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Chronic lymphocytic leukemia (CLL), the most common leukemia worldwide, is associated with increased COVID-19 mortality. Previous studies suggest only a portion of vaccinated CLL patients develop severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibodies. Whether the elicited antibodies are functional and/or accompanied by functional T-cell responses is unknown. This prospective cohort study included patients with CLL who received SARS-CoV-2 and PCV13 vaccines (not concurrently). The primary cohort included adults with CLL off therapy. Coprimary outcomes were serologic response to SARS-CoV-2 (receptor binding domain [RBD] immunoassay) and PCV13 vaccines (23-serotype IgG assay). Characterization of SARS-CoV-2 antibodies and their functional activity and assessment of functional T-cell responses was performed. Sixty percent (18/30) of patients demonstrated serologic responses to SARS-CoV-2 vaccination, appearing more frequent among treatment-naïve patients (72%). Among treatment-naïve patients, an absolute lymphocyte count ≤24 000/µL was associated with serologic response (94% vs 14%; P < .001). On interferon-γ release assays, 80% (16/20) of patients had functional spike-specific T-cell responses, including 78% (7/9) with a negative RBD immunoassay, a group enriched for prior B-cell–depleting therapies. A bead-based multiplex immunoassay identified antibodies against wild-type and variant SARS-CoV-2 (α, β, γ, and δ) in all tested patients and confirmed Fc-receptor binding and effector functions of these antibodies. Of 11 patients with negative RBD immunoassay after vaccination, 6 (55%) responded to an additional mRNA-based vaccine dose. The PCV13 serologic response rate was 29% (8/28). Our data demonstrate that SARS-CoV-2 vaccination induces functional T-cell and antibody responses in patients with CLL and provides the framework for investigating the molecular mechanisms and clinical benefit of these responses. This trial was registered at www.clinicaltrials.gov as #NCT05007860.

Dabigatran etexilate is the first commercially available oral direct thrombin inhibitor. A single trial has studied patients at risk for stroke associated with nonvalvular atrial fibrillation; in this trial, dabigatran 150 mg twice a day met the criteria for superiority over warfarin in preventing stroke and systemic embolism while reducing the rate of hemorrhagic stroke with a similar risk of major bleeding. For the treatment of venous thromboembolism, dabigatran 150 mg twice a day had comparable efficacy and safety versus warfarin. In contrast, dabigatran was less effective than enoxaparin 30 mg twice a day in venous thromboembolism prevention in orthopedic surgery. Advantages of dabigatran over warfarin include its lack of need for routine laboratory monitoring, a fixed-dose regimen, and potentially fewer clinically important drug interactions. Concerns include higher incidences of dyspepsia and gastrointestinal bleeding, twice-daily dosing, and lack of effective antidote. Additional drawbacks include higher drug cost versus warfarin, accumulation in case of renal impairment, higher discontinuation rates due to adverse events, and limited long-term safety and trial data. From a payer perspective, overall costs will be higher with dabigatran compared with warfarin, but dabigatran does meet the threshold to be considered a cost-effective therapy. In addition, the lack of need for regular laboratory monitoring is a quality of life advantage for patients on dabigatran. These observations suggest that dabigatran is a valuable addition to the therapeutic armamentarium for stroke prevention in selected patients with atrial fibrillation although caution should be exercised given the limited data on this agent and higher cost.

A fungus, recovered from a skin lesion of a patient, produced velvety to powdery, white to deep yellow colonies on Sabouraud glucose agar. Microscopically, it produced a large number of cylindric, smooth-walled, three- to eight-celled macroconidia but failed to produce microconidia on a variety of nutritional media such as rice grains, cornmeal dextrose, potato dextrose, Sabouraud glucose, oatmeal and lactrimel agars. It hydrolysed urea in 7 days, perforated hair in vitro and required thiamine for growth. This isolate represents an atypical variant of Trichophyton tonsurans var. sufureum subvar. perforans.

Importance Chemotherapy-related hospitalizations in patients with advanced cancer are common, distressing, and costly. Methods to identify patients at high risk of chemotherapy toxic effects will permit development of targeted strategies to prevent chemotherapy-related hospitalizations. Objective To demonstrate the feasibility of using readily available clinical data to assess patient-specific risk of chemotherapy-related hospitalization. Design, Setting, and Participants Nested case-control study conducted from January 2003 through December 2011 at the Mass General/North Shore Cancer Center, a community-based cancer center in northeastern Massachusetts. The parent cohort included 1579 consecutive patients with advanced solid-tumor cancer receiving palliative-intent chemotherapy. Case patients (n = 146) included all patients from the parent cohort who experienced a chemotherapy-related hospitalization. Controls (n = 292) were randomly selected from 1433 patients who did not experience a chemotherapy-related hospitalization. Exposures Putative risk factors for chemotherapy-related hospitalization—including patient characteristics, treatment characteristics, and pretreatment laboratory values—were abstracted from medical records. Multivariable logistic regression was used to model the patient-specific risk of chemotherapy-related hospitalization. Main Outcomes and Measures Chemotherapy-related hospitalization, as adjudicated by the oncology clinical care team within a systematic quality-assessment program. Results A total of 146 (9.2%) of 1579 patients from the parent cohort experienced a chemotherapy-related hospitalization. In multivariate regression, 7 variables were significantly associated with chemotherapy-related hospitalization: age, Charlson comorbidity score, creatinine clearance, calcium level, below-normal white blood cell and/or platelet count, polychemotherapy (vs monotherapy), and receipt of camptothecin chemotherapy. The median predicted risk of chemotherapy-related hospitalization was 6.0% (interquartile range [IQR], 3.6%-11.4%) in control patients and 14.7% (IQR, 6.8%-22.5%) in case patients. The bootstrap-adjusted C statistic was 0.71 (95% CI, 0.66-0.75). At a risk threshold of 15%, the model exhibited a sensitivity of 49% (95% CI, 41%-57%) and a specificity of 85% (95% CI, 81%-89%) for predicting chemotherapy-related hospitalization. Conclusions and Relevance In patients initiating palliative chemotherapy for cancer, readily available clinical data were associated with the patient-specific risk of chemotherapy-related hospitalization. External validation and evaluation in the context of a clinical decision support tool are warranted.

Fluvastatin, a cholesterol-lowering drug, exhibited minimal activity (MICs of 64 to >128 microg/ml) against Candida species and Cryptococcus neoformans. When fluvastatin was combined with fluconazole or itraconazole, both synergistic and additive effects were noted (fractional inhibitory concentration indices of < or = 0.156 to 0.625; fractional lethal concentration indices of < or = 0.156 to 0.75). This combined fungicidal activity was confirmed by time-versus-killing studies.

Three zygomycetes (order Mucorales), isolated from clinical specimens, whose generic or species identification were uncertain, were definitively identified on the basis of the production of zygospores resulting from mating studies. These three isolates were identified as Mucor circinelloides f. circinelloides, Rhizomucor pusillus, and Absidia corymbifera. The production of true zygospores, the "last word" in zygomycete taxonomy, should be considered as a diagnostic tool for the definitive identification of rare, unusual, or atypical heterothallic zygomycetes. Practical considerations, however, limit this method to reference laboratories.

Zygomycetes is a class of saprophytic fungi causing opportunistic infections. These fungi can cause six distinct clinical manifestations, which can be fatal without rapid diagnosis and treatment. The fungi have a predilection for blood vessel invasion, causing thrombosis, infarction and necrosis of the tissue.A 25-year-old black woman, a drug abuser, delivered a female infant and the placenta en route to the hospital. The estimated gestational age of the infant was 35 weeks. The infant and mother had an unremarkable hospital course. Evaluation of the placenta revealed extensive involvement of the membranes, umbilical cord and chorionic plate by fungal hyphae without any surrounding inflammation. These hyphae were seen invading blood vessels, but there was no evidence of thrombosis or necrosis. The morphology of the hyphae was consistent with Zygomycetes. The mother was contacted and claimed to be well.Only one case of placental involvement by Mucor has been published since 1966. Despite the observation of Zygomyceteslike hyphae in the placenta, both the mother and infant were reported to be doing well.

Dermatophytes, members of the anamorphic genera Epidermophyton, Microsporum, and Trichophyton, are capable of invading keratinous tissue, causing cutaneous infection referred to as dermatophytosis. These species may be anthropophilic, zoophilic, or geophilic based on host preference and natural habitat. These groupings are epidemiologically significant. This article provides a description of the genera and species of the dermatophytes--gross and microscopic--and the tests that may be necessary to confirm their identification.

A fungus, recovered from a skin lesion of a patient, produced velvety to powdery, white to deep yellow colonies on Sabouraud glucose agar. Microscopically, it produced a large number of cylindric, smooth-walled, three- to eight-celled macroconidia but failed to produce microconidia on a variety of nutritional media such as rice grains, cornmeal dextrose, potato dextrose, Sabouraud glucose, oatmeal and lactrimel agars. It hydrolysed urea in 7 days, perforated hair in vitro and required thiamine for growth. This isolate represents an atypical variant of Trichophyton tonsurans var. sufureum subvar. perforans.

Mucor ramosissimus Samutsevitsch is presented for the first time as an etiologic agent of cutaneous zygomycosis in a patient with aplastic anemia on immunosuppressive therapy. This report also represents the third case caused by this species reported in the literature. A biopsy taken from a lesion on the patient's thigh revealed broad, nonseptate, nonbranching hyphae compatible in morphology with a Zygomycete; M. ramosissimus was cultured twice from the thigh lesion. The patient was treated successfully with amphotericin B. Identifying features of M. ramosissimus include the following: numerous sporangia lacking columellae and resembling those of Mortierella spp., short, erect sporangiophores repeatedly branching sympodially; tough, persistent, and diffluent sporangial walls; numerous oidia in chains; extremely low colonies; and restricted growth at 36 degrees C. This paper describes the isolate and strives to alert the clinical microbiologist to this rarely reported pathogen.

A case of pneumonia caused by Cunninghamella bertholletiae is described in a patient with chronic lymphatic leukemia. The species of Cunninghamella, a genus in the order Mucorales, are characterized by the formation of conidia on the surface of an inflated conidiophore (vesicle). C. bertholletiae, not C. elegans, is the most appropriate name for this fungus. This zygomycete was resistant by in vitro sensitivity testing to amphotericin B. The source of the infection is not known.

(1925). The Mode of Action of Bayer ‘205’ on Trypanosomes. Annals of Tropical Medicine & Parasitology: Vol. 19, No. 2, pp. 235-241.

Scolecobasidium humicola, a soil fungus and etiologic agent of phaeohyphomycosis in fish, is herein reported to cause cutaneous lesions in a tortoise, Terrapine carolina var. carolina. S. humicola was isolated from lesions on the foot and dematiaceous hyphae were observed in KOH preparations of the biopsy and in stained preparations. This isolate and others were compared morphologically and physiologically with isolates of Dactylaria gallopava which it resembles. As a result of this investigation, we concluded that D. gallopava may be differentiated from S. humicola macroscopically, by the production in D. gallopava of an extensive diffusible purplish-red to reddish-brown pigment when cultured on Sabouraud dextrose agar; microscopically, by the presence and usually predominance of conidia, whose apical cell is markedly wider than the basal cell, and usually constricted at the septum; and physiologically, by the ability to grow on media containing cycloheximide and by the ability to grow well at 36-45 degrees C. In contrast, S. humicola does not usually produce a diffusible pigment on Sabouraud's dextrose agar or if present, is not extensive; it lacks the wider upper cell; is less constricted or non-constricted at the central septum; grows on media containing cycloheximide, although some inhibition may occur and lastly, does not grow at 36 degrees C or higher. Both species were urease positive, hydrolysed tyrosine but not casein, xanthine, or gelatin.

Two patients are described with subcutaneous infections due to Phialophora richardsiae. Both were diabetics and originally came from subtropical areas. One of the patients had a cystic lesion which was well encapsulated while the other had a large ulcerating lesion with draining sinus tracts. The organisms were found to be susceptible to cycloheximide but resistant to 5-fluorocytosine, miconazole and amphotericin B. There was some variability in the degree of resistance depending upon whether the primary or secondary phialoconidia were tested. While simple excision appears curative for the solitary cystic type of lesion, therapy of the ulcerating form of the disease remains problematic.

Studies of three monoconidial subcultures of each of 10 isolates of Trichophyton soudanense on seven trichophyton agars revealed variations in growth among the subcultures of each isolate and among the isolates themselves on six agars. In contrast, greater consistency and generally good to excellent growth were noted with all isolates on trichophyton agar 1 (basal medium). These results are contrary to those found with other Trichophyton species and suggest that growth on the trichophyton agars is not a suitable test for the identification of T. soudanense.

Gymnothecia with asci and ascospores developed repeatedly and in abundance whenever Trichophyton quinckeanum isolates X-392 and IMI 140691 were paired with Arthroderma simii 678 A. However, repeatable fertile crosses did not occur when all of our 19 isolates of T. quinckeanum were paired with 10 other isolates of A. simii comprising A and a mating types. Additional crosses between these 19 isolates of T. quinckeanum with A. simii and with A. benhamiae revealed that 11 of the 19 isolates of T. quinckeanum produced fertile gymnothecia only when crossed with A. simii 678 A but not when crossed with another isolate of A. simii of the A mating type nor when crossed with mating type a. All 19 isolates mated with A. benhamiae mating type A; therefore, all of our T. quinckeanum isolates were of the a mating type. Study of asci and random ascospores, selected with a micromanipulator, from crosses between several isolates of T. quinckeanum and A. simii 678 A revealed irregularities in the maturation of ascospores, poor ascospore germination, and a predominance of the A. simii phenotype and mating type for those ascospores that germinated and produced mature colonies. All these reactions are characteristic of interspecific crosses. In contrast, ascus analysis of the F1 progeny of crosses between these same isolates of T. quinckeanum with A. benhamiae revealed regular maturation of ascospores, better germination, and essentially a 1:1 segregation of mating types and parental phenotypes. This study confirms the concept that T. quinckeanum is not an independent species and that it is best considered to be a variety of T. mentagrophytes, as reported by Ajello, BostickCheng (1968). Furthermore, our data indicate that T. mentagrophytes var. quinckeanum appears to be more closely related to A. simii than the granular variety of T. mentagrophytes, since fertile gymnothecia resulted from crosses between T. mentagrophytes var. quinckeanum and A. simii but not between T. mentagrophytes var. mentagrophytes and A. simii. Further implications of this study suggest the importance of extensive ascospore analysis when investigating the perfect states of fungi in order to avoid creating unwarranted new species.

Two isolates of Cunninghamella bertholletiae from confirmed cases of human zygomycosis were studied, and their sexual, asexual, and physiologic characteristics described. Minimal inhibitory concentrations for these two isolates, as well as for six other clinical isolates of C bertholletiae, were determined for amphotericin B, flucytosine, and miconazole using a standardized agar dilution technique. All isolates were found to be susceptible to miconazole, but resistant to flucytosine and amphotericin B.

The first evidence of the potential pathogenicity of Mycobacterium thermoresistibile is presented. This mycobacterium, initially identified as Mycobacterium gordonae, was isolated repeatedly from sputum, a bronchoscopy specimen. and later, an open lung biopsy. The distinctive characteristics are described, including the unique ability of the organism to grow at 52 degrees C.

In a survey of 15,272 canine necropsies, natural infection with Mycobacterium tuberculosis was found to have been diagnosed in eight dogs (0.05%). Clinical findings were anorexia, loss of body weight, lethargy, vomiting, and leukocytosis; radiography revealed pleural and pericardial effusion, ascites, and hepatomegaly. Granulomatous lesions with acid-fast bacilli were consistently found. Mycobacterium tuberculosis was isolated from lesions in the lungs, liver, or lymph nodes of five dogs. All eight dogs had a history of contact with human patients with tuberculosis.