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During the coronavirus disease 2019 (COVID-19) pandemic, autopsies have provided valuable insights into the pathogenesis of COVID-19. The precise effect of this pandemic on autopsy procedures in Japan, especially in instances unrelated to COVID-19, has not yet been established. Therefore, we conducted a questionnaire survey from December 2020 to January 2021 regarding the status of pathological autopsy practices in Japan during the first year of the COVID-19 pandemic. The questionnaire was sent to 678 medical facilities with pathologists, of which 227 responded. In cases where a confirmed diagnosis of COVID-19 was not made at the time of autopsy, many facilities counted them as suspected COVID-19 cases if pneumonia was suspected clinically. At around half of the sites, autopsies were prohibited for suspected COVID-19 cases. In addition, the number of autopsies of non-COVID-19 cases during the pandemic period was also investigated, and a significant decrease was observed compared with the incidence in the pre-pandemic period. The COVID-19 pandemic has affected not only the autopsies of COVID-19 cases but also the entire practice of pathological autopsies. It is necessary to establish a system that supports the implementation of pathological autopsy practices during the pandemic of an emerging infectious disease.

Background The most common complication after tetralogy of Fallot repair is pulmonary valve regurgitation. However, concomitant surgery for tricuspid valve regurgitation and/or aortic dilatation is occasionally required. Case presentation A 56-year-old woman who underwent surgery for tetralogy of Fallot at age 29 years was diagnosed with progressive tricuspid valve regurgitation, hepatosplenomegaly, and thrombocytopenia. Moreover, computed tomography and transesophageal echocardiography revealed regurgitation in pulmonary and mitral valves and dilatation of the ascending aorta. One month after splenectomy for increasing platelet count, she underwent pulmonary valve replacement, tricuspid and mitral valve annuloplasty, and ascending aortic replacement. Postoperatively, the intensive care stay was complicated because of ventricular dysfunction and long-term ventilation. After 1 week, the patient was disconnected from the respirator, and she was transferred on the 55th postoperative day to another hospital for rehabilitation, without permanent disabilities. Conclusion We herein reported a patient with repaired TOF who successfully underwent PVR, tricuspid and mitral valve annuloplasty, and ascending aortic replacement.

The prevalence of the Omicron subvariant BA.2.75 is rapidly increasing in India and Nepal. In addition, BA.2.75 has been detected in at least 34 other countries and is spreading globally. However, the virological features of BA.2.75 are largely unknown. Here, we evaluated the replicative ability and pathogenicity of BA.2.75 clinical isolates in Syrian hamsters. Although we found no substantial differences in weight change among hamsters infected with BA.2, BA.5, or BA.2.75, the replicative ability of BA.2.75 in the lungs was higher than that of BA.2 and BA.5. Of note, BA.2.75 caused focal viral pneumonia in hamsters, characterized by patchy inflammation interspersed in alveolar regions, which was not observed in BA.5-infected hamsters. Moreover, in competition assays, BA.2.75 replicated better than BA.5 in the lungs of hamsters. These results suggest that BA.2.75 can cause more severe respiratory disease than BA.5 and BA.2 and should be closely monitored.

For patients who have previously undergone total laryngectomy and a permanent tracheostomy, median full sternotomy is not the ideal surgical approach because of the substantially increased risk of sternal wound complications and tracheal injuries. We present a case in which conventional coronary artery bypass grafting using bilateral internal thoracic arteries was performed safely via a manubrium-sparing sternotomy in a patient who had undergone total laryngectomy and a permanent tracheostoma. We also discuss the appropriate surgical approach for patients with total laryngectomy and a permanent tracheostoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12055-021-01309-8.

Introduction: Pulmonary agenesis is a complete absence of the pulmonary parenchyma, bronchi beyond the bifurcation, and pulmonary vasculature unilaterally or bilaterally. Because of the rare occurrence, its pathophysiology and outcome remain elusive. We evaluate the clinical features and risk factors for mortality due to pulmonary agenesis. Methods: Two patients we experienced are presented as index cases. All reported cases of pulmonary agenesis were collected from online and publication databases between 1955 and 2020. We assessed the impact of comorbidity and intervention on the survival outcome. Results: We identified 230 patients—138 (60%) with right-sided, and 14 (6%) with bilateral agenesis—among 164 articles and our cases. There were 93 (40%) cardiovascular, 70 (30%) skeletal, and 48 (21%) gastrointestinal anomalies; 47 (20%) tracheal stenoses; and 33 (14%) genitourinary anomalies. Fifty-two (23%) patients had isolated pulmonary agenesis. The 2-year overall survival (OS) rate was 66% and there was no subsequent death until 13 years of age. The right agenesis was significantly associated with a lower 2-year OS rate (58% vs. 78%, p=0.019) or more frequent tracheal stenosis (28% vs. 12%, p=0.006) than left-sided disease. A multivariable analysis indicated that tracheal stenosis (hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.5-4.1, p=0.004) and gastrointestinal anomaly (HR 1.9, 95% CI 1.1-3.3, p=0.018) were prognostic factors for mortality. Conclusions: The poor prognostic factors were tracheal stenosis, right agenesis and gastrointestinal anomaly. Tracheal and gastrointestinal controls are targeted at birth and in infancy for the improved survival of unilateral pulmonary agenesis.

A 55-year-old-man underwent laparoscopic sigmoidectomy for sigmoid colon cancer. Preoperative barium enema showed a slightly medial displacement of the descending colon, and the sigmoid colon was quite long. The operative findings showed that the descending colon was not fused with the retroperitoneum and shifted to the midline and the left colon adhered to the small mesentery and right pelvic wall. Thus, a diagnosis of persistent descending mesocolon (PDM) was made. The left colon, sigmoid colon, and superior rectal arteries often branch radially from the inferior mesenteric artery. The sigmoid mesentery shortens, and the inferior mesenteric vein is often close to the marginal vessels. By understanding the anatomical feature of PDM and devising surgical techniques, laparoscopic sigmoidectomy for sigmoid colon cancer with PDM could be performed without compromising its curative effect and safety.

Objective To search the predictive factors of infliximab resistance in intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) patients. Study design. Twenty-seven patients with KD who received infliximab after 4–5 g/kg of IVIG therapy from 2013 to 2015 were consecutively recruited in this study. They were divided into two groups: patients who responded to infliximab (infliximab-responsive group, n = 15) and patients who required additional therapy for the disease control (infliximab-resistant group, n = 12). We analyzed the clinical and laboratory parameters just before the infliximab treatment including serum levels of procalcitonin and cytokines with respect to the infliximab response. Results Serum procalcitonin concentration (P = 0.017), neutrophils to lymphocytes ratio (P = 0.013), and % neutrophils (P = 0.004) were higher, and serum sodium concentration (P = 0.017) was lower in infliximab-resistant group than those of infliximab-responsive group, respectively. Multivariate logistic regression analyses indicated that higher procalcitonin concentration (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.00–5.00, P = 0.046) and lower sodium levels (OR 0.64, 95% CI 0.32–1.00, P = 0.047), but not other variables, were associated with infliximab-resistance. Serum procalcitonin concentrations positively correlated with the serum levels of interleukin-6, soluble tumor necrosis factor receptor type 1 and type 2, respectively. Analyses of the receiver operating characteristic (ROC) curve showed that the cut-off value of procalcitonin 2.0 ng/ml had 58.3% of sensitivity and 93.3% of specificity. ROC analysis yielded an area under the curve (AUC) of 0.739 to predict infliximab-resistance. Conclusion Serum procalcitonin might be an effective biomarker to predict infliximab resistance in severe KD patients who are refractory to IVIG treatment.

No standard treatments have been established for airway hemorrhage during cardiopulmonary bypass (CPB). Herein, we describe two cases of catheter-induced pulmonary hemorrhage during cardiac surgery. In each case, massive hemoptysis was observed during cardiopulmonary bypass (CPB) weaning. A bronchial blocker was inserted into the right bronchus, and extracorporeal membrane oxygenation (ECMO) was initiated to reduce pulmonary blood flow, and stabilize the hemodynamics. ECMO significantly reduced bleeding from the pulmonary artery (PA). Both cases had favorable outcomes following the implementation of extracorporeal membrane oxygenation (ECMO). ECMO is effective at controlling PA bleeding during and after cardiac surgery.

Numerous dark-brown-coloured small spots called “Wischnewski spots” are often observed in the gastric mucosa in the patients dying of hypothermia, but the molecular mechanisms through which they develop remain unclear. We hypothesised that hypothermia may activate the secretion of gastric acid and pepsin, leading to the development of the spots. To investigate this, we performed experiments using organotypic rat gastric tissue slices cultured at 37 °C (control) or 32 °C (cold). Cold loading for 6 h lowered the extracellular pH in the culture medium. The mRNA expression of gastrin, which regulates gastric acid secretion, increased after cold loading for 3 h. Cold loading increased the expression of gastric H+,K+-ATPase pump protein in the apical canalicular membrane and resulted in dynamic morphological changes in parietal cells. Cold loading resulted in an increased abundance of pepsin C protein and an elevated mRNA expression of its precursor progastricsin. Collectively, our findings clarified that cold stress induces acidification by activating gastric H+,K+-ATPase pumps and promoting pepsin C release through inducing progastricsin expression on the gastric mucosa, leading to tiny haemorrhages or erosions of the gastric mucosa that manifest as Wischnewski spots in fatal hypothermia.

Rapid and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in dead bodies is essential to prevent infection among those working with dead bodies. This study focused on the Smart Amplification (SmartAmp) method, which has a short examination time (approximately an hour), is simple to perform, and demonstrates high specificity and sensitivity. This method has already been used for clinical specimens; however, its effectiveness in dead bodies has not been reported. This study examined the SmartAmp method using 11 autopsies or postmortem needle biopsies performed from January to May, 2021 (of these, five cases tested positive for SARS-CoV-2 by quantitative real-time polymerase chain reaction (qRT-PCR) and six cases tested negative). Swab samples were collected from the nasopharynx, oropharynx, or anus and the SmartAmp and qRT-PCR results were compared. For the nasopharynx and oropharynx samples, the same results were obtained for both methods in all cases; however, for the anal swabs, there was one case that was positive according to qRT-PCR but negative according to the SmartAmp method. The SmartAmp method may therefore be less sensitive than qRT-PCR and results may differ in specimens with a low viral load, such as anal swabs. However, in the nasopharynx and oropharynx specimens, which are normally used for testing, the results were the same using each method, suggesting that the SmartAmp method is useful in dead bodies. In the future, the SmartAmp method may be applied not only during autopsies, but also in various situations where dead bodies are handled.

Persistent sciatic artery (PSA) is a rare anomaly that may cause various symptoms, such as aneurysm, rupture, thromboembolism, and sciatica. Direct surgery can be performed to treat PSA aneurysm (PSAA), but is associated with complications; e.g., anatomical problems such as sciatic nerve injury. Herein we report a case of a 74-year-old woman with acute limb ischemia that developed from a distal embolism caused by a thrombus in the left PSAA; favorable results were obtained for her by treatment with a stent-graft after rapid anticoagulation therapy for limb salvage.

Case We report a 2-year-old boy with duodenal ulcer with active bleeding that occurred as a result of norovirus gastroenteritis. On admission, the patient presented with shock accompanied with vomiting and melena. Abdominal contrast enhanced computed tomography scan showed signs of duodenal bleeding. Outcome He was successfully treated with emergent transcatheter arterial embolization. After the treatment, endoscopic examination revealed duodenal ulcer and the stool norovirus antigen test was found to be positive. The patient recovered completely without any sequelae. Conclusion Life-threatening duodenal ulcer bleeding in children can be caused by viral gastroenteritis. When endoscopic therapy is unsuccessful or difficult, in cases of small children, angiographic intervention can be a safe alternative treatment option of gastrointestinal bleeding.

Background Dilatation of the ascending aorta affects those patients with bicuspid aortic valve (BAV), even after valvular surgery, possibly due to tissue fragility. The goal of the study was the molecular characterization of aorta with BAV compared to that with normal tricuspid aortic valve (TAV). Methods and Results: The subjects were patients who underwent surgery for aortic valve stenosis in 2013 and 2014. Nine patients with BAV and 13 with TAV were examined. There was no difference in the clinical characteristics or grade of aortic valve stenosis, but the diameters of the ascending aorta were significantly higher in the BAV group. The ascending aortic specimens were subjected to transcriptome analyses, which revealed the changes in receptor tyrosine kinase (RTK) pathway-related genes between TAV and BAV samples. Immunohistochemical study revealed higher staining of phosphorylated AKT (pAKT) in the media of the ascending aorta in the BAV group, regardless of the size of ascending aorta, whereas total AKT did not show such a difference. Immunofluorescence staining revealed the AKT activation was mainly in the medial vascular smooth muscle cells. Conclusions The results showed that the RTK-AKT pathway in the medial layer of the ascending aorta is activated in aortae with BAV. Activation of this pathway may be associated with fragility and dilatation of the ascending aorta with BAV.

An 8-year-old girl presenting with fulminant myocarditis and cardiogenic shock underwent peripheral extracorporeal membrane oxygenation. She was switched to central extracorporeal membrane oxygenation because of inadequate venous drainage, and an echocardiogram showed left ventricular (LV) thrombus. She underwent removal of the LV thrombus with LV venting. An echocardiogram showed LV thrombus again 2 days later. The LV thrombus was again removed, and a biventricular assist device support was initiated to avoid further thrombus formation. The patient was completely weaned from mechanical circulatory support after 7 days. She recovered fully without any neurologic deficit.

Accretionary prisms are mainly composed of ancient marine sediment scraped from the subducting oceanic plate at a convergent plate boundary. Large amounts of anaerobic groundwater and natural gas, mainly methane (CH4) and nitrogen gas (N2), are present in the deep aquifers associated with an accretionary prism; however, the origins of these gases are poorly understood. We herein revealed regional variations in CH4 and N2 production processes in deep aquifers in the accretionary prism in Southwest Japan, known as the Shimanto Belt. Stable carbon isotopic and microbiological analyses suggested that CH4 is produced through the non-biological thermal decomposition of organic matter in the deep aquifers in the coastal area near the convergent plate boundary, whereas a syntrophic consortium of hydrogen (H2)-producing fermentative bacteria and H2-utilizing methanogens contributes to the significant production of CH4 observed in deep aquifers in midland and mountainous areas associated with the accretionary prism. Our results also demonstrated that N2 production through the anaerobic oxidation of organic matter by denitrifying bacteria is particularly prevalent in deep aquifers in mountainous areas in which groundwater is affected by rainfall.

In most patients with aortic regurgitation (AR), aortic valve replacement (AVR) improves left ventricular (LV) function, but some patients will not have favorable remodeling. Our objectives were to review long term clinical results of AVR for AR and to examine what factors affect the normalization of LV function after AVR for chronic AR.Between 1989 and 2010, 177 patients underwent isolated AVR for chronic pure AR. The patients were divided into 2 groups based on indexed end-systolic LV diameter (iESD): Group L (iESD) ≥25 mm/m(2)) (130 patients) and Group S (iESD25 mm/m(2)) (47 patients).There was no significant difference between groups in late mortality, freedom from cardiac-related death and rehospitalization for heart failure at late follow up after operation. At postoperative follow-up, 16% of patients had not recovered normal LV systolic function. By means of multivariate analysis, iESD and cardiac index (CI) were independent predictors of recovery of LV function and iESD26.7 mm/m(2) and CI2.71 l/min/m(2) were the best cut-off values.Early and late surgical results of AVR for chronic AR were good, but for the preservation of postoperative normal LV function, AVR for AR patients should be performed before iESD reaches 26.7 mm/m(2).

There is limited information available regarding the role of infliximab (IFX) following the acute phase of Kawasaki disease (KD). We aimed to evaluate whether IFX is associated with coronary artery aneurysm (CAA) regression.Between 2005 and 2016, we identified 971 consecutive patients with KD from 3 tertiary institutions, and 49 (5%) with CAAs were enrolled in our study. Patients were divided into 2 groups: 27 who received IFX and 22 who did not. The persistence rate of CAAs was compared between the groups.Age, sex, and duration of the febrile period did not significantly differ between the groups. The maximum value of C-reactive protein was higher in the IFX- than in the non-IFX group. The maximum z-score of CAAs did not differ between the groups. The 2-, 4- and 6-year cumulative persistence rate of CAA was 24%, 24% and 24% in IFX-group, whereas 67%, 52% and 33% in non-IFX group, respectively (P = 0.03). The median duration of CAA regression was 1.1 vs. 4.6 years. Among those who developed medium- or large-sized CAAs, the 2-, 4- and 6-year cumulative persistence rate of CAA was 33%, 33% and 33% in IFX group, whereas 77%, 51% and 48% in non-IFX group, respectively (P = 0.047). Multivariate logistic regression analysis indicated that the maximum z-score (hazard ratio 0.72, p 0.001) and response to IFX (hazard ratio 4.56, p = 0.017) were independently related to regression.IFX therapy was observed to be effective for the early improvement of CAAs in patients with intravenous immunoglobulin-resistant KD.

AimIt is estimated that 1–5% of sudden infant death syndrome (SIDS) cases might be caused by undiagnosed inborn errors of metabolism (IEMs); however, the postmortem identification of IEMs remains difficult. This study aimed to evaluate the usefulness of dried blood spots (DBSs) stored after newborn screening tests as a metabolic autopsy to determine the causes of death in infants and children who died suddenly and unexpectedly.MethodsInfants or toddlers who had suddenly died without a definite diagnosis between July 2008 and December 2012 at Kyushu University Hospital in Japan were enrolled in this study. Their Guthrie cards, which had been stored for several years at 4–8°C, were used for an acylcarnitine analysis by tandem mass spectrometry to identify inborn errors of metabolism.ResultsFifteen infants and children who died at less than 2 years of age and for whom the cause of death was unknown were enrolled for the study. After correcting the C0 and C8 values assuming the hydrolysation of acylcarnitine in the stored DBSs, the corrected C8 value of one case just exceeded the cut-off level for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency screening. Genetic and biochemical analyses confirmed this patient to have MCAD deficiency.ConclusionDBSs stored after newborn screening tests are a promising tool for metabolic autopsy. The appropriate compensation of acylcarnitine data and subsequent genetic and biochemical analyses are essential for the postmortem diagnosis of inborn errors of metabolism.

OBJECTIVE Congenital portosystemic venous shunt (CPSVS) is a rare vascular malformation with a high risk of mortality from pulmonary arterial hypertension (PAH), but the treatment outcome of CPSVS closure remains elusive. Our aim was to investigate the clinical features and establish the optimal management of CPSVS with or without PAH. METHODS Twenty-four patients with CPSVS treated in Kyushu University Hospital between 1990 and 2015 were enrolled in this study. The patients were divided into a PAH group (n = 9) and a non-PAH group (n = 15). Clinical characteristics and outcomes were evaluated. RESULTS The first manifestation of CPSVS at diagnosis (28.5 [1-216] months) was hypergalactosemia in 13 (54%) or PAH in six (25%) patients. PAH was the cause of all three deaths. The PAH group had higher levels of serum total bile acid, manganese, and total bilirubin, along with higher pulmonary vascular resistance index (PVRI) than the non-PAH group (7.2 [5.1-38.1] vs 1.2 [0.5-3.3] unit/m2 , P

OBJECTIVE Chronic inflammation plays a key role in the development of atherosclerosis. Early progression of atherosclerosis has been reported in patients with RA. Cryopyrin-associated periodic syndromes (CAPS) are autosomal dominant autoinflammatory disorders caused by heterozygous NLRP3 gene mutations. Chronic infantile neurological cutaneous and articular (CINCA) syndrome is the most severe form of CAPS and patients display early onset of rash, fever, uveitis and joint manifestations. However, there has been no previous report on atherosclerosis in patients with CAPS. The objective of this study is to assess the development of atherosclerosis in patients with CINCA syndrome. METHODS Intima-media thickness (IMT) of the carotid arteries, stiffness parameter β, ankle brachial index (ABI) and pressure wave velocity (PWV) were evaluated by ultrasonography in 3 patients with CINCA syndrome [mean age 9.0 years (S.D. 5.3)] and 19 age-matched healthy controls [9.3 years (S.D. 4.3)]. RESULTS The levels of carotid IMT, stiffness parameter β and PWV in CINCA syndrome patients were significantly higher than those in healthy controls [0.51 mm (S.D. 0.05) vs 0.44 (0.04), P = 0.0021; 6.1 (S.D. 1.7) vs 3.9 (1.0), P = 0.0018; 1203 cm/s (S.D. 328) vs 855 (114), P = 0.017, respectively]. CONCLUSION Patients with CINCA syndrome showed signs of atherosclerosis from their early childhood. The results of this study emphasize the importance of chronic inflammation in the development of atherosclerosis. Further analysis on atherosclerosis in young patients with CINCA syndrome may provide more insights into the pathogenesis of cardiovascular disease.

Purpose: Pulmonary valve replacement (PVR) improves right ventricular (RV) function in patients with tetralogy of Fallot (TOF). However, the impact of PVR on left ventricular (LV) function and the mechanism of improvement are still unclear. The purpose of this study is to clarify the impact of PVR on LV mechanical efficiency in adult patients with TOF. Methods: Fourteen patients with TOF (age 30.1±11.5 years) who underwent PVR for significant pulmonary insufficiency were enrolled in this study. We measured left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), contractility (end-systolic elastance; Ees), afterload (effective arterial elastance; Ea), and mechanical efficiency (ventriculoarterial coupling; Ea/Ees and the rate of stroke work and pressure-volume area; SW/PVA) on the basis of the echocardiographic data before, after and late after PVR. Ees, Ea and SW/PVA were approximated as follows: Ees=mean arterial pressure/minimal ventricular volume, Ea = maximal ventricular pressure / (maximal ventricular volume-minimal ventricular volume), and SW/PVA=1 / (1 + 0.5 Ea/Ees). Results: LVEDVI, stroke volume and ejection fraction increased significantly after PVR. Contractility (Ees) did not change but afterload (Ea) decreased, and LV mechanical efficiency (Ea/Ees and SW/PVA) improved significantly. These changes were observed just after PVR, and further improvement was not noted in the late period. ![Figure][1] Hemodynamic changes after PVR Conclusions: LV efficiency improves after PVR. Increased pulmonary forward flow and relief of the compression from the RV increase LVEDVI and stroke volume. LV afterload decreases to adapt the increase of stroke volume without the change of contractility. These changes result in the improvement of LV mechanical efficiency. [1]: pending:yes