Real-world efficacy of DA-EPOCH-R/HD-MTX regimen in CD5-positive diffuse large B cell lymphoma: a single-institute analysis.

CD5-positive diffuse large B cell lymphoma (CD5+ DLBCL) is a high-risk lymphoma type. Recently, the PEARL5 (a Phase II trial of DA-EPOCH and Rituximab with HD-MTX therapy for newly diagnosed DLBCL with CD5 expression) study demonstrated the efficacy of the DA-EPOCH-R (cyclophosphamide, etoposide, doxorubicin, vincristine, prednisone, and rituximab)/HD-MTX (high-dose methotrexate) regimen for CD5+ DLBCL. In this report, we revealed the impact of the DA-EPOCH-R/HD-MTX regimen on the clinical course of CD5+ DLBCL in the real-world. We retrospectively compared CD5+ and CD5- DLBCL patients diagnosed from January 2017 to December 2020 and analyzed their clinicopathological characteristics, treatment, and prognosis. There was no difference in age, sex, clinical stage, and cell of origin; however, the CD5-positive group had higher lactate dehydrogenase levels and a worse performance status than the CD5-negative group (p=0.00121 and p=0.0378, respectively). International prognostic index (IPI) was worse in the CD5-positive group than in the CD5-negative group (p=0.0498), but NCCN-IPI (National Comprehensive Cancer Network-IPI) was no different between the two groups. The CD5-positive group was more frequently treated with the DA-EPOCH-R/HD-MTX regimen than the CD5-negative group (p =0.001857). Complete remission rate and 1-year overall survival did not differ between the CD5-positive and -negative groups (90.0% vs 81.4%, p=0.853; 81.8% vs 76.9%, p=0.433). We conclude that the DA-EPOCH-R/HD-MTX regimen is effective for CD5+ DLBCL in this single institute analysis.

Association between gastrointestinal perforation and patent ductus arteriosus in extremely-low-birth-weight infants: a retrospective study of our decade-long experience.

PURPOSE: Management of persistently patent ductus arteriosus (PDA) in extremely low-birth-weight infants (ELBWIs) requires attention due to the risk of tissue hypoperfusion. We investigated the association between PDA and gastrointestinal perforation. METHODS: We performed a retrospective chart review from 2012 to 2021. Preterm (≤ 32 weeks) ELBWIs with PDA after birth who developed necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and idiopathic gastric perforation were included; ELBWIs with congenital heart disease were excluded. Data were analyzed using chi-squared tests with Yates; correction, and Student's t test. RESULTS: Five hundred thirty-five preterm ELBWIs were analyzed, including 20 with NEC, 22 with FIP, and 1 with gastric perforation. In NEC and FIP, the ductus arteriosus remained open in 40% (4/10) and 63.6% (14/22) of cases, respectively, and cyclo-oxygenase inhibitor treatment showed poor efficacy (p = 0.492 and 0.240). The incidence of perforation in NEC (4/9 vs. 6/11, p = 0.653), mortality in NEC (3/4 vs. 3/6, p = 0.895) and FIP (6/14 vs. 3/8, p = 0.838) did not differ according to whether the PDA persisted or resolved. CONCLUSION: The presentation of PDA did not affect the mortality or morbidity of ELBWIs. However, it is essential to consider the possibility of gastrointestinal perforation due to decreased organ blood flow caused by ductal steal.

Potential predictors of the onset of focal intestinal perforation in extremely low birth weight infants based on an analysis of coagulation and fibrinolysis markers at birth: A case-control study based on ten years of experience at a single institution.

PURPOSE: We aimed to investigate potential predictors of focal intestinal perforation (FIP) in extremely low birth weight infants (ELBWIs) among coagulation and fibrinolysis markers at birth. METHODS: We reviewed the medical records of FIP patients and their coagulation and fibrinolysis markers at birth between 2010 and 2019, and matched patients according to gestational age. FIP was diagnosed based on macroscopic intestinal perforation with a punched-out lesion without necrosis. Patient characteristics and blood test results, including coagulation and fibrinolysis marker levels, were compared between the groups. RESULTS: Two hundred forty ELBWIs were enrolled in this study (FIP, n = 18; controls, n = 222). In the FIP group, the gestational age at birth was significantly younger (p = 0.023) and the birth weight was significantly lower (p = 0.007) in comparison to the control group. Furthermore, the FIP group showed significantly lower levels of fibrinogen (p = 0.027) and factor XIII (F-XIII) (p = 0.007). The receiver operating characteristics curves for fibrinogen and F-XIII revealed that the 95% confidence intervals of fibrinogen and F-XIII were 0.530-0.783 (p = 0.027), and 0.574-0.822 (p = 0.007), respectively. CONCLUSIONS: This is the first report focusing on coagulation and fibrinolysis markers in FIP patients at birth. The fibrinogen and F-XIII values at birth are potential predictors of FIP in ELBWIs. TYPE OF STUDY: Study of Diagnostic Test (Case Control Study) LEVEL OF EVIDENCE: : Level IV.

Discrepancy between the survival rate and neuropsychological development in postsurgical extremely low-birth-weight infants: a retrospective study over two decades at a single institution.

PURPOSE: Necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and meconium-related ileus (MRI) are major diseases that cause gastrointestinal disorders in extremely low-birth-weight infants (ELBWIs). We conducted a review to compare the postoperative outcomes of ELBWIs with these diseases in our neonatal intensive-care unit. METHODS: A retrospective chart review of ELBWIs surgically treated for NEC (n = 31), FIP (n = 35), and MRI (n = 16) in 2001-2018 was undertaken. This period was divided into early (2001-2005), middle (2006-2010), and late (2011-2018) periods. Data were analyzed with the Cochran-Armitage test. Statistical significance was defined as p < 0.05. RESULTS: The survival rates in ELBWIs with NEC (early/middle/late: 36.4%/42.9%/61.5%; p = 0.212) and FIP (20%/50%/70.6%; p = 0.012) improved over time; all patients with MRI survived. The neuropsychological development of 24 cases was assessed with the Kyoto Scale of Psychological Development in the Postural-Motor, Cognitive-Adaptative, and Language-Social domains. The mean developmental quotient of all domains was 68.4 (range 18-95) at corrected 1.5 years of age and 69.1 (range 25-108) at chronological 3 years of age, both were considered as poor development. There was no improvement over time (p = 0.899). CONCLUSION: Ideal neuropsychological development was not observed with the improvement of survival rate. Less-invasive surgical intervention and adequate postoperative care are required to encourage further development.

Prophylactic efficacy of enteral antifungal administration of miconazole for intestinal perforation, especially for necrotizing enterocolitis: a historical cohort study at a single institution.

PURPOSE: Despite improvements in neonatal intensive care, the outcomes of extremely-low-birth-weight infants (ELBWIs) with surgical diseases remain to be improved. We started administering enteral miconazole (MCZ) to ELBWIs from 2002 to prevent fungal infection. Since then, the incidence of intestinal perforation has significantly decreased. We investigated this prophylactic effect of MCZ against necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) and explored a new prophylactic concept against intestinal perforation. METHODS: We designed a historical cohort study to evaluate the effect of MCZ for intestinal perforation in ELBWIs who underwent treatment in our neonatal intensive-care unit between January 1998 and December 2005. We divided these cases into two groups: the Pre-MCZ group and the Post-MCZ group. We compared the morbidity, clinical outcomes and pathological features of NEC and FIP. RESULTS: The rate of intestinal perforation with NEC was significantly reduced after the introduction of MCZ (p = 0.007, odds ratio; 3.782, 95% confidence interval; 1.368-12.08). The pathological findings of NEC specimens showed that the accumulation of inflammatory cells was significantly reduced in the Post-MCZ group when compared with the Pre-MCZ group (p < 0.05). CONCLUSIONS: The efficacy of the enteral administration of MCZ on intestinal perforation with NEC highlights a new prophylactic concept in the clinical management of ELBWIs.

Predictive factors affecting the prognosis and late complications of 73 consecutive cases of esophageal atresia at 2 centers.

PURPOSE: While the diagnosis and outcomes of esophageal atresia (EA) have improved, associated anomalies, the management of late complications and growth remain major issues. We analyzed factors that affected the prognosis, late complications and growth. METHODS: We retrospectively reviewed EA patients treated at two centers from 1984 to 2016. Patient characteristics, complications (gastroesophageal reflux [GER], anastomotic stenosis, tracheomalacia, dysphagia) and growth were evaluated. RESULTS: Seventy-three EA patients were treated (overall survival rate:80.8%). The mean birth weight was 2514 ± 509 g in the surviving group, and 2453 ± 567 g in the fatal group excluded chromosomal abnormality (p = 0.76). Cardiac and chromosomal anomalies significantly affected mortality. Postoperative GER and anastomotic stenosis each occurred in 39% of the patients. Only GER was significantly affected by the Gross classification. The standard deviation (SD) values of the EA patients' growth were all lower than in the normal population. The SD of body weight was significantly lower in patients with extremity anomalies. CONCLUSIONS: Associated cardiac and chromosomal anomalies significantly affected the prognosis. GER and anastomotic stenosis were the most common late complications. The growth of the surviving cases was insufficient. These factors will help optimize the therapeutic strategies and postoperative management for EA.

Current characteristics and management of congenital esophageal stenosis: 40 consecutive cases from a multicenter study in the Kyushu area of Japan.

PURPOSE: Congenital esophageal stenosis (CES) is rare, and the available clinical data are limited. We explored the current diagnosis, treatment and outcomes of CES. METHODS: A questionnaire survey was performed using medical records at pediatric surgical centers in the Kyushu area. RESULTS: Over 10 years, 40 patients (24 males) had CES. The incidence of associated anomalies was 52.5% (21/40), and that of esophageal atresia was 20.0% (8/40). The mean age at the diagnosis was 12.0 months (range, 1 day-8.8 years). Seven (17.5%) patients were diagnosed in the neonatal period. Ten (25.0%) developed CES due to tracheobronchial remnants, 27 (67.5%) due to fibromuscular stenosis (FMS) and 1 (2.5%) due to membranous stenosis + FMS. Thirty-six (90.0%) were treated by balloon dilatation (mean, 3 times; range, 1-20). Perforation at dilatation occurred in 7 (17.5%) patients, and all were diagnosed with FMS. Eighteen (45.0%) patients underwent radical operation (3 primary, 15 secondary to dilatation). CONCLUSIONS: Our study clarified the characteristics and outcomes of CES, including neonatal diagnoses. CES occurred in 1 in every 33,000 births in the Kyushu area. Careful attention should be paid, even in cases of dilatation for FMS. CES requires long-term follow-up for symptom persistence after adequate and repeated treatment.

Extracorporeal membrane oxygenation in 61 neonates: Single-center experience.

BACKGROUND: There have been few reports on the outcome of extracorporeal membrane oxygenation (ECMO) in newborn Japanese infants. METHODS: A review was carried out of 61 neonates with ECMO between January 1995 and December 2015 at a single center. ECMO was used in neonates with oxygenation index >20 after conventional treatment. Background factors, such as etiology, vascular access mode (veno-venous [VV] or veno-arterial [VA]), number of days with ECMO, and early ECMO (within 24 h after birth), were analyzed in relation to outcome with respect to survival to hospital discharge (SHD). RESULTS: Survival to hospital discharge was achieved in 35 infants (57%), while the remaining 26 died during hospital stay. Gestational age at birth was significantly higher and number of days with ECMO was significantly lower in SHD infants compared with those with adverse outcome (median, 4.0 vs 5.5 days, respectively; P = 0.008). The SHD rate was significantly higher for those with VV than VA vascular access mode (78%, 18/23 vs 45%, 17/38, respectively; P = 0.016), and for those with than without early ECMO (72%, 28/39 vs 32%, 7/22, respectively; P = 0.003). The SHD rate was relatively high in neonates with meconium aspiration syndrome (86%, 12/14), persistent pulmonary hypertension associated with hypoxic ischemic encephalopathy (75%, 6/8), and emphysema (80%, 4/5). On stepwise logistic regression analysis two independent factors of SHD were identified: early ECMO (OR, 9.63; 95%CI: 2.47-37.6) and ECMO length <8 days (OR, 8.05; 95%CI: 1.94-33.5). CONCLUSIONS: Neonates with early ECMO and those with ECMO duration <8 days may benefit from ECMO with respect to SHD.

Prophylactic efficacy of enteral miconazole administration for neonatal intestinal perforation and its potential mechanism.

PURPOSE: Intestinal perforation (IP) is a fatal complication in extremely low birth weight infants (ELBWI). We started administrating enteral miconazole (MCZ) to ELBWI in 2002. Since then, the incidence of IP has significantly decreased. The aim of this study was to elucidate the prophylactic effect of MCZ for the treatment of neonatal IP, and to establish a new prophylactic concept for this disease. METHODS: In in vivo experiments, the effects of MCZ were examined histopathologically using a mouse model of intestinal ischemia. In in vitro experiments, the cytoprotective effect of MCZ against hypoxia was evaluated using Caco-2 intestinal cells, and its anti-inflammatory potential using a co-culture model of Caco-2 and HL60 cells. RESULTS: MCZ showed a tissue protective effect against intestinal ischemia. MCZ reduced high mobility group-box 1 (HMGB1) release in Caco-2 cells under hypoxic stress and attenuated the potential to activate co-cultured HL60 leukocytes with Caco-2 cells by suppressing interleukin-8 (IL-8). CONCLUSION: MCZ may have preventive roles in the clinical management of IP in ELBWI by the suppression of IL-8 and HMGB-1.

[Remission of acquired hemophilia A following radiation therapy for esophageal cancer].

Although acquired hemophilia A (AHA) often develops in patients with neoplasms, there are few reports on the efficacy of radiation therapy during the bleeding phase of AHA in the prior literature. We herein present a case of AHA experiencing remission soon after radiation therapy for esophageal cancer. A man in his seventies, who had a history of radical nephrectomy for left renal cell carcinoma, received a diagnosis of esophageal cancer. Three months later, he noticed a right thigh hematoma, and was transferred to our hospital. Laboratory data revealed a marked reduction of coagulation factor VIII (FVIII) activity at 0.9% and the inhibitor to FVIII was detected in his serum at 21.8 BU/ml. Under a diagnosis of AHA, the patient received high-dose oral prednisolone, which failed to achieve disease remission. He then underwent radiation therapy to eradicate the underlying esophageal cancer. Despite tapering of the prednisolone dosage, FVIII inhibitor declined to undetectable levels. In this case, radiation therapy for the underlying cancer was associated with achieving complete remission of AHA.

Development and validation of a new instrument for testing functional health literacy in Japanese adults.

This study aimed to develop a reliable and valid measure of functional health literacy in a Japanese clinical setting. Test development consisted of three phases: generation of an item pool, consultation with experts to assess content validity, and comparison with external criteria (the Japanese Health Knowledge Test) to assess criterion validity. A trial version of the test was administered to 535 Japanese outpatients. Internal consistency reliability, calculated by Cronbach's alpha, was 0.81, and concurrent validity was moderate. Receiver Operating Characteristics and Item Response Theory were used to classify patients as having adequate, marginal, or inadequate functional health literacy. Both inadequate and marginal functional health literacy were associated with older age, lower income, lower educational attainment, and poor health knowledge. The time required to complete the test was 10-15 min. This test should enable health workers to better identify patients with inadequate health literacy.

[Development of a short form of the Japanese big-five scale, and a test of its reliability and validity].

Personality scales based on the five-factor model, especially the big-five scale of personality trait adjectives (Wada, 1996), are commonly used in Japan. In this study a short form of the Big-Five Scale was constructed. To avoid changes in the capacity dimension caused by the decrease in the number of items, item selection was conducted after item response theory (IRT) scales were constructed for all the items. In study 1 data was collected from 2099 participants. A generalized partial credit model was applied to the IRT model, and items were selected using the slope and location parameters for each item. Cronbach's alpha showed that the short form, as well as the five sub-scales, had sufficient reliability as a personality test. In study 2, we determined correlations with the NEO-FFI and tested the concurrent validity of the short form. The results indicate that the short form of big-five scale demonstrates sufficient reliability and validity despite the reduced number of items.

Development of a Japanese version of the Epworth Sleepiness Scale (JESS) based on item response theory.

BACKGROUND: Various Japanese versions of the Epworth Sleepiness Scale (ESS) have been used, but none was developed via standard procedures. Here we report on the construction and testing of the developer-authorized Japanese version of the ESS (JESS). METHODS: Developing the JESS involved translations, back translations, a pilot study, and psychometric testing. We identified questions in the ESS that were difficult to answer or were inappropriate in Japan, proposed possible replacements for those questions, and tested them with analyses based on item response theory (IRT) and classical test theory. The subjects were healthy people and patients with narcolepsy, idiopathic hypersomnia, or obstructive sleep apnea syndrome. RESULTS: We identified two of our proposed questions as appropriate replacements for two problematic questions in the ESS. The JESS had very few missing data. Internal consistency reliability and test-retest reliability were high. The patients had significantly higher JESS scores than did the healthy people, and higher JESS scores were associated with worse daytime function, as measured with the Pittsburgh Sleep Quality Index. CONCLUSIONS: In Japan, the JESS provides reliable and valid information on daytime sleepiness. Researchers who use the ESS with other populations should combine their knowledge of local conditions with the results of psychometric tests.

Improving the measurement accuracy of the effort-reward imbalance scales.

BACKGROUND: The effort-reward imbalance (ERI) scale items are answered in a two-step process, but the justification is questioned for the formulation of summary measure by combining information rated in two steps. PURPOSE: To examine whether the basic prerequisites of the ERI scales are empirically satisfied and to seek ways to improve the rating procedure. METHODS: A polytomous item response theory (IRT) model was applied to the responses of 20,256 workers who completed the ERI scales. To determine the most appropriate statistical justification, three alternative scoring algorithms were compared with regard to the test properties revealed by the IRT analyses and efficiencies of screening performance and criterion validity against depressive symptomatology. RESULTS: The rated raw-score units did not reflect the hypothesized order of lowest stress levels to highest stress levels. Exchanging or collapsing the lowest two categories of a Likert scaled item, where data of different quality are combined, solved this problem, thereby making the test content more appropriate. The modified rating improved the efficiencies of screening performance and the correlation of the stress summary measures against health criterion, i.e., depression. CONCLUSION: An avoidable measurement error exists in the current ERI scales. Modifying the rating procedure can improve the measurement accuracy.

Validation of the Japanese version of the Quality of Life-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA).

OBJECTIVE: To evaluate validity and reliability of the Japanese version of the Quality of Life-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). DESIGN: Observational study; cross-sectional, longitudinal. METHODS: Seventy-five adults with growth hormone deficiency completed the SF-36 (a generic health-related QOL scale) and the QoL-AGHDA before growth hormone replacement therapy and approximately 3 weeks later (when the therapy began). A sample (n=1000) of controls from the general population was also studied. We computed rates of missing data, measured reproducibility and internal consistency reliability, and tested for known-groups validity, concurrent validity, unidimensionality (by principle component analysis), and content validity. RESULTS: Rates of missing data were low (0-1.4%). The mean of QoL-AGHDA scores in the patients was 8.2 (SD, 6.4). The scores were reproducible (k=0.41-0.78), and internally consistent (alpha=0.91) and the scale was unidimensional. QoL-AGHDA scores were associated with SF-36 scores as hypothesized. Scores were significantly higher in the patients than in controls (8.1+/-0.7, and 5.6+/-0.2, P<0.001). Discrimination between patients and controls was slightly better using scores on the "General Health" and "Role Physical" subscale of the SF-36 as explanatory variables than using QoL-AGHDA scores. CONCLUSIONS: The QoL-AGHDA's reliability, validity, and rates of missing data were satisfactory, and the scale was confirmed to be unidimensional. However, because some subscales of the SF-36 were better for discriminating patients from controls, the content validity of the QoL-AGHDA may need to be re-evaluated.

Iliopsoas abscess in the neonate.

Iliopsoas abscess (IPA) is rare, especially in the neonatal period. The major presenting symptoms of IPA are leg or groin swelling, limitation of leg motion, and pain. The etiologies of IPA in many cases remain unknown, and the etiologic agent in many cases is Staphylococcus aureus. Ultrasonography and computed tomography are useful in diagnosing this disease. Antibiotics therapy and appropriate drainage are effective, and the prognosis is good. The authors present a neonatal case of IPA and discuss clinical symptoms, etiologic agents, methods of diagnosis and therapy, and prognosis.

Cardiac lymphangioma: case report and review of the literature.

Cardiac lymphangioma is uncommon and constitutes one of the rare forms of cardiac diseases. A 6-year-old girl had an abnormal electrocardiogram in a screening test on admission to an elementary school. Echocardiogram, computed tomogram, and magnetic resonance imaging showed a mediastinal multicystic mass that was adjacent to the left ventricle of the heart. The tumor was found to be originated in myocardium by left thoracotomy and pericadiotomy. A partial resection of tumor and a pericardial window were done. This case, to the authors' knowledge, represents the sixth reported case of cardiac lymphangioma.

Does the external appearance of a Meckel's diverticulum assist in choice of the laparoscopic procedure?

In the era of laparoscopic surgery, the resection of a Meckel's diverticulum is a good indication for a laparoscopic procedure. In this paper, the relationship between the distribution of gastric heterotopia (GH) and the external appearance of the diverticulum was studied for the proper choice of the laparoscopic procedure. Symptomatic diverticula containing GH in eight patients were analyzed with regard to the distribution of gastric mucosa and the external appearance. While the long diverticula had the GH at the distal end, in the short diverticula it occurred in almost any area. For long diverticula, simple transverse resection with a stapling device is recommended. However, in short diverticula ileal resection with end-to-end anastomosis or wedge resection after exteriorization is recommended.