Can bispectral index be an early marker in the diagnosis of brain death?

BACKGROUND: The diagnosis of brain death is a clinical condition in which it is difficult to perform confirmatory tests due to the ineligible clinical status of the patient. Prior to confirmatory tests, the use of a BIS monitor to determine the time of brain death is important for organ transplants, cost-effectiveness and reducing stressful wait of the family. OBJECTIVE: This study aimed to use BIS monitoring for early detection of brain death. METHODS: BIS monitoring was performed in 12 patients who were clinically diagnosed with brain death in our intensive care unit during a two-year period. RESULTS: All patients had diffuse brain injury. The BIS score was zero in all patients. However, two patients could not be legally diagnosed with brain death because confirmatory tests could not be performed due to the clinical status. In one patient, the BIS score was zero and blood flow was present on the first computed tomography angiography of the brain; however, the cerebral blood flow was absent on the second imaging after two days. CONCLUSION: It was believed that BIS monitoring could be a parameter to use for detection of brain death in patients with severe brain injury. However, future research is needed in this regard.

Severe Pediatric Traumatic Brain Injury Treatment Approaches of Pediatric Intensivists in Turkey PICUs: National Survey Results.

OBJECTIVE: In patients with severe traumatic brain injury, it is possible to obtain a good long- term prognosis, prevent secondary injury, and decrease morbidity and mortality with the administration of appropriate treatments in the acute period. This study aims to evaluate the approaches of the pediatric intensive care specialists in Turkey towards the follow-up and treatment of severe traumatic brain injury by using a survey that had been prepared in light of the current pediatric severe traumatic brain injury guideline. MATERIALS AND METHODS: The survey, which included 45 questions, was prepared on the SurveyMonkey® system sent by e-mail to the centers, which were members of the Turkish Society of Pediatric Emergency and Intensive Care Medicine. RESULTS: A total of 45 centers participated in the survey. In all centers, computed tomography of the brain was found to be the first choice as an imaging method for traumatic brain inju- ries. In terms of hyperosmolar therapy, 30 (66.6%) centers stated that they used 3% hypertonic saline, and 16 (35.5%) centers stated using 3% hypertonic saline+mannitol. Forty (86.96%) cen- ters stated that they did not use prophylactic hyperventilation in the first 48 hours. A total of 44 centers (97.78%) stated that they administered prophylactic antiepileptic drugs in the first 7 days while the most preferred antiepileptic drug was levetiracetam. CONCLUSION: The results of our survey supported that the pediatric intensive care specialists in Turkey planned a large percentage of the treatment for patients with severe traumatic brain injury in line with the published traumatic brain injury guidelines.

Low Cardiac Output Syndrome After Cardiac Surgery: A Life-Threatening Condition from the Perspective of Pediatric Intensivists.

Low cardiac output syndrome is a clinical picture insourcing from insufficient oxygen sup- ply to tissues so as to meet the metabolic demand, myocardial dysfunction, and cardiovas- cular insufficiency. Low cardiac output syndrome is seen in nearly 25% of pediatric patients who underwent corrective or palliative surgery due to congenital heart defects. It is a clinical condition occurring typically 6-18 hours after surgery in pediatric patients undergoing cardiac surgery and causes organ failure, prolonged hospital and intensive care hospitalization time, increased resource utilization, and mortality. The identification and correct management of this serious complication in the early period is very important. However, there is no clear con- sensus or consensus report on the follow-up of this patient group and the definition of low cardiac output syndrome. Clinicians generally produced low cardiac output syndrome defini- tions according to their own approach. In this review, we aim to draw attention to low cardiac output syndrome and hope to summarize the pathophysiology, etiology, clinical definition, and treatment options of low cardiac output syndrome as a life-threatening condition in pediatric intensive care unit.

COVID-19-associated multisystem inflammatory syndrome in children: Experiences of three centres in Turkey.

BACKGROUND: The pathogenesis and clinical manifestations of the multisystem inflammatory syndrome in children (MIS-C) has not yet been fully elucidated and there is no clear consensus on its treatment yet. OBJECTIVES: To evaluate our patients diagnosed with MIS-C and present them to the literature in order to contribute to the better understanding of this new disease, which entered paediatric practice with the SARS-CoV-2 peak. METHODS: In this study, 17 MIS-C cases diagnosed according to the Centers for Disease Control and Prevention criteria were included. RESULTS: Of the patients, 7 (41.2%) had a comorbidity. Gastrointestinal system involvement was the most prominent in the patients (70.6%). Laparotomy was performed in 3 patients due to acute abdomen. Two patients had neurological involvement. Of the patients, 15 (88.2%) received intravenous immunoglobulin and 13 (76.5%) received both intravenous immunoglobulin and methylprednisolone. Two patients received invasive mechanical ventilation and 4 patients received high flow rate nasal cannula oxygen therapy. One of our patients who needed invasive mechanical ventilation and high vasoactive-inotrope support died despite all supportive treatments including plasmapheresis and extracorporeal membrane oxygenation. CONCLUSIONS: MIS-C picture can have a fatal course and may present with severe gastrointestinal and neurological signs. Unnecessary laparotomy should be avoided.

A trend skill that makes pediatric intensivists stand out: Critical care echocardiography.

Recently, the use of point-of-care ultrasonography (POCUS) by pediatricians especially in emergency and intensive care departments has become increasingly popular. Critical care echocardiography (CCE) quickly and accurately identifies cardiac function, allowing intensivists to manage critically ill pediatric patients by manipulating vasoactive-inotrope-fluid treatment based on the echocardiographic results. Training courses for POCUS are increasingly available and more intensivists are learning how to use CCE. In this review, we focus on the importance and utility of CCE in pediatric intensive units and how it assists in the management of hemodynamically unstable pediatric patients. We highlight the common measurements carried out by intensive care specialists and emphasize the role of the CCE methods in PICUs.

Sedation and Analgesia Practices in Pediatric Intensive Care Units: A Survey of 27 Centers from Turkey.

The management and monitoring of sedoanalgesia are important measures in improving the efficacy of procedures and mechanical ventilation, as well as reducing adverse effects and preventing withdrawal syndrome, and delirium in pediatric intensive care units (PICUs). As there is an ongoing need to clarify the best approach to sedoanalgesia in PICUs, we aimed to analyze the current approaches in sedation, analgesia, withdrawal, and delirium practices among PICUs in Turkey. Twenty-seven PICUs completed the survey. Only 9 (33.3%) and 13 (48.1%) centers had a written protocol for analgesia and sedation, respectively. Paracetamol and a combination of midazolam and fentanyl were preferred in 51.8 and 40% of the PICUs for postoperative periods, respectively, and 81.4% of the units preferred ketamine for short-term interventions. For prolonged sedation in mechanically ventilated children, a combination of benzodiazepines and opiates were the most preferred first-line agents with a very high percentage of 81.4%, whereas ketamine and dexmedetomidine accounted for 62.9 and 18.5%, respectively, as second-line options. Although sedative and analgesic agent preferences were comparable with the relevant literature, we should focus on developing a standardized, evidence-based algorithm for sedation and analgesic drugs.

Current situation of pediatric intensive care specialty and pediatric intensive care units in Turkey: Results of a national survey.

OBJECTIVE: In this study, we have planned to present the results of a national survey performed to evaluate the last situation of pediatric intensive care specialty and pediatric intensive care units in Turkey. MATERIAL AND METHODS: We have sent an electronic survey which includes 47 questions about the characteristics of pediatric intensive care units, staff, and equipment to members of the Turkish Society of Pediatric Emergency and Intensive Care via email. RESULTS: A total of 58 participant units responded to our survey. 93.2% of the centers have tertiary level pediatric intensive care units. There were 841 tertiary level pediatric intensive care beds. There were 35 pediatric intensive care faculty members, 44 pediatric intensive care specialists, and 53 pediatric intensive care fellows. In the participant units, the total number of invasive mechanical ventilators in the units was 806, the number of specific non-invasive mechanical ventilators was 126. It was learned that 79.3% of the centers could apply continuous renal replacement therapy, 84.4% of therapeutic plasma exchange, 46.5% of extracorporeal membrane oxygenation. CONCLUSION: We see that the way we have traveled in the 20 years since the establishment of the first units is very important and proud. The number of educated new generation pediatric intensive care specialists and the well-equipped pediatric intensive care units established by these specialists in every region of our country together with the fellowship education applied in many centers make a great contribution to the treatment of the critically ill pediatric patient population in our country.

Evaluation of ultrasonographic optic nerve sheath diameter and central retinal artery Doppler indices by point-of-care ultrasound in pediatric patients with increased intracranial pressure.

BACKGROUND: Measurement of the optic nerve sheath diameter (ONSD) with point-of-care ultrasound (POCUS) is a non-invasive and radiation-free technique that can be used to assess increased intracranial pressure (ICP). Ophthalmic artery and central retinal artery Doppler indices can be used like transcranial Doppler to evaluate increased ICP. This study aims to examine the diagnostic value of ONSD measurements and central retinal artery Doppler indices in the evaluation of pediatric patients with increased ICP. METHODS: This was a prospective, case-controlled single center study. The study group was comprised of a total of 38 pediatric patients with increased ICP and the control group included 19 healthy children. Ophthalmic ultrasound was performed and ONSD and central retinal artery Doppler indices were measured. RESULTS: The mean age of the study group was 80.84 ± 65.12 months. The mean ONSD was 5.9 ± 0.8 (3.6-8.1) mm in the study group and the mean resistive index (RI) was 0.71 ± 0.08 (min:0,55-max:1) and was significantly greater than the control group (p < 0.001 and p < 0.001, respectively). In terms of predicting increased ICP, the ONSD measurement was the strongest parameter, with its area under the curve: 0.767 (95 percent confidence interval: 0.68-0.85). In the study group, the cut-off value for ONSD was 5.8 mm (66 percent sensitivity, 100 percent specificity) and the cut-off value for RI was 0.68 (63 percent sensitivity, 83 percent specificity). CONCLUSIONS: Point-of-care ultrasound is a noninvasive and important tool in pediatric intensive care units. Our study is significant as one of the few pediatric studies where central retinal artery Doppler indices are evaluated in addition to OSND, in patients with increased ICP.

Evaluation of the relationship between NIRS (near-infrared spectroscopy) and optic nerve sheath diameter measurement in children with increased intracranial pressure: a pilot study.

BACKGROUND: The increased intracranial pressure (ICP) syndrome may emerge depending on many different neurological factors and the early diagnosis and treatment are important for the prevention of neurologic damage and related mortality. In recent years, the follow-up of increased ICP with non-invasive methods has been rising. In this study, our objective was to determine the significance and any possible correlation between Optic Nerve Sheath Diameter (ONSD) and Near Infrared Spectroscopy (NIRS) in children with increased ICP. METHODS: Patients who were hospitalized in our pediatric ICU at Çukurova University Medical Faculty between June 2018 and June 2019 due to the suspicion of increased ICP were included in this study. The demographic characteristics of patients, diagnosis at admission, results of the cranial CT and MRI examinations, and results of the simultaneous ONSD and NIRS measurements were recorded. RESULTS: A total of 36 patients were included in our study. With respect to the diagnosis, non-traumatic causes were at the forefront in 30 patients (83.3%), and the most common causes were meningoencephalitis (n = 9; 25%) and non-traumatic bleeding (n = 7; 19.4%). Six of the patients were under the age of one year (16.7%), and the mean values of ONSD and NIRS were 4.8 ± 0.7 mm and 71.1 ± 12.4% respectively in this group. Fourteen patients were in the one to ten year age group and the mean values of ONSD and NIRS were 6.1 ± 0.6 mm and 72.7 ± 9.3% respectively. Sixteen patients were over ten years of age (44.4%), and the mean values of ONSD and NIRS were 5.6 ± 0.7 mm and 74.2 ± 16% respectively. There was no correlation between the ONSD and NIRS values (r:0.307; p = 0.068). CONCLUSION: Our study showed that ONSD measurements were helpful in children with increased ICP and reflected the increase in ICP. However, our study also demonstrated that ONSD was not in correlation with the NIRS monitoring. We believe that there is a need for further studies focused on the use of ONSD and NIRS in the monitoring of increased ICP.

Is Ocular Sonography a Reliable Method for the Assessment of Elevated Intracranial Pressure in Children?

Point-of-care ultrasound has been widely used by clinicians at the bedside in recent years. Various types of point-of-care ultrasound practices are employed, especially in pediatric emergency rooms and intensive care units. Pediatric intensive care specialists perform point-of-care ultrasound virtually as a part of physical examination since it provides just-in-time vital clinical information, which could assist in acute management strategies in critically ill patients. Measurement of optic nerve sheath diameter using point-of-care ultrasound is a noninvasive and radiation-free technique to determine raised intracranial pressure. Ophthalmic artery and central retinal artery Doppler indices can be used as transcranial Doppler to assess raised intracranial pressure. The aim of this review was to provide detailed information on ultrasonographic measurements of optic nerve sheath diameter and central retinal artery Doppler indices as techniques of interest for predicting increased intracranial pressure in pediatric patients in view of the literature.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is a clinical picture that indicates severe acute hypoxemic respiratory insufficiency. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are convenient, uncomplicated, and inexpensive parameters that can be used in detecting the severity of the disease. The prognostic role of NLR and PLR in patients with pediatric ARDS is unknown. The aim of this study was to investigate if there was any relationship between initial hematological parameters and the stages of ARDS, duration of mechanical ventilation and the length of intensive care stay in pediatric ARDS. MATERIAL AND METHODS: Of 34 patients diagnosed with ARDS, 5 excluded, a total of 29 patients who were followed in our pediatric intensive care unit between 2016 and 2018 were retrospectively enrolled. Patients were retrospectively registered in terms of demographical features, disease severity scores (PIM2, PRISM III, PELOD scores), lymphocyte, neutrophil and platelet counts and NLR, PLR values in complete blood count during intensive care unit stay and on the day of discharge, the stages of ARDS, duration of mechanical and the length of intensive care stay. RESULTS: There was a significant relationship between NLR values and ARDS stages on the first day of the admittance (P = .003). There was a moderate correlation between NLR and PELOD scores on the day of admittance and it was statistically significant (r = 0.45, P = .026). There was no correlation between mechanical ventilation time and the length of intensive care stay and NLR-PLR values. Platelet-to-lymphocyte ratio was not identified as a prognostic factor in our study. CONCLUSION: In diagnosis of the severity of ARDS with severe acute hypoxemic respiratory insufficiency, NLR is a convenient and inexpensive parameter that can only be calculated by complete blood count.

Central venous pressure, global end-diastolic index, and the inferior vena cava collapsibility/distensibility indices to estimate intravascular volume status in critically ill children: A pilot study.

BACKGROUND: The assessment of the volume status in critically ill paediatric patients in intensive care units is vitally important for fluid therapy management. The most commonly used parameter for detecting volume status is still central venous pressure (CVP); however, in recent years, various kinds of methods and devices are being used for volume assessment in intensive care units. OBJECTIVES: We aimed to evaluate the relationship between CVP, the global end-diastolic index (GEDI), and ultrasound measurements of the collapsibility and distensibility indices of the inferior vena cava (IVC) in paediatric patients undergoing Pulse index Contour Cardiac Output (PiCCO) monitoring. METHODS: Fifteen patients receiving PiCCO monitoring were prospectively included in the study. Forty-nine PiCCO measurements were evaluated, and simultaneous CVP values were noted. After each measurement, IVC collapsibility (in spontaneously breathing patients) and distensibility (in mechanically ventilated patients) indices were measured with bedside ultrasound. RESULTS: The mean age was 93.2 ± 61.3 months. Significant and negative correlations of the GEDI were found with the IVC collapsibility index (in spontaneously breathing patients) and the IVC distensibility index (in mechanically ventilated patients) (r = -0.502, p < 0.001; r = -0.522, p = 0.001, respectively). A significant and weakly positive correlation was found between the GEDI and CVP (r = 0.346, p = 0.015), and a significant and negative correlation was found between the IVC collapsibility index and CVP (r = -0.482, p = 0.03). The correlation between the IVC distensibility index and CVP was significant and negative (r = -0.412, p = 0.04). CONCLUSION: The use of PiCCO as an advanced haemodynamic monitoring method and the use of bedside ultrasound as a noninvasive method are useful to evaluate the volume status in critically ill paediatric patients in intensive care. These methods will gradually come to the fore in paediatric intensive care.

Point-of-care ultrasound assessment of the inferior vena cava distensibility index in mechanically ventilated children in the operating room

Background and aim: Point-of-care ultrasound imaging of the inferior vena cava distensibility index is a potential indicator for determining fluid overload and dehydration in the mechanically ventilated patients. Data on inferior vena cava distensibility index and inferior vena cava distensibility variability are limited in mechanically ventilated pediatric patients. That is why our aim in this study was to measure inferior vena cava distensibility index and to obtain mean values in pediatric patients, ventilated in the operating room before the ambulatory surgical procedure started. Materials and methods: This crosssectional study was performed between February 2019 and February 2020. Ultrasonographic measurements were performed in a total of 125 children. Results: In a period of 13 months, the measurements were performed in a total of 125 children, of which 120 (62.5% male) met the criteria and were included in the study. Overall inferior vena cava distensibility index (%): mean ± SD: 6.8 ± 4.0, median (min­max): 5.7 (1.4­19.6), IQR: 3.8­8.7. Overall inferior vena cava distensibility variability (%): mean ± SD: 6.5 ± 3.7, median (min­max): 5.5 (1.4­17.8), IQR: 3.7­8.4. Conclusion: Our study is the largest series of children in the literature in which inferior vena cava distensibility index measurements were investigated.

Ultrasonographic inferior vena cava collapsibility and distensibility indices for detecting the volume status of critically ill pediatric patients.

Especially in recent years, the use of point-of-care ultrasound by non-radiologist clinicians has become widespread. Point-of-care ultrasound provides rapid responses to the problems of critically ill patients at the bedside. This technique has many important advantages, including being non-invasive, cheap, repeatable, painless, and radiation-free. Numerous studies have revealed the most important clinical benefits of point-of-care ultrasound use by pediatric intensive care providers. The inferior vena cava is a vessel that is highly sensitive to fluid changes. The inferior vena cava diameter can be measured by a point-of-care ultrasound, and represents a critical parameter in assessing the patient's fluid status. The inferior vena cava collapsibility index (in spontaneously breathing patients) and the inferior vena cava distensibility index (in mechanically ventilated patients) are calculated by determined formulas by using maximum and minimum diameters of the inferior vena cava. The indices are important guides for pediatric intensive care providers for managing their patients' fluid treatment. Although some authors claim it is not a reliable method, the technique is coming to fore in intensive care units day by day, and has an increasing trend among pediatric intensive care specialists. Here, we aim to give detailed information on the ultrasonographic inferior vena cava diameter measurement methods, and calculations of the inferior vena cava collapsibility index and inferior vena cava distensibility index, and emphasize the importance of a noninvasive, bedside, and objective method of detecting the volume status of critically ill patients for pediatric intensive care specialists according to the published literature.

Point-of-care ultrasound use in pediatric intensive care units in Turkey.

BACKGROUND: Point-of-care ultrasound is commonly used in pediatric intensive care units in recent years. The aim of this study was to find an answer to the question `where are we now in Turkish pediatric intensive care units for point-of-care ultrasound use?`. METHODS: This was a multicenter, descriptive study in which we developed an online survey. We asked 45 questions about point-of-care ultrasound using fields and training status of clinicians in pediatric intensive care units. RESULTS: A total of 29 units responded to the questions completely. Of all included units 41.4% were in public hospitals, 6.9% in city hospitals (public-private partnership) and 51.7% in university hospitals. The most common use of point-of-care ultrasound was central venous catheter insertion. Lung ultrasound use rates for detection of pleural effusion, evaluation of pneumothorax, and diagnosis of pneumonia were 93.1%, 86.2%, and 34.5%, respectively. Critical care echocardiography use rate was 79.3%. In 89.7% of the units, intensive care specialists had been specifically trained for the use of point-of-care ultrasound. CONCLUSIONS: Our study showed that point-of-care ultrasound was not only used for central venous catheterization but also for widespread fields in pediatric intensive care units. With an experienced team, it is possible to perform rapid, noninvasive and repeatable ultrasonographic assessment of patients. In our view point-of-care ultrasound is the new stethoscope of critical care physicians.

Effects of Sedation and/or Sedation/Analgesic Drugs Administered during Central Venous Catheterization on the Level of End-tidal Carbon Dioxide Measured by Nasal Cannula in Our PICU.

AIMS AND OBJECTIVES: Sedatives and analgesics are commonly used in pediatric intensive care units during minor invasive procedures. Here, we aimed to measure the changes in end-tidal carbon dioxide (EtCO2) levels with different sedation/analgesic drug administrations (midazolam, ketamine, midazolam + ketamine/fentanyl) during central venous catheterization. MATERIALS AND METHODS: This prospective study included 44 patients who needed sedation/analgesia for central venous catheterization. Patients were sedated with midazolam, ketamine, or midazolam + fentanyl/ketamine. End-tidal carbon dioxide values were measured before and after sedation-analgesia with nasal cannula and recorded from the capnograph. Oxygen saturation (SO2) was monitored by pulse oximetry. Whether respiratory depression occurred during the process was recorded. RESULTS: During the procedure, 15 (34%) patients were given 0.1 mg/kg dose of midazolam described as group I, 18 (41%) patients were given 1 mg/kg dose of ketamine only described as group II, and 11 (25%) patients who could not be effective sedated with a single sedative-analgesic agent were given either 1 mg/kg dose of ketamine or 2 µg/kg dose of fentanyl together with 0.1 mg/kg dose of midazolam described as group III. According to our findings, hypoxia (54.5%) and hypercarbia (45.5%) were detected higher in group III but it was not statistically significant (p = 0.255, p = 0.364). Hypercarbia was detected in 29.5% patients, in 62% of these patients hypercarbia was accompanied by hypoxia, and 38% had only hypercarbia. When presedation and postsedation EtCO2 values were compared, we detected a statistically significant difference in all groups. CONCLUSION: We detected hypercarbia unaccompanied by hypoxemia in 38% patients. And we think that we have identified these patients early due to measurement of EtCO2 by nasal cannula. This study demonstrated that EtCO2 monitoring via nasal cannula is a feasible and practical way to follow ventilation during sedation/analgesia. HOW TO CITE THIS ARTICLE: Aslan N, Yildizdas D, Horoz OO, Arslan D, Coban Y, Sertdemir Y. Effects of Sedation and/or Sedation/Analgesic Drugs Administered during Central Venous Catheterization on the Level of End-tidal Carbon Dioxide Measured by Nasal Cannula in Our PICU. Indian J Crit Care Med 2020;24(8):705-708.

Optic Nerve Sheath Diameter and Retinal Artery Resistive Index Measurements with Bedside Ophthalmic Ultrasound in Pediatric Patients with Pseudotumor Cerebri Syndrome.

Pseudotumor cerebri syndrome (PTCS) is characterized by raised intracranial pressure (ICP) with no neuroradiological abnormalities. Ocular ultrasound has been in use to measure optic nerve sheath diameter (ONSD), and retinal artery Doppler indices have been used for indirect assessment of ICP by pediatric intensivists. Here, we aimed to evaluate the correlation of the lumbar puncture (LP) opening pressure with the ultrasonographic ONSD and retinal resistive index (RRI) measures in patients with PTCS. And we wanted to find an answer to the following question: Can ultrasonographic ONSD measures serve as a follow-up tool in patients with PTCS? A prospective, single-center, case-control study was performed by pediatric intensive care and pediatric neurology departments. A total of 7 patients with PTCS were evaluated as patient group and 15 healthy children were evaluated as control group. The mean age of patient group was 138.8 ± 43.7 months. The mean right ONSD was 6.7 ± 0.5 mm and the mean left ONSD was 6.7 ± 0.6 mm. The mean right RRI value was 0.73 ± 0.03 and the mean left RRI was 0.73 ± 0.09. For the patient group, ONSD and RRI values of both eyes were statistically significant higher values than for the control group. The mean LP opening pressure was 56.57 ± 16.36 cmH 2 O. We detected strong, positive, and statistically significant correlations between the LP opening pressure and ONSD baseline measures for both the right eye ( r = 0.882, p = 0.009) and the left eye ( r = 0.649, p = 0.004). There was no correlation between opening pressure in LP and RRI measurements. We detected a statistically significant decrease in the right ONSD and left ONSD values and visual analog scale scores at the third-month follow-up. Our study results demonstrate that ultrasonographic ONSD measurements can be used as a noninvasive tool for assessment of the ICP at first admission and can be used as a follow-up tool in PTSC patients.