Successful treatment of intestinal malakoplakia in a French Bulldog.

Malakoplakia is a rare granulomatous inflammation mainly been reported in the urinary bladder of dogs. Only one case of canine colonic malakoplakia has been reported to date; however, successful treatment of this disease has not been reported. Here, we report a case of colonic malakoplakia in a 5-month-old spayed female French Bulldog. The dog was referred to a veterinarian because of chronic diarrhea and mucinous blood feces; empirical treatment did not improve its condition. Histologically, numerous macrophages containing periodic acid-Schiff-positive granules infiltrated the lamina propria of the large intestine. Furthermore, targetoid basophilic inclusion bodies (Michaelis-Gutmann bodies) were observed. Complete clinical remission was achieved after 8 months of enrofloxacin treatment and favorable progress after 2 months of medication.

Efficacy of Health Surveillance and Polymerase Chain Reaction Testing in Judo During the COVID-19 Pandemic.

Background The COVID-19 pandemic necessitated infection control for all sporting activities. More careful infection control measures are required in judo, where close contact with opponents cannot be avoided. The Medical Science Committee of the All Japan Judo Federation (AJJF) established infection control guidelines for daily practice and competitions. Infection control measures were also implemented at the national tournament organized by the AJJF. Objective and methods This study aimed to examine the effectiveness of pre-tournament health surveys and PCR testing in guidelines for judo tournaments. Participants had to complete a health survey one to two weeks before the tournament. Initially, PCR testing was performed on all athletes; however, the final policy was to conduct PCR testing only on athletes with an infected person (risk team testing method). The effectiveness of these methods was also examined. Results In 16 competitions between October 2020 and March 2023, 6980 contestants were registered, and PCR testing was performed on 3672 athletes; 29 (0.79%) had a positive PCR test. Only two contestants were unable to attend the tournament because of the health survey. No competition-related cluster outbreaks were observed. From May 2022, the competition was held under the guideline that only teams at risk of infection were tested and could only compete when they tested negative. No teams were tested according to this guideline. In the competitions organized within this guideline, only one person could not compete because of the information provided in the health survey. No clusters were observed in any of the competitions. The incidence of COVID-19 infection in the first week after the convention was 20 (0.60%) in testing only at-risk teams and 21 (0.57%) in testing all competitors, which was not significantly different.(p=0.62) Conclusion During the COVID-19 epidemic, health surveillance was necessary to prevent the registration of competitors at risk of infection prior to tournaments. If teams at risk of infection could be identified, PCR testing of all athletes might not be mandatory, and competitions could be organized safely. The Judo infectious disease control guidelines we have developed might be used for other contact sports in the future when other infectious diseases are prevalent.

Potential marker subset of blood-circulating cytokines on hematopoietic progenitor-to-Th1 pathway in COVID-19.

In this study, we analyzed a relatively large subset of proteins, including 109 kinds of blood-circulating cytokines, and precisely described a cytokine storm in the expression level and the range of fluctuations during hospitalization for COVID-19. Of the proteins analyzed in COVID-19, approximately 70% were detected with Bonferroni-corrected significant differences in comparison with disease severity, clinical outcome, long-term hospitalization, and disease progression and recovery. Specifically, IP-10, sTNF-R1, sTNF-R2, sCD30, sCD163, HGF, SCYB16, IL-16, MIG, SDF-1, and fractalkine were found to be major components of the COVID-19 cytokine storm. Moreover, the 11 cytokines (i.e., SDF-1, SCYB16, sCD30, IL-11, IL-18, IL-8, IFN-γ, TNF-α, sTNF-R2, M-CSF, and I-309) were associated with the infection, mortality, disease progression and recovery, and long-term hospitalization. Increased expression of these cytokines could be explained in sequential pathways from hematopoietic progenitor cell differentiation to Th1-derived hyperinflammation in COVID-19, which might also develop a novel strategy for COVID-19 therapy with recombinant interleukins and anti-chemokine drugs.

Emergence of SARS-CoV-2 with Dual-Drug Resistant Mutations During a Long-Term Infection in a Kidney Transplant Recipient.

Introduction: Various therapeutic agents are being developed for the treatment of coronavirus disease 2019 (COVID-19). Therefore, it is crucial to accumulate information regarding the features of drug-resistant viruses to these antiviral drugs. Methods: We investigated the emergence of dual-drug resistance in a kidney transplant recipient who received sotrovimab (from day 0) and remdesivir (RDV) (from day 8 to day 17). We sequenced the whole viral genomes from nasopharyngeal swabs taken on day 0 and seven points after starting treatment (on days 12, 19, 23, 37, 43, 48, and 58). The genetic traits of the wild-type (day 0) and descendant viruses (after day 12) were determined by comparing the genomes with those of a Wuhan strain and the day 0 wild-type strain, respectively. Three viral isolates (from samples collected on days 0, 23, and 37) were investigated for their escape ability and growth kinetics in vitro. Results: The sotrovimab resistant mutation (S:E340K) and the RDV resistant mutation RdRp:V792I (nt: G15814A) emerged within 12 days (day 12) and 11 days (day 19) after the treatment, respectively. The day 23 isolate harboring S:E340K/RdRp:V791I was resistant to both sotrovimab and RDV, showing 364- and 2.73-fold higher resistance respectively, compared with the wild-type. Moreover, compared with the day 23 isolate, the day 37 isolate accumulated multiple additional mutations and had a higher level of resistance to both drugs. Conclusion: Drug-resistant variants with double mutations (S:E340K/RdRp:V791I) became dominant within 23 days after starting treatment, suggesting that even a combination therapy involving sotrovimab and RDV, dual-drug resistant viruses may emerge rapidly in immunocompromised patients. The dual-resistant variants had lower virus yields than those of the wild-type virus in vitro, suggesting that they paid a fitness cost.

The Efficacy of Health Surveys and Polymerase Chain Reaction Tests Prior to Judo Tournaments During the COVID-19 Pandemic.

Background As of October 2021, sports activities require preventive measures against coronavirus disease 2019 (COVID-19) infection. Judo, a close-contact sport, demands careful prevention with great consideration to the risk of infection. The All Japan Judo Federation Medical Science Committee (AJJF) designed COVID-19 prevention protocols from a medical perspective and developed policies for safe regular practices and tournaments. Objective and Methods We aim to examine the efficacy of health surveys and polymerase chain reaction (PCR) tests prior to judo tournaments, as mandated by the tournament policy. Infection prevention managers were installed prior to tournaments. Two weeks prior to each tournament, these managers drafted health inventory forms for athletes and related parties to check for COVID-19-associated symptoms. Although PCR testing prior to tournaments was not required by policy, the AJJF conducted them (directly and by mail) prior to six tournaments from October 2020 to September 2021 for athletes whose health inventory forms listed no symptoms. Results One of the athletes was not tested and was unable to participate in a tournament due to the symptoms indicated in their health inventory form. Testing began in October 2020 and was conducted until September 2021 for 2,073 athletes over the duration of six tournaments. The SARS-CoV-2 virus was detected in 11 (0.29%) athletes. In tournaments held until April 2021, SARS-CoV-2 was detected in only one of the 1,173 (0.08%) athletes tested. However, prior to tournaments held from July 2021 onward, when variants became prevalent, SARS-CoV-2 was detected in 10 (1.1%) of the 900 athletes tested (p < 0.05). No clusters were reported in association with any tournament. Conclusion We believe that drafting health inventory forms two weeks prior to judo tournaments was essential and kept the participants alert. However, as variants emerged, some participants who were positive could not be detected through their inventory forms; this demonstrates the need for caution when relying on health inventory forms alone.

Differences in the sequence of PlcR transcriptional regulator-binding site affect sphingomyelinase production in Bacillus cereus.

Bacillus cereus is an opportunistic pathogen that often causes severe infections such as bacteremia, with sphingomyelinase (SMase) being a crucial virulence factor. Although many strains of B. cereus carry the SMase gene, they are classified as SMase-producing and nonproducing strains. The reason for different SMase production among B. cereus strains remains unknown. In this study, we investigated the relationship between SMase and the PlcR transcriptional regulation system to clarify the mechanism leading to varied SMase production among B. cereus strains. We analyzed the sequence of the PlcR box, which is a transcriptional regulator-binding site, located at the promoter region of SMase and phosphatidylcholine-specific phospholipase C. Based on differences in the PlcR box sequences, we classified the B. cereus strains into three groups (I, II, and III). SMase expression and activity were hardly detected in Group III strains. In Group I strains, SMase activity and its expression were maximal at the onset of the stationary phase and decreased during the stationary phase, whereas those were maintained during the stationary phase in Group II stains. On injection of B. cereus strains into mice or incubation with macrophages for phagocytosis assay, the SMase-producing Group I and II strains showed higher pathogenicity than Group III strains. These findings suggest that PlcR box sequence in B. cereus affects the production of SMase, which may provide important clinical information for the detection of highly pathogenic B. cereus strains.

Two cases of novel coronavirus infection (COVID-19) with transient viral elevation using semi-quantitative real-time reverse transcription PCR and symptom relapse after completion of 10 days of favipiravir treatment.

The coronavirus disease of 2019 (COVID-19), which began in Wuhan, China, at the end of 2019, is spreading around the world and causing many deaths, mainly from pneumonia. Currently, there are no specific drugs to treat COVID-19, and existing antiviral drugs are being used as an alternative. One of these is favipiravir, a new type of influenza drug. However, its efficacy, dosage, and duration of administration are still under study. In this case study, we administered favipiravir to patients with COVID-19 and determined the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 pathogen, using semi-quantitative real-time reverse transcription PCR in sputum samples. We report on two patients in whom the viral load increased again after completion of 10 days of favipiravir treatment and a transient relapse of symptoms was observed.

A case of urgent colonoscopic hemostasis of a cecal hemorrhagic ulceration in a patient receiving heparin for COVID-19 coagulopathy.

COVID-19 rarely causes lower gastrointestinal bleeding even though its RNA has been detected in patient's stool. Urgent colonoscopy in a COVID-19 patient with massive bloody stool requires various procedural and equipment considerations. Here, we present a case of colonoscopic hemostasis of a cecal hemorrhagic ulceration in a patient on heparin for COVID-19 coagulopathy. We also share various management methods for the prevention of COVID-19 contamination. A 71-year-old man was diagnosed with COVID-19 pneumonia and subsequently underwent hemodiafiltration. Heparin was initiated for COVID-19 coagulopathy. At day 42, the patient experienced 2000 mL of bloody stool. An operator performed urgent colonoscopy with three assistants in a negative-pressure room with full personal protective equipment. A hemorrhagic ulceration was detected at the cecum, and endoscopic hemostasis was performed. Immunohistochemistry was positive for cytomegalovirus. Postprocedure, the endoscopic systems were thoroughly cleaned, and specific measures for endoscope reprocessing and disinfection were performed to prevent contamination with COVID-19.

Usefulness and Safety of Remote Continuous Glucose Monitoring for a Severe COVID-19 Patient with Diabetes.

Diabetes is associated with mortality and severity of coronavirus disease (COVID-19). Protecting against infection in health care workers at high risk of COVID-19 is critical. This report investigates the usefulness and safety of remote continuous glucose monitoring (CGM) in a patient with diabetes and severe interstitial pneumonia caused by the coronavirus disease. The Dexcom G4 Platinum CGM system® was used to monitor blood glucose (BG) levels from outside the patient's isolation room. Continuous insulin infusion rates and boluses were determined based on the patient's BG levels. Real-time CGM made it possible to track BG trends and prevent dramatic variations in BG, although the rate of insulin infusion changed dynamic. Furthermore, the need for health care workers to enter the isolation room was minimized because the Dexcom G4 Platinum CGM system can evaluate from a distance of up to 6.0 m.

Impact of host- and early treatment-related factors on mortality in ICU patients with candidemia: a bicentric retrospective observational study.

BACKGROUND: Candidemia is one of the most life-threatening infections among critically ill patients in the intensive care unit. However, the number of studies on the impact of host- and early treatment-related factors on mortality in this cohort is limited. The aim of this study was to investigate the relationship between clinically relevant factors, including early treatment (appropriate antifungal therapy and/or central venous catheter removal) and mortality in intensive care unit patients with candidemia. METHODS: We performed a retrospective observational study in two Japanese University hospitals between January 2007 and December 2016. Adult intensive care unit patients with candidemia who met the following inclusion criteria: (1) ≥ 18 years old; (2) admitted in intensive care unit at the time of onset; and (3) central venous catheter in situ at the time of onset were included. We performed univariate and multivariate logistic regression analysis to identify factors associated with 30-day crude mortality. RESULTS: A total of 68 patients met the inclusion criteria, 47 (69%) of whom were males. The median age was 68.0 (interquartile range, 61.0-76.0) years. The most common causative Candida species was Candida albicans (40 [59%] patients). With respect to the source of infection, central venous catheter-related candidemia was the most frequent (30 [44%] patients). Thirty-day crude mortality was 54% (37 patients). In multivariate logistic regression analysis, Acute Physiology and Chronic Health Evaluation II score (1-point increments) was the only factor that was independently associated with higher 30-day crude mortality. Other variables, including appropriate antifungal therapy and/or central venous catheter removal ≤ 24 h and ≤ 48 h following onset, did not significantly influence mortality. CONCLUSIONS: Candidemia in intensive care unit patients is still associated with high 30-day crude mortality rates. The only predictor of death was Acute Physiology and Chronic Health Evaluation II score ≤ 24 h following candidemia onset. Early empiric antifungal therapy and/or early CVC removal conferred no significant clinical benefit on survival in this patient population.

Secondary in-hospital epidemiological investigation after an outbreak of Pseudomonas aeruginosa ST357.

The secondary in-hospital epidemiological investigation for drug-resistant Pseudomonas aeruginosa infections was conducted to evaluate the in-hospital situation and identify any associations between exoenzyme genotypes and other genotypes and antimicrobial resistance characteristics, at the University Hospital in Kyoto, Japan, following a reported outbreak of antimicrobial-resistant P. aeruginosa ST357 between 2005 and 2014. Twelve of the 546 P. aeruginosa isolates collected during the follow-up period were resistant to more than two classes of antimicrobials. All isolates were resistant to fluoroquinolones and 8 (66.7%) showed carbapenem resistance. None of the isolates fulfilled the clinical criteria for multidrug-resistant P. aeruginosa. All isolates were metallo-ß-lactamase test-negative. Among five exoS (-)exoU (+) isolates, three possessing a class 1 integron with gene cassette aadB + cmlA6 were classified as ST357, and one isolate containing a class 1 integron with aacA31 was ST235. Collectively, the second survey results confirm that the initial outbreak is currently undergoing convergence. By combining data from the first and second surveys, we showed that prevalent STs such as ST357 and ST235 are associated with fluoroquinolone resistance, class 1 integron-associated resistance to ß-lactams and aminoglycosides, and cytotoxic exoU (+) genotypes. With the current worldwide spread of ST357 and ST235 isolates, it is important to evaluate epidemiological trends for high-risk P. aeruginosa isolates by continuous hospital monitoring.

[A Case of Aortic Graft Infection Due to Listeria monocytogenes Detected by Microarray-Based, Multiplexed, Automated Molecular Diagnosis System].

A 80-year-old man was transferred to our hospital for hemoptysis caused by erosion(perforation) of thoracic aortic stent graft infection into the airway. Blood cultures on admission detected Gram-positive rods, and a microarray-based, multiplexed, automated molecular diagnosis instrument (Verigene® system) identified Listeria spp. Although Listeria monocytogenes is rare organism of stent graft infection, we were able to start appropriate antibiotic therapy on the second hospital day due to rapid identification of bacteria. Verigene® system is considered to be useful in severe infectious diseases including stent graft infections, even if the causative organism is rare.

Essential human resources for antimicrobial stewardship teams in Japan: Estimates from a nationwide survey conducted by the Japanese Society of Chemotherapy.

Implementation of antimicrobial stewardship programs (ASPs) with multidisciplinary antimicrobial stewardship teams (ASTs) is critical for appropriate antimicrobial use at healthcare facilities. Although the Japanese medical reimbursement system was revised to allow fees for ASP implementation, several concerns remain, including understaffing and enforcement of the recommendations on ASTs and ASPs in practice. Furthermore, there are no recommendations on full-time equivalents (FTEs) of the core members in ASTs in Japan. This committee report presents our recommendations on ASTs based on an analysis of the nationwide survey on implemented ASPs and staff FTEs at 1358 healthcare facilities conducted by the Japanese Society of Chemotherapy. Our report provides a directive for structural and financial support of ASTs and should aid in planning for the enhancement of AST practices and the organization of new ASTs.

Impact of inappropriate empiric antimicrobial therapy on mortality in pediatric patients with bloodstream infection: a retrospective observational study.

Inappropriate empiric antibiotic therapy for bloodstream infection could be associated with mortality in adults. However, data for pediatric patients have been scarce. The purpose of this study was to investigate the impact of an inappropriate empiric antibiotic therapy on mortality in pediatric patients with bloodstream infection. We retrospectively analyzed the data of pediatric patients with consecutive positive blood culture in the university hospital between 2007 and 2016. The association between the use of inappropriate empiric therapy and mortality was investigated. A total of 247 bacteremia events in 223 pediatric patients were analyzed. Overall, 208 (84%) events were hospital acquired and 16 (6%) patients died within 28 days. The most frequent causative microorganisms were Gram-positive bacteria (150 events, 61%), followed by Gram-negative bacteria (90 events, 36%) and Candida spp. (7 events, 3%). Inappropriate empiric antibiotic therapy was prescribed within 48 h in 34 (16%) events. Significantly better 28-day survival rates were obtained in patients that received appropriate empiric antibiotic therapy compared with those who received inappropriate therapy (p = 0.004). Multivariate Cox regression analysis showed that inappropriate empiric antibiotic therapy was an independent prognostic factor of 28-day mortality (hazard ratio, 4.39; 95% confidence interval, 1.48-11.94; p = 0.01), after adjusting for age and McCabe score. Inappropriate empiric antibiotic therapy was associated with poor 28-day mortality in pediatric patients with bloodstream infection. Strategies to increase appropriate selection of empiric antibiotic therapy might be an option for improving survival in pediatric patients with bloodstream infection.

An outbreak of fluoroquinolone-resistant Pseudomonas aeruginosa ST357 harboring the exoU gene.

Antimicrobial-resistant isolates of Pseudomonas aeruginosa collected from 2005 to 2014 in a university hospital in Kyoto, Japan, were retrospectively analyzed by multilocus sequence typing (MLST), exoenzyme genotype determination, integron characterization, and clinical associations. During the study, 1573 P. aeruginosa isolates were detected, and 41 of these were resistant to more than two classes of antimicrobial agents. Twenty-five (61.0%) isolates were collected from urine. All isolates were resistant to ciprofloxacin, 8 (19.5%) isolates showed resistance to imipenem/cilastatin, and 8 (19.5%) isolates showed resistance to meropenem. None of the isolates fulfilled the clinical criteria for multidrug-resistant P. aeruginosa. All isolates were negative in the metallo-ß lactamase test. Thirty-six (87.8%) isolates were of the exoS-exoU+ genotype and 5 (12.2%) isolates were of the exoS+exoU- genotype. Among 36 exoS-exoU+ isolates, 33 (80.5%) were ST357, and 3 (7.3%) were ST235. Five isolates of exoS+exoU- were ST186, ST244, ST314, ST508, and ST512. Thirty-three isolates were positive for class 1 integrons and four different class 1 integrons were detected: aminoglycoside (2') adenyltransferase and chloramphenicol transporter (AadB+CmlA6), OXA-4 ß-lactamase and aminoglycoside 3'-adenyltransferase (OXA4+AadA2), AadB alone, and aminoglycoside acetyltransferase alone (AacA31). Among the 41 patients from which the isolates originated, the most common underlying disease was cancer in 16 patients (39%), and 9 patients (22.0%) died during the hospitalization period. There was no statistical correlation between MLST, exoenzyme genotype, and patient mortality. The results indicated outbreaks of fluoroquinolone-resistant P. aeruginosa in immunocompromised patients mainly due to the propagation of potentially virulent ST357 isolates possessing the exoU+ genotype.