Pyelonephritis with bacteremia caused by Salmonella Choleraesuis in a Japanese patient with carcinoma of unknown primary origin: A case report.

Salmonella enterica subspecies enterica serovar Choleraesuis (S. Choleraesuis) is a nontyphoidal Salmonella pathogen that causes swine paratyphoids. S. Choleraesuis is a zoonotic pathogen transmitted to humans via contaminated food and causes sepsis. Here, we report a rare case of pyelonephritis caused by S. Choleraesuis in a Japanese patient with a carcinoma of unknown primary origin. On the day of admission, the patient was diagnosed with pyelonephritis associated with ureteral stent obstruction. He had no history of raw pork consumption or gastrointestinal symptoms. Gram-negative rods were isolated from urine and blood cultures, identified as Salmonella enterica subsp. enterica using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The serological typing results were O7: -: 1 and 5; however, the serotypes could not be determined. The isolate was identified as S. Choleraesuis using multilocus sequence typing, nucleotide sequence analysis of the fliC gene, and biochemical examination. Four days after a 14-day course of intravenous piperacillin-tazobactam (9 g/day), the patient showed relapse of the condition. Subsequently, the patient was treated with intravenous ceftriaxone (2 g/day) and oral amoxicillin (1000 mg/day) for 14 days each; recurrence was not observed. This novel case of pyelonephritis with bacteremia was caused by S. Choleraesuis in Japan. Conventional testing methods could not identify the serotypes; however, the case highlights the importance of adopting advanced diagnostic techniques based on molecular biology to ensure accurate pathogen identification.

Cholangitis with bacteremia due to Pseudomonas nitroreducens in a patient with pancreatic neuroendocrine tumors: a case report.

BACKGROUND: Pseudomonas nitroreducens is a non-fermenting, gram-negative, rod-shaped bacterium commonly inhabiting soil, particularly soil contaminated with oil brine. To our knowledge, no cases of human infection with P. nitroreducens have been previously reported. Here, we present the first documented case of cholangitis caused by P. nitroreducens in a patient with bacteremia. CASE PRESENTATION: A 46-year-old Japanese man with an advanced pancreatic neuroendocrine tumor was hospitalized with fever and chills. Four days before admission, the patient developed right upper abdominal pain. Two days later, he also experienced fever and chills. Endoscopic retrograde cholangiopancreatography was performed on the day of admission, and the patient was diagnosed as having cholangitis associated with stent dysfunction. Gram-negative rods were isolated from blood cultures, but attempts to identify the bacteria using VITEK2 and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with VITEK MS ver. 4.7.1 (bioMérieux Japan Co. Ltd., Tokyo, Japan) were unsuccessful. Finally, the organism was identified as P. nitroreducens using MALDI-TOF MS with a MALDI Biotyper (Bruker Daltonics Co., Ltd., Billerica, MA, USA) and 16 S ribosomal RNA sequencing. Despite thorough interviews with the patient, he denied any exposure to contaminated soil. The patient was treated with intravenous cefepime and oral ciprofloxacin for 16 days based on susceptibility results, achieving a good therapeutic outcome. At the outpatient follow-up on day 28, the patient was in good general condition. CONCLUSIONS: This is the first reported human case of cholangitis with bloodstream infection caused by P. nitroreducens. This report provides clinicians with novel insights into the clinical manifestations and diagnostic methods necessary for the accurate diagnosis of P. nitroreducens, along with guidance on treatment.

Successful management of surgical site infection caused by Mycobacterium mageritense in a breast cancer patient.

Mycobacterium mageritense (M. mageritense), a nontuberculous mycobacterium, is classified as a rapidly growing mycobacterium, class IV in the Runyon Classification. This bacterium is found in soil, water, and other habitats. Infections caused by M. mageritense are relatively rare and no treatment protocol has been established. Herein, we report a case of skin and soft tissue infection caused by M. mageritense. A 49-year-old woman underwent surgery for right breast cancer. Four months after surgery, a surgical site infection was found, and M. mageritense was identified in the wound culture using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Based on the sensitivity results, the patient was treated with levofloxacin and doxycycline for 4 months. In addition to antimicrobial agents, aggressive surgical interventions led to a favorable course of treatment. In conclusion, successful treatment of skin and soft tissue infections with M. mageritense requires surgical intervention whenever possible, aggressive susceptibility testing, and appropriate antimicrobial therapy.

Identification of Pathways for Production of D-Glucaric Acid by Pseudogluconobacter saccharoketogenes.

Pseudogluconobacter saccharoketogenes produces glucaric acid from D-glucose via two pathways, i.e., through D-glucuronic acid or D-gluconic acid. These pathways are catalyzed by alcohol dehydrogenase, aldehyde dehydrogenase, and gluconate dehydrogenase. Although D-glucaraldehyde and L-guluronic acid are also theorized to be produced in pathways throsugh D-glucuronic acid and D-gluconic acid, respectively, no direct data to identify these intermediates have been reported. In this study, the intermediates were purified and identified as D-glucaraldehyde and L-guluronic acid. The substrate specificities of the three enzymes on these intermediates and their oxidation products were studied, and the roles of alcohol, aldehyde, and gluconate dehydrogenases in D-glucaric acid-producing pathways were elucidated using the intermediates. Additionally, the substrate specificities of alcohol and aldehyde dehydrogenases on some alcohols, aldehydes, and aldoses were determined. Alcohol dehydrogenase showed wide substrate specificities, whereas the substrates oxidized by aldehyde dehydrogenase were limited. A 30-L scale reaction using the resting cells of Rh47-3 revealed that D-glucaric acid was produced from D-glucose and D-gluconic acid in 60.3 mol% (7.0 g/L) and 78.6 mol% (22.5 g/L) yields, respectively.

Peritonitis with bacteremia due to Christensenella hongkongensis identified via ribosomal RNA sequencing in a Japanese patient with advanced colorectal adenocarcinoma: A case report.

Background: Christensenella hongkongensis is an obligately anaerobic, catalase-positive, motile, non-sporulating, gram-positive coccobacillus. Human infections are rare and have not been previously reported in Japan. Herein, we report the first case of perforated peritonitis with C. hongkongensis bacteremia in Japan. Case presentation: A 61-year-old Japanese man with advanced colorectal adenocarcinoma presented with fever and abdominal pain. Abdominal computed tomography revealed a low-density area with thinning of the sigmoid colon wall and air outside the intestinal tract, which was diagnosed as perforated peritonitis. Cultures of the ascitic fluid isolated Bacteroides fragilis, Bacteroides eggerthii, Parabacteroides distasonis, Enterococcus avium, and Candida albicans. Gram-positive rods were detected in the blood culture on admission after 4 days. The isolate was identified as C. hongkongensis via 16S ribosomal RNA (16S rRNA) sequencing. The patient underwent open abdominal washout and drainage via a transverse colon bifurcation colostomy. Intravenous meropenem (3 g/day) was administered for 5 days, followed by intravenous piperacillin-tazobactam (9 g/day) for 6 days, and then levofloxacin (500 mg/day) and metronidazole (1500 mg/day) intravenously for 15 days. Postoperatively, the patient gradually recovered. He was transferred to another palliative care hospital on day 38 after admission for worsening advanced colorectal cancer condition. Conclusion: Bacteremia caused by C. hongkongensis is rare. 16S rRNA sequencing should be considered for the identification of gram-positive anaerobic rods that are difficult to diagnose by conventional methods.

Reduction strategies for inpatient oral third-generation cephalosporins at a cancer center: An interrupted time-series analysis.

Oral third-generation cephalosporins (3GCs) are not recommended for use owing to their low bioavailability and the risk of emergence of resistant microorganisms with overuse. A standardized and effective method for reducing their use is lacking. Here, in a 60-month, single-institution, interrupted time-series analysis, which was retrospectively conducted between April 1, 2017, and March 31, 2022, we evaluated the effectiveness of a four-phase intervention to reduce the use of 3GCs in patients at a cancer center: Phase 1 (pre-intervention), Phase 2 (review of clinical pathways), Phase 3 (establishment of infectious disease consultation service and implementation of antimicrobial stewardship program), and Phase 4 (educational lecture and pop-up displays for oral antimicrobials at the time of ordering). Although no significant changes were observed in Phases 3 and 4, the first intervention resulted in a significant decrease in the trend and level of days of therapy (DOT) for 3GCs. The level for cephalexin DOT and the trend for sulfamethoxazole-trimethoprim DOT increased in Phase 4, and the trend for amoxicillin and amoxicillin-clavulanate DOT increased in Phase 3. Macrolide DOT showed a decreasing trend in Phases 2 and 4 and decreasing and increased levels in Phases 3 and 4, respectively; no change was observed for quinolones. Actual and adjusted purchase costs of 3GCs decreased significantly during all study periods, while those for oral antimicrobials decreased in Phase 2, and actual purchase costs increased in Phases 3 and 4. No significant reduction in resistant organisms, length of hospital stay, or mortality was observed. This is the first study on the effects of oral 3GC reduction strategies in patients with cancer. We conclude that even facilities that substantially use antimicrobials can efficiently reduce the use of 3GCs.

[Treatment Strategy with Immune Checkpoint Inhibitors and Genetic Testing for Colorectal Cancer with Microsatellite Instability-High].

Recently, pembrolizumab have been approved for advanced solid tumor with microsatellite instability-high, and nivolumab including combination therapy with ipilimumab for colorectal cancer with microsatellite instability-high, and usefulness of those 3 checkpoint inhibitors have been paid attention. Genetic testing is essential for selecting molecular-targeted drugs in colorectal cancer; however, the type of tests and their optimal timing are becoming more complicated. Hence, this article reviews the gene mutation tests used for advanced colorectal cancer, the molecular mechanism of colorectal cancer with microsatellite instability-high, the clinical development status of immune checkpoint inhibitors, and the future perspective on treatment strategy.

Femoral osteomyelitis caused by oral anaerobic bacteria with mixed bacteremia of Campylobacter rectus and Parvimonas micra in a chronic periodontitis patient: a case report.

BACKGROUND: Campylobacter rectus is a gram-negative rod, and Parvimonas micra is a gram-positive coccus, both of which are oral anaerobes that cause chronic periodontitis. Chronic periodontitis can cause bacteremia and systemic diseases, including osteomyelitis. Hematogenous osteomyelitis caused by anaerobic bacteria is uncommon, and to date, there have been no reports of mixed bacteremia with C. rectus and P. micra. Here, we report the first case of osteomyelitis of the femur caused by anaerobic bacteria with mixed bacteremia of C. rectus and P. micra caused by chronic periodontitis. CASE PRESENTATION: A 75-year-old man with chronic periodontitis, hyperuricemia, and benign prostatic hyperplasia was admitted to the hospital with a fracture of the left femur. The patient had left thigh pain for 4 weeks prior to admission. Left femoral intramedullary nail fixation was performed, and a large amount of abscess and necrotic tissue was found intraoperatively. The cultures of abscess specimens were identified as P. micra, Fusobacterium nucleatum, and C. rectus. C. rectus and P. micra were also isolated from blood cultures. C. rectus was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16 S ribosomal RNA sequencing. Sulbactam-ampicillin was administered for approximately 1 month, after which it was replaced by oral clavulanic acid-amoxicillin for long-term suppressive treatment. CONCLUSIONS: Only five cases of bloodstream infection with C. rectus have been reported, and this is the first report of mixed bacteremia with P. micra. Clinicians should consider that chronic periodontitis caused by rare oral anaerobic bacteria can cause systemic infections, such as osteomyelitis.

Cholangitis with Sphingobacterium multivorum and Acinetobacter junii bacteremia in a patient with gastric cancer: A case report.

INTRODUCTION: Sphingobacterium is an aerobic, glucose non-fermenting, Gram-negative rod bacterium that has been isolated from soil, plants, food, and water sources, including in hospitals. Reports of systemic infections caused by Sphingobacterium multivorum (S. multivorum) are rare, and their clinical and microbiological characteristics remain unclear. Moreover, conventional microbiological methods have limited ability to identify S. multivorum. We report the first case of obstructive cholangitis with bacteremia caused by S. multivorum in a patient with gastric cancer. CASE REPORT: A 68-year-old woman with advanced gastric cancer, hypertension, and hyperlipidemia was admitted with obstructive jaundice, and subsequently developed obstructive cholangitis during the hospital stay. S. multivorum were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S ribosomal RNA sequencing of the patient's blood samples. Based on the antibiotic susceptibility results of the isolates, cefepime was administered intravenously for 14 days, with good therapeutic outcomes. CONCLUSIONS: S. multivorum infection is rare, and its microbiology and pathogenicity in humans is mostly unknown. Therefore, multiple diagnostic approaches should be used to identify S. multivorum, and antimicrobial therapy should be selected based on the in vitro susceptibility. This report provides clinicians with novel information on the clinical manifestations and diagnostic methods for an accurate diagnosis of S. multivorum.

Clinical and microbiological features of obstructive cholangitis with bloodstream infection caused by Pandoraea apista identified by MALDI-TOF mass spectrometry and ribosomal RNA sequencing in a cancer patient.

BACKGROUND: Pandoraea species are multidrug-resistant glucose-nonfermenting gram-negative bacilli that are usually isolated from patients with cystic fibrosis (CF) and from water and soil. Reports of diseases, including bloodstream infections, caused by Pandoraea spp. in non-CF patients are rare, and the clinical and microbiological characteristics are unclear. The identification of Pandorea spp. is limited by conventional microbiological methods and may be misidentified as other species owing to overlapping biochemical profiles. Here, we report the first case of obstructive cholangitis with bacteremia caused by Pandoraea apista in a patient with advanced colorectal cancer. A 61-year-old man with advanced colorectal cancer who underwent right nephrectomy for renal cell carcinoma 4 years earlier with well-controlled diabetes mellitus was admitted to our hospital with fever for 2 days. The last chemotherapy (regorafenib) was administered approximately 3 weeks ago, and an endoscopic ultrasound-guided hepaticogastrostomy was performed 2 weeks ago under hospitalization for obstructive jaundice. Two days prior, he presented with fever with chills. He was treated with piperacillin-tazobactam for obstructive cholangitis and showed improvement but subsequently presented with exacerbation. Bacterial isolates from the blood and bile samples were identified as P. apista using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S ribosomal RNA sequencing. Based on the susceptibility results of the isolates, he was successfully treated with oral trimethoprim-sulfamethoxazole 160 mg/800 mg/day for 14 days for P. apista infection. CONCLUSIONS: Pandoraea species are often misidentified. Therefore, multiple approaches should be used to identify them, and decisions regarding antimicrobial treatment should be based on actual in vitro susceptibility. Only seven cases of Pandoraea spp. bloodstream infections have been reported, and we report the first case of cholangitis with bacteremia.

Effects of infectious disease consultation and antimicrobial stewardship program at a Japanese cancer center: An interrupted time-series analysis.

In cancer patients, appropriate diagnosis and management of infection are frequently challenging owing to subtle or atypical presentation. We investigated the effectiveness of infectious disease (ID) consultations and the Antimicrobial Stewardship Program (ASP) in a Japanese cancer center. This 36-month-period, single-institution, interrupted time series analysis was retrospectively conducted during April 1, 2018-March 31, 2021, to evaluate a two-phase intervention: Phase 1 (notification of antimicrobials by the infection control team) and Phase 2 (establishing an ID consultation service and implementing ASP). Among 32,202 patients hospitalized, 22,096 and 10,106 hospitalizations occurred at baseline and during intervention period, respectively. The Antimicrobial Stewardship Team (AST) provided feedback on specific broad-spectrum antimicrobials in 913 instances (347 appropriate [38%]; 566 inappropriate [62%]), and 440 ID consultations were completed, with a 75% overall acceptance rate for AST suggestions. In Phase 2, monthly carbapenem days of therapy (CAR-DOT) decreased significantly, and narrow-spectrum antibiotic usage increased significantly in both trend and level; monthly DOT of antipseudomonal agents decreased significantly in trend. The results of these analyses of antimicrobial use are consistent with the DOT-based data based on antimicrobial use density (AUD). The total number of inpatient specimens increased significantly; the trend of multidrug-resistant Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus infections decreased, without changes in the incidence of other resistant organisms, all-cause in-hospital mortality, and length of stay. Actual and adjusted CAR purchase costs per patient-day decreased without significant changes in the actual and adjusted purchase cost per patient-day for all intravenous antimicrobials. Combining ID consultation and ASP reduced carbapenem use without negative patient outcomes. Their implementation could facilitate establishment of safe cancer treatment facilities in Japan and improve prognosis in cancer patients.

Exceptional Response of Pancreatic Acinar Cell Carcinoma and Bile Duct Cancer to Platinum-Based Chemotherapy in a Family With a Germline BRCA2 Variant.

ABSTRACT: Pancreatic cancer and its rare subtype, acinar cell carcinoma (PACC), frequently harbor germline and/or somatic variants in homologous recombinant genes, including BRCA2. Individuals possessing germline pathogenic BRCA2 variants are known to have a higher risk of developing various cancers, including breast, ovarian, pancreatic, and bile duct cancers (BDCs). It has been reported that tumors positive for BRCA1/2 variants are sensitive to platinum-based agents. Thus, BRCA1/2 germline testing and comprehensive genomic profiling are recommended to identify genetic susceptibility and to indicate optimal targeted therapy. Here, we report familial occurrence of PACC and BDC associated with BRCA2; both tumors responded exceptionally well to platinum-based chemotherapy. A 37-year-old man was diagnosed with unresectable PACC with a germline BRCA2 variant. He was treated with oxaliplatin-containing chemotherapy and conversion surgery, and remains alive without tumor recurrence after more than 36 months. His father also possessed the identical germline BRCA2 variant and was diagnosed with extrahepatic BDC with lymph node metastases. The tumors showed marked shrinkage upon treatment with cisplatin-containing chemotherapy. Our cases underscore the importance of comprehensive genomic profiling and genetic testing for BRCA2 to ensure optimal therapeutic options for PACC as well as to identify high-risk individuals with various cancers in the family.

Identification of Enzymes from Pseudogluconobacter saccharoketogenes Producing d-Glucaric Acid from d-Glucose.

In 2004, the US Department of Energy listed d-glucaric acid as one of the top 12 bio-based chemicals and a potential biopolymer building block. In this study, we show that Pseudogluconobacter saccharoketogenes strains can produce d-glucaric acid from d-glucose, although in low yield because of the generation of the byproduct 2-keto-d-gluconic acid in large quantities. To improve d-glucaric acid yield, we generated Rh47-3, a P. saccharoketogenes IFO14464 mutant, which produced d-glucaric acid from d-gluconic acid and d-glucose with 81 and 53 mol% yields, respectively. Furthermore, the key enzymes involved in d-glucaric acid production, alcohol dehydrogenase (Ps-ADH), aldehyde dehydrogenase (Ps-ALDH), and gluconate 2-dehydrogenase (Ps-GADH), were purified and their roles in d-glucaric acid synthesis were evaluated. Ps-ADH and Ps-ALDH catalyzed d-glucaric acid production, which was mediated by d-gluconic acid and d-glucuronic acid pathways. In contrast, Ps-GADH inhibited d-glucaric acid production by promoting the formation of 2-keto-d-gluconic acid from d-glucose.

A Schizophyllum commune fungus ball in a lung cancer cavity: a case report.

BACKGROUND: Schizophyllum commune is a basidiomycete that lives in the environment and can cause infections, mainly those of the respiratory system. Although S. commune is increasingly reported as a cause of allergic bronchopulmonary mycosis and sinusitis, cases of fungal ball formation are extremely uncommon. Identification of S. commune is difficult using routine mycological diagnostic methods, and in clinically suspicious cases, internal transcribed spacer sequencing should be used for diagnosis. Here, we report a first case of lung cancer with a fungal ball formation of S. commune, confirmed by analyzing the internal transcribed spacer. CASE PRESENTATION: A 76-year-old man with diabetes and hypertension was admitted to the hospital with a chief complaint of hemosputum, which he had for about 19 months. A computed tomography image of the patient's chest showed a cavity and internal nodule in the left upper lobe of his lung. A left upper lobectomy was performed, and histopathological examination revealed squamous cell carcinoma of the lung and a fungal ball. The isolate from the surgical specimen was identified as S. commune by analyzing the internal transcribed spacer. The patient had no recurrence of the infection during 5 months of follow-up. CONCLUSIONS: Only three cases of lung fungal balls caused by S. commune have been previously reported, and this is the first case of lung cancer cavity with a fungal ball formation. In cases of fungal ball formation in the lung, S. commune should be considered a possible causative microorganism.

Real-world outcome of universal screening for Lynch syndrome in Japanese patients with colorectal cancer highlights the importance of targeting patients with young-onset disease.

Despite the recommendations of the latest guidelines, the practical efficacy of universal screening for identifying Lynch syndrome (LS) among patients with colorectal cancer (CRC) may be limited in the real world due to infrequent referrals and the difficulties of genetic testing. Thus, the present study aimed to retrospectively analyze the results of universal screening of patients with CRC at a referral hospital in Japan. Immunohistochemistry was performed for mismatch repair proteins [including DNA mismatch repair protein MSH6 (MSH6), mismatch repair endonuclease PMS2 (PMS2), DNA mismatch repair protein Msh2 (MSH2) and DNA mismatch repair protein Mlh1 (MLH1)] and BRAF V600E mutation. Tumors that showed the following were considered to indicate LS and patients with such tumors were designated as genetic testing candidates (GTCs): i) Loss of MSH6/MSH2; ii) loss of MSH6 alone; iii) loss of PMS2 alone; and iv) loss of PMS2/MLH1 with negative BRAF V600E. MLH1 methylation and BRAF V600E mutation were analyzed in deficient mismatch repair (dMMR) tumors retrospectively. The frequency of dMMR and GTCs in an independent cohort of patients with young-onset CRC were also investigated. Universal screening revealed dMMR tumors, GTCs and LS probands in 7.3, 3.9 and 0.4%, respectively, of 463 patients with CRC. Although dMMR tumors were observed in both younger (<50 years) and older (≥60 years) patients, the GTCs were enriched in younger individuals. Evaluation of mismatch repair status in an independent cohort confirmed the high rate of GTCs in patients with young-onset CRC. The low detection rate of LS demonstrated in this study questions the implementation of routine universal screening in regions with low prevalence of LS. Considering the enrichment of GTCs in young-onset CRCs, age-restricted strategies may be simple and efficient practical alternatives to universal screening in the real world.

A case of Salmonella osteomyelitis mimicking a malignant tumor of the humerus in an immunocompetent adult patient identified using broad-range polymerase chain reaction with sequencing of a biopsied specimen.

BACKGROUND: Salmonella infections are associated with gastroenteritis, enteric fever, bacteremia, focal infection, and chronic carrier state. Cases of Salmonella osteomyelitis are uncommon and mainly occur in individuals with immunosuppressive conditions. Herein, we report a case of Salmonella osteomyelitis that required differentiation from malignancy in an immunocompetent adult patient. CASE PRESENTATION: A 31-year-old previously healthy male truck driver presented with a 2-week history of pain in his left upper arm. He had fallen off the back of a truck 2 months previously and injured the left side of his body. He also had bloody diarrhea and fever. Computed tomography and magnetic resonance imaging revealed a lesion that appeared to be a bone tumor in the left humerus, and the patient was referred to our cancer center from another clinic. Culture of a biopsy specimen of the left humerus was negative; however, the consensus sequence in broad-range polymerase chain reaction (PCR) showed the highest similarity to the 16S rRNA gene of Salmonella enterica subspecies enterica. Curettage of the left humerus was performed, and the patient was administered levofloxacin for 6 weeks. He recovered left arm function and had no recurrence during 2 months of follow-up. CONCLUSIONS: When the culture of blood or biopsy specimens is negative in situations wherein a specific infection is suspected, broad-range PCR with sequencing should be considered to determine the causative organism.

Challenges in the diagnosis and management of central line-associated blood stream infection due to Exophiala dermatitidis in an adult cancer patient.

BACKGROUND: Exophiala (Wangiella) dermatitidis is a clinically relevant black yeast. Although E. dermatitidis rarely causes human infection, it can cause superficial and deep-seated infections, and cutaneous and subcutaneous diseases. Cases of fungemia and central line-associated bloodstream infections due to E. dermatitidis are extremely uncommon, and their clinical manifestations and prognosis are still not well-known. Herein, we report a case of central line-associated bloodstream infections in a patient with cancer. These infections were caused by melanized yeast that was finally identified as E. dermatitidis via internal transcribed spacer sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. CASE PRESENTATION: A 75-year-old man with thoracic esophageal cancer and early gastric cancer presented with a 1-day history of fever during his hospitalization at our hospital. A central venous port was placed in the patient for total parenteral nutrition. Two E. dermatitidis isolates were recovered from two blood samples drawn at different times from a peripheral vein and this central venous port. The isolate was identified as E. dermatitidis by internal transcribed spacer sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The central venous port was removed, and the patient was administered micafungin and voriconazole. Although the minimum inhibitory concentrations of E. dermatitidis for voriconazole and minimum effective concentrations for micafungin were 2 µg/mL and 4 µg/m, respectively, the bacteremia was successfully treated. CONCLUSIONS: Although no clear treatment guidelines have been proposed for E. dermatitidis infections, immediate removal of central venous catheters is the key to improving central line-associated bloodstream infections.

Pulmonary infections mimicking malignancy on bronchoscopy: A retrospective single-center study in Japan.

BACKGROUND: Pulmonary infections can imitate pulmonary neoplasms. Pulmonary tuberculosis (TB) is a typical example of an infection that mimics cancer and results in unexpected exposure of healthcare workers to TB. A large number of patients with suspected lung malignancy are referred to cancer centers, although the epidemiology of the final diagnosis is unclear in Japan. This study aimed to determine the frequency and nature of pulmonary infections that imitate malignancy among patients with presumed lung cancer that is subsequently diagnosed as a pulmonary infection based on bronchoscopy findings. We also aimed to identify the prevalence of formerly undiagnosed pulmonary tuberculosis that could pose an occupational risk to healthcare workers. METHODS: This single-center retrospective cross-sectional study included patients with suspected pulmonary malignancy who underwent bronchoscopy at a tertiary care cancer center in Japan between April 2017 and March 2020. Electronic medical records of the bronchoscopy database were reviewed to identify the final diagnoses recorded by physicians. RESULTS: Among the 460 patients enrolled in the present study, 362 (78.7%) and 8 (1.7%) had primary or metastatic pulmonary lesions and benign lesions, respectively. Sixty-six patients (14.3%) had nonspecific findings or other pulmonary diseases. Infection was confirmed in 24 patients (5.2%). Mycobacterial infections (n = 16) were the most frequent infectious disease; four patients had TB and 12 had nontuberculous mycobacterial infections. CONCLUSIONS: Despite the rare occurrence of TB in patients with suspected lung malignancy, healthcare workers should remain vigilant regarding the possibility of TB to prevent occupational exposure during invasive procedures such as routine bronchoscopy.

Attitudes toward and current status of disclosure of secondary findings from next-generation sequencing: a nation-wide survey of clinical genetics professionals in Japan.

The management of secondary findings (SFs), which are beyond the intended purpose of the analysis, from clinical comprehensive genomic analysis using next generation sequencing (NGS) presents challenges. Policy statements regarding their clinical management have been announced in Japan and other countries. In Japan, however, the current status of and attitudes of clinical genetics professionals toward reporting them are unclear. We conducted a questionnaire survey of clinical genetics professionals at two time points (2013 and 2019) to determine the enforcement of the SF management policy in cases of comprehensive genetic analysis of intractable diseases and clinical cancer genome profiling testing. According to the survey findings, 40% and 70% of the respondents stated in the 2013 and 2019 surveys, respectively, that they had an SF policy in the field of intractable diseases, indicating that SF policy awareness in Japan has changed significantly in recent years. Furthermore, a total of 80% of respondents stated that their facility had established a policy for clinical cancer genome profiling testing in the 2019 survey. In both surveys, the policies included the selection criteria for genes to be disclosed and the procedure to return SFs, followed by recommendations and proposals regarding SFs in Japan and other countries. To create a better list of the genes to be disclosed, further examination is needed considering the characteristics of each analysis.

Oxidation of isomaltose, gentiobiose, and melibiose by membrane-bound quinoprotein glucose dehydrogenase from acetic acid bacteria.

Membrane-bound quinoprotein glucose dehydrogenase from acetic acid bacteria produces lactobionic acid by the oxidation of lactose. Its enzymatic activity on lactose and maltose is much lower than that on D-glucose. For that reason, the activity of the enzyme on disaccharides has been considered low. In this study, we show that the isomaltose-oxidizing activity of acetic acid bacteria is much higher than their lactose-oxidizing activity. In addition to isomaltose, the enzyme oxidized gentiobiose and melibiose to the same extent. According to the characteristics of the isomaltose-oxidizing activity and investigations using dehydrogenase-deficient mutant bacteria, we identified the responsible enzyme as membrane-bound quinoprotein glucose dehydrogenase.Abbreviations: AAB: acetic acid bacteria; m-GDH: membrane-bound quinoprotein glucose dehydrogenase; DCIP: 2,6-dichlorophenolindophenol; DP: degree of polymerization; HPAEC-PAD: high-performance anion-exchange chromatography with pulsed amperometric detection; NMR: nuclear magnetic resonance; TLC: thin layer chromatography; COSY: correlation spectroscopy.