An immune-protein score combining TRAIL, IP-10 and CRP for predicting severe COVID-19 disease.

COVID-19 patients are oftentimes over- or under-treated due to a deficit in predictive management tools. This study reports derivation of an algorithm that integrates the host levels of TRAIL, IP-10, and CRP into a single numeric score that is an early indicator of severe outcome for COVID-19 patients and can identify patients at-risk to deteriorate. 394 COVID-19 patients were eligible; 29% meeting a severe outcome (intensive care unit admission/non-invasive or invasive ventilation/death). The score's area under the receiver operating characteristic curve (AUC) was 0.86, superior to IL-6 (AUC 0.77; p = 0.033) and CRP (AUC 0.78; p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The score differentiated severe patients who further deteriorated from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001). The score accurately predicted COVID-19 patients at-risk for severe outcome, and therefore has potential to facilitate timely care escalation and de-escalation and appropriate resource allocation.

Alert-Grouping: Smart Personalization of Monitoring System Thresholds to Help Healthcare Teams Struggle with Alarm Fatigue in Intensive Care.

In Intensive Care Units (ICUs), patients are monitored using various devices that generate alerts when specific metrics, such as heart rate and oxygen saturation, exceed predetermined thresholds. However, these alerts can be inaccurate and lead to alert fatigue, resulting in errors and inaccurate diagnoses. We propose Alert grouping, a "Smart Personalization of Monitoring System Thresholds to Help Healthcare Teams Struggle Alarm Fatigue in Intensive Care" model. The alert grouping looks at patients at the individual and cluster levels, and healthcare-related constraints to assist medical and nursing teams in setting personalized alert thresholds of vital parameters. By simulating the function of ICU patient bed devices, we demonstrate that the proposed alert grouping model effectively reduces the number of alarms overall, improving the alert system's validity and reducing alarm fatigue. Implementing this personalized alert model in ICUs boosts medical and nursing teams' confidence in the alert system, leading to better care for ICU patients by significantly reducing alarm fatigue, thereby improving the quality of care for ICU patients.

Development and validation of a knowledge-driven risk calculator for critical illness in COVID-19 patients.

Facing the novel coronavirus disease (COVID-19) pandemic, evidence to inform decision-making at all care levels is essential. Based on the results of a study by Petrilli et al., we have developed a calculator using patient data at admission to predict critical illness (intensive care, mechanical ventilation, hospice care, or death). We report a retrospective validation of the calculator on 145 consecutive patients admitted with COVID-19 to a single hospital in Israel. Despite considerable differences between the original and validation study populations, of 18 patients with critical illness, 17 were correctly identified (sensitivity: 94.4%, 95% CI, 72.7%-99.9%; specificity: 81.9%, 95% CI, 74.1%-88.2%). Of 127 patients with non-critical illness, 104 were correctly identified. Our results indicate that published knowledge can be reliably applied to assess patient risk, potentially reducing the cognitive burden on physicians, and helping policymakers better prepare for future needs.

Extended Follow-up of an Educational Intervention Encouraging Appropriate Use of Blood Transfusions.

INTRODUCTION: A restrictive transfusion strategy of packed red blood cells (PRBCs) has been associated with at least non-inferior patient outcomes in a variety of clinical settings. In December 2014, we conducted an educational intervention which consisted of an oral presentation and computerized notifications at a single tertiary medical center. OBJECTIVE: The aim of this study was to examine the long-term effects of a simple and low-cost educational intervention aimed to promote awareness to transfusion guidelines. METHODS: We retrospectively analyzed all PRBC transfusions ordered between 2014 and 2017. The primary end point was defined as the percentage of PRBC transfused to patients with hemoglobin (Hb) ≥8 g/dL. RESULTS: Between 2014 and 2017, a total of 27,475 PRBCs were transfused in our medical center. There was a continuous reduction in the percentage of PRBCs transfused at a Hb level ≥8 g/dL between 2014 and 2017, with a matching increase in the PRBC percentage trans-fused at Hb <7 g/dL (OR reduction of 42%, 95% CI 0.54-0.62 and OR increase of 68% [95% CI 1.56-1.81], respec-tively). CONCLUSION: A simple educational intervention likely contributed to sustained improvement in the appropriateness of PRBC transfusions.

Intravenous immunoglobulin-induced acute thrombocytopenia.

BACKGROUND: Intravenous immunoglobulin (IVIG) has known efficacy in various hematologic conditions, including immune thrombocytopenic purpura. STUDY DESIGN AND METHODS: We present the clinical course of a patient with splenic marginal zone lymphoma, who developed acute thrombocytopenia on three consecutive episodes, with nadir counts of 27 × 109 , 50 × 109 , and 9 × 109 /L, upon administration of Intratect IVIG for hypogammaglobulinemia. An immunofluorescence test applying flow cytometry and monoclonal antibody immobilization of platelet antigens (MAIPA) assay were used to evaluate the reaction between IgG present in the IVIG preparations and the patient's or healthy donors' platelets (PLTs). RESULTS: A strong direct binding reaction was observed between the patient's PLTs and Intratect IgG using both methods. A similar reaction failed to materialize with controls. Binding was not antigen specific according to MAIPA. CONCLUSIONS: This is the first reported case of thrombocytopenia as a possible adverse effect of IVIG.

The Ethics Committee at the Patient's Bedside (ECatPB): a retrospective view on the past two years.

The Ethics Committee at the Patient's Bedside (ECatPB) was established at Beilinson Hospital and began its activity a few years ago. A retrospective viewpoint will enable us to reflect on moral dilemmas and ethical conflicts as sources of professionals' moral distress. The activities of the ECatPB will be reviewed through sample cases and in the light of the promotion of optimal treatment. Five dominant contributions of the ECatPB will be discussed: prevention of moral distress; positioning the committee as an integral and inseparable component of the medical institution's daily life; cultivating the advisory, rather than punitive, character of the committee; maintaining constant ethics dialogues with patients, caregivers and professionals; and communications with guardians in light of informed consent or informed refusal. The summary ofthis paper will include conclusions, recommendations and personal notes.

Community optimized management for better eating after hospital sTay among geriatric patients of poor socio-economic status - The COMEAT study.

INTRODUCTION: In patients suffering from disease-related and socioeconomic malnutrition and being discharged from hospital, continuity of care is challenging. Lack of adequate nutrition may lead to increase in morbidity and mortality. The aim of this study was to overcome the handicap of limited nutrition access in this category of patients and to study its consequences on clinical outcome. METHODS: Hospitalized patients screened to be at risk of malnutrition were approached and if diagnosed as suffering from malnutrition and from limited financial resources, they were randomized to receive a delivered daily dinner tray for 6 months and an assistance during the meal by a philanthropic association, or to regular food. At entry to the study, patients were assessed by indirect calorimetry, bioimpedance, Hospital Anxiety and Depression Scale (HADS), Functional independence measure (FIM) and SF 36 quality of life questionnaire. The latest questionnaires were reproduced after 3 and 6 months. Survival was followed at 6 months. The student t-test, the paired t-test, ANOVA were used. 180 days survival curves were expressed using the Kaplan-Meier method. RESULTS: 631 patients were screened and 60 patients were randomized. There was no difference between groups. Survival at 6 months was improved significantly in the intervention group (87%) compared to the control group (65%, p<005). HADS did significantly improve at 3 months and other parameters (FIM, SF 36) were not changed significantly. CONCLUSIONS: In hospitalized patients at nutritional risk, lunch home delivery, supported by a physical company after hospital discharge was associated with significantly lower mortality rates and improved depression and anxiety scores in elderly patients suffering from socioeconomic related malnutrition.

Factors Associated With Off-Label Oncology Prescriptions: The Role of Cost and Financing in a Universal Healthcare System.

Purpose: Various solutions have been put forward for prescribing and reimbursing treatments outside their registered indications within universal healthcare systems. However, most off-label oncology prescriptions are not reimbursed by health funds. This study characterized the financing sources of off-label oncology use and the predictors of the decision to forego treatment. Materials and Methods: All 708 off-label oncology requests submitted for approval in a large tertiary cancer center in Israel between 2016 and 2018 were examined for disease and patient sociodemographic characteristics, costs and financing sources, and the factors predicting actual off-label drug administration using multivariate logistic regression analysis. Results: The mean monthly cost of a planned off-label treatment was ILS54,703 (SD = ILS61,487, median = ILS39,928) (approximately US$ 15,500). The main sources of funding were private health insurance (25%) and expanded access pharma company plans (30%). Approximately one third (31%) of the requests did not have a financing source at the time of approval. Of the 708 requests, 583 (or 82%) were filled and treatment was initiated. Predictors for forgoing treatment were the impossibility of out-of-pocket payments or the lack of a financing solution (OR = 0.407; p = 0.005 and OR = 0.400; p < 0.0005). Conclusion: Although off-label recommendations are widespread and institutional approval is often granted, a large proportion of these prescriptions are not filled. In a universal healthcare system, the financing sources for off-label treatments are likely to influence access.

Risk-factors for re-admission and outcome of patients hospitalized with confirmed COVID-19.

Burden of COVID-19 on Hospitals across the globe is enormous and has clinical and economic implications. In this retrospective study including consecutive adult patients with confirmed SARS-CoV-2 who were admitted between 3/2020 and 30/9/20, we aimed to identify post-discharge outcomes and risk factors for re-admission among COVID-19 hospitalized patients. Mortality and re-admissions were documented for a median post discharge follow up of 59 days (interquartile range 28,161). Univariate and multivariate analyses of risk factors for re-admission were performed. Overall, 618 hospitalized COVID-19 patients were included. Of the 544 patient who were discharged, 10 patients (1.83%) died following discharge and 50 patients (9.2%) were re-admitted. Median time to re-admission was 7 days (interquartile range 3, 24). Oxygen saturation or treatment prior to discharge were not associated with re-admissions. Risk factors for re-admission in multivariate analysis included solid organ transplantation (hazard ratio [HR] 3.37, 95% confidence interval [CI] 2.73-7.5, p = 0.0028) and higher Charlson comorbidity index (HR 1.34, 95% CI 1.23-1.46, p < 0.0001). Mean age of post discharge mortality cases was 85.0 (SD 9.98), 80% of them had cognitive decline or needed help in ADL at baseline. In conclusion, re-admission rates of hospitalized COVID-19 are fairly moderate. Predictors of re-admission are non-modifiable, including baseline comorbidities, rather than COVID-19 severity or treatment.

Evaluation of Seropositivity Following BNT162b2 Messenger RNA Vaccination for SARS-CoV-2 in Patients Undergoing Treatment for Cancer.

Importance: Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response to messenger RNA SARS-CoV-2 vaccines is unclear. Objective: To evaluate rates of antispike (anti-S) antibody response to a BNT162b2 vaccine in patients with cancer who are undergoing systemic treatment vs healthy controls. Design, Setting, and Participants: This prospective cohort study included 102 adult patients with solid tumors undergoing active intravenous anticancer treatment and 78 controls who received the second dose of the BNT162b2 vaccine at least 12 days before enrollment. The controls were taken from a convenience sample of the patients' family/caregivers who accompanied them to treatment. The study was conducted between February 22, 2021, and March 15, 2021 at Davidoff Cancer Center at Beilinson Hospital (Petah Tikva, Israel). Interventions: Blood samples were drawn from the study participants. Serum samples were analyzed and the titers of the IgG antibodies against SARS-CoV-2 spike receptor-binding domain were determined using a commercially available immunoassay. Seropositivity was defined as 50 or greater AU/mL. Main Outcomes and Measures: The primary outcome was the rate of seropositivity. Secondary outcomes included comparisons of IgG titers and identifying factors that were associated with seropositivity using univariate/multivariable analyses. Results: The analysis included 180 participants, which comprised 102 patients with cancer (median [interquartile range (IQR)] age, 66 [56-72] years; 58 men [57%]) and 78 healthy controls (median [IQR] age, 62 [49-70] years; 25 men [32%]). The most common tumor type was gastrointestinal (29 [28%]). In the patient group, 92 (90%) were seropositive for SARS-CoV 2 antispike IgG antibodies after the second vaccine dose, whereas in the control group, all were seropositive. The median IgG titer in the patients with cancer was significantly lower than that in the controls (1931 [IQR, 509-4386] AU/mL vs 7160 [IQR, 3129-11 241] AU/mL; P < .001). In a multivariable analysis, the only variable that was significantly associated with lower IgG titers was treatment with chemotherapy plus immunotherapy (ß, -3.5; 95% CI, -5.6 to -1.5). Conclusions and Relevance: In this cohort study of patients with cancer who were receiving active systemic therapy, 90% of patients exhibited adequate antibody response to the BNT162b2 vaccine, although their antibody titers were significantly lower than those of healthy controls. Further research into the clinical relevance of lower titers and their durability is required. Nonetheless, the data support vaccinating patients with cancer as a high priority, even during therapy.

Observational cohort study of IP-10's potential as a biomarker to aid in inflammation regulation within a clinical decision support protocol for patients with severe COVID-19.

BACKGROUND: Treatment of severely ill COVID-19 patients requires simultaneous management of oxygenation and inflammation without compromising viral clearance. While multiple tools are available to aid oxygenation, data supporting immune biomarkers for monitoring the host-pathogen interaction across disease stages and for titrating immunomodulatory therapy is lacking. METHODS: In this single-center cohort study, we used an immunoassay platform that enables rapid and quantitative measurement of interferon γ-induced protein 10 (IP-10), a host protein involved in lung injury from virus-induced hyperinflammation. A dynamic clinical decision support protocol was followed to manage patients infected with severe acute respiratory syndrome coronavirus 2 and examine the potential utility of timely and serial measurements of IP-10 as tool in regulating inflammation. RESULTS: Overall, 502 IP-10 measurements were performed on 52 patients between 7 April and 10 May 2020, with 12 patients admitted to the intensive care unit. IP-10 levels correlated with COVID-19 severity scores and admission to the intensive care unit. Among patients in the intensive care unit, the number of days with IP-10 levels exceeding 1,000 pg/mL was associated with mortality. Administration of corticosteroid immunomodulatory therapy decreased IP-10 levels significantly. Only two patients presented with subsequent IP-10 flare-ups exceeding 1,000 pg/mL and died of COVID-19-related complications. CONCLUSIONS: Serial and readily available IP-10 measurements potentially represent an actionable aid in managing inflammation in COVID-19 patients and therapeutic decision-making. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04389645, retrospectively registered on May 15, 2020.

Parental Occupational Exposure is Associated With Their Children's Psychopathology: A Study of Families of Israeli First Responders.

OBJECTIVE: To examine the association between parental occupational exposure to traumatic events and their children's mental health in families of First Responders (FRs), a neglected area of research. METHODS: In 208 families of Israeli FRs, children's symptoms and comorbidity patterns of seven psychiatric disorders were regressed on parental work-related variables, controlling for relevant covariates. RESULTS: Having a father working as a FR and higher paternal exposure were associated with a greater number of separation anxiety and posttraumatic stress symptoms, respectively. Maternal exposure was associated with a greater number of symptoms of generalized anxiety, panic disorder, depression, and oppositional defiant disorder, and with increased odds of comorbid internalizing symptomatology. CONCLUSIONS: Additional research on children of FRs is encouraged. An adaption to this understudied population of family-centered interventions available for military families could inform targeted prevention efforts.

Association between cultural factors and readmissions: the mediating effect of hospital discharge practices and care-transition preparedness.

OBJECTIVES: The study examines whether hospital discharge practices and care-transition preparedness mediate the association between patients' cultural factors and readmissions. METHODS: A prospective study of internal medicine patients (n=599) examining a culturally diverse cohort, at a tertiary medical centre in Israel. The in-hospital baseline questionnaire included sociodemographic, cultural factors (Multidimensional Health Locus of Control, family collectivism, health literacy and minority status) and physical, mental and functional health status. A follow-up telephone survey assessed hospital discharge practices: use of the teach-back method, providers' cultural competence, at-discharge language concordance and caregiver presence and care-transition preparedness using the care transition measure (CTM). Clinical and administrative data, including 30-day readmissions to any hospital, were retrieved from the healthcare organisation's data warehouse. Multiple mediation was tested using Hayes's PROCESS procedure, model 80. RESULTS: A total of 101 patients (17%) were readmitted within 30 days. Multiple logistic regressions indicated that all cultural factors, except for minority status, were associated with 30-day readmission when no mediators were included (p<0.05). Multiple mediation analysis indicated significant indirect effects of the cultural factors on readmission through the hospital discharge practices and CTM. Finally, when the mediators were included, strong direct and indirect effects between minority status and readmission were found (B coefficient=-0.95; p=0.021). CONCLUSIONS: The results show that the association between patients' cultural factors and 30-day readmission is mediated by the hospital discharge practices and care transition. Providing high-quality discharge planning tailored to patients' cultural characteristics is associated with better care-transition preparedness, which, in turn, is associated with reduced 30-day readmissions.

Patients' ratings of the in-hospital discharge briefing and post-discharge primary care follow-up: The association with 30-day readmissions.

OBJECTIVE: We examined whether patients' ratings of their in-hospital discharge briefing and their post-discharge Primary Care Physicians' (PCP) review of the discharge summary are associated with 30-day readmissions. METHODS: A prospective study of 594 internal-medicine patients at a tertiary medical-center in Israel. The in-hospital baseline questionnaire included sociodemographic characteristics, physical, mental, and functional health status. Patients were surveyed by phone about the discharge and post-discharge processes. Clinical data and health-service use was retrieved from a central data-warehouse. Multivariate regressions modeled the relationship between in-hospital baseline characteristics, discharge briefing, PCP visit indicator, the PCP discharge summary review, and 30-day readmissions. RESULTS: The extent of the PCPs' review of the hospital discharge summary at the post-discharge visit was rated higher than the in-hospital discharge briefing (3.46 vs. 3.17, p = 0.001) and was associated with lower odds of readmission (OR=0.35, 95% CI 0.26-0.45). The model that included this assessment performed better than the in-hospital baseline, the in-hospital discharge-briefing, and the PCP visit models (C-statistic = 0.87, compared with: 0.70, 0.81, 0.81, respectively). CONCLUSIONS: Providing extensive post-discharge explanations by PCPs serves as a significant protective factor against readmissions. PRACTICE IMPLICATIONS: PCPs should be encouraged to thoroughly review the discharge summary letter with the patient.

Initial test of emergency procedure performance in temporary negative pressure isolation by using simulation technologies.

STUDY OBJECTIVE: The potential of infectious disease spread in diseases such as tuberculosis, infectious disease epidemic such as avian flu and the threat of terrorism with agents capable of airborne transmission have focused attention on the need for increased surge capacity for patient isolation. Total negative pressure isolation using portable bioisolation tents may provide a solution. The study assesses the ability of health care workers to perform emergency procedures in this environment. METHODS: Physician performance in completing predetermined critical actions in 5 emergency care scenarios inside and outside of a bioisolation tent ("setting") was studied in an advanced medical simulation laboratory. By design, no pretraining of subjects about total negative pressure isolation use occurred. Impact of setting on time to completion of predetermined critical actions was the primary outcome measured. Secondary variables studied included impact of study groups, scenarios, and run order (inside or outside of the tent first). Subjective assessments were obtained through questionnaires. RESULTS: Four teams of 3 physicians completed 5 emergency patient care scenarios during 2 4-hour sessions. Mean time to completion of critical actions was for tent/no tent 298 seconds/284 seconds (P=.69, one way ANOVA), respectively. Mean time to completion for first versus second performance of a scenario in the crossover design was 338 versus 243 (P=.01). The mean score for self-assessed performance did not differ according to setting. CONCLUSION: The ability of physicians naive to the total negative pressure isolation environment to perform emergency medical critical actions was not significantly degraded by a simulated bioisolation tent patient care environment.

Multicultural Transitions: Caregiver Presence and Language-Concordance at Discharge.

INTRODUCTION: Patients with low health literacy (HL) and minority patients encounter many challenges during hospital to community transitions. We assessed care transitions of minority patients with various HL levels and tested whether presence of caregivers and provision of language-concordant care are associated with better care transitions. METHODS: A prospective cohort study of 598 internal medicine patients, Hebrew, Russian, or Arabic native speakers, at a tertiary medical center in central Israel, from 2013 to 2014.HL was assessed at baseline with the Brief Health Literacy Screen. A follow-up telephone survey was used to administer the Care Transition Measure [CTM] and to assess, caregiver presence and patient-provider language-concordance at discharge. RESULTS: Patients with low HL and without language-concordance or caregiver presence had the lowest CTM scores (33.1, range 0-100). When language-concordance and caregivers were available, CTM scores did not differ between the medium-high and low HL groups (68.7 and 66.9, respectively, p = 0.118). The adjusted analysis, showed that language-concordance and caregiver presence during discharge moderate the relationship between HL and patients' care transition experience (p < 0.001). CONCLUSIONS: Language-concordance care and caregiver presence are associated with higher patients' ratings of the transitional-care experience among patients with low HL levels and among minorities.

Preparedness of the Israeli health system for a biologic warfare event.

The threat of a disease outbreak resulting from biologic warfare has been of concern for the Israeli health system for many years. In order to be prepared for such an event the health system has formulated doctrines for various biologic agents and defined the logistic elements for the procurement of drugs. During the last 4 years, and especially after the West Nile fever epidemic in 2000, efforts to prepare the healthcare system and the relevant organizations were accelerated. The Director-General of the Ministry of Health nominated a Supreme Steering Committee to fill in the gaps and upgrade the preparedness of the health system for an unusual disease outbreak. This committee and its seven subcommittees established appropriate guidelines, communication routes among different organizations, and training programs for medical personnel. The anthrax outbreak in the United States found the healthcare system in the hub of the preparation process, and all modes of action were intensified. Further work by hospitals, primary care clinics and all other institutes should be increased to maintain a state of proper preparedness.

Evaluation of CO2 accumulation in respiratory protective devices.

A simple mathematical model was developed to grade the results of the fraction of inspiratory CO2 levels in respiratory protective devices (RPDs). Using this model, the level of FiCO2 of two chemical warfare RPDs was monitored during the examination of 54 young male volunteers at rest and exercise. No set of results distributed in a normal Gaussian mode; therefore, parametric statistics could not be used to analyze the group's results. Yet the model allowed simple and insightful evaluation of the results, stressing differences between the similar RPDs. We suggest continued use of the analysis model as a tool for quantitative evaluation of results and further understanding of the respiratory patterns of RPDs.

[Anthrax--an overview at 2002].

BACKGROUND: Bacillus anthracis, the causative agent of anthrax, is well known in human history as a major cause of disease in domestic and wild animals and as a rare condition in humans. For the last seventy years, anthrax was developed and occasionally stored as an agent of biological weapon arsenal in numerous countries. The incubation period in humans is 1-6 days and the disease may be present as three distinct clinical syndromes: cutaneous, inhalational, and gastrointestinal disease. The major concern in regard of biological warfare is the inhalational form of anthrax, which starts as a febrile flu-like disease. The development of malaise, fatigue, cough and mild chest discomfort is followed by severe respiratory distress with dyspnea, diaphoresis, stridor, and cyanosis. Shock and death occur within 24-36 hours after onset of severe symptoms. Physical findings are non-specific, but a widened mediastinum is usually seen on chest x-ray. A positive blood culture, immunohistochemical methods and the use of the polymerase chain reaction method confirm the diagnosis. Although effectiveness may be limited after severe symptoms are present, a high dose of antibiotic treatment should be administered and aggressive supportive therapy may be necessary. In the situation of an anthrax attack, as was recently seen in the United States, penicillin is no longer recommended as an acceptable first line therapy. In this case, ciprofloxacin or doxycycline is the recommended drug of choice since penicillin-resistant strains may be used, as well as the possibility of the emergence of an inducible beta-lactamase positive bacterium. Since a high infecting dose may exacerbate the clinical course of the disease, a combination antibiotic regimen should be considered. The disease is not contagious and standard precautions are sufficient. Pre-exposure prophylaxis is based on a vaccine administration, while post-exposure prophylaxis is feasible by the initial use of oral ciprofloxacin or doxycycline. In this article we reviewed the literature with emphasis on the recent medical reports from the United States analyzing the eleven cases of inhalational anthrax as well as the new guidelines for diagnosis and treatment that resulted from the bioterrorism attack in October 2001. Although physical findings were non-specific, abnormal findings on chest x-rays were present in all the eleven cases. A positive blood culture, immunohistochemical methods and the use of the polymerase chain reaction method were highly valuable in revealing and confirming the diagnosis of anthrax. In the case of an attack with anthrax spores, the likelihood of exposure to a large infective dose of high quality spores, may require a prolonged period of treatment as well as prolonged post-exposure therapy.

Which nutritional regimen for the comorbid complex intensive care unit patient?

Intensive care patient nutritional therapy has been standardized by guidelines for decades. However, the same nutritional regimen to such a heterogeneous population seems a difficult task. These patients have various genotypes, numerous comorbidities, different severities and lengths of acute illness, and multiple interventions. Therefore, a new way of approaching the complexity of these patients is required, progressing from the whole body to compartments, organs, pericellular space, and cellular metabolism. We propose to untangle the complexity of intensive care unit patients by analyzing the complexity and deciding on the appropriate measures. These activities should aim towards personalized identification and prediction of adequate recovery measures, considering the generalization of guidelines based on the accumulated experience. Defining the specific nutrition supplement to affect various body niches could produce a significant contribution to the monitoring of nutritional complications, better understanding of the published nutritional interventions, and wise use of the nutritional tool in the complex patient.