[Defining sensitivity and specificity for quality control of organized cancer screening using Prefectural Cancer Registry data in Japan].

Objective　To decrease cancer mortality by implementing cancer screening programs, rigorous quality control measures that utilize standardized indicators are imperative. In Japan, although each municipality performing cancer screening programs implements quality control for their programs using the checklist authorized by the Ministry of Health, Labour and Welfare, compliance with all the items listed is not possible because calculating sensitivity and specificity using cancer registry data is difficult under these circumstances. This report elucidates the methodology for calculating indicators, including sensitivity and specificity, by delineating the parameters of false-negative cases within population-based cancer screening programs in Japan. Furthermore, the inherent challenges associated with ensuring the quality control of cancer screening procedures are expounded upon in this report.Method　Data from the Prefectural Cancer Registry of Japan and cancer screening records compiled by municipalities were used to differentiate true-positive, true-negative, false-positive, and false-negative cases based on the combination of screening test outcomes and subsequent cancer incidence.Results　A false-negative case was defined as an examinee who received a cancer diagnosis within one year after undergoing the screening test, notwithstanding the negative judgment of the cancer screening decision. The duration for judgment of true-positive, true-negative, and false-negative cases was also extended to one year. Cancer identification after cancer screening was ascertained using data from the Prefectural Cancer Registry, ensuring uniform categorization of the four cases. Subsequently, sensitivity and specificity values were calculated for municipalities conducting cancer screening programs.Conclusion　Sensitivity and specificity are indispensable metrics for the inherent quality control of cancer screening because these parameters directly assess the efficacy of screening tests. The anticipated increase in the number of municipalities engaged in comprehensive quality control of cancer screening in Japan is poised to enhance the efficiency of cancer control policies. This augmentation will be accomplished through the meticulous utilization of the sensitivity and specificity values elucidated in the present report. The forthcoming challenges involve the proliferation of medical institutes reporting their adherence to the checklist stipulated by the National Cancer Center of Japan and the widespread dissemination of fundamental knowledge pertaining to cancer screening.

Whole genome sequencing and pan-genome analysis of Staphylococcus/Mammaliicoccus spp. isolated from diabetic foot ulcers and contralateral healthy skin of Algerian patients.

BACKGROUND: Diabetic foot infections (DFIs) are the most common complications of diabetic foot ulcers (DFUs), and a significant cause of lower extremity amputation. In this study we used whole genome sequencing to characterize the clonal composition, virulence and resistance genetic determinants of 58 Staphylococcus/Mammaliicoccus spp. isolates from contralateral healthy skin and DFU from 44 hospitalized patients. RESULTS: S. aureus (n = 32) and S. epidermidis (n = 10) isolates were recovered from both DFUs and healthy skin, whereas, S. haemolyticus (n = 8), M. sciuri (n = 1), S. hominis (n = 1) and S. simulans (n = 3) were recovered exclusively from healthy skin. In contrast, S. caprae (n = 2) and S. saprophyticus (n = 1) were recovered only from DFUs. Among S. aureus isolates, MRSA were present with high prevalence (27/32, 84.4%), 18 of which (66.7%) were from DFUs and 9 (33.3%) from healthy skin. In contrast, the coagulase-negative Staphylococcus (CoNS)/Mammaliicoccus isolates (n = 26), in particular S. epidermidis and S. haemolyticus were more prevalent in healthy skin, (10/26, 38.5%) and (8/26, 30.8%), respectively. MLST, spa and SCCmec typing classified the 32 S. aureus isolates into 6 STs, ST672, ST80, ST241, ST1, ST97, ST291 and 4 unknown STs (STNF); 8 spa types, t044, t037, t3841, t1247, t127, t639, t937 and t9432 and 2 SCCmec types, type IV and type III(A). Among CoNS, the S. epidermidis isolates belonged to ST54, ST35 and ST640. S. haemolyticus belonged to ST3, ST25, ST29, ST1 and ST56. The sole M. sciuri isolate was found to carry an SCCmec type III(A). A wide range of virulence genes and antimicrobial resistance genes were found among our isolates, with varying distribution between species or STs. The pan-genome analysis revealed a highly clonal population of Staphylococcus isolates, particularly among S. aureus isolates. Interestingly, the majority of S. aureus isolates including MRSA, recovered from the healthy skin and DFUs of the same patient belonged to the same clone and exhibited similar virulence/resistance genotype. CONCLUSIONS: Our study provides clinically relevant information on the population profile, virulence and antibiotic resistance of Staphylococcus/Mammaliicoccus spp. in DFIs, which could serve as a basis for further studies on these as well as other groups of pathogens associated with DFIs.

Haplotype networks of SARS-CoV-2 infections in the Diamond Princess cruise ship outbreak.

The Diamond Princess cruise ship was put under quarantine offshore Yokohama, Japan, after a passenger who disembarked in Hong Kong was confirmed as a coronavirus disease 2019 case. We performed whole-genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly from PCR+ clinical specimens and conducted a phylogenetic analysis of the outbreak. All tested isolates exhibited a transversion at G11083T, suggesting that SARS-CoV-2 dissemination on the Diamond Princess originated from a single introduction event before the quarantine started. Although further spreading might have been prevented by quarantine, some progeny clusters could be linked to transmission through mass-gathering events in the recreational areas and direct transmission among passengers who shared cabins during the quarantine. This study demonstrates the usefulness of haplotype network/phylogeny analysis in identifying potential infection routes.

[Giant Bullae Misdiagnosed as Pneumothorax:Report of a Case].

A 46-year-old man was taken to a hospital by ambulance because of sudden onset of dyspnea, and was inserted chest drainage tube with a diagnosis of right-sided tension pneumothorax on chest X-ray. Since the chest drainage was not effective, he was transferred to our institute. Based on chest computed tomography (CT) findings, a diagnosis of giant bullae of the right lung was made, and surgical treatment was performed. Postoperatively, the improvement of respiratory function was confirmed.

Synthesis of 2-hydroxytetrahydrofurans by Wacker-type oxidation of 1,1-disubstituted alkenes.

1,1-Disubstituted alkenes feature high steric hindrance, which renders their Wacker-type oxidation difficult. We demonstrate the stereoselective synthesis of 2-hydroxytetrahydrofurans via the Wacker-type oxidation of 3-methyl-3-buten-1-ols by using a PdCl2(MeCN)2/NO/BQ catalyst system under 1 atm O2 in H2O or H2O/DMF.

Postoperative anastomotic stricture following excision of choledochal cyst: a systematic review and meta-analysis.

PURPOSE: Postoperative anastomotic stricture (PAS) is a well-known complication after correcting choledochal cyst (CC). Although the exact cause of PAS is unknown, various risk factors, such as Todani classification type IV-A, hepaticoduodenostomy, and narrow anastomosis have been reported to be associated with PAS. As far as we know, there is no report with a cumulative analysis of such risk factors of PAS. This systematic review and meta-analysis aimed to investigate the risk factors of PAS following surgical correction of CC in children. METHODS: A systematic literature search for relevant articles was performed in four databases using the combinations of the following terms "Congenital biliary dilatation", "Congenital choledochal cyst", "Choledochal cyst", "Stenosis", "Stricture", and "Complication" for studies published between 1973 and 2022. The relevant cohorts of PAS were systematically searched for clinical presentation and outcomes. RESULTS: The search strategy identified 795 reports. Seventy studies met the defined inclusion criteria, reporting a total of 206 patients with PAS. There is no prospective study in this search. The incidence of PAS was 2.1%. The proportion of Todani classification of the patient with PAS was higher in type IV-A with significant difference (2.0% in type I and 10.1% in type IV-A (p = 0.001)). Fourteen studies reported a comparison between hepaticojejunostomy and hepaticoduodenostomy. There was no significant difference between the two groups (p = 0.36). Four studies reported the diameter of the anastomosis at the primary surgery. The mean diameter was 12.5 mm. Nine studies reported a comparison between laparoscopic surgery and open surgery. Pooled odds ratio of PAS did not show a statistical difference (p = 0.29). CONCLUSIONS: This study suggests that close careful follow-up is important in the patients with type IV-A of CC who underwent excision surgery, considering the possibility of PAS.

Surveillance in hospitalized children with infectious diseases in Japan: Pre- and post-coronavirus disease 2019.

INTRODUCTION: The epidemic of coronavirus disease 2019 (COVID-19) rapidly spread worldwide, and the various infection control measures have a significant influence on the spread of many infectious diseases. However, there have been no multicenter studies on how the number of hospitalized children with various infectious diseases changed before and after the outbreak of COVID-19 in Japan. METHODS: We conducted a multicenter, prospective survey for hospitalized pediatric patients in 18 hospitals in Hokkaido Prefecture, Japan, from July 2019 to February 2021. We defined July 2019 to February 2020 as pre-COVID-19, and July 2020 to February 2021 as post-COVID-19. We surveyed various infectious diseases by sex and age. RESULTS: In total, 5300 patients were hospitalized during the study period. The number of patients decreased from 4266 in the pre-COVID-19 period to 701 (16.4%) post-COVID-19. Patients with influenza and RSV decreased from 308 to 795 pre-COVID-19 to zero and three (0.4%) post-COVID-19. However, patients with adenovirus (respiratory infection) only decreased to 60.9% (46-28) of pre-COVID levels. Patients with rotavirus, norovirus, and adenovirus gastroenteritis decreased markedly post-COVID-19 to 2.6% (38-1), 27.8% (97-27) and 13.5% (37-5). The number of patients with UTIs was similar across the two periods (109 and 90). KD patients decreased to 31.7% (161-51) post-COVID-19. CONCLUSIONS: We suggest that current infection control measures for COVID-19 such as wearing masks, washing hands, and disinfecting hands with alcohol are effective against various infectious diseases. However, these effects vary by disease.

Clinical Outcomes and Medical Costs of Hydration Therapy with Hydroxyethyl Starch (130/0.4) or Acute Single Infarction.

OBJECTIVES: To investigate the effects of hydration with or without Hydroxyethyl Starch (HES) 130/0.4 on neurological outcomes and medical costs during hospitalisation in patients with a single infarction (SI) in the posterior lenticulostriate artery (LSA) territory. MATERIALS AND METHODS: In this retrospective, single-centre, non-blinded cohort study, SI in the posterior LSA was defined as an ischaemic lesion with a high-signal intensity area ≥20 mm. All patients received basic stroke care within 48 h of symptom onset between April 2015 and January 2019. Patients were divided into the following two groups by clinician's preference: 1) those administered HES 130/0.4 and 2) those receiving other infusion fluid. The relationships between hospital costs and hydration therapy type were examined. RESULTS: Eighteen (31%) of 58 patients received HES 130/0.4. The HES group had a significantly lower total cost than the control group (3.6 vs. 6.4 million yen, p=0.006). Moreover, the HES group had a significantly shorter hospital stay duration (79.5 vs. 141.0 days) and lower National Institutes of Health Stroke Scale score on day 7. Multivariate analysis found that HES 130/0.4 administration was an independent factor associated with high costs. CONCLUSIONS: Hydration therapy with HES 130/0.4 significantly decreased the total costs and hospitalisation duration of patients with SI in the posterior LSA territory.

Exercise endurance capacity is markedly reduced due to impaired energy homeostasis during prolonged fasting in FABP4/5 deficient mice.

BACKGROUND: Skeletal muscle prefers carbohydrate use to fatty acid (FA) use as exercise intensity increases. In contrast, skeletal muscle minimizes glucose use and relies more on FA during fasting. In mice deficient for FABP4 and FABP5 (double knockout (DKO) mice), FA utilization by red skeletal muscle and the heart is markedly reduced by the impairment of trans-endothelial FA transport, with an increase in glucose use to compensate for reduced FA uptake even during fasting. We attempted to determine whether prolonged fasting affects exercise performance in DKO mice, where constant glucose utilization occurs. RESULTS: A single bout of treadmill exercise was performed in the fed and fasted states. The initial speed was 10 m/min, and gradually increased by 5 m/min every 5 min up to 30 m/min until the mice stopped running. Running distance was significantly reduced by DKO genotype and prior fasting, leading to the shortest distance in fasted DKO mice. Levels of glycogen in skeletal muscle and the liver were nearly depleted in both WT and DKO mice during prolonged fasting prior to exercise. Levels of TG in skeletal muscle were not reduced by exercise in fasted DKO mice, suggesting that intramuscular TG was not utilized during exercise. Hypoglycaemia was accelerated in fasted DKO mice, and this acceleration could be due to constant glucose utilization by red skeletal muscle and the heart where FA uptake is diminished due to defective trans-endothelial FA transport. Taken together, energy supply from serum and storage in skeletal muscle were very low in fasted DKO mice, which could lead to a significant reduction in exercise performance. CONCLUSIONS: FABP4/5 have crucial roles in nutrient homeostasis during prolonged fasting for maintaining exercise endurance capacity.

[Preoperative Chemotherapy and Risk Factors for Colorectal Liver Metastases].

Between February 2007 and December 2013, 65 liver resections for colorectal metastases were performed in our institution. Preoperative chemotherapy was conducted in 47 patients, of whom 42 were treated with modified FOLFOX6 (mFOLFOX6)-based preoperative chemotherapy. For cases of solitary tumors smaller than 2 cm that are located in the liver surface area, we selected upfront surgery. In the patients who underwent preoperative chemotherapy and upfront surgery, the 3-year OS was 73.9% (Grade A: 81.8%, Grade B: 77.8%, and Grade C: 0%) and the 5-year OS was 62.5%. The 3-year OS in the preoperative chemotherapy group was 63.3%. OS did not differ significantly between the patients who were grouped according to the time of metastasis onset or the extent of metastasis according to the Japanese classification. In the multivariate analysis, no statistical differences were found between the risk factors for recurrence. However, further follow up is needed. Moreover, we believe that the relationships of morphological response to chemotherapy, pathological response, and clinical prognosis should be assessed in the future.

Long-term survival and conditional survival of cancer patients in Japan using population-based cancer registry data.

Although we usually report 5-year cancer survival using population-based cancer registry data, nowadays many cancer patients survive longer and need to be followed-up for more than 5 years. Long-term cancer survival figures are scarce in Japan. Here we report 10-year cancer survival and conditional survival using an established statistical approach. We received data on 1,387,489 cancer cases from six prefectural population-based cancer registries in Japan, diagnosed between 1993 and 2009 and followed-up for at least 5 years. We estimated the 10-year relative survival of patients who were followed-up between 2002 and 2006 using period analysis. Using this 10-year survival, we also calculated the conditional 5-year survival for cancer survivors who lived for some years after diagnosis. We reported 10-year survival and conditional survival of 23 types of cancer for 15-99-year-old patients and four types of cancer for children (0-14 years old) and adolescent and young adults (15-29 years old) patients by sex. Variation in 10-year cancer survival by site was wide, from 5% for pancreatic cancer to 95% for female thyroid cancer. Approximately 70-80% of children and adolescent and young adult cancer patients survived for more than 10 years. Conditional 5-year survival for most cancer sites increased according to years, whereas those for liver cancer and multiple myeloma did not increase. We reported 10-year cancer survival and conditional survival using population-based cancer registries in Japan. It is important for patients and clinicians to report these relevant figures using population-based data.

Changes in pathological and biochemical findings of systemic tissue sites in familial amyloid polyneuropathy more than 10†years after liver transplantation.

OBJECTIVE: To elucidate the long-term effects of liver transplantation (LT) on familial amyloid polyneuropathy (FAP). METHODS: We investigated clinicopathological and biochemical characteristics of systemic tissues in four autopsied cases of FAP patients surviving more than 10 years after LT and seven autopsied cases without LT. For analysing the truncated form of transthyretin (TTR) in amyloid, we also employed specimens from additional 18 FAP patients. RESULTS: Several tissue sites such as the heart, tongue and spinal cord had moderate-to-severe amyloid deposits but other tissues showed no or mild amyloid deposition. Those findings seemed similar to those observed in senile systemic amyloidosis (SSA), a sporadic amyloidosis caused by wild-type (WT) TTR. Also, amyloid deposits in systemic tissue sites except for the spinal cord in patients after LT derived mostly from WT TTR secreted from the normal liver grafts. In addition, in non-transplantation patients, proportions of WT TTR seemed to be relatively high in those tissue sites in which patients after LT had severe amyloid deposition, which suggests that WT TTR tends to form amyloid in those tissue sites. Finally, although the truncation of TTR in amyloid deposits did not depend on undergoing LT, we elucidated the truncation of TTR occurred predominantly in patients from non-endemic areas of Japan, where FAP amyloidogenic TTR V30M patients are late onset and low penetrance, compared with patients from an endemic area of Japan. CONCLUSIONS: FAP may shift to systemic WT TTR amyloid formation after LT, which seems to be similar to the process in SSA. The truncation of TTR in amyloid deposits may depend on some genetic or environmental factors other than undergoing LT.

Risk Factors Contributing to Disparities in Medical Treatment and Lower Survival Rates among Patients with Non-Small Cell Lung Cancer Induced by Residential Areas.

OBJECTIVE: Because of a lack of medical resources for cancer treatment, particularly in rural areas, there are disparities in receiving medical treatment between urban and rural area. This study examined the association between residential area or areal deprivation index (ADI) and lack of surgical treatment or chemotherapy in patients with non-small cell lung cancer (NSCLC) in rural area, Japan. METHODS: We analyzed the Aomori population-based cancer registry data from 926 cancer patients with NSCLC diagnosed between January and December 2014. Multivariable logistic regression and Cox proportional hazards models were used to examine association of patients' residential area/ADI with either surgery/chemotherapy or survival time, respectively. The residential area was divided into six medical areas based on the location of specialist hospitals. The medical areas were defined by Aomori Prefecture. RESULTS: The residential area (medical area) was strongly associated with access to cancer treatment for patients with NSCLC and ultimately contributed to lower survival rates. There was no significant influence in the distance from home to hospital and areal deprivation. CONCLUSION: We identified the risk factors related to a lack of medical treatment and shorter survival in rural area, Japan.

On the fence: Combining multimodal imaging and laparoscopy for diagnosing tuberculous peritonitis.

Tuberculous peritonitis (TB peritonitis) is one of the most challenging forms of extrapulmonary TB to diagnose. While tumor markers can be elevated in patients with TB peritonitis, FDG-PET/CT can aid in distinguishing TB peritonitis from malignancies, if an apron-like omentum pattern is seen. Laparoscopy is crucial for accurate and early diagnosis.

A PKG inhibitor increases Ca(2+)-regulated exocytosis in guinea pig antral mucous cells: cAMP accumulation via PDE2A inhibition.

In antral mucous cells, acetylcholine (ACh, 1 µM) activates Ca(2+)-regulated exocytosis, consisting of an initial peak that declines rapidly (initial transient phase) followed by a second slower decline (late phase) lasting during ACh stimulation. The addition of 8-bromo-cGMP (8-BrcGMP) enhanced the initial phase, which was inhibited by the protein kinase G (PKG) inhibitor guanosine 3',5'-cyclic monophosphorothoiate, ß-phenyl-1,N(2)-etheno-8-bromo, Rp-isomer, sodium salt (Rp-8-BrPETcGMPS, 100 nM). However, Rp-8-BrPETcGMPS produced a delayed, but transient, increase in the exocytotic frequency during the late phase that was abolished by a protein kinase A (PKA) inhibitor (PKI-amide), suggesting that Rp-8-BrPETcGMPS accumulates cAMP. The cGMP-dependent phosphodiesterase 2 (PDE2), which degrades cAMP, may exist in antral mucous cells. The PDE2 inhibitor BAY-60-7550 (250 nM) mimicked the effect of Rp-8-BrPETcGMPS on ACh-stimulated exocytosis. Measurement of the cGMP and cAMP contents in antral mucosae revealed that ACh stimulates the accumulation of cGMP and that BAY-60-7550 accumulates cAMP similarly to Rp-8-BrPETcGMPS during ACh stimulation. Analyses of Western blot and immunohistochemistry demonstrated that PDE2A exists in antral mucous cells. In conclusion, Rp-8-BrPETcGMPS accumulates cAMP by inhibiting PDE2 in ACh-stimulated antral mucous cells, leading to the delayed, but transient, increase in the frequency of Ca(2+)-regulated exocytosis. PDE2 may prevent antral mucous cells from excessive mucin secretion caused by the cAMP accumulation.

Cultural differences in explicit and implicit support provision and underlying motivations for self-esteem, closeness, and relational concerns.

This research explores how culture influences the motivations underlying explicit (emotional and instrumental) and implicit (companionship and attentiveness) support provision. Two studies (N = 1,106) compared the responses of European Americans and Japanese individuals to a close other's stressful event. The results showed that European Americans were more likely than Japanese to provide explicit support and more motivated to increase the close other's self-esteem and feeling of closeness. Conversely, Japanese individuals were more likely to provide attentiveness support, motivated by concern for an entire group and a friend. These findings support the motivation as a mediator hypothesis. On the other hand, the culture as a moderator hypothesis applied to the association between concern for an entire group motivation and implicit support provision. Specifically, concern for an entire group motivation predicted companionship support provision only in Japanese, while it predicted attentiveness support provision mainly in European Americans.

Study on enteral nutrient components causing decreased gastric phenytoin absorption.

BACKGROUND: Previously, we revealed that coadministration of particular enteral nutrients (ENs) decreases plasma concentrations and gastric absorption of phenytoin (PHT), an antiepileptic drug, in rats; however, the mechanism has not been clarified. METHODS: We measured the permeability rate of PHT using a Caco-2 cell monolayer as a human intestinal absorption model with casein, soy protein, simulated gastrointestinal digested casein protein (G-casein or P-casein) or simulated gastrointestinal digested soy protein (G-soy or P-soy), dextrin, sucrose, degraded guar gum, indigestible dextrin, calcium, and magnesium, which are abundant in the ENs, and measured the solution's properties. RESULTS: We demonstrated that casein (40 mg/ml), G-soy or P-soy (10 mg/ml), and dextrin (100 mg/ml) significantly decreased the permeability rate of PHT compared with the control. By contrast, G-casein or P-casein significantly increased the permeability rate of PHT. We also found that the PHT binding rate to casein 40 mg/ml was 90%. Furthermore, casein 40 mg/ml and dextrin 100 mg/ml have high viscosity. Moreover, G-casein and P-casein significantly decreased the transepithelial electrical resistance of Caco-2 cell monolayers compared with casein and the control. CONCLUSION: Casein, digested soy protein, and dextrin decreased the gastric absorption of PHT. However, digested casein decreased PHT absorption by reducing the strength of tight junctions. The composition of ENs may affect the absorption of PHT differently, and these findings would aid in the selection of ENs for orally administered PHT.

Assay of enzymes forming AMP+PPi by the pyrophosphate determination based on the formation of 18-molybdopyrophosphate.

The formation of 18-molybdopyrophosphate anion has been studied to develop a simple and rapid assay of the enzymatic reaction involving ATP→AMP+PPi(P(2)O(7)(4-)). By the addition of P(2)O(7)(4-) anion to an acidic acetonitrile-water solution containing MoO(4)(2-) anion, the colorless Mo(VI) solution immediately became yellow due to the formation of 18-molybdopyrophosphate anion. The absorbance of the P(2)O(7)(4-)-Mo(VI) mixture at, for example, 450nm was proportional to the analytical concentration of P(2)O(7)(4-) anion. Although the test Mo(VI) solution remained colorless by the addition of AMP, it gradually turned to yellow by ATP. The undesired color development is attributed to the formation of a yellow molybdophosphate species accompanied by the dissociation of PO(4)(3-) from the unstable ATP molecule. However, the color development became much slower when ethylenediaminetetraacetic acid was added into an assay mixture, where ATP may form a kinetically stable species. Thus, P(2)O(7)(4-) anion can be determined spectrophotometrically in the enzymatic reaction mixture containing ATP. By the addition of ascorbic acid, the yellow P(2)O(7)(4-)-Mo(VI) mixture turned to blue due to the reduction of the molybdopyrophosphate anion. Thus, P(2)O(7)(4-) anion can be detected colorimetrically by the blueness. The spectrophotometric and colorimetric methods could be applied advantageously to the assay of acetyl-CoA synthetase.