion abnormalities by echocardiogram were a key criterion for diagnosis and were present in all 21 with varying degrees of depressed left ventricular function (severe [8], moderate [6], mild [2], and low normal [5]). Ejection fraction ranged from 20% to 54% (median, 43% [IQR, 34%-51%]). Mitral regurgitation was present in 19 (90%), left atrial dilation in 15 (71%), and pulmonary hypertension in 18 (86%). ECG was abnormal in 19 (90%). Median troponin I was 0.18 (IQR, 0.12-0.56) ng/mL. Median BNP (B-type natriuretic peptide) was 2100 (IQR, 924-2325) pg/mL. Seventeen had documented coronary thrombosis by cardiac catheterization. Seventeen (81%) were treated with intracoronary tPA (tissue-type plasminogen activator) followed by systemic heparin, AT (antithrombin), and intravenous nitroglycerin, and 4 (19%) were treated with systemic heparin, AT, and intravenous nitroglycerin alone. Nineteen of 21 recovered. One died (also had infradiaphragmatic total anomalous pulmonary venous return). One patient required a ventricular assist device and later underwent heart transplant; this patient was diagnosed late at 5 weeks of age and did not respond to tPA. Nineteen of 21 (90%) regained normal left ventricular function (ejection fraction, 60%-74%; mean, 65% [IQR, 61%-67%]) at latest follow-up (median, 6.8 [IQR, 3.58-14.72] months). Two of 21 (10%) had residual trivial mitral regurgitation. After analysis of these results, we present our current algorithm, which developed and matured over time, to manage neonatal myocardial infarction. We experienced a lower mortality rate for infants with neonatal infarction than that reported in the literature. We propose a post hoc algorithm that may lead to improvement in patient outcomes following coronary artery thrombus.

P427 Exploring phenotype and treatment of inflammatory bowel disease in the elderly

Abstract Background On a background of an ageing population, approximately, 10–15% of new cases of IBD are diagnosed in patients over the age of, 60.1,2 Studies show IBD in the elderly is increasing, including both the groups of patients diagnosed at a younger age, and de novo elderly IBD. Older patients are more likely to have other co-morbidities and be concurrently prescribed other medications, which may impact the choice and timing of therapies for their disease. It is not clear if IBD in older age is different phenotypically from that in younger counterparts, and whether current management algorithms can be used safely in this cohort. Aims of the study were to evaluate the IBD phenotype and use of therapies in the elderly (≥75 years) and younger (18–74 years) patients, and to assess for differences in adverse outcomes between both cohorts on immunosuppressants (IMs) and/or biologics. Methods A retrospective study was performed on, 173 IBD patients at Imperial College Healthcare NHS Trust over a two-year period., 91 elderly IBD patients were compared with, 82 younger patients, matched by gender and IBD subtype. Analysis included chi-squared tests with Fisher’s correction. Results There were, 55 elderly patients and, 51 younger matched patients with ulcerative colitis (UC) where no differences in disease extent, remission or surgeries were seen. There were, 36 elderly patients and, 31 younger matched patients with Crohn’s disease (CD). There was less ileocolonic disease in the older CD cohort compared to younger patients (27.8% versus, 51.6%, p=0.046) (figure 1). Medication use in UC was the same regardless of age. There was significantly higher use of IMs and biologics in younger patients with CD (51.6%) versus the older cohort (25%, p=0.047) (figure 2). In elderly patients with CD, a significantly greater mortality was seen in patients on IMs/biologics (27.3%) than those not on these medications (8%, p=0.023) (figure 3). The rate of VTE was higher (18.2% versus, 0%) in those on these treatments with a trend towards significance. Conclusion Overall, this retrospective study demonstrated that elderly IBD patients in this cohort appear to be mostly phenotypically similar to younger patients. However, elderly Crohn’s patients were less likely to be escalated to IMs/biologic treatments than their younger comparators. In view of the higher rate of adverse events recorded in the Crohn’s group managed with these treatments, this may be justified. Further, larger studies in the long-term outcomes of these patients are required. Reference 1. Charpentier C et al. Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study. Gut., 2014;63(3),423–432

Chronic Covert Brain Infarctions and White Matter Hyperintensities in Patients With Stroke, Transient Ischemic Attack, and Stroke Mimic.

BackgroundThis study was conducted to compare frequencies of chronic brain infarctions (CBIs) and white matter hyperintensities (WMHs) as well as their associations with established early recurrence risk scores in patients with transient ischemic attack (TIA) and stroke mimics compared with ischemic stroke.Methods and ResultsSingle‐center cohort study including consecutive patients with TIA, stroke mimics, and acute ischemic stroke, with available magnetic resonance imaging from January 2015 to December 2017. Blinded raters adjudicated WMH (age‐related white matter changes score) and CBI according to established definitions. A total of 2112 patients (median [Q1–Q3] age 71 [59–80] years, 43% women, National Institutes of Health Stroke Scale score of 2 [1–7], 80% ischemic stroke, 18% TIA, 2% stroke mimics) were included. While CBIs were present in only 10% of patients with stroke mimic, they were detected in 28% of TIAs and 38% of ischemic strokes (P<0.001). WMHs were less pronounced (0, 0–1) in patients with stroke mimic, but there was no difference between TIA (1, 1–2) and ischemic stroke (0, 1–2) patients. CBIs (adjusted odds ratio, 0.3; 95% CI, 0.1–0.9) were associated with a lower rate of stroke mimic as the final diagnosis, while WMHs were not (adjusted odds ratio per point, 1.3; 95% CI, 0.7–2.2). WMH (β per point, 0.4; 95% CI, 0.3–0.6) and presence of CBI (β, 0.6; 95% CI, 0.3–0.9) were associated with a higher cardiovascular risk profile according to the ABCD3‐I score. The accuracy of prediction was good for high‐risk TIA (cross‐validated area under the receiver operating characteristic curve, 0.89; 95% CI, 0.79–0.93) on the basis of brain imaging, age, and sex.ConclusionsCBI and WMH differ between patients with stroke mimic and patients with TIA/ischemic stroke and are closely associated with established recurrence risk scores. Prospective studies need to clarify whether including brain frailty markers may contribute to the refinement of current management algorithms and risk stratifications.

Neurological update: treatment escalation in multiple sclerosis patients refractory to fingolimod\u2014potentials and risks of subsequent highly active agents

A critical issue in the management of relapsing MS (RMS) is the discontinuation of disease-modifying treatments (DMT) due to lack of efficacy, intolerability or impending risks. With new therapeutic agents introduced into the treatment of RMS, immediate- and long-term consequences of sequential drug use, as well as the effect of the sequence in which the drugs are given, are unclear but may affect efficacy, adverse events, and long-term immunocompetence. In the absence of clinical studies specifically addressing these concerns, observations from clinical practice are of particular value in guiding current management algorithms. Prompted by a study published by Ferraro et al. in this journal, we set out to provide an overview of the published real-world evidence on the effectiveness and safety of switching from fingolimod to another DMT in patients with active RMS. Seventeen publications reporting relevant information were identified. The literature suggests that immune cell depletion induced by alemtuzumab or ocrelizumab is associated with an increased risk of relapse and worsening disability in patients switching from fingolimod compared to patients switching from other therapeutic agents. However, the evidence reported for natalizumab and cladribine is inconclusive. While shortening of the washout period may limit early disease reactivation after fingolimod discontinuation, there is no strong evidence that the duration of the washout period or the absolute lymphocyte count at baseline are predictors of attenuated long-term efficacy. Further real-world studies are required to better understand outcomes among patients who are under-represented in controlled trials.

Role of aripiprazole in the management of behavioural and psychological symptoms of dementia: a narrative review.

Behavioural and psychological symptoms of dementia affect in a great way quality of life of both patients and their caregivers, which increases the risk of patient institutionalisation when such symptoms are poorly controlled. One of the drugs that are used for controlling behavioural and psychological symptoms of dementia (BPSD) is aripiprazole. This narrative review aims to solve three basic questions. Is aripiprazole useful for the management of these symptoms? Does aripiprazole play a substantial role regarding safety and efficacy, compared with the other pharmacological options available for the same purpose? Has aripiprazole gained importance in treatment regimens of these symptoms, in current clinical practice? We conclude that aripiprazole is effective to manage BPSD. Moreover, it has shown a good safety profile compared with other antipsychotics in advanced disease and frail patients. Thus, aripiprazole has gained importance in current management algorithms for dementia patients mainly due to its efficacy regarding rapid control of agitation and aggressiveness.

Adhesive Capsulitis Embolization: A Case of Particle Embolization for Refractory Shoulder Pain Secondary to Adhesive Capsulitis

Adhesive capsulitis (AC) is an inflammatory process characterized by limited shoulder mobility and pain. The prevalence of AC is as high as 5% in the general population but increases up to 20% in patients with diabetes. The current management algorithm for AC consists of physical therapy followed by pharmacological treatment. Surgical options are reserved for those with refractory pain. Adhesive capsulitis embolization (ACE) is a new minimally invasive procedure that involves particle embolization of the inflammatory vessels linked to chronic shoulder pain. Early studies show promising results with significant improvement in shoulder pain and mobility. The present case describes a 40-year-old woman who underwent ACE for refractory shoulder pain and discusses the postoperative management of ACE.

Adaptive real-time optimal energy management strategy based on equivalent factors optimization for hybrid fuel cell system

Fuel cell, a new kind of energy supply equipment, has several advantages such as high efficiency, low noise, and no emission. Proton exchange membrane fuel cell (PEMFC) is considered to have the potential to take the place of the conventional engine on unmanned underwater vehicle (UUV). Besides the power sources in the hybrid power system, the energy management system (EMS) is crucial to operating performance. In this paper, an on-line adaptive equivalent hydrogen consumption minimization strategy (ECMS) is proposed to solve the problem of prior knowledge demand and poor adaptability of current energy management algorithms. In this presented method, a battery state of charge (SOC) constituted penalty term is designed to calculate the equivalent factor (EF), and then the equivalent factor obtained by optimization is substituted into the original objective equation to realize the real-time energy regulation. In this paper, a typical UUV load curve is used to verify the control effect under different working conditions, and the performance is compared with three conventional algorithms’. Simulation results show that the hydrogen consumption of proposed algorithm is close to the optimal solution obtained in offline environment, and it is reduced by more than 3.79% compared with the traditional online methods.

Spotlight on Tocilizumab in the Treatment of CAR-T-Cell-Induced Cytokine Release Syndrome: Clinical Evidence to Date.

Immune-based therapies such as chimeric antigen receptor (CAR)-T-cell therapy have revolutionized the landscape of cancer treatment in recent years. Although this class of therapy has demonstrated impressive clinical efficacy against cancers that were once thought to be incurable, its success is in part limited by unique toxicities which can be severe or even fatal. Cytokine release syndrome (CRS) is the most commonly observed toxicity and occurs as a result of non-antigen specific immune activation. Similar to macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH), CRS is associated with elevated levels of several cytokines including interleukin-6 (IL-6) that serve as a driver for host immune dysregulation. As a direct anti-cytokine drug, tocilizumab has been a cornerstone in the treatment of CAR-T-associated CRS through its ability to dampen CRS without compromising CAR-T-cell function. However, optimal timing of administration is yet unknown. Here, we review the use of tocilizumab in the management of CAR-T-associated CRS, emphasizing on the clinical efficacy across various CAR constructs and its role in current CRS management algorithms. We also discuss alternative therapies that may be considered for refractory CRS therapy and the use of tocilizumab in the current COVID-19 global pandemic.

Blunt and Penetrating Liver Trauma have Similar Outcomes in the Modern Era

The trend in liver trauma management has progressively become increasingly conservative. However, a vast majority of literature focuses heavily on the management of blunt trauma. This study reviews the management of hepatic trauma at a major trauma center in a developing world setting, in order to compare blunt and penetrating liver trauma and to define current management algorithms and protocols. All patients who sustained liver trauma between 2012 to 2018 were identified in the Hybrid Electronic Medical Registry and extracted for further analysis. A total of 808 patients with hepatic trauma were managed by our trauma center. There were 658 males and 150 females. The mean age was 30 years (standard deviation 13.3). A total of 68 patients died (8.2%) and a total of 290 (35%) patients required intensive care unit admission. The mean presenting shock index was 0.806 (standard deviation 0.67-1.0), the median Injury Severity Score was 18 (interquartile range 10-25) and the mean Revised Trauma Score was 12 (standard deviation 11-12). There were 367 penetrating and 441 blunt liver injuries. The age distribution was similar in both groups. There were significantly less females in the penetrating group. The shock index and the Injury Severity Score on presentation were significantly worse in the blunt group, respectively: 0.891 (standard deviation 0.31) versus 0.845 (standard deviation 0.69) (p < 0.001) and score 21 (interquartile range 13-27) versus 16 (interquartile range 9-20) (p < 0.01). The opposite applied to the Revised Trauma Score of 11.75 (standard deviation 0.74) versus 11.19 (standard deviation 1.3) (p < 0.001). There were significantly more associated intra-abdominal injuries in the penetrating group than the blunt group, in particular that of hollow organs, and 84% of patients with a penetrating injury underwent a laparotomy while only 33% of the blunt injuries underwent a laparotomy. The mortality rate was comparable between both groups. Hepatic trauma is still associated with a high morbidity rate, although there have been dramatic improvements in mortality rates over the last three decades. The mortality rates for blunt and penetrating liver trauma are now similar. Non-operative management is feasible for over two-thirds of blunt injuries and for just under 20% of penetrating injuries.

Memory-aware resource management algorithm for low-energy cloud data centers

The continuous advancement of cloud computing technology has driven the vigorous development of cloud data centers. This manifests itself not only in increasing numbers, but also in rapid expansion scale. At the same time, the problems of high energy consumption, high cost and high carbon emissions began to stand out. These factors have become a bottleneck restricting the further development of cloud computing technology. As a result of the application of virtualization technology, mature cloud service providers use virtual machines instead of physical machines to provide users with computing, storage and other services. Therefore, the scheduling algorithm of cloud tasks and virtual machines has been widely studied by academia as a core problem. However, most of the current cloud data center resource management algorithms take CPU utilization as the main consideration, and increase the CPU utilization through virtual machine integration to reduce the energy consumption of cloud data centers. However, these algorithms will cause waste and low utilization of other resources in the cloud data center due to excessive consideration of CPU utilization. This paper systematically analyzes the mapping relationship between cloud tasks, virtual machines and physical machines. At the same time, the performance of cloud tasks, virtual machines, and physical machines is modeled in the cloud data center. By comprehensively considering the CPU and memory characteristics of cloud tasks, the memory priority cloud task mapping rule is established. Based on the rule, the memory-aware resource management algorithm for low-energy cloud data centers (MALE) is proposed. The algorithm maps cloud tasks and deploys virtual machines according to the memory requirements of the cloud tasks, thereby achieving the goal of simultaneously reducing the total fee of cloud users and the energy consumption of cloud data centers. Finally, the algorithm is compared with the other three algorithms. The experimental simulation results show that the effect of the proposed algorithm in this paper is significantly better than the comparison algorithm for the total fee of cloud users and the energy consumption of the cloud data center.