Use of healthy-donor granulocyte transfusions to treat infections in neutropenic patients with myeloid or lymphoid neoplasms: experience in 74 patients treated with 373 granulocyte transfusions.

BACKGROUND/AIMS: Despite limited evidence for efficacy, granulocyte transfusions (GTX) are used to prevent and treat opportunistic infections in patients with neutropenia. METHODS: Three hundred and seventy-three GTX given to 74 patients were assessed retrospectively. RESULTS: GTX were discontinued because of clinical improvement more often in patients with severe infections than in patients without severe infections (27 vs. 12%; p ≤ 0.002), whereas deaths resulted in discontinuation of GTX therapy less often in patients with severe infections than without (8 vs. 39%; p ≤ 0.002). Patients who died by 12 weeks after GTX initiation were more likely to have leukemia (p = 0.03), not to have recovery of neutrophil counts (p < 0.0001), and to have started GTX during a critical care unit stay (p < 0.001). Uses of granulocyte colony-stimulating factor (p ≤ 0.02) and interferon-γ (p ≤ 0.04) were more common in patients who survived. In patients with comorbidities (31%; odds ratio, OR, 12.6; 95% confidence interval, CI, 2.4-65.7; p ≤ 0.003), GTX was started in the critical care unit (OR 8.8; 95% CI 2.5-30.9; p < 0.001), and a high total bilirubin level at the end of GTX (OR 2.1; 95% CI 1.1-4.2; p = 0.03) had a higher probability of death 12 weeks after GTX therapy commenced. CONCLUSIONS: The possibility that a niche population may benefit from GTX requires further assessment.

Merkel Cell Carcinoma Masquerading Clinically as a Cyst in a Young Patient.

Merkel cell carcinoma (MCC) is an extremely rare and aggressive tumor. Here we report an unusual MCC that manifested as an abruptly enlarging, painful skin lesion over the right antecubital fossa and masqueraded as an epidermal cyst in a 42-year-old male. The lesion was surgically excised and subjected to histopathologic and immunohistochemical examinations. The subsequent analysis allowed for the diagnosis of MCC. Clinicians should always be cognizant of MCC, which can be easily misdiagnosed. Early diagnosis and appropriate treatment are keys to improving the survival rates of MCC patients.

Granulocyte macrophage colony-stimulating factor in 66 patients with myeloid or lymphoid neoplasms and recipients of hematopoietic stem cell transplantation with invasive fungal disease.

BACKGROUND/AIMS: Adding granulocyte macrophage colony-stimulating factor (GM-CSF) may improve the response to antifungal therapy in immunosuppressed patients with invasive fungal disease (IFD). METHODS: We retrospectively assessed 66 patients in whom GM-CSF was given during antifungal therapy. RESULTS: Severe neutropenia (77%) and refractory/relapsed cancer (65%) were common in the group. Prior to GM-CSF therapy, 15% of patients received high-dose corticosteroids for a median of 30 ± 16 days [median cumulative dose (c.d.) 1,184 ± 1,019 mg], and 9 received steroids during GM-CSF therapy for a median of 16 ± 12 days (median c.d. 230 ± 1,314 mg). Mild toxic effects were noted in 9% of patients; there were no cases of cardiopulmonary toxicity. All-cause deaths were observed in 68% of patients and 48% died of progressive IFD. High-dose corticosteroids prior to GM-CSF (OR 24; 95% CI 2.21-264.9; p ≤ 0.009), GM-CSF started in the intensive care unit (OR 10; 95% CI 1.66-63.8; p ≤ 0.01), concurrent granulocyte transfusions (OR 5; 95% CI 1.27-16.8; p ≤ 0.02) and proven/probable IFD (OR 4; 95% CI 1-16.2; p ≤ 0.05) predicted antifungal treatment failure. CONCLUSIONS: GM-CSF adjuvant therapy was tolerated without serous toxicity and antifungal treatment failure remained a challenge in patients treated with high-dose systemic corticosteroids.

Phase 1 study of safety, pharmacokinetics, and antiviral activity of SARS-CoV-2 neutralizing monoclonal antibody ABBV-47D11 in patients with COVID-19.

ABBV-47D11 is a neutralizing monoclonal antibody that targets a mutationally conserved hydrophobic pocket distal to the ACE2 binding site of SARS-CoV-2. This first-in-human safety, pharmacokinetics, and antiviral pharmacodynamic assessment in patients with COVID-19 provide an initial evaluation of this antibody that may allow further development. This multicenter, randomized, double-blind, and placebo-controlled single ascending dose study of ABBV-47D11 (180, 600, or 2400 mg) as an intravenous infusion, was in hospitalized and non-hospitalized (confined) adults with mild to moderate COVID-19. Primary outcomes were grade 3 or higher study drug-related adverse events and infusion-related reactions. Secondary outcomes were pharmacokinetic parameters and concentration-time profiles to Day 29, immunogenicity (anti-drug antibodies), and antiviral activity (change in RT-PCR viral load) from baseline to Days 15 and 29. ABBV-47D11 single doses up to 2400 mg were safe and tolerated and no safety signals were identified. The pharmacokinetics of ABBV-47D11 were linear and showed dose-proportional increases in serum concentrations with ascending doses. The exploratory anti-SARS-CoV-2 activity revealed a reduction of viral load at and above the 600 mg dose of ABBV-47D11 regardless of patient demographics and baseline characteristics, however; because of the high inter-individual variability and small sample size a statistical significance was not reached. There is potential for anti-SARS-CoV-2 activity with ABBV-47D11 doses of 600 mg or higher, which could be evaluated in future clinical trials designed and powered to assess viral load reductions and clinical benefit.

Central venous catheter-associated Nocardia bacteremia in cancer patients.

Central venous catheters, often needed by cancer patients, can be the source of Nocardia bacteremia. We evaluated the clinical characteristics and outcomes of 17 cancer patients with Nocardia bacteremia. For 10 patients, the bacteremia was associated with the catheter; for the other 7, it was a disseminated infection. N. nova complex was the leading cause of bacteremia. Nocardia promoted heavy biofilm formation on the surface of central venous catheter segments tested in an in vitro biofilm model. Trimethoprim- and minocycline-based lock solutions had potent in vitro activity against biofilm growth. Patients with Nocardia central venous catheter-associated bloodstream infections responded well to catheter removal and antimicrobial drug therapy, whereas those with disseminated bacteremia had poor prognoses.

Palatal mucormycosis in patients with hematologic malignancy and stem cell transplantation.

We present two patients with acute myelogenous leukemia who developed palatal mucormycosis, as well as a review of 15 well described reported cases of the same condition in patients who had hematologic malignancy and had undergone hematopoietic stem cell transplantation. Early diagnosis of palatal mucormycosis requires high suspicion of the disease along with a thorough oral examination. Mucormycosis is a devastating disease with a high mortality rate, thereby stressing the importance for early appropriate antifungal therapy in immunocompromised patients with palatal lesions while awaiting the results of histopathology and cultures.

Bacterial Endocarditis of Anatomically Normal Native Pulmonic Valve with No Predisposing Risk Factors: Case Report and Review.

Right-sided native valve infective endocarditis (IE) includes tricuspid valve (TV) and pulmonic valve (PV). It represents 10% of all cases. However, it is more common in persons who inject drugs or in presence of cardiac implantable electronic device (CIED). Pulmonic valve endocarditis is a rare infection and represents ∼1% of all cases. Our case represents a patient with large pulmonic valve vegetation with no known common risk factors for right-sided IE.

High-dose caspofungin as a component of combination antifungal therapy in 91 patients with neoplastic diseases and hematopoietic stem cell transplantation: a critical review of short-term and long-term adverse events.

The antifungal activity of echinocandins is concentration dependent. Previously, we demonstrated that high-dose caspofungin (HD-CSP; 100 mg daily) was well tolerated in 34 immunosuppressed patients with cancer and may have favorably influenced outcomes. We retrospectively assessed all 91 patients in whom HD-CSP was given for the treatment of invasive fungal disease (IFD). The median number of doses was 18.5 ± 21.5, and in 8 (9%) patients more than 40 doses were given. Most (62%) of the patients had leukemia. A total of 45 (49%) patients had undergone stem cell transplantation; 80% received allogeneic grafts and 47% had graft-versus-host disease. High-dose corticosteroids were given during antifungal therapy in 26 (29%) patients. In all, 8 (9%) patients had new elevation in serum bilirubin during HD-CSP therapy; normalization occurred after voriconazole and HD-CSP were discontinued in 4 patients each. No other short-term or delayed adverse events were observed. In all, 40 (44%) patients died of IFD. High-dose corticosteroids during HD-CSP (odds ratio [OR] 8, 95% confidence interval [CI] 2.1-30.4; P < .002) and starting HD-CSP in the critical care unit (OR 67.5, 95% CI 5.25-868.9; P < .001) were associated with death from fungal disease. Prolonged HD-CSP therapy was well tolerated. Drug-induced hyperbilirubinemia may pose a potential limitation for continued HD-CSP use in highly susceptible patients with hematologic neoplasms and stem cell transplantation.

Immunohistochemical characteristics of ganglionated plexuses in the human gallbladder

Indirect triple immunolabelling techniques were used to identify the presence of choline acetyl-transferase (ChAT), neuronal nitric oxide synthase (nNOS), Dopamine beta-hydroxylase (DβH), neuromedin U-8 (NMU-8), and neuropeptide Y (NPY) in the ganglionated plexuses of the human gallbladder. Of all the intrinsic cholinergic neurons examined, NMU-8-immunoreactive (-IR) neurons appeared to be the most populous, followed closely by neurons containing NPY-IR. nNOS-IR neurons were often observed to coexist with ChAT, NMU, and NPY. Occasionally, these nNOS positive neurons were seen triple labeled with ChAT, NMU-8, and NPY. Results also indicate that not all nNOS and NMU-8-IR coexistent neurons express NPY immunoposi-tivity. Our findings suggest that these intrinsic neurons may be categorized into a distinct population of neurons that express both inhibitory and excita-tory capabilities.Intrinsic cholinergic neurons that were ChAT-IR displayed a spectrum of immunopositivity. Interestingly, a small subpopulation of these neurons ap-peared to be extremely weak ChAT-IR or simply ChAT-immunonegative. These occasionally obser-ved ChAT-immunonegative neurons at times ex-pressed single immunopositivity for NMU-8 or nNOS, while more frequently, these ChAT-immunonegative neurons were found to be single immunopositive, or at times, double immunopositi-ve for NMU-8-, NPY-, or nNOS-IR.Dopamine beta-hydroxylase (DβH) antibodies were used to confirm the lack of intrinsic sympat-hetic innervation in the human gallbladder. As suspected, in all the sections examined, DβH-IR neu-rons were not detected. The only indication of DβH immunopositivity was noted among delicate fibers surrounding the neurons and blood vessels within the organ

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Streptococcus agalactiae toxic shock-like syndrome: two case reports and review of the literature.

We present 2 patients with Streptococcus agalactiae toxic shock-like syndrome and review another 11 well-reported cases from the literature. Streptococcal toxic shock-like syndrome is a devastating illness with a high mortality rate, therefore we stress the importance of early supportive management, antimicrobial therapy, and surgical intervention. Toxic shock-like syndrome is likely to be underestimated in patients with invasive Streptococcus agalactiae infection who present with shock. Early diagnosis requires high suspicion of the illness, along with a thorough mucocutaneous examination. Streptococcus agalactiae produces uncharacterized pyrogenic toxins, which explains the ability of the organism to cause toxic shock-like syndrome.

Characteristics of, and risk factors for, infections in patients with cancer treated with dasatinib and a brief review of other complications.

Dasatinib has transformed the treatment of chronic myelogenous leukemia, resulting in durable remissions and prolonged survival. The spectrum of infectious complications during and after dasatinib therapy is not known. Retrospective analysis of records among 69 patients treated with dasatinib showed that 35 (51%) developed 57 episodes of infection. Twenty-nine (51%) episodes occurred during neutropenia, and 25 (44%) were microbiologically confirmed. Compared with patients who did not develop infection with dasatinib therapy, patients with infection were significantly more likely to have acute lymphocytic leukemia (51% vs. 18%; p ≤ 0.005) and to have received high-dose corticosteroids (51% vs. 26%; p ≤ 0.05). Patients with infection were also more likely to have received dasatinib with another antineoplastic agent (57% vs. 35% without infection; p = 0.09). On multivariate analysis, treatment with three or more cycles of dasatinib increased the risk of infection (odds ratio 11.7; 95% confidence interval 2.5-54.3; p = 0.002). The presence of comorbidities tended to increase the risk of infection (odds ratio 3.9; 95% confidence interval 0.9-17.9; p = 0.07). Interestingly, viral infections, including a single case of cytomegalovirus colitis, were uncommon (7%). The rate of death in 57 patients during follow-up was non-significantly higher in patients with infection versus those without infection (35% vs. 18%; p = 0.18). Infection-associated deaths were noted in only two patients (10%) who had an infection and died. The results of our analysis suggest that antibacterial prophylaxis is important in patients who develop neutropenia during dasatinib therapy, although routine antifungal and anti-cytomegalovirus prophylaxis may not be necessary.

Rhodococcus bacteremia in cancer patients is mostly catheter related and associated with biofilm formation.

Rhodococcus is an emerging cause of opportunistic infection in immunocompromised patients, most commonly causing cavitary pneumonia. It has rarely been reported as a cause of isolated bacteremia. However, the relationship between bacteremia and central venous catheter is unknown. Between 2002 and 2010, the characteristics and outcomes of seventeen cancer patients with Rhodococcus bacteremia and indwelling central venous catheters were evaluated. Rhodococcus bacteremias were for the most part (94%) central line-associated bloodstream infection (CLABSI). Most of the bacteremia isolates were Rhodococcus equi (82%). Rhodococcus isolates formed heavy microbial biofilm on the surface of polyurethane catheters, which was reduced completely or partially by antimicrobial lock solution. All CLABSI patients had successful response to catheter removal and antimicrobial therapy. Rhodococcus species should be added to the list of biofilm forming organisms in immunocompromised hosts and most of the Rhodococcus bacteremias in cancer patients are central line associated.