Prevalence, Temporal Change, and Determinants of Anxiety and Depression in Hospitalized Patients With Heart Failure.

BACKGROUND: Anxiety and depression may be under-recognized in patients with heart failure (HF). We therefore investigated the prevalence and temporal change of these symptoms in hospitalized patients with HF. METHODS AND RESULTS: We prospectively evaluated consecutive hospitalized patients with HF using the Hospital Anxiety and Depression Scale (HADS) on admission and at discharge. The HADS-A (anxiety) and HADS-D (depression) scores were categorized as follows; 0-7, no symptoms; 8-10, mild; and 11-21, significant anxiety or depression. Symptom worsening was defined as the HADS category at discharge being poorer than that on admission. Of 224 patients (mean age 77.5 years), 35 (16%) and 62 (28%) had significant symptoms of anxiety and depression, respectively. During hospitalization, the HADS-A significantly decreased (on admission; median 6 [interquartile range (IQR) 3-9] vs at discharge; median 4 [IQR 2-7], P < .01), whereas the HADS-D did not improve (on admission; median 8 [IQR 5-11] vs at discharge; median 8 [IQR 4-11], P =.82). Anxiety and depression worsened during hospitalization in 19 (10%) and 40 (21%) patients, respectively. Advanced age, higher natriuretic peptide levels, and acute-on-chronic HF were associated with worsening anxiety, and longer hospitalization length was associated with worsening depression. CONCLUSIONS: Anxiety and depression were common and depression persisted during HF hospitalization.

Three Autopsy Cases of Non-Meningococcal Waterhouse-Friderichsen Syndrome with Hypoplastic Spleen or Post-Splenectomy Status.

We report three cases of Waterhouse-Friderichsen syndrome (WFS) that were confirmed during forensic autopsies. Case 1 involved a man in his 50s post-splenectomy. Bacteriological examination revealed Streptococcus pneumoniae (S. pneumonia). The patient was considered to have died of asphyxiation after aspirating vomit. Case 2 involved a man in his 40s. Bacteriological examination again revealed S. pneumoniae. Histopathological examination showed hypoplasia of the spleen. This patient was considered to have died of multiple-organ failure due to sepsis, disseminated intravascular coagulation, and WFS. Case 3 involved a post-splenectomy woman in her 60s with a history of systemic lupus erythematosus. Bacteriological examination revealed Streptococcus oralis. This patient was considered to have died of multiple-organ failure due to sepsis, disseminated intravascular coagulation, and WFS. These three cases were included among forensic autopsies conducted in the last 5 years. WFS has been considered a rare disease, but may be more frequent than previously assumed. If a mildly ill patient displays a sudden change in status and dies within a short period of time, we consider it necessary to perform not only bacteriological examinations, but also histopathological examination of the spleen during autopsy.

Successful treatment with atezolizumab combination chemotherapy in a patient with high-grade fetal adenocarcinoma of the lung: A case report.

High-grade fetal lung adenocarcinoma (H-FLAC) is a rare tumor, with little known of its response to chemotherapy with or without an immune checkpoint inhibitor or of its molecular profile. We report the first case of a 56-year-old man with stage IV H-FLAC who was successfully treated with carboplatin plus nab-paclitaxel in combination with atezolizumab. In addition, the tumor was found to be positive for amplification of the human epidermal growth factor receptor 2 gene.

Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencing.

Even though the mother and the fetus of placental mammals are immunologically non-self with respect to one other, mutual exchange of small numbers of cells between them is known to occur. Maternal cells entering the fetus, called maternal microchimeric cells (MMc cells), are thought to be involved in different physiological phenomena, such as establishing immune tolerance, tissue repair, and the pathogenesis or deterioration of some inflammatory diseases and congenital malformations. While specific MMc cell types have been reported as associated with these phenomena, the contribution of MMc cells to these different outcomes remains unknown. As one possibility, we hypothesized that different embryos have differing repertoires of MMc cell types, leading to or biasing embryos toward different fates. To date, no studies have succeeded in identifying the MMc cell type repertoire of a single embryo. Accordingly, here, we isolated MMc cells from whole mouse embryos, determined their types, and analyzed their MMc cell type variability. By combining our previously established, whole-embryonic MMc isolation method with single-cell RNA sequencing, we successfully estimated the cell type repertoires of MMc cells isolated from 26 mouse embryos. The majority of MMc cells were immune-related cells, such as myeloid cells and granulocytes. We also detected stem cell-like MMc cells expressing proliferation marker genes and terminally differentiated cells. As hypothesized, we noted statistically significant inter-individual variation in the proportion of immune-related cells in the different embryos. We here successfully estimated MMc cell types in individual whole mouse embryos. The proportion of immune-related cells significantly differed among the individual embryos, suggesting that the variations are one of the potential mechanisms underlying the differing MMc-related physiological phenomena in offspring. These findings provide insight into cell-level epigenetics by maternal cells.

Treatment with Sotrovimab and Casirivimab/Imdevimab Enhances Serum SARS-CoV-2 S Antibody Levels in Patients Infected with the SARS-CoV-2 Delta, Omicron BA.1, and BA.5 Variants.

Background: The neutralizing ability of sotrovimab and casirivimab/imdevimab against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is attenuated in the subvariant BA.5. However, the efficacy of sotrovimab in the clinical setting remains to be investigated. Methods: Patients admitted to Kishiwada City Hospital with COVID-19 delta, omicron BA.1, or BA.5 subvariants were evaluated retrospectively for serum SARS-CoV-2 S and N antibody levels using the Elecsys Anti-SARS-CoV-2 assay. Results: In patients with COVID-19 during the BA.5 wave of the COVID-19 pandemic, anti-SARS-CoV-2 S antibody titers (median [interquartile range]) increased from 2154.0 (864.0−6669.3) U/mL on day 0 to 21,371.0 (19,656.3−32,225.0) U/mL on day 3 in the group treated with sotrovimab (N = 40) and were significantly higher than in the group treated with remdesivir plus dexamethasone plus baricitinib (p < 0.001). Conclusion: Treatment with sotrovimab could prevent severe disease in high-risk patients infected with SARS-CoV-2 subvariant BA.5.

Assessment of lateral pterygoid muscle and temporomandibular joint disc after Le Fort I osteotomy with and without intentional pterygoid plate fracture and sagittal split ramus osteotomy in class II and class III patients.

The aim of the study was to examine lateral pterygoid muscle (LPM) and temporomandibular joint (TMJ) disc before and after Le Fort I osteotomy with and without intentional pterygoid plate fracture and sagittal split ramus osteotomy (SSRO) in class II and class III patients. Le Fort I osteotomy and SSRO were performed in class II and class III patients. LPM measurements using oblique sagittal computed tomography (CT) images and TMJ disc position using magnetic resonance imaging (MRI) were examined. Statistical comparisons were performed for the LPM and TMJ between class II and class III patients and between those with and without intentional pterygoid plate fracture in Le Fort I osteotomy. The subjects comprised 60 female patients (120 sides), with 30 diagnosed as class II and 30 as class III. Preoperatively, the width of the condylar attachment, width at eminence, length of the LPM, angle of the LPM, and square of the LPM were significantly smaller in the class II group than in the class III group (p < 0.05). After 1 year, the width of the condylar attachment, width at eminence, and angle of the LPM remained significantly smaller in the class II group than in the class III group (p < 0.0001). TMJ disc position was significantly related to the width of the condylar attachment of the LPM, both pre- and postoperatively (p < 0.0001). However, postoperative disc position did not change in all patients. Next, the class II patients (60 sides) were divided into two groups who underwent Le Fort I osteotomy with or without intentional pterygoid plate fracture. Changes in all measurements of the LPM showed no significant differences between these two groups. Our study suggested that TMJ disc position classification could be associated with the width of condylar attachment of the LPM before and after surgery, while the surgical procedure, including Le Fort I osteotomy with intentional pterygoid plate fracture, might not affect postoperative LMP or disc position in class II patients.

Poor prognosis of patients with severe COVID-19 admitted to an infectious disease intensive care unit during the pandemic caused by the Delta variant in Japan.

During the surge of coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) delta variant, our institution operated an intensive care unit (ICU) for patients with severe COVID-19. The study aim was to determine the survival rate and treatment outcomes of patients with severe COVID-19 treated in the ICU during the surge. A total of 23 consecutive patients with severe COVID-19 were admitted to the ICU between August 5 and October 6, 2021. Patients received multidrug therapy consisting of remdesivir, tocilizumab, heparin, and methylprednisolone. The patients were divided into two groups based on the ordinal scale (OS): a non-invasive oxygen therapy (OS-6) group, and an invasive oxygen therapy (OS-7) group. There were 13 (57%) and 10 (43%) patients in the OS-7 and OS-6 groups, respectively. All patients were unvaccinated. Sixteen patients (70%) were male. The median age was 53 years; the median body mass index (BMI) was 30.3 kg/m2; and the median P/F ratio on admission was 96. The 30-day survival rate was 69% and was significantly poorer in the OS-7 group (54%) than in the OS-6 group (89%; p = 0.05). The prevalence of obesity (p = 0.05) and the Sequential Organ Failure Assessment (SOFA) score on admission (p < 0.01) were significantly higher in the OS-7 group. Seven patients in the OS-7 group (54%) developed bacteremia. A low P/F ratio on admission was a significant unfavorable prognostic factor (hazard ratio: 10.9; p = 0.03). The survival rate was poor, especially in patients requiring invasive oxygen therapy. More measures are needed to improve the treatment outcomes of patients with severe COVID 19.

Comprehensive symptom assessment using Integrated Palliative care Outcome Scale in hospitalized heart failure patients.

AIMS: Patients with heart failure (HF) may have variable unrecognized symptom burdens. We sought to investigate the details, determinants, and prognostic significance of symptom burden in hospitalized patients with HF. METHODS AND RESULTS: We prospectively evaluated consecutive hospitalized patients with HF as primary diagnosis at our institution using the Integrated Palliative care Outcome Scale (IPOS) both on admission and at discharge. The IPOS, which is a well-validated multi-dimensional symptom assessment scale among advanced illness, consists of 17 questions for enquiring about physical symptoms (10 items), emotional symptoms (4 items) and communication and practical issues (3 items) using a 5-point Likert scale (0 [best]-4 [worst] points). Clinically relevant symptoms were defined as ≥2 points for each IPOS item. Worsening symptom burden was defined as the total IPOS score at discharge being poorer than that on admission. Of 294 patients (mean age: 77.5 ± 12.0 years, male: 168 patients, New York Heart Association class IV: 96 patients, mean left ventricular ejection fraction [LVEF]: 44%, and median N-terminal pro B-type natriuretic peptide [NT-proBNP] level: 4418 ng/L), the median (IQR) total IPOS score on admission was 19 (12, 27) and they were widely distributed (minimum: 0 - maximum: 52). The total IPOS score on admission was not correlated with the HF severity, including LVEF (Spearman's ρ = -0.05, P = 0.43), NT-proBNP levels (Spearman's ρ = 0.08, P = 0.20) or in-hospital mortality prediction model (GWTG-HF risk score) (Spearman's ρ = 0.01, P = 0.90). Total IPOS scores significantly decreased during hospitalization as a whole (median [IQR]: 13 [6, 21] at discharge; P < 0.001 vs. those on admission). All of the four emotional symptoms (patient anxiety, depression, family anxiety and feeling at peace) remained in the top 5 of clinically relevant symptoms at discharge, whereas none of 10 physical symptoms were nominated. Worsening symptom burden was noted in 28% of the patients during hospitalization, and was independently associated with higher all-cause mortality after discharge (hazard ratio: 2.28, 95% confidence interval: 1.02-5.09; P = 0.044) even after adjustment by age and HF mortality prediction model (MAGGIC risk score). CONCLUSIONS: We revealed that hospitalized patients with HF had multi-dimensional symptom burdens which varied among individuals and were not correlated with the disease severity. Emotional symptoms, such as anxiety and depression, were the main clinically relevant symptoms at discharge. A worsening IPOS score was noted in a quarter of patients with HF and was associated with a poor prognosis, suggesting the importance of holistic symptom assessment during the course of hospitalization for HF.

Highly sensitive sex determination method using the exon 1 region of the amelogenin gene.

Sex determination is a crucial factor in the identification of unidentified human remains. Sex determination by DNA analysis is particularly useful because it can be applied to samples for which morphological characteristics are unavailable. Because samples handled in forensic DNA typing are easily degraded by environmental factors and microorganisms, there is a need for a method that can accurately determine sex even in highly decayed samples. Previous studies mainly used sex differences in an intron of the amelogenin gene. However, this region is highly polymorphic, and there are cases where accurate sexing cannot be performed because of genetic mutations in the target region. Thus, for reliable sex determination, it is desirable to select loci with as few non-sexual polymorphisms as possible. In this study, we focused on the exon 1 region of the amelogenin gene, which has very little polymorphism other than sex differences. We developed a primer set for sex determination and compared it with the GlobalFiler™ PCR Amplification Kit (GF), which is widely used for forensic DNA typing. The results showed that the amount of DNA required for accurate sex determination was 25 pg for both methods, achieving equivalent sensitivity. Next, we compared the two methods using ancient human skeletons and found that the present method with its shorter amplicon was considerably superior to GF. The present method is simple, rapid, inexpensive, and suitable for analyzing highly degraded samples. Therefore, this method is expected to contribute to forensic sciences and physical anthropology.

Whole embryonic detection of maternal microchimeric cells highlights significant differences in their numbers among individuals.

During pregnancy in placental mammals, small numbers of maternal cells (maternal microchimeric cells, or MMc cells) migrate into the fetus and persist decades, or perhaps for the rest of their lives, and higher frequencies of MMc cells are reported to correlate with variety of phenomena, such as immune tolerance, tissue repair, and autoimmune diseases. While detection of these MMc cells is considered in all pregnancies, their frequency differs largely according to tissue type and disease cases, and it remains unclear whether the number of MMc cells differs significantly among embryos in normal pregnancies. Here, for the first time, we developed a whole embryonic detection method for MMc cells using transgenic mice and counted live MMc cells in each individual embryo. Using this technique, we found that the number of MMc cells was comparable in most of the analyzed embryos; however, around 500 times higher number of MMc cells was detected in one embryo at the latest stage. This result suggests that the number of MMc cells could largely differ in rare cases with unknown underlying mechanisms. Our methodology provides a basis for testing differences in the numbers of MMc cells among individual embryos and for analyzing differences in MMc cell type repertoires in future studies. These data could provide a hint toward understanding the mechanisms underlying the variety of apparently inconsistent MMc-related phenomena.

Computed tomography assessment of mandibular morphologic changes and the inferior mandibular border defect after sagittal split ramus osteotomy.

OBJECTIVE: This study aimed to assess mandibular morphologic changes to the condyle, ramus, mandibular body, and inferior mandibular border defect after sagittal split ramus osteotomy in class II and III patients. STUDY DESIGN: The relationships among the condyle, ramus, and mandibular body measured by computed tomography preoperatively and postoperatively were assessed and factors related to the reduction of the condylar square and mandibular inferior border defect were examined. RESULTS: Patients included 72 female patients with jaw deformity (36 skeletal class II cases, 36 skeletal class III cases). Postoperative reduction of the condylar square was significantly correlated with preoperative condylar height in patients with class II (P = .0297) vs preoperative condylar height and preoperative mandibular height in patients with class III (P < .0001). A mandibular inferior border defect was found in 18 of 72 class II sides (25.0%) and was significantly related to the position of the osteotomy line and attachment side of the inferior border cortex (P < .0001). CONCLUSIONS: This study's findings suggest that the postoperative reduction of the condyle could be associated with preoperative condylar height. However, the mandibular inferior border defect in class II advancement surgery could be independently associated with technical factors in sagittal split ramus osteotomy.

Evaluation of condylar surface CT values related to condylar height reduction after orthognathic surgery.

This study was performed to evaluate the relationship between condylar height reduction and changes in condylar surface computed tomography (CT) values in jaw deformity patients following orthognathic surgery. Mandibular advancement by sagittal split ramus osteotomy (SSRO) with Le Fort I osteotomy was performed in class II patients, and mandibular setback by SSRO with Le Fort I osteotomy was performed in class III patients. The maximum CT values (pixel values) at five points on the condylar surface and the condylar height, ramus height, condylar square, ramus angle, and gonial angle in the sagittal plane were measured preoperatively and 1 year postoperatively. Disc position was classified as anterior disc displacement (ADD) or other types by using magnetic resonance imaging (MRI). Ninety-two condyles of 46 female patients were prepared for this study. Their temporomandibular joints (TMJs) were divided into two groups based on class (46 joints in class II and 46 joints in class III) and two groups based on the findings (25 joints with ADD and 67 joints with other findings). ADD with and without reduction was observed in two joints in the class III group and in 23 joints in the class II group. The distribution of ADD incidence had not changed 1 year after surgery. Condylar height decreased 1 year after surgery in both class II patients (mandibular advancement) (p < 0.0001) and class III patients (mandibular setback) (p = 0.0306). Similarly, condylar height decreased 1 year after surgery both in patients who showed ADD (p = 0.0087) and those with other types (p = 0.0023). Significant postoperative increases at all angle sites on the condylar surface were found in the class II (p < 0.05) and ADD (p < 0.05) groups. This study showed that an enhanced condylar surface CT value might be one sign of condylar height reduction related to sequential condylar resorption, in combination with ADD.