Invasive pulmonary aspergillosis real-world outcomes: Clinical features and risk factors associated with increased mortality.

Invasive pulmonary aspergillosis (IPA) is a severe fungal infection that primarily affects immunocompromised patients and is associated with high mortality. Contemporary clinical characteristics of IPA and "real-world" estimates and predictors of associated mortality are inadequate. TriNetX, a global research network, was queried to identify adult patients with IPA diagnoses based on the ICD-10 code B44.0. We performed a propensity score-matched analysis comparing clinical characteristics among patients who survived versus non-survivors at 1 year. We identified 4371 patients with IPA. We found neoplasms, solid organ transplant recipients, hematologic malignancies, and aplastic anemia as the most predominant risk factors. The overall 1-year mortality was 32% for IPA. 1-year mortality was highest for patients with COVID-19 in the ICU, followed by those with acute myeloid leukemia and aplastic anemia (54%, 50%, and 39%, respectively). After propensity score matching, severe sepsis, pleural effusion, and candidiasis were mortality contributors within a year after diagnosis. Liver injury, systemic glucocorticoid exposure over the previous 6 months, lower lymphocyte and CD4 counts, elevated ferritin, LDH, thrombocytopenia, anemia, or elevated glycosylated hemoglobin (HbA1c) were independent predictors of mortality at 1 year. Voriconazole was the most common treatment (67%). The annual incidence of IPA was 0.001%, increasing to 0.02% among critically ill patients in the ICU. IPA continues to have a very high mortality. We encourage prospective studies to validate and refine the identified clinical markers linked to increased mortality.

Invasive pulmonary aspergillosis (IPA) is common among immunocompromised patients. Analyzing a global research network, we found 32% of patients with IPA died a year after diagnosis. We identified the primary underlying conditions, contributors, and predictors of mortality.

Kinetic analysis of pathogenicity and tissue tropism of gyrovirus 3 in experimentally infected chickens.

Gyrovirus 3 (GyV3), the third novel emerging species of the genus Gyrovirus of the Anelloviridae family, has been described in multiple hosts. Epidemiologically, there are suggestions that GyV3 is associated with diarrhea/proventriculitis, however, no direct causal evidence exists between GyV3 infection and specific clinical diseases. Herein, we infected special pathogen-free (SPF) chickens with GyV3, and then assessed the pathogenicity and tissue tropism. The results revealed that GyV3 induced persistent infection characterized by diarrhea, aplastic anemia, immunosuppression, and persistent systemic lymphocytic inflammation. Clinically, the infected chickens presented ruffled feathers, diarrhea, anemia, and weight loss. Aplastic anemia was characterized by progressive depletion of hematopoietic cells in the bone marrow, immunosuppression was associated with atrophy of the thymus, spleen, and bursa of Fabricious, progressive lymphocytic inflammations were characterized by proventriculitis, adrenalitis, pancreatitis, hepatitis, nephritis, and bronchitis. Viral loads of GyV3 in tissues exhibited "M", "N", "W" or "V" type dynamic changes. The highest level of viral loads was reported in bone marrow at 7dpi, followed by the adrenal gland at 2 dpi, the sciatic nerve at 7 dpi, and bile at 35 dpi. The bone marrow and kidney demonstrate the strongest immunostaining of GyV3-VP1 antigen and were suggested as the target tissues of GyV3. Collectively, GyV3 is an immunosuppressive pathogenic virus that targets the bone marrow and kidney in chickens. Exploring the pathogenicity and tissue tropism of GyV3 will guide the basic understanding of the biology of GyV3 and its pathogenesis in chickens.

Bone marrow aplasia with pancytopenia and hemorrhage in a Japanese Black calf.

Severe leukopenia was incidentally found in a newborn Japanese Black calf by blood testing during the clinical trial of an iron dextran drug (day 1). At that time, no clinical problems were observed. On day 15, the calf presented with a high rectal temperature and tachypnea. Treatment with antibiotics and non-steroidal anti-inflammatory drugs did not improve clinical signs. Anemia, melena, and prolonged bleeding were also recorded. Necropsy findings revealed subcutaneous petechial hemorrhage and severe bone marrow aplasia. This is the first confirmed case of pancytopenia and hemorrhage associated with bone marrow aplasia in a Japanese Black calf.

Aplastic anemia in two kittens following a prescription error.

A medication error resulted in two kittens being treated with azathioprine (12 and 12.5 mg/kg) instead of azithromycin for 2 weeks. On clinical examination, the kittens were febrile, weak, and had oronasal hemorrhage. Complete blood cell counts indicated severe bone marrow suppression. Treatment consisted of multiple transfusions, antibiotics, and granulocyte colony-stimulating factor. One of the kittens responded to therapy and had a complete recovery. The other kitten was treated for 40 days with no clinical response before dying. Both kittens also contracted Mycoplasma hemofelis infection from a contaminated blood transfusion.

Pancytopenia with bleeding tendency associated with bone marrow aplasia in a Holstein calf.

An 11-day-old Holstein calf presented with a high rectal temperature and tachypnea. Treatment with antibiotics and non-steroidal anti-inflammatory drugs did not improve the clinical signs. Bleeding tendency, with several hemorrhage spots on the body surface, appeared five days after admission. Severe pancytopenia was observed in the blood examination. The calf died on the 11th day after admission with severe bleeding from an injection site. Necropsy findings revealed that the pancytopenia had resulted from severe bone marrow aplasia. A congenital disorder was suspected to be the cause of pancytopenia associated with bone marrow aplasia.

Aplastic anemia in cats - clinicopathological features and associated disease conditions 1996-2004.

A retrospective study of 128 feline bone marrow reports identified 13 cases of aplastic anemia. Clinical diagnoses included chronic renal failure (n=5), feline leukemia virus infection (n=2), hyperthyroidism treated with methimazole (n=1) and idiopathic aplastic anemia (n=5). In some cats, starvation may play a role in the development of marrow aplasia. Some cats with aplastic anemia can have prolonged survival without resolution of the pancytopenia.

Induction of aplastic anemia by intra-bone marrow inoculation of a molecularly cloned feline retrovirus.

Intra-bone marrow inoculation of cells infected with molecularly cloned feline retrovirus (FeLV-C-Sarma [FSC]) associated with aplastic anemia was examined to test the hypothesis that cell-to-cell transmission of virus might facilitate marrow cell infection and anemogenesis, a possibility suggested by in-vitro co-culture experiments. IBM inoculation of either FSC-infected feline marrow cells or fibroblasts of weanling cats bypassed age-related restriction of FSC replication, initiated viremia, caused irreversible depletion of erythroid burst forming units, and induced rapid fatal aplastic anemia. A second significant finding observed with FSC infection was pronounced systemic lymphoid depletion. The direct bone marrow inoculation system described facilitates experimental study of retrovirus-target cell interactions involved in erythroid aplasia.

Experimental induction of hemorrhagic-aplastic anemia in chickens. I. Etiology.

Exposure to infectious bursal disease virus (IBDV) at 1 day old followed by inclusion body hepatitis virus (IBHV) inoculation at 36 days produced typical lesions of hemorrhagic-aplastic anemia syndrome (HAS). The lesions included severe anemia, widespread hemorrhages, and dermatitis. HAS could not be induced in the first 4 weeks of life in chickens inoculated at one day old with IBHV alone or in combination with IBDV. It was concluded that the immunosuppressive effects of IBDV failed to alter the pathogenicity of IBHV in chicks less than 4 weeks old. This resistance was considered to be age-related. Subcutaneous inoculation of day-old chicks with IBDV produced a more severe infection than did oral exposure. Serial passage of IBHV in day-old chicks had no significant effect on the viral pathogenicity.

The roles of the infectious bursal agent and several avian adenoviruses in the hemorrhagic-aplastic-anemia syndrome and gangrenous dermatitis.

The effect that breeder-flock immune status regarding the infectious bursal agent (IBA) and two avian adenoviruses (DPI-1 and DPI-2) has on the susceptibility of their commercially reared Delmarva broiler progeny to the hemorrhagic-aplastic-anemia syndrome and concurrent gangrenous dermatitis was determined. Lack of immunity to the IBA in breeder flocks was related to an increased susceptibility of progeny to anemia and dermatitis. Breeder-flock immunity to the two adenoviruses tested could not be related to the resistance or susceptibility of their progeny to the hemorrhagic-aplastic-anemia syndrome and gangrenous dermatitis.

Experimental induction of hemorrhagic-aplastic anemia in chickens. II. Serum protein changes.

The serologic response of chickens to infectious bursal disease virus (IBDV) and inclusion body hepatitis virus (IBHV) was analyzed. Inoculation at one day old with either IBDV or IBHV significantly (P less than 0.05) reduced levels of serum gamma-globulins at 4 weeks postinoculation. This response was not elicited by inoculation of IBDV together with IBHV. Birds with experimentally induced or naturally occurring hemorrhagic anemia syndrome (HAS) had serum proteins quantitatively and qualitatively changed from those of controls. Serum protein profiles did not coincide, however, in experimentally infected and naturally infected chickens. Among naturally infected chickens, those that were IBHV-positive upon culture had significantly (P less than 0.05) lower hematocrit values.

Myeloid and megakaryocytic hypoplasia in related standardbreds.

Myeloid and megakaryocytic bone marrow hypoplasia in association with moderate to profound neutropenia was observed in 8 young Standardbred horses sired by the same stallion; 7 horses were intermittently thrombocytopenic. Evaluation of serial neutrophil counts in 2 horses suggested that a cyclic variation in neutrophil numbers was present, that lymphocyte numbers increased when neutrophil counts decreased, and that platelet counts decreased when neutrophil counts decreased. Preliminary bone marrow cultures indicated that myeloid progenitor cells were present and that these cells were able to respond to exogenous growth factors by differentiating. A bone marrow microenvironment or growth factor defect is suspected. Seven of 8 horses died or were euthanized. One horse with moderate neutropenia and a normal platelet count has been racing for 3 years. Necropsies in 4 horses did not reveal a cause for the myeloid hypoplasia. A familial basis for the disease is suspected.

Clinical efficacy and safety of recombinant canine erythropoietin in dogs with anemia of chronic renal failure and dogs with recombinant human erythropoietin-induced red cell aplasia.

The efficacy and safety of recombinant canine erythropoietin (rcEPO) therapy was evaluated in 19 dogs with anemia of chronic renal failure (group 1) and 6 dogs with chronic renal failure and recombinant human erythropoietin (rhEPO)-induced red cell aplasia (group 2). Hematocrit (Hct) and absolute reticulocyte count (ARC) were monitored weekly for the first 8 weeks, CBC (including ARC) and serum iron profiles were evaluated monthly, and serum biochemical analyses were performed every 2 months for 6 (group 2) to 12 (group 1) months. For group 1 dogs, median Hct and ARC increased significantly during the 1st week of rcEPO treatment, and median Hct was sustained at >35% after week 5. In contrast, median Hct and ARC for group 2 did not change significantly with rcEPO treatment, even with doses greater than those used in group 1. Nevertheless, 2 (33%) of the 6 dogs in group 2 developed erythroid hyperplasia, reticulocytosis, and increases in Hct with rcEPO treatment. Although median systolic blood pressure did not change significantly in either group, 5 dogs developed systolic blood pressures > or = 180 mm Hg during the study. Appetite and energy level improved in most group 1 dogs with increases in Hct. Recombinant cEPO stimulated erythrocyte production in dogs with nonregenerative anemia secondary to chronic renal failure without causing the profound erythroid hypoplasia that can occur in rhEPO-treated dogs. Unfortunately, rcEPO was not as effective in restoring erythrocyte production in dogs that had previously developed rhEPO-induced red cell aplasia.

Effect of canine parvovirus on erythroid progenitors in phenylhydrazine-induced regenerative hemolytic anemia in dogs.

The effects of canine parvovirus (CPV) infection in dogs with hemolytic anemia was compared with the clinical effects of human parvovirus-induced aplastic anemia in human beings with chronic regenerative anemias. Phenylhydrazine was used to induce a transient, severe, hemolytic anemia in dogs to evaluate the effects of CPV infection on rapidly dividing bone marrow precursors. Erythrocyte colony-forming unit bone marrow cultures and cytologic examination of bone marrow were used to determine the effects of CPV infection on erythroid bone marrow precursors. The induced hemolytic anemia regenerated rapidly and although the bone marrow was infected, it was determined that CPV infection did not induce a detectable decrease in erythroid progenitors in dogs with severe hemolytic anemia.

Bone marrow necrosis in the dog.

Bone marrow necrosis in 4 dogs was characterized by refractory anemia with or without leukopenia and thrombocytopenia. Romanovsky-stained bone marrow had a diffuse blue discoloration, and marrow particles were elongated. Degenerating cells, cellular debris, and vacuolated macrophages also were seen. Examination of bone marrow sections revealed extensive replacement of normal stroma by necrotic debris and hemorrhage. The cause of the necrosis was not determined. Concomitant disorders included chronic ehrlichiosis, estrogen toxicosis, malignancy, endometrial cystic hyperplasia, and glomerulonephritis.

Aplastic anemia associated with estrus in pet ferrets.

Aplastic anemia in association with estrus was diagnosed in 6 pet ferrets. The ferrets had been examined because of anorexia, depression, and lethargy of 2-5 days' duration. Consistent clinical findings were pale mucous membranes and enlargement of the vulva. Hemorrhages were found in 3 ferrets. Hematologic findings included severe anemia, thrombocytopenia, granulocytopenia, and hypocellularity of the bone marrow. The aplastic anemia was attributed to prolonged estrogenic exposure in ferrets with protracted estrus.

Drug-associated aplastic anemia in dogs: eight cases (1984-1988).

Records of 8 dogs with drug-associated aplastic anemia were reviewed. Drugs suspected as being causative included estradiol cyclopentylpropionate (3 dogs), phenylbutazone (2 dogs), meclofenamic acid (1 dog), trimethoprim-sulfadiazine and fenbendazole (1 dog), and quinidine (1 dog). Five of the dogs died or were euthanatized. One dog with estrogen-associated aplasia recovered after prolonged treatment. The dogs with trimethoprim-sulfadiazine and quinidine-associated marrow aplasia recovered promptly after treatment was discontinued.

Bone marrow hypoplasia in a feminized dog with an interstitial cell tumor.

Bone marrow hypoplasia and feminization developed in a 10-year-old male German Shepherd Dog with interstitial cell tumor. Clinical abnormalities included pyrexia, pale mucous membranes, signs of abdominal pain, large left testis, atrophied right testis, and feminization. Abnormal laboratory findings included pancytopenia, bacteremia, bacteriuria, and pyuria. Results of cytologic examination of a bone marrow aspirate were consistent with aplastic anemia. Serum estradiol concentration was high, and serum testosterone concentration was low, compared with normal values for male dogs. The left testicular mass was identified as an interstitial cell tumor. Other causes of the aplastic anemia or feminization were not found.

Responsive estrogen-induced aplastic anemia in a dog.

A 4-year-old Airedale Terrier that had developed estrogen-induced aplastic anemia had a complete recovery after supportive treatment and weekly administrations of nandrolone decanoate. The anemia was induced iatrogenically by administration of estradiol cypionate (2 mg, IM each time) at 48- to 72-hour intervals. Clinical signs included lethargy, anorexia, and weakness; hemoglobin was 6.8 g/dl, PCV was 21%, and WBC was 1,500/dl. Supportive treatment included blood transfusions and administration of antibiotics, corticosteroids, and vitamins. Hematologic values returned to normal by day 81, and the dog has remained healthy for one year after treatment.

Association of feline leukemia virus with lymphosarcoma and other disorders in the cat.

Two hundred fifty Boston cats with disorders such as lymphosarcoma, myeloproliferative disease, anemia, glomerulonephritis, pregnancy abnormalities, feline infectious peritonitis, toxoplasmosis, and various bacterial infections were examined for feline leukemia virus (FeLV) by immunofluorescence. Antibody titers against feline oncornavirus-associated cell membrane antigen (FOCMA) were tested in 133 of these cats. The tests for FeLV and FOCMA antibody were also conducted among healthy cats not known to have been exposed to FeLV, as well as among healthy cats from households where FeLV was known to be present. Most of the cats with lymphosarcoma and the other aforementioned disorders were infected with FeLV and low FOCMA antibody titers. Healthy cats known to have been exposed to FeLV were often viremic, but those that remained healthy were able to develop high FOCMA antibody titers. Healthy cats without known prior exposure to FeLV were unlikely to be viremic but often had detectable FOCMA antibody titers, indicating that some exposure occurs under natural conditions in the Boston area. The association of FeLV with infections other than lymphosarcoma was assumed to be caused by the immunosuppresive effect of FeLV, thus allowing development of disease.

Aplastic anemia associated with trimethoprim-sulfadiazine and fenbendazole administration in a dog.

A dog that was treated with trimethoprim-sulfadiazine and fenbendazole developed transient aplastic anemia. The onset of bone marrow aplasia at 14 days after initiation of treatment and remission of it after cessation of treatment suggested that the aplasia was drug-induced. A hematologically normal dog treated with the same drug combination failed to develop hematologic dyscrasia. Because of the potential toxic effects of trimethoprim-sulfadiazine and/or fenbendazole, animals under treatment with this combination should be monitored by use of periodic CBC.