Adherence to and clinical utility of "quality indicators" for Staphylococcus aureus bacteremia: a retrospective, multicenter study.

BACKGROUND: We aimed to improve the prognosis, treatment, and management of Staphylococcus aureus bacteremia (SAB) by evaluating the association between adherence to quality indicators (QIs) and clinical outcomes in patients with their clinical outcomes. METHODS: We retrospectively collected clinical and microbiological data on hospitalized patients with SAB from 14 hospitals (three with > 600, two with 401-600, five with 201-400, and four with ≤ 200 beds) in Japan from January to December 2022. The SAB management quality was evaluated using the SAB-QI score (ranging from 0 to 13 points), which consists of 13 QIs (grouped into five categories) based on previous literature. RESULTS: Of the 4,448 positive blood culture episodes, 289 patients with SAB (6.5%) were enrolled. The SAB-QI scores ranged from 3 to 13, with a median score of 9 points. The SAB-QI score was highest in middle-sized hospitals with 401-600 beds. Adherence to each of the four QI categories (blood culture, echocardiography, source control, and antibiotic treatment) was significantly higher in survived cases than in fatal cases. Kaplan-Meier curves with log-rank tests demonstrated that higher adherence to SAB-QIs indicated a better prognosis. Logistic regression analysis revealed that age, methicillin resistance, multiple comorbidities (≥ 2), and low SAB-QI score were significantly associated with 30-day mortality in patients with SAB. CONCLUSIONS: Our study highlights that greater adherence to the SAB-QIs correlates with improved patient outcomes. Management of patients with SAB should follow these recommended indicators to maintain the quality of care, especially for patients with poor prognosticators.

Threat of Staphylococcus aureus Pneumonia in Severe COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) has been spreading worldwide with unprecedented rapidity. Staphylococcus aureus is reported to frequently cause bacterial complications in patients with COVID-19. We herein present two additional cases of S. aureus pneumonia involving such patients. The first case was an obese 48-year-old man without any particular underlying diseases. The second case was another patient, a 72-year-old man, with hypertension, dyslipidemia, and steatohepatitis. Both patients developed methicillin-susceptible S. aureus pneumonia in the clinical course of COVID-19, to which antibiotic therapy with cefazolin was effectively administered. Through these cases, we emphasize that S. aureus secondary infections should be well cared with a high degree of caution in a case of critically ill COVID-19 patients.

Persistent methicillin-resistant Staphylococcus aureus bacteremia in an adult patient with Netherton's syndrome: A case report.

Netherton's syndrome, a rare congenital disorder, is clinically characterized by chronic dermatologic disorders such as ichthyosiform erythroderma and ichthyosis linearis circumflexa. Curable treatment is yet to be established, and corticosteroid ointment is required to maintain good dermatological condition. Because of the permanent skin barrier impairment, patients with Netherton's syndrome are considered to be vulnerable to cutaneous infections. However, its clinical characteristics are yet to be elucidated due to the limited number of reported cases. Herein, we describe the clinical course of a patient who developed persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A 19-year-old Japanese woman who had been diagnosed with Netherton's syndrome in her infancy and had been applying topical corticosteroid agents all over her body since her then, was referred to our hospital because of persistent MRSA bacteremia and secondary adrenal insufficiency. The patient was diagnosed with a central line-associated bloodstream infection and was appropriately treated with antibiotics and corticosteroid therapies. We assume that the damaged skin barrier due to the congenital dermatological disorder causes a disruption in the normal bacterial flora of the skin, leading to the invasion of harmful bacteria, such as S. aureus. In addition, internal (humoral immunodeficiency by decreased antibody against bacterial polysaccharide antigens) and external (prolonged and systemic use of corticosteroid ointment) factors bring about an immunodeficiency state in such patients. We highlight that in the absence of radical treatment, clinicians need to recognize that patients with Netherton's syndrome are vulnerable to bacterial infections owing to the mixture of immunosuppressive factors.

Preparation of leukotriene B(4) inhibitory active 2- and 3-(2-aminothiazol-4-yl)benzo[b]furan derivatives and their growth inhibitory activity on human pancreatic cancer cells.

A series of 2-(2-aminothiazol-4-yl)benzo[b]furan and 3-(2-aminothiazol-4-yl)benzo[b]furan derivatives were prepared, and their leukotriene B(4) inhibitory activity and growth inhibitory activity in cancer cell lines were evaluated. Several compounds showed strong inhibition of calcium mobilization in CHO cells overexpressing human BLT(1) and BLT(2) receptors and growth inhibition to human pancreatic cancer cells MIA PaCa-2. 3-(4-Chlorophenyl)-2-[5-formyl-2-[(dimethylamino)methyleneamino]thiazol-4-yl]-5-methoxybenzo[b]furan 8b showed the most potent and selective inhibition for the human BLT(2) receptor, and its IC(50) value was smaller than that of the selected positive control compound, ZK-158252. 3-(4-Chlorophenyl)-2-[2-[(dimethylamino)methyleneamino]-5-(2-hydroxyethyliminomethyl)thiazol-4-yl]-5-methoxybenzo[b]furan 9a displayed growth inhibitory activity towards MIA PaCa-2.

Variations in aganglionic segment length of the enteric neural plexus in Mowat-Wilson syndrome.

BACKGROUND/PURPOSE: Patients with zinc finger homeo box 1B (ZFHX1B) mutations or deletions develop multiple congenital anomalies including Hirschsprung disease, known as Mowat-Wilson syndrome (MWS). In this study, we investigated variations in the enteric neural plexus abnormalities in MWS using morphometry-based histopathologic analysis. METHODS: Seven patients with MWS (3 with mutations in exon 8 of ZFHX1B and 4 with deletions) who had undergone modified Duhamel's operations for Hirschsprung disease were examined. Surgically resected rectosigmoid specimens were analyzed morphometrically. RESULTS: The length of the aganglionic segment was longer than 3 cm in all the patients with deletions. In 3 patients with mutations, the aganglionic region was not detected in the surgically resected specimens; however, the parameters of the ganglions and plexus were significantly smaller than those of controls (cloaca and aproctia), indicative of a transitional zone. Variation in the severity of pathological changes among the 3 patients with mutations was also noted. CONCLUSIONS: The variations in myenteric plexus pathologies in MWS appear to be caused by both variations in ZFHX1B abnormalities and epigenetic factors.

Protease-activated receptor-2 (PAR-2)-related peptides induce tear secretion in rats: involvement of PAR-2 and non-PAR-2 mechanisms.

Protease-activated receptor-2 (PAR-2) plays an extensive role in the regulation of digestive exocrine secretion. The present study examined whether PAR-2-related peptides could modulate tear secretion in rats and analyzed the underlying mechanisms. SLIGRL-NH(2), a PAR-2-activating peptide (PAR-2-AP) derived from mouse/rat PAR-2, when administered i.v. in combination with amastatin, an aminopeptidase inhibitor, evoked tear secretion, whereas LRGILS-NH(2), a PAR-2-inactive reversed peptide, had no such effect. In contrast, LSIGRL-NH(2), a partially reversed peptide known to be inactive with PAR-2, caused tear secretion equivalent to the effect of SLIGRL-NH(2). SLIGKV-NH(2), a human-derived PAR-2-AP, also induced significant tear secretion though to a lesser extent, whereas neither VKGILS-NH(2), a reversed peptide, nor LSIGKV-NH(2), a partially reversed peptide, produced any secretion. In desensitization experiments, after the first dose of SLIGRL-NH(2), the second dose of SLIGRL-NH(2) produced no tear secretion, whereas the response to LSIGRL-NH(2) was only partially inhibited by preadministration of SLIGRL-NH(2). Preadministration of LSIGRL-NH(2) abolished the response to subsequently administered LSIGRL-NH(2) but not SLIGRL-NH(2). The tear secretion induced by LSIGRL-NH(2) but not by PAR-2-APs was blocked by atropine or hexamethonium. Mast cell depletion due to repeated doses of compound 48/80 did not alter the effect of SLIGRL-NH(2) or LSIGRL-NH(2). Finally, IGRL-NH(2), a possible core structure of LSIGRL-NH(2), triggered tear secretion in an atropine-reversible manner. Our findings suggest that the PAR-2-APs SLIGRL-NH(2) and SLIGKV-NH(2) cause tear secretion, most likely via PAR-2 and that LSIGRL-NH(2), a PAR-2-inactive peptide, and IGRL-NH(2), its key structure, trigger tear secretion by stimulating parasympathetic nerves via an unidentified target molecule.

Suppression by protease-activated receptor-2 activation of gastric acid secretion in rats.

Activation of protease-activated receptor-2 (PAR-2), a receptor activated by trypsin/tryptase, induces neurally mediated gastric mucus secretion accompanied by mucosal cytoprotection. In the present study, we investigated whether PAR-2 could modulate gastric acid secretion in rats. Messenger RNAs for PAR-2 and PAR-1 were detected in the gastric mucosa and smooth muscle. The PAR-2-activating peptide SLIGRL-NH(2), but not the inactive control peptide, when administered i.v., strongly suppressed gastric acid secretion in response to carbachol, pentagastrin or 2-deoxy-D-glucose in the rats with a pylorus ligation. The PAR-2-mediated suppression of acid secretion was resistant to cyclooxygenase inhibition or ablation of sensory neurons by capsaicin. Our results provide novel evidence that in addition to stimulating neurally mediated mucus secretion, activation of PAR-2 suppresses gastric acid secretion independently of prostanoid production or sensory neurons. These dual actions of PAR-2 would result in gastric mucosal cytoprotection.

Family attitude scale: measurement of criticism in the relatives of patients with schizophrenia in Japan.

Expressed emotion (EE) is traditionally measured with the Camberwell Family Interview (CFI), but the CFI requires considerable time for both execution and evaluation. As an alternative, we investigated the validity of the Family Attitude Scale (FAS), a questionnaire developed for the measurement of EE. The CFI, the FAS, the General Health Questionnaire (GHQ), and the Five-Minute Speech Sample (FMSS) were administered in 57 members of the families of 41 patients with acute episodes of schizophrenia. The relative sensitivity and specificity of EE assessment with the FAS compared with the criticism component of the CFI were 100% and 88.5%, respectively. EE assessment based on criticism as assessed with the FMSS compared with the CFI had a sensitivity of 40.0% and a specificity of 90.4%. The GHQ score tended to be higher in the high-scoring FAS group than in the low-scoring FAS group. The FAS showed excellent validity for the measurement of critical aspects of family attitudes, and the FAS score reflected the state of psychological health of the families.