Serum monoclonal immunoglobulin light-chain detection differs between immunofixation electrophoresis methods in patients with AL amyloidosis.

Serum immunofixation electrophoresis (IFE) is often performed for screening monoclonal proteins (M proteins) in immunoglobulin light-chain amyloidosis (AL amyloidosis). However, the performance of serum IFE for detecting M protein in AL amyloidosis patients is often insufficient. In this study, we examined the detection rate of serum M protein in newly diagnosed AL amyloidosis patients and analyzed differences in M protein detection between IFE methods. Among 60 patients newly diagnosed with AL amyloidosis, 22 had undetectable serum M protein by IFE with the Epalyzer2 system. Samples with undetectable M protein had significantly lower involved serum-free light-chain (iFLC) and a smaller difference between involved and uninvolved serum-free light-chain (dFLC) values than samples with IFE-detectable monoclonal light chains. When samples that tested negative for M protein by the Epalyzer2 system were retested by IFE with the HYDRASYS 2 system, 50% had IFE-detectable monoclonal light chains. The IFE system and reagents used may affect serum monoclonal immunoglobulin light-chain detection in AL amyloidosis patients, especially those with low iFLC or low dFLC samples. More attention should be paid to the performance of IFE systems, since it may affect the diagnostic and therapeutic evaluation of AL amyloidosis patients.

Faster surgery initiation in oral cancer patients during the COVID-19 pandemic in Osaka, Japan.

BACKGROUND: We investigated the impact of the COVID-19 pandemic on oral cancer (OC), comparing diagnosis and number of pre-operative days in the diagnosis of OC in 2019 (pre-COVID-19) and that in 2020 (during the COVID-19 pandemic). METHODS: Using data from a cancer registry-based study on the impact of COVID-19 on cancer care in Osaka (CanReCO), we collected details of sex, age, residential area, cancer site, date of diagnosis, clinical stage at first treatment and number of pre-operative days in OC patients. RESULTS: A total of 1470 OC cases were registered. Incidence of OC before and during COVID-19 was 814 and 656 cases, respectively. During the first wave of the pandemic (March to May 2020), incidence was about half that in the same period in 2019 (2019; n = 271, 2020; n = 145). Number of pre-operative days (median number of days between the first hospital visit and surgery date) was significantly shorter during the COVID-19 year (24.5 days) than in the pre-COVID-19 year (28 days, p = 0.0015). CONCLUSIONS: Incidence of OC during the COVID-19 pandemic was lower than in pre-COVID-19. Despite disruption in the healthcare system, the number of pre-operative days for OC cases was shorter during the pandemic.

Chloride Reduction Therapy with Furosemide: Short-Term Effects in Children with Acute Respiratory Failure.

From the perspective of the Stewart approach, it is known that expansion of the sodium chloride ion difference (SCD) induces alkalosis. We investigated the role of SCD expansion by furosemide-induced chloride reduction in pediatric patients with acute respiratory failure. We included patients admitted to our pediatric intensive care unit intubated for acute respiratory failure without underlying diseases, and excluded patients receiving extracorporeal circulation therapy (extracorporeal membrane oxygenation and/or renal replacement therapy). We classified eligible patients into the following two groups: case-those intubated who received furosemide within 24 hours, and control-those intubated who did not receive furosemide within 48 hours. Primary outcomes included SCD, partial pressure of carbon dioxide (PaCO 2 ), and pH results from arterial blood gas samples obtained over 48 hours following intubation. Multiple regression analysis was also performed to evaluate the effects of SCD and PaCO 2 changes on pH. Twenty-six patients were included of which 13 patients were assigned to each of the two groups. A total of 215 gas samples were analyzed. SCD (median [mEq/L] [interquartile range]) 48 hours after intubation significantly increased in the case group compared with the control group (37 [33-38] vs. 31 [30-34]; p = 0.005). Although hypercapnia persisted in the case group, the pH (median [interquartile range]) remained unchanged in both groups (7.454 [7.420-7.467] vs. 7.425 [7.421-7.436]; p = 0.089). SCD and PaCO 2 were independently associated with pH ( p < 0.001 for each regression coefficient). As a result, we provide evidence that SCD expansion with furosemide may be useful in maintaining pH within the normal range in pediatric patients with acute respiratory failure complicated by concurrent metabolic acidosis.

A case of severe oral mucosal GVHD induced by heterologous SARS-CoV-2 vaccination after cord blood transplantation.

Patients who have undergone hematopoietic cell transplantation (HCT) are at a higher risk of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection than the general population. Therefore, early vaccination is recommended for post-transplant patients. Although exacerbation of chronic graft-versus-host disease (cGVHD) after the initial vaccination has been reported, it is unknown whether severe cGVHD occurs when different RNA vaccines are combined. We treated a patient who developed severe oral mucosal cGVHD after receiving two different RNA vaccines. Visual inspection showed that the patient presented with typical mucocutaneous cGVHD, and cGVHD in this case responded well to low-dose steroids compared to common oral GVHD exacerbations. Histopathological findings revealed T cell, B cell, and conspicuous neutrophil infiltration. Multiple doses of SARS-Cov2 vaccination are required in post-transplant recipients. In conclusion, it is essential to obtain the vaccination history of allo-HSCT recipients with cGVHD exacerbation. Furthermore, reviewing the pathological findings may help treat patients with lower doses of steroids.

The Utility of Performing Anaerobic Blood Cultures in Pediatric Intensive Care Units.

BACKGROUND: Several reports have suggested that routine use of anaerobic blood culture bottles together with aerobic bottles may improve blood culture positivity. However, the information is still limited regarding the utility of anaerobic blood culture bottles in the pediatric intensive care unit (PICU), where bacteremia due to anaerobic bacteria is relatively rare. METHODS: A retrospective observational study was conducted at a PICU in a tertiary children's hospital in Japan from May 2016 to January 2020. Patients aged ≤15 years old with bacteremia, for which both aerobic and anaerobic blood cultures were submitted, were included in the study. We investigated whether the positive blood culture cases were from aerobic or anaerobic bottles. We also compared the amount of blood inoculated into culture bottles to determine the effect of blood volume on the rate of detection. RESULTS: During the study period, a total of 276 positive blood cultures from 67 patients were included in this study. Among the paired blood culture bottles, 22.1% were positive only for the anaerobic bottles. Escherichia coli and Enterobacter cloacae were the most common pathogens that were detected in anaerobic bottles only. Obligate anaerobic bacteria were detected in 2 (0.7%) bottles. There was no significant difference in the amount of blood inoculated into aerobic and anaerobic culture bottles. CONCLUSIONS: The use of anaerobic blood culture bottles in the PICU may increase the detection rate of facultative anaerobic bacteria.

Nelarabine-induced myelopathy in patients undergoing allogeneic hematopoietic cell transplantation: a report of three cases.

Nelarabine is an effective treatment for T-cell acute lymphoblastic leukemia/lymphoma. Myelopathy is a rare but serious adverse event associated with this drug. Three patients who received nelarabine at the National Cancer Center Hospital from December 2014 to March 2021 developed myelopathy 20 days before, 12 days after, and 29 days after allogeneic hematopoietic cell transplantation (allo-HCT), respectively. Magnetic resonance imaging showed that two of the patients had lesions in the dorsal column or medulla oblongata, and one had no abnormalities in the head or spine. Despite treatment with intravenous immunoglobulin and methylprednisolone, all patients became unable to walk. One patient died on day 101 after allo-HCT due to progressive neurotoxicity. The other two patients showed spontaneous improvement in neurological symptoms, but one died of mucormycosis on day 476. Autopsy revealed spongiosis in the posterior funiculus in both patients who died, and also in the medulla oblongata in one patient. In the surviving patient, positron emission tomography on day 84 showed abnormal accumulation, suggesting continued inflammation. These cases demonstrated pathophysiological features of nelarabine-induced myelopathy and indicate that allo-HCT may worsen the condition. It is necessary to elucidate the underlying mechanism and establish diagnostic methods and therapies.

[New Attempt of Radiation Oncology Section to Radiotherapy for Head and Neck Cancer].

Oral care is important for patients with head and neck cancer who undergo radiotherapy because these patients encounter various symptoms, which decrease their quality of life(QOL). Oral mucositis is considered the major side effect of radiation, and the dose-volume parameters can serve as predictors of the occurrence of severe oral mucositis. Therefore, understanding radiation treatment planning(e. g., prescription dose and irradiated volumes of the organs at risk)and providing oral healthcare before, during, and after radiotherapy are essential for maintaining patients' QOL. METHODS: An RT viewer (Climb Medical Systems) was installed into the inhouse hospital information system to provide education regarding radiation treatment planning to medical staff members (dentists and nurses) by medical physicists. RESULTS: Patients can undertake appropriate oral care before radiotherapy, and this intervention has potential for reducing the radiation-related side effect. CONCLUSION: Education regarding radiation treatment planning by medical physicists using the RT viewer could improve the knowledge of medical staffs regarding the predictors of radiation-induced side effects for. By introducing the appropriate intervention of oral care before radiotherapy, it may be feasible to maintain patients' QOL.

Plasma exchange and infliximab as a third-line therapy for refractory infantile Kawasaki disease.

BACKGROUND: The treatment for Kawasaki disease (KD) patients refractory to intravenous immunoglobulin (IVIG) therapy is still controversial, and the efficacy of plasma exchange (PE) and infliximab (IFX) therapy for infantile KD is unknown. METHODS: A total of 22 infantile KD patients refractory to initial and additional IVIG, who received either PE or IFX as third-line therapy from October 2008 to February 2020 were examined retrospectively. The patients' sex, age, days of first IVIG, days of PE or IFX therapy, laboratory data preceding PE or IFX therapy, coronary artery lesions (CALs), and adverse effects were investigated. RESULTS: Thirteen patients received PE and nine patients received IFX as the third-line therapy. For the median age at onset, the median days of first IVIG and PE or IFX, and pre-PE or IFX therapy blood test results, there were no significant between-group differences. At admission, and before and after the third-line therapy, there were also no significant differences in occurrence of CALs. The frequency of serious adverse events was significantly higher in the PE group than in the IFX group. CONCLUSIONS: Although there were no significant differences in patient background, blood test results, or frequency of CALs, the frequency of adverse events was significantly higher in the PE group. With the trend of expansion of IFX therapy for KD patients refractory to IVIG, the role of PE as the additional therapy may become more limited.

Spontaneous and reflex movements after diagnosis of clinical brain death: A lesson from acute encephalopathy.

BACKGROUND: Organ transplantation after brain death (BD) of the donor has been promoted in many countries as an established medical treatment. However, some problems with brain-dead organ transplantation have been reported. For example, there is no evidence as to the optimal observation period for a diagnosis and no evidence to support the interpretation of the various body movements observed after the determination of BD. CASE REPORT: A previously healthy 17-month-old girl with severe febrile convulsive status was transferred to our intensive care unit. The convulsions were refractory and the patient required respiratory management due to whole brain edema on head CT. Later she was diagnosed with acute encephalopathy. The patient showed a flat EEG, no responses on auditory brainstem responses (ABR), and loss of brainstem reflexes on repeated daily examinations. No apnea test was performed. Based on the diagnosis of clinical BD, coordinator of Japan Organ Transplant Network explained about organ donation on the 17th day of the disease. Subsequently, the family responded that they could not consent to organ donation, and the patient did not proceed to the legal BD determination. Around five weeks after the onset, spontaneous body movements began to appear, as not only the spinal reflexes but also the brainstem involvement. CONCLUSION: The pathophysiology of acute encephalopathy is largely unknown, and it is difficult to determine the observation period necessary for BD determination. What we have learned from this case is that clinical BD remains ambiguous and cannot be confirmed even with a thorough neurological examination, EEG, and ABR.

Estimating the insertion length of pediatric peripherally inserted central catheters.

BACKGROUND: It is difficult to determine the insertion length of peripherally inserted central catheters (PICCs) without fluoroscopy. The objectives of this study were to examine the relationship between the length from the anterior axillary point to the level of the carina (Lcarina ) and patient's height, and to obtain possible estimation formulas that can be considered for validation in future studies. METHODS: We retrospectively analyzed PICCs from the upper arm in the pediatric intensive care unit (PICU) between May 2017 and September 2018. We evaluated the relationship between Lcarina and the patient's height using linear regression. We also conducted simulated performance assessment of simplified formulas based on the observed relationships. RESULTS: Fifty-four PICCs from the right arm and 49 from the left for patients at the median age of 1 year were analyzed. The following linear correlations between Lcarina and the patient's height were observed: 0.105 × height (cm) + 1.53 (cm) (P < 0.001, R2 = 0.71) from the right arm, and 0.125 × height (cm) + 1.21 (cm) (P < 0.001, R2 = 0.65) from the left arm. In the simulated performance assessment, with a simplified formula, [0.1 × height (cm) + 1 (cm)], 93% (50/54) of the PICCs from the right arm and 96% (47/49) from the left arm were expected to be inserted in the subclavian vein, innominate vein, or superior vena cava. CONCLUSIONS: The level of the carina was correlated with the patient's height. A simplified formula, 0.1 × height (cm) + 1, seemed to perform acceptably and appeared to be worth validating in future studies.

Neurological impairment in children with acute liver failure following liver transplantation-A single-center experience.

BACKGROUND: Although overall survival of ALF has improved, neurological restoration after recovery from ALF may not always be satisfactory. The purpose of this study was to investigate the occurrence and possible causes of NI in children with ALF following LT. METHODS: We retrospectively examined all children younger than 16 years old with ALF who subsequently underwent LT at our center between January 2005 and December 2016. NI was assessed in December 2016 using the six-point Pediatric Cerebral Performance Category score and was defined as any increase in the score. RESULTS: There were 62 children with median age 10 months (quartile range 5-34). The etiology of ALF was indeterminate in 47 children (75.8%). The median duration from admission to LT was 5.5 days (quartile range 4-7), and 96.8% (60/62) received living donor LT. The overall survival was 83.9% (52/62) in a median follow-up period of 4.2 years. Mild-to-moderate NI was observed in 23.1% (12/52) of the survivors. Possible causes of NI were underlying systemic disease (n = 3), perioperative brain lesion (n = 2), and unclassified (n = 7). All seven patients with unclassified NI were less than 12 months old. The unclassified NI causes were presumed to be ALF, its perioperative care, and the vulnerable infant brain. CONCLUSIONS: NI in children with ALF following LT was not rare and should be prevented. Further investigations are required to clarify the characteristics of the patients with unclassified NI.

Hematological and biochemical characteristics and diagnostic imaging results in acute T cell-mediated rejection after pediatric liver transplantation.

BACKGROUND: Liver biopsy is the gold standard for diagnosing TCMR after LT. However, complications caused by liver biopsy may occur especially during the immediate post-transplantation period and other effective methods for predicting TCMR have not been established. Thus, we investigated whether hematological and biochemical characteristics and Doppler ultrasonography findings are associated with acute TCMR. METHODS: A multiple logistic regression analysis was performed to identify the prognostic factors of acute TCMR, defined as a RAI ≥4. Then, a ROC curve analysis was conducted to evaluate for diagnostic performance. The relationship between prognostic factors and each histological category of RAI was investigated. RESULTS: Eighty-nine liver biopsies were performed on 85 patients between January 2012 and December 2019. The RAI of 62 (69.7%) liver biopsies was ≥4. AEC (×104 /µl), direct bilirubin level (mg/dl), and MHVV (cm/s) were found to be associated with acute TCMR (OR: 4.96, 95% CI: 1.44-17.0, p = .011; OR: 1.41, 95% CI: 1.04-1.91, p = .025; OR: 1.05, 95% CI: 1.02-1.08, p < .001, respectively). The area under the ROC curves for predicting acute TCMR was 0.86 (95% CI: 0.78-0.94). There was a correlation between AEC, direct bilirubin level, and MHVV as well as the severity of RAI. CONCLUSIONS: AEC, direct bilirubin level, and MHVV were the independent risk factors for acute TCMR. This study could provide information regarding the identification of patients requiring liver biopsy.

Prevention of acute graft-versus-host disease in adult T-cell leukemia-lymphoma patients who received mogamulizumab before allogeneic hematopoietic cell transplantation.

Mogamulizumab (Mog) is effective against adult T-cell leukemia-lymphoma (ATL), but as we reported previously, Mog increases the incidence of severe acute GVHD when administered before allogeneic hematopoietic cell transplantation (allo-HCT). Here, we report the cases of two ATL patients who did not develop acute GVHD despite receiving Mog before allo-HCT. Case 1: a 63-year-old female who underwent allo-HCT from an HLA-matched donor 2 months after the last dose of Mog. Case 2: a 47-year-old male with ATL that relapsed 3 months after first allo-HCT. He received eight doses of Mog and underwent a second allo-HCT from a haploidentical donor 4 months after the last dose of Mog. Mog blood levels were measured and lymphocytes analyzed by mass cytometry. Mog blood levels measured before starting the conditioning regimens were low. A small proportion of regulatory T cells (Tregs) was detected before and shortly after allo-HCT. When using Mog before allo-HCT, it is important to consider the number of Mog doses and the interval from the last dose of Mog to allo-HCT. Analyzing Mog blood levels and Treg counts before and after allo-HCT should also be useful.

Impact of extensive negative pressure wound therapy on neonatal respiration: A case report.

An extensive topical negative pressure wound therapy (NPWT) from the abdominal to chest walls in neonates may decrease the compliance of the chest wall. Therefore, it is important to monitor respiratory function carefully during the procedure.

Effect of sodium-chloride ion difference on pH regulation.

BACKGROUND: In the Stewart approach, the difference between the cation and anion concentrations, especially between sodium, accounting for the majority of cations, and chloride, comprising the majority of anions, is an important factor in pH regulation. This study investigated the effect of sodium-chloride ion difference (SCD) on pH regulation comparing with those of PaCO2 and lactate. METHODS: Arterial blood gas samples measured at our pediatric intensive care unit of a tertiary children's hospital between January and June 2020 were included. Samples that met the following criteria were excluded: samples collected from patients taking potassium bromide and samples with lactate concentration of >25 mmol/L. From the eligible data, pH was chosen as the dependent variable and SCD, lactate, and PaCO2 as independent variables, and then, a multiple regression analysis was performed. RESULTS: In total, 5360 samples were included. Of these, five samples were excluded according to the exclusion criteria. Finally, 5355 samples were analyzed. As the variance inflation factors were <2.0 for all three variables, there was no multicollinearity. The following model was derived: pH = 7.384 + [0.97 × SCD (mEq/L) - 0.66 × PaCO2 (mmHg) - 1.33 × Lac (mmol/L)] × 10-2 (adjusted R-squared = 0.73; P value < 0.001). Based on the standardized partial regression coefficients (ß), pH was affected in the order of PaCO2 (ßPaCO2 = -0.95), SCD (ßSCD = 0.72), and lactate (ßlactate = -0.33). CONCLUSIONS: The prevention of SCD reduction, together with respiratory and metabolic management, is important for pH regulation.

Life-threatening oral mucositis following chemotherapy in a pediatric patient.

Severe oral mucositis as a complication of chemotherapy may lead to airway obstruction and require prolonged intubation. As its course is consistent with the course of neutropenia, airway management strategies should be determined individually.

Ultrasound-Guided Postpyloric Feeding Tube Placement in Critically Ill Pediatric Patients.

OBJECTIVES: Various methods to insert postpyloric feeding tubes at the bedside have been reported, but the optimal method remains controversial. The objective of this study was to evaluate the effect of ultrasound-guided postpyloric feeding tube placement in critically ill children. DESIGN: Single-center retrospective observational study. SETTING: PICU of tertiary children's hospital. PATIENTS: Children under the age of 16 who underwent postpyloric feeding tube placement in our PICU between September 2017 and August 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 115 patients were included in this study: 30 patients underwent ultrasound-guided postpyloric feeding tube placement and 85 patients underwent blind postpyloric feeding tube placement; the insertion attempts were 32 and 93, respectively. There were no significant differences in patient demographics between the ultrasound-guided group and the blind group. The first-pass success rate of the ultrasound-guided group was higher than that of the blind group (94% [30/32] vs 57% [53/93]; p < 0.001). The median insertion time in the ultrasound-guided group with successful postpyloric feeding tube insertion was 18 minutes (interquartile range, 15-25; range, 8-45; n = 21). There were no complications or adverse events during the placement. CONCLUSIONS: In this single-center study, ultrasound-guided postpyloric feeding tube placement was feasible and a significantly high first-pass success rate was observed for critically ill children. Additional investigation with a larger pool of operators and randomized controlled patient assignment is required.