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A 9-year-old girl presented to clinic with sore throat and fever. “Doughnut” lesions were seen on the palate, and throat culture confirmed infection with group A beta-hemolytic streptococcus.

Pernicious anemia is a macrocytic anemia caused by vitamin B12 deficiency that results from a lack of intrinsic factor. Lack of intrinsic factor may be caused by atrophic gastritis and damage to the oxyntic mucosa and parietal cells, which normally produce hydrochloric acid and intrinsic factor. Glossitis presents in up to 25% of people with pernicious anemia, initially as bright red plaques that may evolve into atrophy of the lingual papillae. Oral manifestations of pernicious anemia, including glossitis and stomatitis, may occur in the absence of anemia and represent an early clinical sign of vitamin B12 deficiency. Other causes of glossitis include nutritional deficiencies of vitamin B12, folic acid, riboflavin and niacin. Here, Kobayashi and Iwasaki examine the case of a 69-year-old Japanese woman with pernicious anemia.

The study by Lefranc et al. confirmed that rapamycin, which is a TOR inhibitor, increased the susceptibility of the Candida spp. to caspofungin (Lefranc et al., 2024). [...]it is believed that the combination of these drugs has a synergistic effect because amphotericin B exerts a sub-lethal activity that creates pores in fungal cells, enabling the penetration of the antimicrobial agents used in combination (Brennan-Krohn et al., 2021). [...]due to its intrinsic immunosuppressive properties, rapamycin has the potential to worsen infections as an adverse effect. [...]there are difficulties with drug interactions.

The pathophysiology of SAE encompasses the TLR4/NF-κB pathway as well as various signal transduction pathways, including mitogen-activated protein kinase (MAPK), Janus kinase/signal transduction and activator of transcription (JAK/STAT), and Nod-like receptor protein 3 (NLRP3) inflammasome, among others. [...]we investigated the potential of a multifaceted therapeutic strategy that integrates inhibitors aimed at each of these signaling pathways. According toTable 1, the neuroprotective effects of minocycline are multifaceted, indicating that its mechanism of action is not restricted to the inhibition of the TLR4 pathway by LPS stimulation but also involves the TLR2 pathway in response to stimulation by various pathogens (Staphylococcus aureus) (Zou et al., 2025). [...]it has been established that the activation of microglia can be inhibited in non-infectious conditions, such as cerebral ischemia (Yrjänheikki et al., 1998). [...]caution must be observed when generalizing these findings to the management of SAE. In a recent meta-analysis of body temperature data from JSF case reports, we identified a significant hypothermic effect in the tetracycline and fluoroquinolone combination group in comparison to the tetracycline monotherapy group.

[...]PLCγ induces an increase in Ca2+ and triggers the calcineurin and NFAT pathways. [...]Syk-dependent reactive oxygen species (ROS) production activates the nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome, which triggers caspase-1 activation and cleaves pro-IL-1b to generate IL-1b. Additionally, caspofungin has an inhibitory effect on host immune cells against Syk (Itoh et al., 2021), which promotes the suppression of COVID-19 severity by inhibiting inflammatory cytokines, immunothrombosis, and ARDS. [...]we believe that empirical administration of caspofungin to COVID-19 patients may prevent worsening of prognosis by preventing fungal infection complications in addition to reducing the severity of COVID-19, but is especially recommended in hospitalized COVID-19 patients with risk factors for fungal infection complications, such as heart failure and bacterial co-infection.

Sepsis is a systemic reaction to an infection and resulting in excessive production of inflammatory cytokines and chemokines. It sometimes results in septic shock. The present study aimed to identify quinolone antibiotics that can reduce tumor necrosis factor alpha (TNFα) production and to elucidate mechanisms underlying inhibition of TNFα production. We identified quinolone antibiotics reduced TNFα production in lipopolysaccharide (LPS)-stimulated THP-1 cells. Sitafloxacin (STFX) is a broad-spectrum antibiotic of the quinolone class. STFX effectively suppressed TNFα production in LPS-stimulated THP-1 cells in a dose-dependent manner and increased extracellular signal-regulated kinase (ERK) phosphorylation. The percentage of intracellular TNFα increased in LPS-stimulated cells with STFX compared with that in LPS-stimulated cells. TNFα converting enzyme (TACE) released TNFα from the cells, and STFX suppressed TACE phosphorylation and activity. To conclude, one of the mechanisms underlying inhibition of TNFα production in LPS-stimulated THP-1 cells treated with STFX is the inhibition of TNFα release from cells via the suppression of TACE phosphorylation and activity. STFX may kill bacteria and suppress inflammation. Therefore, it can be effective for sepsis treatment.

We aimed to detect possible changes in Candida species distribution over time and to know the antifungal susceptibility profile of isolates obtained from patients with bloodstream infection (BSI) due to this pathogen. Risk factors associated with 30-day mortality were also assessed. We conducted a retrospective cohort study of patients diagnosed with Candida BSI at a Japanese university hospital from 2013 to 2021. The change in the distribution pattern of the Candida spp. isolated was examined by considering three successive sub-periods of 3 years each. Risk factors for 30-day mortality were determined using Cox regression analysis. In the entire study period, Candida albicans was the most frequent species (46.7%), followed by Candida glabrata (21.5%) and Candida parapsilosis (18.7%). There was no change in Candida species distribution comparing the three sub-periods analyzed. All isolates were susceptible to micafungin, and most were susceptible to fluconazole, except for C. glabrata. No isolates were resistant to amphotericin B or voriconazole. The overall 30-day mortality was 40.2%. Univariate analysis revealed an association between 30-day mortality and central venous catheter (CVC) removal at any time, high Pitt bacteremia score (PBS), and high Charlson comorbidity index (CCI). Multivariate Cox analysis found that high PBS was the only independent predictor of 30-day mortality; subsequent multivariate Cox regression demonstrated that early CVC removal significantly reduced 30-day mortality. Candida species distribution and antifungal susceptibility profile in our hospital remained similar from 2013 to 2021. Early CVC removal may improve candidemia outcomes.

Purpose The Japanese Society of Medical Oncology (JSMO) published a guideline (GL) on febrile neutropenia (FN) in 2017. This study aims to identify promoting factors and disincentives for complying with GL recommendations according to attributes of doctors providing chemotherapy. Methods A questionnaire survey was conducted with SurveyMonkey™ for physician members of the Japanese Association of Supportive Care in Cancer and relevant academic organizations. Each question had four options (always do, do in more than half of patients, do in less than half, do not at all) and a free description form. Responses were analyzed according to the respondents’ attributes. Result Seven hundred eighty-eight out of retrieved 801 responses were available for analysis. Multivariable analysis demonstrated that the percentage of GL users was higher among women and Japanese Society of Clinical Oncology members. The overall compliance rate was higher among women, JSMO members, and board-certified medical oncologists. Internists emphasized the significance of collecting blood cultures at FN onset, and surgeons stressed the importance of G-CSF prophylaxis. Hematologists were less likely to adhere to recommendations on risk assessment of FN by the Multinational Association of Supportive Care in Cancer score and administration of gammaglobulin products. However, those are acceptable due to the characteristics of their practice. Eight recommendations had no difference in compliance rates between users and non-users, some of whose statements were ambiguous and discretionary. Conclusion Women were more likely to use and adhere to GL. The recommendations should be developed considering the characteristics of specialty and subspecialty and avoiding ambiguity and discretionary statements.

Objective Methicillin-resistant (MR) Staphylococcus aureus bacteremia (SAB) is associated with higher mortality rates than methicillin-susceptible (MS) SAB. This study assessed potential predictors of mortality and evaluated the association of methicillin resistance with mortality in patients with SAB. Methods We conducted a retrospective cohort study in patients with hospital-acquired SAB, from 2009 to 2018. Clinical features of patients with MR-SAB were compared with those of patients with MS-SAB and predictors of 30-day mortality were determined using Cox regression analysis. Results Among 162 patients, 56.8% had MR-SAB. Overall 30-day mortality was 19.1%; MR-SAB had higher mortality (25.0%) than MS-SAB (11.4%). Univariate analysis highlighted long-term hospitalization, prior antibiotics use, and delayed initiation of appropriate antibiotics as risk factors. Cox regression analysis showed that respiratory tract source, Pitt bacteremia score, Charlson comorbidity index, and appropriate antibiotic therapy within 24 hours were independently and significantly associated with 30-day mortality outcome. Conclusions Methicillin resistance was not an independent risk factor for mortality in patients with SAB. Early, appropriate antibiotic treatment is an important prognostic factor.

Although Sepsis-3 doesn’t require evidence of bacteremia to diagnose sepsis, clinicians often want to identify the causative pathogen at autopsy. In principle, if the blood cultures are the same at ante- and postmortem, the cause of death is obvious. However, interpretations of postmortem blood cultures are often difficult due to discordance, negativity, mixed infection, and contamination, of pathogens occupying ≥ 50% of the tests. To increase specificity identifying agonal phase sepsis in the situations where blood cultures are discordant, multiple or negative at postmortem, we established a scoring system using blood cultures, procalcitonin (PCN) showing highest sensitivity and specificity for postmortem serum, and bone marrow polyhemophagocytosis (PHP). Histological sepsis showed significantly higher levels of culture score (2.3 ± 1.5 vs. 0.4 ± 0.5, p  < 0.001), PHP score (2.5 ± 0.8 vs. 1.0 ± 1.1, p  < 0.001), and PCN score (1.8 ± 0.8 vs. 0.8 ± 0.6, p  < 0.01) than non-septic patients. Receiver operating characteristic curve analysis indicated that estimation of three scores was the most reliable indicator for recognizing agonal phase sepsis. These findings suggest that the combination of these three inspections enables to determine the pathological diagnoses of sepsis even it is not obvious by discordant, mixed or negative blood cultures.