Translational Critical Care Medicine

Preface of Journal of Translational Critical Care Medicine Kaijiang Yu, Zhiyong Peng Journal of Translational Critical Care Medicine 2019 1(1):1-1

Translational Critical Care Medicine: Integrating State-of-the-Art Knowledge between Bench and Bedside Xiaofeng Jia, Zhiyong Peng Journal of Translational Critical Care Medicine 2019 1(1):2-3

Combining Therapy of Octreotide and Glucocorticoid in the Treatment of a Lung Adenocarcinoma Patient with Acute Respiratory Distress Syndrome Xue-Zhong Xing, Hai-Jun Wang, Shi-Ning Qu, Chu-Lin Huang Journal of Translational Critical Care Medicine 2019 1(1):4-6 A 63-year-old male who was diagnosed with adenocarcinoma of the right lower lobe presented with 1 week of fever, cough, and progressive dyspnea and admitted to the Intensive Care Unit (ICU). After intubation, physical examination revealed copious, light bloody sputum and diffuse crackles and rales on lung auscultation. The patient was diagnosed as Stage IV adenocarcinoma, septic shock (lung infection), and acute respiratory distress syndrome. His oxygenation failed to improve despite sedation, restrictive fluid therapy, and methylprednisolone, antimicrobials therapy, protective ventilation, plasma supplement, and anticoagulation. Respiratory secretions suctioned from her endotracheal tube averaged 1.0 L daily. On day 2 after admission, octreotide was infused to control sputum volume. The patient's respiratory secretions decreased significantly, and on day 8, the ventilator mode was changed to pressure support ventilation, and the patient was extubated and dismissed from ICU.

Angiotensin in Clinical Practice Ehsan Ahmadnia, Anna Hall, Marlies Ostermann Journal of Translational Critical Care Medicine 2019 1(1):7-11 Interest in the use of angiotensin (AT) (particularly in the context of shock) had been rekindled by recent randomized trial data (notably the AT II for the Treatment of High-Output Shock-3 study). This review article outlines the renin–AT system in health and during sepsis as well as the proposed clinical uses of AT II. The potential for wider application within critical care is also considered.

Multimodal Monitoring Technologies for Pathophysiology and Management of Traumatic Brain Injury Yujie Chen, Qianwei Chen, Jian Sun, Lijun Zhang, Liang Tan, Hua Feng Journal of Translational Critical Care Medicine 2019 1(1):12-19 Despite decades of efforts, severe traumatic brain injury (TBI) is still the leading cause for mortality and immobility of children and young adults worldwide and is a great burden to the health-care system. After injury, the oxygen supply is conventionally considered the monitoring parameter in a neurosurgical Intensive Care Unit. However, the overall mortality rate has only slightly improved since the late twentieth century. Evolving evidence suggests that dysfunction of oxygen utilization might be the underlying pathophysiology of secondary brain injury, which should also be a key parameter for multimodal monitoring and management after severe TBI. In this review, we summarize the current and advanced understanding of multimodal monitoring for severe TBI along with novel noninvasive technologies in this field. By continuously monitoring patients with severe TBI, the use of multimodal monitoring technologies including (but not limited to) computed tomography, cerebral microdialysis, near-infrared spectroscopy, magnetic resonance spectroscopy, high-performance liquid chromatography, and magnetic induction phase shift method will be crucial for observing disease changes such as intracranial pressure and brain tissue oxygen partial pressure as well as developing potential therapeutic strategies after severe TBI.

Neuromonitoring in Malignant Middle Cerebral Artery Infarction: A Review of Literature Songyu Chen, Ke Wang, Chengcheng Zhou, Sajan Pandey, Liang Gao Journal of Translational Critical Care Medicine 2019 1(1):20-27 Malignant middle cerebral artery infarction is a devastating subtype of ischemic stroke, which carries a significant mortality rate (up to 80%) despite of conservative treatment. On the other hand, surgical decompressive procedure is the only established therapy to rescue the adverse effects of malignant edema and thus improve outcome. Accordingly, the early recognition of a possible malignant course as well as prediction of outcome is crucial for clinical decision-making. Numerous neuromonitoring techniques have been applied to address this issue. In theory, these techniques have the potential to present the information needed to guide targeted and timely intervention before irreversible damage takes place. However, the results were heterogeneous yet conflicting. We examined and summarized the recent evidence in this review, which may shed light on current trends.

Using Clinical Decision Support Systems for Acute Kidney Injury Pragmatic Trials Kianoush Kashani, Nooshin Dalili, Rickey E Carter, John A Kellum, Ravindra L Mehta Journal of Translational Critical Care Medicine 2019 1(1):28-34 Following the initial introduction of clinical decision support systems (CDSS) into the clinical practice in the 1970s, the complexity and performance quality of CDSSs have increased. The current literature on the efficacy and effectiveness of such systems shows conflicting results. While some studies show a clear benefit in quality-of-care improvement, others fail to replicate these outcomes. Heterogeneity of studies and the complexity of CDSS characteristics drive these conflicting conclusions. The lower cost and the easier implementation of pragmatic clinical trials provide an excellent platform to prove the effectiveness of CDSS in the real-world scenarios. To achieve better results, a series of explanatory trials are needed to identify the most effective CDSS in controlled settings. Therefore, utilization of both explanatory and pragmatic trial designs is necessary to evaluate the safety and efficacy of CDSS on the care of patients with acute kidney injury (AKI) in the acute setting. In this review, the authors provide an overview of the literature on critical care-related CDSS, its characteristics and dimensions, differences between pragmatic and explanatory trials, and potential proposals for both trial designs for AKI.

The Short- and Long-Term Burden of Acute Kidney Injury Jonah G Powell-Tuck, Jorge Cerda, Marlies Ostermann Journal of Translational Critical Care Medicine 2019 1(1):35-41 Acute kidney injury (AKI) is a common complication of acute illness and carries a significant risk of mortality and morbidity, resulting in high health-care-associated costs. The incidence of AKI appears to be rising, making it ever more important to understand its acute and chronic consequences. In this review, we explore the evolving epidemiology of AKI, describe the impact of AKI on other organs, and discuss the short- and long-term effects of AKI on mortality and morbidity and its economic burden.

The 19th Acute Disease Quality Initiative (ADQI) Meeting Report Zhiyong Peng Journal of Translational Critical Care Medicine 2019 1(1):42-43 EDITORIALS   Preface of Journal of Translational Critical Care Medicine p. 1 Kaijiang Yu, Zhiyong Peng DOI:10.4103/jtccm.jtccm_16_18   [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta Translational Critical Care Medicine: Integrating State-of-the-Art Knowledge between Bench and Bedside p. 2 Xiaofeng Jia, Zhiyong Peng DOI:10.4103/jtccm.jtccm_18_18   [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta CONSENSUS REPORT Combining Therapy of Octreotide and Glucocorticoid in the Treatment of a Lung Adenocarcinoma Patient with Acute Respiratory Distress Syndrome p. 4 Xue-Zhong Xing, Hai-Jun Wang, Shi-Ning Qu, Chu-Lin Huang DOI:10.4103/jtccm.jtccm_8_18   A 63-year-old male who was diagnosed with adenocarcinoma of the right lower lobe presented with 1 week of fever, cough, and progressive dyspnea and admitted to the Intensive Care Unit (ICU). After intubation, physical examination revealed copious, light bloody sputum and diffuse crackles and rales on lung auscultation. The patient was diagnosed as Stage IV adenocarcinoma, septic shock (lung infection), and acute respiratory distress syndrome. His oxygenation failed to improve despite sedation, restrictive fluid therapy, and methylprednisolone, antimicrobials therapy, protective ventilation, plasma supplement, and anticoagulation. Respiratory secretions suctioned from her endotracheal tube averaged 1.0 L daily. On day 2 after admission, octreotide was infused to control sputum volume. The patient's respiratory secretions decreased significantly, and on day 8, the ventilator mode was changed to pressure support ventilation, and the patient was extubated and dismissed from ICU. [ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta REVIEW ARTICLES Angiotensin in Clinical Practice p. 7 Ehsan Ahmadnia, Anna Hall, Marlies Ostermann DOI:10.4103/jtccm.jtccm_1_18   Interest in the use of angiotensin (AT) (particularly in the context of shock) had been rekindled by recent randomized trial data (notably the AT II for the Treatment of High-Output Shock-3 study). This review article outlines the renin–AT system in health and during sepsis as well as the proposed clinical uses of AT II. The potential for wider application within critical care is also considered. [ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta Multimodal Monitoring Technologies for Pathophysiology and Management of Traumatic Brain Injury p. 12 Yujie Chen, Qianwei Chen, Jian Sun, Lijun Zhang, Liang Tan, Hua Feng DOI:10.4103/jtccm.jtccm_2_18   Despite decades of efforts, severe traumatic brain injury (TBI) is still the leading cause for mortality and immobility of children and young adults worldwide and is a great burden to the health-care system. After injury, the oxygen supply is conventionally considered the monitoring parameter in a neurosurgical Intensive Care Unit. However, the overall mortality rate has only slightly improved since the late twentieth century. Evolving evidence suggests that dysfunction of oxygen utilization might be the underlying pathophysiology of secondary brain injury, which should also be a key parameter for multimodal monitoring and management after severe TBI. In this review, we summarize the current and advanced understanding of multimodal monitoring for severe TBI along with novel noninvasive technologies in this field. By continuously monitoring patients with severe TBI, the use of multimodal monitoring technologies including (but not limited to) computed tomography, cerebral microdialysis, near-infrared spectroscopy, magnetic resonance spectroscopy, high-performance liquid chromatography, and magnetic induction phase shift method will be crucial for observing disease changes such as intracranial pressure and brain tissue oxygen partial pressure as well as developing potential therapeutic strategies after severe TBI. [ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta Neuromonitoring in Malignant Middle Cerebral Artery Infarction: A Review of Literature p. 20 Songyu Chen, Ke Wang, Chengcheng Zhou, Sajan Pandey, Liang Gao DOI:10.4103/jtccm.jtccm_3_18   Malignant middle cerebral artery infarction is a devastating subtype of ischemic stroke, which carries a significant mortality rate (up to 80%) despite of conservative treatment. On the other hand, surgical decompressive procedure is the only established therapy to rescue the adverse effects of malignant edema and thus improve outcome. Accordingly, the early recognition of a possible malignant course as well as prediction of outcome is crucial for clinical decision-making. Numerous neuromonitoring techniques have been applied to address this issue. In theory, these techniques have the potential to present the information needed to guide targeted and timely intervention before irreversible damage takes place. However, the results were heterogeneous yet conflicting. We examined and summarized the recent evidence in this review, which may shed light on current trends. [ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta Using Clinical Decision Support Systems for Acute Kidney Injury Pragmatic Trials p. 28 Kianoush Kashani, Nooshin Dalili, Rickey E Carter, John A Kellum, Ravindra L Mehta DOI:10.4103/jtccm.jtccm_6_18   Following the initial introduction of clinical decision support systems (CDSS) into the clinical practice in the 1970s, the complexity and performance quality of CDSSs have increased. The current literature on the efficacy and effectiveness of such systems shows conflicting results. While some studies show a clear benefit in quality-of-care improvement, others fail to replicate these outcomes. Heterogeneity of studies and the complexity of CDSS characteristics drive these conflicting conclusions. The lower cost and the easier implementation of pragmatic clinical trials provide an excellent platform to prove the effectiveness of CDSS in the real-world scenarios. To achieve better results, a series of explanatory trials are needed to identify the most effective CDSS in controlled settings. Therefore, utilization of both explanatory and pragmatic trial designs is necessary to evaluate the safety and efficacy of CDSS on the care of patients with acute kidney injury (AKI) in the acute setting. In this review, the authors provide an overview of the literature on critical care-related CDSS, its characteristics and dimensions, differences between pragmatic and explanatory trials, and potential proposals for both trial designs for AKI. [ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta The Short- and Long-Term Burden of Acute Kidney Injury p. 35 Jonah G Powell-Tuck, Jorge Cerda, Marlies Ostermann DOI:10.4103/jtccm.jtccm_7_18   Acute kidney injury (AKI) is a common complication of acute illness and carries a significant risk of mortality and morbidity, resulting in high health-care-associated costs. The incidence of AKI appears to be rising, making it ever more important to understand its acute and chronic consequences. In this review, we explore the evolving epidemiology of AKI, describe the impact of AKI on other organs, and discuss the short- and long-term effects of AKI on mortality and morbidity and its economic burden. [ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta MEETING REPORT The 19th Acute Disease Quality Initiative (ADQI) Meeting Report p. 42 Zhiyong Peng DOI:10.4103/jtccm.jtccm_17_18   [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta

Incidence, Risk Factors, and Outcomes of Intra-Abdominal Hypertension in Critically Ill Patients—A Prospective Multicenter Study (IROI Study)

Objectives: To identify the prevalence, risk factors, and outcomes of intra-abdominal hypertension in a mixed multicenter ICU population. Design: Prospective observational study. Setting: Fifteen ICUs worldwide. Patients: Consecutive adult ICU patients with a bladder catheter. Interventions: None. Measurements and Main Results: Four hundred ninety-one patients were included. Intra-abdominal pressure was measured a minimum of every 8 hours. Subjects with a mean intra-abdominal pressure equal to or greater than 12 mm Hg were defined as having intra-abdominal hypertension. Intra-abdominal hypertension was present in 34.0% of the patients on the day of ICU admission (159/467) and in 48.9% of the patients (240/491) during the observation period. The severity of intra-abdominal hypertension was as follows: grade I, 47.5%; grade II, 36.6%; grade III, 11.7%; and grade IV, 4.2%. The severity of intra-abdominal hypertension during the first 2 weeks of the ICU stay was identified as an independent predictor of 28- and 90-day mortality, whereas the presence of intra-abdominal hypertension on the day of ICU admission did not predict mortality. Body mass index, Acute Physiology and Chronic Health Evaluation II score greater than or equal to 18, presence of abdominal distension, absence of bowel sounds, and positive end-expiratory pressure greater than or equal to 7 cm H2O were independently associated with the development of intra-abdominal hypertension at any time during the observation period. In subjects without intra-abdominal hypertension on day 1, body mass index combined with daily positive fluid balance and positive end-expiratory pressure greater than or equal to 7 cm H2O (as documented on the day before intra-abdominal hypertension occurred) were associated with the development of intra-abdominal hypertension during the first week in the ICU. Conclusions: In our mixed ICU patient cohort, intra-abdominal hypertension occurred in almost half of all subjects and was twice as prevalent in mechanically ventilated patients as in spontaneously breathing patients. Presence and severity of intra-abdominal hypertension during the observation period significantly and independently increased 28- and 90-day mortality. Five admission day variables were independently associated with the presence or development of intra-abdominal hypertension. Positive fluid balance was associated with the development of intra-abdominal hypertension after day 1. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. The Incidence, Risk Factors, and Outcomes of Intra-Abdominal (IROI) Study Investigators are listed in the Acknowledgments. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://bit.ly/29S62lw). ConvaTec Limited (Deerside, United Kingdom) provided either the Abdo-Pressure (Foley manometer method) or AbViser systems (modified Kron's method) for intra-abdominal pressure measurements free of charge for all participating sites if products were licensed in the respective countries. Dr. Reintam Blaser received funding (honoraria for advisory board meetings or speaker fees) from Nestlé, Fresenius, and Nutricia, and shedisclosed she is a member of Executive Committee of the Abdominal Compartment Society. Drs. Regli, De Keulenaer, and Kimball disclosed that ConvaTec Limited (Deerside, United Kingdom) provided either Abdo-Pressure (modified Kron's method) or AbViser systems (Foley Manometer method) for intra-abdominal pressure measurements free of charge for all the participating sites if products were licensed in the countries. ConvaTec Limited had no influence on study design, analysis of data, or manuscript preparation. Dr. Joel Starkopf has received speaker fees from B. Braun and Fresenius. Dr. Greiffenstein received funding from Zimmer Biomet, DuPuy Synthes, and KLS Martin, and he disclosed that Atox Bio Ltd. (http://www.atoxbio.com) is sponsoring a Phase III Drug trial for which he is Principal Investigator at his site/hospital, but he does not receive any funds directly. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: annika.reintam.blaser@ut.ee Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://bit.ly/2QoagQK

Cardioprotection by Humoral Factors Released After Remote Ischemic Preconditioning Depends on Anesthetic Regimen

Objectives: Remote ischemic preconditioning (RIPC) is a practicable and noninvasive method to protect the heart against ischemia reperfusion injury. Unfortunately results from clinical studies are not convincing. Propofol is suggested to be an inhibiting factor of cardioprotection by RIPC, but the underlying mechanism is still unknown. We investigated whether after RIPC the release of humoral factors and/or the direct cardioprotective effect at the myocardium is inhibited by propofol. Design: Randomized, prospective, blinded laboratory investigation. Setting: Experimental laboratory. Patients/Subjects: Male Wistar rats. Interventions: Repetitive hind limb ischemia in rats—blood plasma transfers to isolated rat heart. Measurements and Main Results: In male Wistar rats (six groups, each n = 6/group), RIPC was induced by four cycles of 5 minutes bilateral hind limb ischemia alternately with 5 minutes of reperfusion. Blood samples were taken with (RIPC) and without RIPC (Con). Rats received continuous anesthesia with pentobarbital (Pento, 40 mg/kg body weight/hr) or propofol (Prop, 12 mg/kg body weight/hr), respectively. Cardioprotective properties of the blood plasma was investigated in the rat heart in vitro (six groups, each n = 6/group) perfused with Krebs-Henseleit buffer alone or with propofol (10 µM). Plasma was administered over 10 minutes before myocardial ischemia. All hearts underwent 33 minutes of global ischemia followed by 1 hour of reperfusion. At the end of the experiments, infarct size was determined by triphenyl-tetrazolium-chloride staining. RIPC plasma from pentobarbital anesthetized rats (Pento-RIPC) reduced infarct size from 64% (62–71%) (Pento-Con) to 34% (30–39%) (p

http://bit.ly/2VpJLhE

Transvenous Renal Biopsy of Critically Ill Patients: Safety and Diagnostic Yield

Objectives: Transvenous renal biopsy is an alternative way to obtain kidney samples from patients with bleeding risk factors (e.g., antiplatelet therapy and anticoagulation or coagulation disorders). This study was undertaken to determine the safety and diagnostic yield of transvenous renal biopsy of critically ill patients. Design: Monocenter, retrospective, observational cohort study. Setting: A 26-bed French tertiary ICU. Patients: All patients undergoing in-ICU transvenous renal biopsy between January 2002 and February 2018. Interventions: None. Measurements and Main Results: Eighty patients (male/female sex ratio, 0.95; mean ± SD age, 47.3 ± 18.3 yr) were included. A histologic diagnosis was obtained for 77 patients (96.3%), with acute tubular necrosis being the most frequent: 23 (29.9%). A potentially treatable cause was found for 47 patients (58.7%). The numbers of patients with 0, 1, 2, or 3 factors (i.e., antiplatelet therapy, thrombopenia [

http://bit.ly/2QqsK3m

Being Convinced and Taking Responsibility: A Qualitative Study of Family Members’ Experience of Organ Donation Decision and Bereavement After Brain Death

Objectives: Family members of brain dead patients experience an unprecedented situation in which not only they are told that their loved one is dead but are also asked to consider organ donation. The objective of this qualitative study was to determine 1) what it means for family members to make the decision and to take responsibility, 2) how they interact with the deceased patient in the ICU, 3) how family members describe the impact of the process and of the decision on their bereavement process. Design: Qualitative study using interviews with bereaved family members who were approached for organ donation after the death of their relative in the ICU (brain death). Setting: Family members from 13 ICUs in France. Subjects: Bereaved family members who were approached for organ donation after the death of their relative in the ICU (brain death). Intervention: None. Measurements and Results: Twenty-four interviews were conducted with 16 relatives of organ donor patients and with eight relatives of nonorgan donor patients. Three themes emerged: 1) taking responsibility—relatives explain how they endorse decisional responsibility but do not experience it as a burden, on the contrary; 2) ambiguous perceptions of death—two groups of relatives emerge: those for whom ambiguity hinders their acceptance of the patient's death; those for whom ambiguity is an opportunity to accept the death and say goodbye; and 3) donation as a comfort during bereavement. Conclusions: In spite of caregivers' efforts to focus organ donation discussions and decision on the patient, family members feel a strong decisional responsibility that is not experienced as a burden but a proof of their strong connection to the patient. Brain death however creates ambivalent experiences that some family members endure whereas others use as an opportunity to perform separation rituals. Last, organ donation can be experienced as a form of comfort during bereavement provided family members remain convinced their decision was right. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://bit.ly/29S62lw). Supported, in part, by the Agence de la Biomédecine (France). Drs. Kentish-Barnes', Cohen-Solal's, and Souppart's institutions received funding from Agence de la Biomédecine. Dr. Azoulay's institution received funding from Fisher & Paykel, Gilead, MSD, and Ablynx, and he received fees for lectures from Gilead, Alexion, Baxter, MSD, and Astellas. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: nancy.kentish@aphp.fr Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://bit.ly/2Vt80vi

Improved Guideline Adherence and Reduced Brain Dysfunction After a Multicenter Multifaceted Implementation of ICU Delirium Guidelines in 3,930 Patients

Objectives: Implementation of delirium guidelines at ICUs is suboptimal. The aim was to evaluate the impact of a tailored multifaceted implementation program of ICU delirium guidelines on processes of care and clinical outcomes and draw lessons regarding guideline implementation. Design: A prospective multicenter, pre-post, intervention study. Setting: ICUs in one university hospital and five community hospitals. Patients: Consecutive medical and surgical critically ill patients were enrolled between April 1, 2012, and February 1, 2015. Interventions: Multifaceted, three-phase (baseline, delirium screening, and guideline) implementation program of delirium guidelines in adult ICUs. Measurements and Main Results: The primary outcome was adherence changes to delirium guidelines recommendations, based on the Pain, Agitation and Delirium guidelines. Secondary outcomes were brain dysfunction (delirium or coma), length of ICU stay, and hospital mortality. A total of 3,930 patients were included. Improvements after the implementation pertained to delirium screening (from 35% to 96%; p

http://bit.ly/2Vvwq7p

How I treat venous thrombosis in children Contraindications to specific antithrombotic therapies in infants and children

Unfractionated heparin

Known allergy

History of HITs

Low-molecular-weight heparin

Known allergy

History of HITs

Invasive procedure within the previous 24 h

Systemic TPA

Known allergy

Active bleeding

Central nervous system ischemia/hemorrhage/surgery within the previous 10 d (includes birth asphyxia)

Surgery within the previous 7 d

Invasive procedure within the previous 3 d

Seizures within the previous 48 h

Thrombolysis by interventional radiology

Known allergy

In cases where needed, inability to place a vena cava filter

Limitations are size of involved vessels and experience of interventionalists

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895344/