The modern face of esophageal candidiasis in an oncology center: Correlating clinical manifestations, endoscopic grade, and pathological data in 323 contemporary cancer patients.

OBJECTIVES: Clinical presentation and outcomes of esophageal candidiasis (EC) in cancer patients are scarcely studied in the azole era, as is the correlation between clinical, endoscopic, and histopathological EC manifestations. METHODS: We retrospectively reviewed the risk factors, clinical features, and outcomes of pathology-documented EC cases at MD Anderson Cancer Center. We further assessed associations between presence of symptoms, standardized 4-stage endoscopic grade (Kodsi classification), histopathological data, and fluconazole treatment failure. RESULTS: Among 323 cancer patients with EC, 89% had solid tumors, most commonly esophageal cancer (29%). Thirty-three percent of EC patients were asymptomatic. The proportion of symptomatic EC patients significantly increased with endoscopic grade (P = 0.005). Among 202 patients receiving oral fluconazole, 27 (13%) had treatment failure. Underlying esophageal disease was the only independent predictor of fluconazole treatment failure (odds ratio: 3.88, P = 0.005). Endoscopic grade correlated significantly with Candida organism burden (Correlation coefficient [ρ] = 0.21, P < 0.01) and neutrophilic inflammation (ρ = 0.18, P < 0.01). Candida invasion of the squamous mucosal layer was associated with treatment failure (P = 0.049). CONCLUSIONS: EC was predominantly encountered in patients with solid tumors. One-third of EC patients were asymptomatic, challenging traditional symptom-based diagnosis. The development of integrated clinicopathological scoring systems could further guide the therapeutic management of cancer patients with EC.

A Rare Cause of Empyema and Bacteremia Due to Shewanella Species in Alcoholic Cirrhosis Patients: A Case Report and Comprehensive Review of Literature.

BACKGROUND Shewanella spp. are gram-negative facultative anaerobic, oxidase-positive, motile bacilli that are ubiquitous but commonly occur in seawater and can cause opportunistic infection. Reports on the risk factors for Shewanella infection, its severity, antibiotic susceptibility, and prognosis are limited. This report is of a 78-year-old man with alcoholic cirrhosis presenting with bacteremia and empyema due to infection with Shewanella spp. CASE REPORT A 78-year-old man with alcoholic cirrhosis (Child-Pugh B) presented to our emergency room with a high fever. He had eaten raw fish one week prior to admission. Chest computed tomography showed a right unilateral pleural effusion, and he was hospitalized with suspected empyema. Shewanella spp. was detected in the pleural effusion and blood cultures. We initiated piperacillin/tazobactam and vancomycin empirically and switched to ceftriaxone; the effusion was successfully treated using antibiotics and pleural drainage. However, on hospitalization day 53, the patient died of aspiration pneumonia. In our literature review, we extracted 125 reported cases (including our case) and found that men were disproportionately affected (81%); median age was 61.6 (56-75) years; underlying diseases included hepatobiliary disease (33%), malignancy (25%), and cardiac disease (24%); Shewanella spp. infection sites were skin and soft tissue (35%), respiratory system (18%), and hepatobiliary system (11%); and management included antibiotics (100%), drainage (16%), and debridement (16%). The survival rate was 74% with antibiotics alone. CONCLUSIONS Our case highlights that clinicians should recognize Shewanella spp. as a cause of empyema and bacteremia in patients with liver cirrhosis, and that microbiological diagnosis with antibiotic sensitivity testing and treatment should be undertaken urgently to prevent fatal sepsis.

Disseminated Histoplasmosis in a Patient with Myelofibrosis on Ruxolitinib: A Case Report and Review of the Literature on Ruxolitinib-Associated Invasive Fungal Infections.

Ruxolitinib, a selective inhibitor of Janus kinases, is a standard treatment for intermediate/high-risk myelofibrosis (MF) but is associated with a predisposition to opportunistic infections, especially herpes zoster. However, the incidence and characteristics of invasive fungal infections (IFIs) in these patients remain uncertain. In this report, we present the case of a 59-year-old woman with MF who developed disseminated histoplasmosis after seven months of ruxolitinib use. The patient clinically improved after ten weeks of combined amphotericin B and azole therapy, and ruxolitinib was discontinued. Later, the patient received fedratinib, a relatively JAK2-selective inhibitor, without relapse of histoplasmosis. We also reviewed the literature on published cases of proven IFIs in patients with MF who received ruxolitinib. Including ours, we identified 28 such cases, most commonly due to Cryptococcus species (46%). IFIs were most commonly disseminated (39%), followed by localized lung (21%) infections. Although uncommon, a high index of suspicion for opportunistic IFIs is needed in patients receiving JAK inhibitors. Furthermore, the paucity of data regarding the optimal management of IFIs in patients treated with JAK inhibitors underscore the need for well-designed studies to evaluate the epidemiology, pathobiology, early diagnosis, and multimodal therapy of IFIs in patients with hematological malignancies receiving targeted therapies.

Invasive fusariosis in patients with leukaemia in the era of mould-active azoles: increasing incidence, frequent breakthrough infections and lack of improved outcomes.

OBJECTIVES: Historically, patients with leukaemia and invasive fusariosis (IF) have experienced poor outcomes in the setting of persistent immunosuppression. Herein, we retrospectively reviewed the incidence, presentation and outcomes of IF that are scarcely studied in contemporary cohorts of leukaemia patients. METHODS: We identified adult leukaemia patients with proven or probable IF at MD Anderson Cancer Center during 2009-21. Independent risk factors for 42 day mortality after IF diagnosis were determined using a multivariable logistic regression model. Combined with historical data, the annual IF incidence density over the past 23 years was estimated using Poisson regression analysis. RESULTS: Among 140 leukaemia patients with IF (114 proven), 118 patients (84%) had relapsed/refractory leukaemia and 124 (89%) had neutropenia at IF diagnosis. One hundred patients (71%) had pulmonary IF, 88 (63%) had disseminated IF and 48 (34%) had fungaemia. Coinfections were common (55%). Eighty-nine patients (64%) had breakthrough IF to mould-active triazoles. Most patients (84%) received combination antifungal therapy. Neutrophil recovery [adjusted OR (aOR), 0.04; 95% CI, 0.01-0.14; P < 0.0001], pulmonary IF (aOR, 3.28; 95% CI, 1.11-9.70; P = 0.032) and high SOFA score (aOR, 1.91 per 1-point increase; 95% CI, 1.47-2.50; P < 0.0001) were independent predictors of 42 day mortality outcomes. From 1998 to 2021, IF incidence density increased significantly at an annual ratio of 1.03 (95% CI, 1.01-1.06; P = 0.04). CONCLUSIONS: IF is predominantly seen in patients with relapsed/refractory leukaemia and increasingly seen as a breakthrough infection to mould-active triazoles. Despite frequent combination antifungal therapy, high mortality rates have persisted in patients with lasting neutropenia.

Invasive mucorales sinusitis in a young patient with Emberger syndrome and newly diagnosed AML: A case report and literature review of invasive fungal infections in GATA2 deficiency.

Germline pathogenic variants (PVs) in the gene encoding the GATA2 transcription factor can result in profound reductions of monocytes, dendritic cells, natural killer cells and B cells. GATA2 PVs are associated with an increased risk of myeloid malignancies and a predisposition to nontuberculous mycobacterial and human papillomavirus infections. Additionally, invasive fungal infections (IFIs) have been reported in individuals with GATA2 PVs, even in the absence of myeloid malignancies. In this report, we present the case of a 40-year-old man with Emberger syndrome (GATA2 mutation, recently diagnosed acute myeloid leukaemia [AML] and history of lymphedema with hearing loss) who developed Mucorales sinusitis while receiving his first course of remission induction chemotherapy. Additionally, we review the literature on all published cases of proven IFIs in patients with GATA2 PVs. Clinicians should be aware that patients with GATA2 PVs could be vulnerable to opportunistic IFIs, even in the absence of AML and antineoplastic therapy. Furthermore, the distinctly unusual occurrence of mucormycosis during the first course of induction chemotherapy for AML in our patient indicates that patients with germline GATA2 PVs receiving induction chemotherapy for AML might be at high risk for early onset of IFIs due to aggressive, opportunistic moulds.

International multicenter study comparing COVID-19 in patients with cancer to patients without cancer: Impact of risk factors and treatment modalities on survivorship.

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03). Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality. Funding: National Cancer Institute and National Institutes of Health.

Burnout and its associated factors among healthcare workers and the general working population in Japan during the COVID-19 pandemic: a nationwide cross-sectional internet-based study.

OBJECTIVES: To examine the prevalence and the associated factors of burnout among both healthcare workers (HCWs) and the general working population, which has not yet been unknown, using large-scale, nationwide data. DESIGN: Cross-sectional internet-based study. SETTING: Nationwide internet survey conducted between 8 and 26 February 2021 in Japan. PARTICIPANTS: Workers aged 20-64 years. We classified the workers as HCWs and the general working population. EXPOSURES: Demographic characteristics (age, sex and marital status), socioeconomic status (education, employment and income), health-related, work-related and industry-related factors (smoking, alcohol use, physical and psychiatric comorbidities, working hours, types of healthcare professionals, experience on the COVID-19 frontline and working industries). MAIN OUTCOME MEASURES: Burnout defined as a score of ≥3 points on the Mini-Z Single-Item Burnout Scale. RESULTS: Of the included 12 650 workers, 1087 were HCWs. After inverse probability weighting on data from the 2016 Comprehensive Survey of Living Conditions, burnout in HCWs and the general working population was 33.5% (95% CI 29.2% to 38.0%) and 31.0% (95% CI 29.7% to 32.4%), respectively. In the weighted multivariable modified Poisson regression models, working 60 hours or more was associated with burnout in all workers (HCWs: prevalence ratio (PR) 2.52, 95% CI 1.68 to 3.76; general population: PR 1.26, 95% CI 1.07 to 1.48). Widowed/separated compared with married was associated with burnout only among HCWs (PR 1.69, 95% CI 1.16 to 2.47), whereas presence of physical or psychiatric comorbidities was associated with burnout among the general working population (PR 1.14, 95% CI 1.03 to 1.28; and PR 1.65, 95% CI 1.45 to 1.87, respectively). CONCLUSIONS: Burnout was prevalent in both HCWs and the general working population in Japan. Both common and specific risk factors were observed. Our findings highlight the need for the general workplace policy and targeted interventions for burnout prevention.

International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship.

Background: In this international multicenter study we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were more likely to be pancytopenic, and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding two weeks (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms (p≤0.01). By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46; 95% CI 1.03 to 2.07; p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55; 95% CI 3.34 to6.20; p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58; CI 0.39-0.88; p=0.009). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who did not (5.9% vs 17.6%; p=0.03). Conclusions: Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality. Condensed Abstract: In this large multicenter worldwide study of 4015 patients with COVID-19 that included 1115 patients with cancer, we found that cancer is an independent risk factor for increased 30-day all-cause mortality. Remdesivir is a promising treatment modality to reduce 30-day all-cause mortality.

Predicting bacteremia caused by Streptococcus anginosus group: A new scoring method.

BACKGROUND: Viridans group streptococci (VGS) are the most common causative organisms of infective endocarditis. Among VGS, the Streptococcus anginosus group (SAG) is often associated with abscess formation, and delayed diagnosis leads to increased morbidity and mortality. This study aims to examine the factors associated with SAG bacteremia and develop a predictive scoring method. METHODS: This single-center retrospective case-control study of patients with VGS bacteremia compared the background and clinical characteristics between the SAG and non-SAG groups. The univariate analysis used the χ2 test and t-test. The multivariate analysis was conducted using logistic regression. RESULTS: Out of 161 patients, 95 had SAG and 66 had non-SAG bacteremia. Age >63 years: 2 points (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.64-7.54); solid tumor: 2 points (OR = 4.44, 95% CI: 1.42-6.77); C-reactive protein >7.61 mg/dL: 3 points (OR = 5.40, 95% CI: 2.49-11.72), and white blood cell count >8550/µL: 2 points (OR = 2.76, 95% CI: 1.29-2.91) were found to be independently associated with SAG bacteremia. After totaling the above variables and adding 1 point for diabetes mellitus, the area under the receiver operating curve was 0.81 (95% CI: 0.74-0.88). The sensitivity and specificity were 51% and 88%, respectively, at a cut-off of 6 points. CONCLUSIONS: In patients with VGS bacteremia, a score of 6 points or higher using this method predicts SAG with high specificity.

Management of Porcelain Gallbladder, Its Risk Factors, and Complications: A Review.

The porcelain gallbladder condition describes gallbladder calcification. While gallbladder calcification is believed to increase the risk of developing gallbladder cancer, recent reports have shown that the malignancy risk is much lower than previously reported. Symptomatic patients with porcelain gallbladder should be recommended for cholecystectomy, but the management of asymptomatic patients is debatable. Based on recent evidence, prophylactic cholecystectomy is not routinely recommended in all patients with porcelain gallbladder. From the assessment of the current literature, there are three essential factors in the management of patients with porcelain gallbladder: (1) symptoms or complications of gallbladder disease, (2) calcification pattern and (3) patient age and comorbidities. Patients who do not undergo cholecystectomy should be educated about the symptoms of gallbladder diseases, and a thorough discussion is essential between patients and clinicians.

Campylobacter fetus bacteremia and meningitis in an acute lymphoblastic leukemia patient undergoing maintenance therapy: a case report.

BACKGROUND: Campylobacter fetus is an uncommon Campylobacter species, and its infections mainly cause infective endocarditis, aortic aneurysm, and meningitis rather than enteritis. It is more likely to be detected in blood than Campylobacter jejuni or Campylobacter coli, specifically reported in 53% of patients. In our case, C. fetus was detected in both blood and cerebrospinal fluid (CSF) cultures. CASE PRESENTATION: A 33-year-old woman, who was on maintenance chemotherapy for acute lymphoblastic leukemia (ALL), presented to our clinic with chief complaints of severe headache and nausea. Blood and CSF cultures revealed C. fetus. We administrated meropenem 2 g intravenously (IV) every 8 h for 3 weeks, and she was discharged without neurological sequelae. CONCLUSION: We encountered a case of C. fetus meningitis without gastrointestinal symptoms, neck stiffness or jolt accentuation in a patient with ALL. Undercooked beef was considered the source of C. fetus infection in this case, suggesting that the need for a neutropenic diet and safe food handling be considered.

Aspergillus meningitis in a patient with chronic lymphocytic leukemia.

Central nervous system aspergillosis is relatively rare and difficult to diagnose. Here, we report a case of 90-year-old man with chronic lymphocytic leukemia who presented with a month-long gradually worsening headache followed by 3 days of low-grade fever associated with altered mental status. Aspergillus meningitis diagnosed using Aspergillus galactomannan antigen in the cerebrospinal fluid and treated with voriconazole. Delayed diagnosis and treatment of Aspergillus meningitis is typically associated with high mortality; therefore, it is imperative to include this disease in the differential diagnoses of subacute meningitis.

Calculus pyelonephritis associated with ureterocutaneostomy.

A 79-year-old woman with a history of total hysterectomy for cervical cancer with ureterocutaneostomy presented with high fever. She had tenderness and a hard lump around the ureterocutaneostomy site. Computed tomography scan revealed 1.5 cm ureteral calculus in ureterocutaneous fistula (Fig. 1A) associated with bilateral hydronephrosis (Fig. 1B) and we performed a transureteral stent insertion. Blood culture grew methicillin-sensitive Staphylococcus aureus (MSSA), Haemophilus parainfluenzae, Veillonella species and Bacteroides fragilis and urine culture revealed Escherichia coli, MSSA, and Enterococcus faecalis. The patient's clinical signs and symptoms gradually improved with ampicillin/sulbactam. Patients with urinary diversions including ureterocutaneostomy and iliac conduits are at increased risk of urolithiasis (1), which can cause sepsis, pyelonephritis, and renal insufficiency (2). Since most patients become colonized with a multitude of bacteria including Enterobacteriaceae and skin flora such as Staphylococcus aureus and Streptococcus spp., we should empirically treat with broad-spectrum antimicrobials until the culture results are available. Early diagnosis and urological intervention are required because it can be life-threatening with delayed treatment.

A case of primary ductal adenocarcinoma of the lacrimal gland: histopathological and immunohistochemical study.

We encountered primary ductal adenocarcinoma of the lacrimal gland in a 67-year-old Japanese man. To the best of our knowledge, only three cases of primary ductal adenocarcinoma of the lacrimal gland have been reported in the literature. The patient was admitted because of visual disturbance, and a mass measuring about 3 cm in diameter was revealed in the right orbit. The mass was resected, and primary ductal adenocarcinoma of the lacrimal gland was diagnosed histopathologically. He died from recurrence at the primary site and metastasis to the brain, lungs, liver, common bile duct, and pancreas 2 years and 10 months after surgery although adjunctive orbital radiotherapy was given. Immunohistochemically, the characteristics of cancer cells were similar to those of salivary duct carcinoma, namely positivity for cytokeratin (CK) 7, 10, 17, 18, 19, and 34betaE12, and negativity for CK20. It was not clear whether the ductal adenocarcinoma originated from the ductal or acinar epithelium of the lacrimal gland, because the immunohistochemical features of both epithelia were identical.