Syndecan-1 as a prognostic biomarker in COVID-19 patients: a retrospective study of a Japanese cohort.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact, with millions of confirmed cases and deaths worldwide. While most cases are mild, a subset progresses to severe respiratory complications and death, with factors such as thromboembolism, age, and underlying health conditions increasing the risk. Vascular endothelial damage has been implicated in severe outcomes, but specific biomarkers remain elusive. This study investigated syndecan-1 (SDC-1), a marker of endothelial damage, as a potential prognostic factor for COVID-19, focusing on the Japanese population, which is known for its aging demographics and high prevalence of comorbidities. METHODS: A multicenter retrospective study of COVID-19 patients in Fukushima Prefecture in Japan who were admitted between February 2020 and August 2021 was conducted. SDC-1 levels were measured along with other clinical and laboratory parameters. Outcomes including thrombosis, 28-day survival, and disease severity were assessed, and disease severity was categorized according to established guidelines. RESULTS: SDC-1 levels were correlated with disease severity. Patients who died from COVID-19 had greater SDC-1 levels than survivors, and the area under the receiver operating characteristic curve (AUC) analysis suggested the potential of the SDC-1 level as a predictor of mortality (AUC 0.714). K‒M analysis also revealed a significant difference in survival based on an SDC-1 cutoff of 10.65 ng/mL. DISCUSSION: This study suggested that SDC-1 may serve as a valuable biomarker for assessing COVID-19 severity and predicting mortality within 28 days of hospitalization, particularly in the Japanese population. However, further investigations are required to assess longitudinal changes in SDC-1 levels, validate its predictive value for long-term survival, and consider its applicability to new viral variants. CONCLUSIONS: SDC-1 is emerging as a potential biomarker for assessing the severity and life expectancy of COVID-19 in the Japanese population, offering promise for improved risk stratification and patient management in the ongoing fight against the virus.

Development and external validation of the DOAT and DOATS scores: simple decision support tools to identify disease progression among nonelderly patients with mild/moderate COVID-19.

BACKGROUND: During the fifth wave of the coronavirus disease 2019 (COVID-19) pandemic in Japan, which took place between June and September 2021, a significant number of COVID-19 cases with deterioration occurred in unvaccinated individuals < 65 years old. However, the risk factors for COVID-19 deterioration in this specific population have not yet been determined. This study developed a prediction method to identify COVID-19 patients < 65 years old who are at a high risk of deterioration. METHODS: This retrospective study analyzed data from 1,675 patients < 65 years old who were admitted to acute care institutions in Fukushima with mild-to-moderate-1 COVID-19 based on the Japanese disease severity criteria prior to the fifth wave. For validation, 324 similar patients were enrolled from 3 hospitals in Yamagata. Logistic regression analyses using cluster-robust variance estimation were used to determine predictors of disease deterioration, followed by creation of risk prediction scores. Disease deterioration was defined as the initiation of medication for COVID-19, oxygen inhalation, or mechanical ventilation starting one day or later after admission. RESULTS: The patients whose condition deteriorated (8.6%) tended to be older, male, have histories of smoking, and have high body temperatures, low oxygen saturation values, and comorbidities, such as diabetes/obesity and hypertension. Stepwise variable selection using logistic regression to predict COVID-19 deterioration retained comorbidities of diabetes/obesity (DO), age (A), body temperature (T), and oxygen saturation (S). Two predictive scores were created based on the optimism-corrected regression coefficients: the DOATS score, including all of the above risk factors, and the DOAT score, which was the DOATS score without oxygen saturation. In the original cohort, the areas under the receiver operating characteristic curve (AUROCs) of the DOATS and DOAT scores were 0.81 (95% confidence interval [CI] 0.77-0.85) and 0.80 (95% CI 0.76-0.84), respectively. In the validation cohort, the AUROCs for each score were both 0.76 (95% CI 0.69-0.83), and the calibration slopes were both 0.80. A decision curve analysis confirmed the clinical practicability of both scores in the validation cohort. CONCLUSIONS: We established two prediction scores that can quickly evaluate the risk of COVID-19 deterioration in mild/moderate patients < 65 years old.

Real-world clinical outcomes of treatment with casirivimab-imdevimab among patients with mild-to-moderate coronavirus disease 2019 during the Delta variant pandemic.

Background: Mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reduce the efficacy of neutralizing monoclonal antibody therapy against coronavirus disease 2019 (COVID-19). We here evaluated the efficacy of casirivimab-imdevimab in patients with mild-to-moderate COVID-19 during the Delta variant surge in Fukushima Prefecture, Japan. Methods: We enrolled 949 patients with mild-to-moderate COVID-19 who were admitted to hospital between July 24, 2021 and September 30, 2021. Clinical deterioration after admission was compared between casirivimab-imdevimab users (n = 314) and non-users (n = 635). Results: The casirivimab-imdevimab users were older (P < 0.0001), had higher body temperature (≥ 38°C) (P < 0.0001) and greater rates of history of cigarette smoking (P = 0.0068), hypertension (P = 0.0004), obesity (P < 0.0001), and dyslipidemia (P < 0.0001) than the non-users. Multivariate logistic regression analysis demonstrated that receiving casirivimab-imdevimab was an independent factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.263-0.763; P = 0.0023). Furthermore, in 222 patients who were selected from each group after matching on the propensity score, deterioration was significantly lower among those receiving casirivimab-imdevimab compared to those not receiving casirivimab-imdevimab (7.66% vs 14.0%; p = 0.021). Conclusion: This real-world study demonstrates that casirivimab-imdevimab contributes to the prevention of deterioration in COVID-19 patients after hospitalization during a Delta variant surge.

Acute Gastric Volvulus Successfully Treated by Endoscopic Reduction in a 6-Year-Old Girl and a Review of the Japanese Literature.

A previously healthy 6-year-old girl suddenly developed severe abdominal pain and nausea. She was diagnosed with acute gastric volvulus, and a nasogastric tube was inserted to decompress the stomach. The volvulus did not reduce spontaneously; therefore, we performed endoscopic reduction on day 3 and were able to treat her successfully. We reviewed the Japanese literature on endoscopic reduction for gastric volvulus in children. Fifteen cases have been reported since 1994. There are no reports of perforation during the procedure. Patients whose general condition is stable and who have no severe anatomic anomalies are good candidates for endoscopic reduction.

Real-world clinical outcomes of treatment with molnupiravir for patients with mild-to-moderate coronavirus disease 2019 during the Omicron variant pandemic.

It is unclear whether molnupiravir has a beneficial effect on vaccinated patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We here evaluated the efficacy of molnupiravir in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron variant surge in Fukushima Prefecture, Japan. We enrolled patients with mild-to-moderate COVID-19 who were admitted to hospitals between January and April, 2022. Clinical deterioration after admission was compared between molnupiravir users (n = 230) and non-users (n = 690) after 1:3 propensity score matching. Additionally, we performed forward stepwise multivariate logistic regression analysis to evaluate the association between clinical deterioration after admission and molnupiravir treatment in the 1:3 propensity score-matched subjects. The characteristics of participants in both groups were balanced as indicated by covariates with a standardized mean difference of < 0.1. Regarding comorbidities, there was no imbalance between the two groups, except for the presence of hypertension, dyslipidemia, diabetes mellitus, and cardiac disease. The clinical deterioration rate was significantly lower in the molnupiravir users compared to the non-users (3.90% vs 8.40%; P = 0.034). Multivariate logistic regression analysis demonstrated that receiving molnupiravir was a factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.206-0.973; P = 0.042), independent of other covariates. This real-world study demonstrates that molnupiravir contributes to the prevention of deterioration in COVID-19 patients after hospitalization during the Omicron variant phase.

Functional evaluation of an artificial anal sphincter using shape memory alloys.

This article describes an implantable artificial anal sphincter using shape memory alloys and its in vivo assessment in porcine models. The new design was developed as a low invasive prosthesis with a simple structure to solve the problem of severe fecal incontinence in patients with hypoplastic sphincters or without anal sphincters and especially for ostomates. The artificial anal sphincter consists of two shape memory alloy (SMA) plates as the main functional parts to perform two basic functions when the SMA artificial sphincter is fitted around intestines (i.e., an occlusion at body temperature and an opening function on heating). Our previous assessments with short-term animal experiments revealed promising properties with the occlusion function of the device, although some complications, such as overpressure induced ischemia, heat burn, and infections, remained. This article addresses the concerns related to the practical use of the device, the power supplement to drive the actuator, and overheating protection of the device inside bodies. Results of chronic animal experiments of up to 4 weeks suggested great potential for the improved device.

[Gastroesophageal reflux in neurologically impaired children].

We present here the indication, procedure and results of surgical treatment of gastroesophageal reflux (GER) for neurologically impaired children. We decide its indication based on clinical symptoms and findings of upper GI series, esophageal pH monitoring and GI fiberscopy, respecting the QOL of the patient and family. Laparoscopic fundoplication has become the first choice in surgical treatment of GER because of its good results. However, an anti-reflux procedure is not effective in patients with intractable aspiration. A laryngotracheal separation procedure should be applied for these cases.

Postoperative psychological status of children with anorectal malformations.

Our purpose was to clarify factors that influence the level of depression of Japanese children with anorectal malformations (ARM). The subjects comprised 66 children with ARM, aged 0-16 years, and their mothers. Patients were divided into three groups (Group 1: aged 0-5 years, Group 2: 6-11 years, and Group 3: 12-16 years). The level of depression of the children aged 6-16 years was investigated by Kovac's children's depression inventory (CDI). The psychological status of their mothers was assessed by Spielberger's state-trait anxiety index (STAI) and Zung's self-rating depression scale (SDS). The classification of ARM and the clinical condition were also investigated. Defecation scores were assigned for the degree of bowel dysfunction. The level of depression in the patients was more marked in Group 3 than in Group 2 according to the CDI score. Significant correlations between the CDI score of the child and the STAI-1, STAI-2 and SDS scores of the mother were observed in Group 2, but not in Group 3. In Group 2, the STAI-1 score of the mothers was significantly influenced by the degree of bowel dysfunction in her child. In Group 3, the CDI score was significantly correlated with the constipation score. This study revealed that bowel dysfunction is the important factor that influences the level of depression of the children with ARM. In the period of childhood during which the child attends primary school, bowel dysfunction indirectly influences the level of depression of children through the psychological status of mothers. However, bowel dysfunction directly influences the level of depression of children in adolescent patients.

Social adaptation of children with congenital fecal dysfunction: from the viewpoint of the mother-child relationship.

Excretory dysfunction associated with congenital anal anomalies (a generic term that includes anal atresia and Hirschsprung's disease) is presumed to greatly affect the psychology of the affected children. In this study, we conducted a survey on the psychological status of children with excretory dysfunction, and investigated the relationship between the affected children and their families in addition to their social life. Four children with fecal dysfunction due to a congenital anal anomaly and their mothers were interviewed. The results of psychological tests in the children and mothers along with our findings in the interviews with the children and mothers, were included in the data analysis. We found that regardless of the degree of excretory dysfunction, the child's state of mind was influenced by whether the mother exhibited warmth or criticism towards her child and whether there was a support system for the mother and child. We suggest that psychiatric consultation is necessary for these children.

Psychosocial liaison-consultation for the children who have undergone repair of imperforate anus and Hirschsprung disease.

OBJECTIVE: The aim of this study was to investigate the psychological status of Japanese children with congenital anorectal malformation and their mothers to develop appropriate psychiatric interventions. METHOD: The subjects comprised 50 children with congenital anorectal malformation aged 0 to 16 years and their mothers. The psychology of children aged 7 to 16 years was investigated by Kovacs' Children's Depression Inventory (CDI). The psychology of their mothers was assessed by Spielberger's State-Trait Anxiety Index (STAI) and Zung's Self-rating Depression Scale (SDS). RESULTS: Depression was more marked in the children aged 12 to 16 years than in those aged 7 to 11 years according to the CDI. The mothers of preschool children showed higher levels of anxiety and depression than those of school-aged children, according to the STAI and SDS. Significant correlations between the CDI score of the children and the STAI or SDS score of the mothers were observed only among children aged 7 to 11 years. CONCLUSIONS: The frequency of depression and anxiety among children with congenital anorectal malformation and that among their mothers was associated with the age of the child. Long-term postoperative psychosocial support for the children and their mothers may be required, taking into account the age of the child.

Clinical characteristics and management of congenital esophageal stenosis: a report on 14 cases.

PURPOSE: The aim of this study was to review 14 patients with congenital esophageal stenosis (CES) from diagnostic and therapeutic points of view. METHODS: From 1976 to 1999, 14 patients with CES were treated at the authors' hospital. In each diagnostic examination, an esophagogram, 24-hour pH monitoring, a manometric study, and an endoscopy were performed. The medical, radiologic, and operative reports of these patients were reviewed. RESULTS: Esophagogram results showed an abrupt stenosis in 5 patients and a tapered stenosis in 9. After 24-hour pH monitoring and an endoscopy, we were able to rule out the possibility of gastroesophageal reflux with esophagitis in most of the patients. Of the 11 patients who initially underwent bougienage or balloon dilatation, 8 of them had recurrent stenosis. Eleven patients required surgical treatment, including the 8 who had recurrent stenosis after undergoing dilatation. Nine of the patients underwent a resection of the stenotic segment and esophago-esophagostomy. An antireflux procedure was performed on 2 patients. Another patient had an esophageal rupture, which required a jejunal interposition. A histopathologic study showed that tracheobronchial remnants were present in 6 patients, and fibromuscular thickening was found in 4 patients. CONCLUSIONS: The efficacy of dilatation seems to be limited and may even result in severe complications such as an esophageal rupture. In this study, most patients ultimately required surgical treatment. Surgical repair for CES is the authors' preferred treatment, although initial dilatation may be effective for some patients.

Biliary atresia with associated complicated anorectal and urogenital malformations.

We report on a girl with biliary atresia (BA) who also suffered with anorectal agenesis without fistula and complicated urogenital malformation. The outcome of patients with these severe anomalies is poor, but she has survived without liver and/or renal transplantation for more than 3 years. A careful treatment plan for each anomaly in addition to prevention of cholangitis and urinary tract infection is indispensable for managing these complicated anomalies.

Development of an implantable artificial anal sphincter using a shape memory alloy.

BACKGROUND/PURPOSE: The authors created a new artificial anal sphincter using a shape memory alloy (AS-SMA) to treat fecal incontinence and evaluated its validity. METHODS: AS-SMA consists of 2 Ti-Ni plates to sandwich the intestine and generates a pressure of 55 mm Hg at its resting position. With the electric power supply, the 2 metals bend to form an almondlike shape making a maximum gap of 33 mm between each other at the temperature of 55 degrees C. The device was attached to the colostomy in a piglet and was operated several times a day for 1 month. Fecal continence, bowel movements, and general condition of the piglet were recorded. After the experiment, tissue damage around the device was investigated. RESULTS: Fecal continence was obtained while the device was in the resting position. When it was operated, bowel movements were observed. The bowel movements to operations ratio was 82:105 (78%). During the experiment, the animal had neither abdominal distension nor vomiting. At the autopsy, there was mild inflammation and shallow burns around the device. No compression injury was detected. CONCLUSIONS: AS-SMA achieved fecal continence of the colostomy. With reduction of the associated side effects, it would be a potential substitute for an impaired anal sphincter.

Recent progress in artificial organ research at Tohoku University.

Tohoku University has developed various artificial organs over the last 30 years. Pneumatic driven ventricular assist devices with a silicone ball valve have been designed by the flow visualization method, and clinical trials have been performed in Tohoku University Hospital. On the basis of these developments, a pneumatic driven total artificial heart has been developed and an animal experimental evaluation was conducted. The development of artificial organs in Tohoku University has now progressed to the totally implantable type using the transcutaneous energy transmission system with amorphous fibers for magnetic shielding. Examples of implantable systems include a vibrating flow pump for ventricular assist device, an artificial myocardium by the use of shape memory alloy with Peltier elements, and an artificial sphincter for patients with a stoma. An automatic control system for artificial organs had been developed for the ventricular assist devices including a rotary blood pump to avoid suction and to maintain left and right heart balance. Based upon the technology of automatic control algorithm, a new diagnostic tool for evaluating autonomic nerve function has been developed as a branch of artificial organ research and this new machine has been tested in Tohoku University Hospital. Tohoku University is following a variety of approaches aimed at innovation in artificial organs and medical engineering fields.