A case of disseminated cryptococcosis with abdominal involvement due to Cryptococcus neoformans species complex in a Ragdoll cat and false-negative cryptococcal antigen lateral flow tests due to the postzone phenomenon.

Although cryptococcosis is the most common systemic fungal disease of cats, abdominal involvement is rarely reported. The pathogenesis of cryptococcosis usually involves sinonasal colonisation, followed by tissue invasion and sinonasal infection, with possible subsequent spread to the lungs and/or direct extension into the central nervous system (CNS), for example, via the cribriform plate. Further haematogenous spread can occur to any tissue, including skin and the CNS. This report describes a case of disseminated cryptococcosis due to Cryptococcus neoformans species complex in a 13-year-old cat, the fourth documented Australian feline case with abdominal involvement. The cat presented with a chronic history of upper respiratory disease that progressed to severe lethargy and anorexia. An autopsy revealed striking peritonitis with multifocal abdominal involvement affecting the liver, spleen, adrenal glands, kidneys, pancreas and mesentery. Cryptococcal organisms were also observed in organs within the thoracic cavity, sinonasal tissues and the CNS. Testing of abdominal fluid and serum for cryptococcal antigen using a commercially available lateral flow assay using neat fluid specimen initially tested false-negative. However, after dilution of the sample to 1:64, a positive result was obtained, confirming a postzone phenomenon. Taken together, the collective findings were indicative of widely disseminated cryptococcosis due to Cryptococcus neoformans with atypical involvement of the abdominal cavity.

Abdominal cryptococcosis in dogs and cats: 38 cases (2000-2018).

INTRODUCTION: To report the clinical presentation, laboratory and imaging findings, treatment and outcome of abdominal cryptococcosis in dogs and cats in Australia. MATERIALS AND METHODS: Canine and feline cases from Australia were retrospectively identified (2000 to 2018) via laboratory and referral centre searches for abdominal cryptococcosis diagnosed by cytology (needle aspirates) or histopathology (biopsy or necropsy) of abdominal organs/tissues. Signalment, presenting complaints, clinical signs, laboratory findings, medical imaging, latex cryptococcal antigen agglutination test (LCAT) titres, treatment and outcome data was collected. RESULTS: Thirty-eight cases were included (35 dogs, three cats) in the study. Median age of presentation was 2 years for dogs and 6 years for cats. Common presenting complaints included vomiting (23/38), lethargy (19/38) and inappetence/anorexia (15/38). Abdominal ultrasound (25/38 cases) revealed mesenteric and intestinal lesions in most of the cases. On surgical exploration, seven cases had an intestinal lesion associated with an intussusception. Nineteen cases had a pre-treatment LCAT performed, with a median initial titre of 1:2048 (range 1:2 to 65,536). Twenty-four cases (23 dogs, one cat) received treatment, either medical, surgical or both. Median survival time for cases with combined medical and surgical treatment, surgical treatment alone or medical treatment alone was 730, 140 and 561 days, respectively. Eleven remain alive at the time of follow up. CLINICAL SIGNIFICANCE: Abdominal cryptococcosis although rare should be a considered as a diagnostic possibility in an especially young dog presenting with gastro-intestinal signs. Older dogs can also present with this condition and should not be euthanised based on imaging alone due to the likenesses with neoplasia. With appropriate treatment and monitoring many dogs may have a prolonged survival period and some may be cured.

Predictors of the course of quality of life during therapy in women with primary breast cancer.

PURPOSE: Multimodal therapies affect the quality of life (QoL) of patients with primary breast cancer (PBC). The objectives of this prospective study were to explore the changes in QoL from diagnosis to conclusion of adjuvant therapy and to identify predictive factors of QoL. METHODS: Before surgery (t1), before onset of adjuvant treatment (t2) and after completion of adjuvant chemo- or radiotherapy (t3), patients with PBC (n = 759) completed the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire, Charlson Comorbidity Index, Patient Health Questionnaire and Perceived Involvement in Care Scales. Predictors of the course of global QoL were estimated using multinomial logistic regression. Effect estimates are odds ratios (OR) and their 95% confidence intervals (CIs). RESULTS: Global QoL improved between t1 and t3, while physical functioning, emotional functioning and fatigue deteriorated. QoL before surgery was more often poor in patients <60 years (OR 2.2, 95% CI 1.5-3.1) and in those with comorbid mental illnesses (OR 8.6, CI 5.4-13.7). Forty-seven percentage reported good global QoL both at t1 and at t3. QoL improved in 28%, worsened in 10% and remained poor in 15%. Compared to patients with consistently good global QoL, a course of improving QoL was more often seen in patients who had received a mastectomy and in those with intense fear of treatment before surgery. A course of decreasing QoL was more often found in patients who were treated with chemotherapy. QoL stayed poor in patients with chemotherapy, mastectomy and intense fear. There was no evidence that radiotherapy, progressive disease or perceived involvement impact the course of QoL. CONCLUSIONS: Younger age and comorbid mental illnesses are associated with poor QoL pre-therapeutically. QoL is more likely to stay or become poor in patients who receive chemotherapy.

Clinical management of Brucella suis infection in dogs and implications for public health.

BACKGROUND: Brucellosis caused by Brucella suis is a notifiable disease that has recently emerged in dogs in New South Wales (NSW). Given the potential for zoonotic transmission, euthanasia of affected dogs is recommended, but this action is not mandatory. We report the clinical management of three dogs that underwent treatment at their owners' request. CASE REPORTS: A 14-month-old spayed female crossbreed originally obtained from an urban animal shelter underwent extensive investigations in 2011-12 for lameness and back pain, culminating in decompressive laminectomy. Diagnosis of multifocal discospondylitis and spinal empyema was made, with B. suis cultured from surgical biopsy specimens. The dog responded to long-term treatment using rifampicin and doxycycline. A second case of B. suis infection was diagnosed in January 2016 in a 3-year-old crossbreed pig-hunting dog with unilateral testicular enlargement. Following serological diagnosis the dog was given preliminary therapy using rifampicin and doxycycline, the affected testis was resected and the patient given a further month of combination therapy. In March 2016 a 7-year-old crossbreed pig-hunting dog with brucellosis was handled similarly, although both testes were removed. CONCLUSION: Brucellosis should be considered in the differential diagnosis of back pain, discospondylitis, lameness, abortion, prostatic abscessation and testicular/epididymal enlargement in dogs, especially if there is exposure to feral pigs or consumption of uncooked feral pig meat. Euthanasia is the only guarantee of reducing the public health risk to zero. However, where treatment is desired by the owner, combination therapy using rifampicin and doxycycline appears to be effective, when combined with surgical resection of infected tissues. Further monitoring of dogs during and after treatment is required to document cure.

Equine Pulmonary Cryptococcosis: A Comparative Literature Review and Evaluation of Fluconazole Monotherapy.

Cryptococcus is the most common fungal respiratory pathogen in Australian horses, manifesting primarily as pulmonary granulomas. Disease severity at presentation is dependent on the athletic use of the horse. The diagnosis and estimation of disease severity are centred around clinical findings, cytological evaluation of respiratory tract secretions, diagnostic imaging, and antigen titre testing. Both the lateral flow assay and the latex cryptococcal antigen titre are used, and important similarities and differences between species are discussed. Cryptococcus gattii occurs with greater frequency than Cryptococcus neoformans in equine pulmonic cryptococcosis and can be successfully treated with enteral fluconazole monotherapy, with disease severity determining treatment length.

Immunohistochemical Analysis of Leucocyte Subsets in the Sinonasal Mucosa of Cats with Upper Respiratory Tract Aspergillosis.

Leucocyte populations in the sinonasal mucosa of cats with and without upper respiratory tract aspergillosis were compared using immunohistochemistry and computer-aided morphometry. Inflammation was identified in the nasal mucosa of all affected cats, comprising predominantly of lymphoplasmacytic infiltration of the lamina propria associated with epithelial proliferation and degeneration. There was intense and diffuse expression of class II antigens of the major histocompatibility complex, associated with sites of hyphal invasion with hyperplasia and ulceration of the epithelium adjacent to fungal elements. Significantly more CD79b(+) cells, total lymphocytes, immunoglobulin (Ig)-expressing cells and MAC387(+) cells infiltrated the epithelium and more IgG(+) cells and total Ig-expressing cells infiltrated the lamina propria in affected cats compared with controls. Importantly, the inflammatory profile in affected cats was not consistent with the T helper (Th)1 and Th17 cell-mediated response that confers protective acquired immunity against invasive aspergillosis in dogs and people and in murine models of the infection. This finding may help to explain the development of invasive aspergillosis in systemically immunocompetent cats.

Autochthonous feline leprosy caused by Mycobacterium sp. strain Tarwin affecting a cat from the Central Coast of New South Wales.

CASE REPORT: A 5-year-old Domestic Shorthair-cross was presented with a raised, alopecic skin nodule affecting the external surface of the right upper lip with an adjacent second smaller satellite lesion. Fine needle aspiration cytology revealed numerous intracellular and extracellular negatively stained bacilli. Histopathology confirmed granulomatous inflammation with multinucleate giant cell formation and abundant intracellular acid-fast bacilli, consistent with a mycobacterial aetiology. PCR testing of the fresh tissue from the satellite lesion and subsequent sequence analysis identified Mycobacterium sp. strain Tarwin. The skin lesion was surgically excised and clarithromycin 62.5 mg twice daily was administered to the cat for 25 days. CONCLUSION: There was no recurrence of the lesion at the time of writing, 16 months after the surgery. This is the second autochthonous case of feline leprosy caused by M. sp. strain Tarwin originating in New South Wales, Australia.

[Gynecological cancers in patients with inflammatory rheumatic diseases]. / Gynäkologische Malignome bei Patientinnen mit rheumatisch­entzündlichen Systemerkrankungen.

The risk of gynecological cancers in patients with inflammatory rheumatic diseases only seems to be elevated with respect to cervical cancer and mainly in patients with systemic lupus erythematosus. There is increasing evidence for an influence of the immune system on tumor control of gynecological malignancies; however, an adverse influence of immunosuppressive treatment in rheumatic patients was indicated only for the risk of cervical cancer. In contrast, biologics could not be shown to cause an increased risk of cervical cancer but data on this topic are limited. General screening recommendations exist for breast cancer and cervical cancer. Recommendations for follow-up after oncological treatment are presented. Because of limited evidence immunosuppressive and biological treatment should be applied with great restraint at least within the first 5 years after curative oncological treatment also for gynecological tumors. As far as breast cancer is concerned an even longer interval is under discussion.

Some pharmacokinetic indices of oral fluconazole administration to koalas (Phascolarctos cinereus) infected with cryptococcosis.

Three asymptomatic koalas serologically positive for cryptococcosis and two symptomatic koalas were treated with 10 mg/kg fluconazole orally, twice daily for at least 2 weeks. The median plasma Cmax and AUC0-8 h for asymptomatic animals were 0.9 µg/mL and 4.9 µg/mL·h, respectively; and for symptomatic animals 3.2 µg/mL and 17.3 µg/mL·h, respectively. An additional symptomatic koala was treated with fluconazole (10 mg/kg twice daily) and a subcutaneous amphotericin B infusion twice weekly. After 2 weeks the fluconazole Cmax was 3.7 µg/mL and the AUC0-8 h was 25.8 µg/mL*h. An additional three koalas were treated with fluconazole 15 mg/kg twice daily for at least 2 weeks, with the same subcutaneous amphotericin protocol co-administered to two of these koalas (Cmax : 5.0 µg/mL; mean AUC0-8 h : 18.1 µg/mL*h). For all koalas, the fluconazole plasma Cmax failed to reach the MIC90 (16 µg/mL) to inhibit C. gattii. Fluconazole administered orally at either 10 or 15 mg/kg twice daily in conjunction with amphotericin is unlikely to attain therapeutic plasma concentrations. Suggestions to improve treatment of systemic cryptococcosis include testing pathogen susceptibility to fluconazole, monitoring plasma fluconazole concentrations, and administration of 20-25 mg/kg fluconazole orally, twice daily, with an amphotericin subcutaneous infusion twice weekly.

Validation of ultrasonography in detecting structural disease of the urogenital tract of the koala, Phascolarctos cinereus.

A retrospective review of case records of ultrasonography and necropsy outcomes of 62 koalas was used to investigate the accuracy of ultrasonography in assessing koala urogenital tract structural disease at the Port Macquarie Koala Hospital. The results showed high concordance, supporting ultrasonography as an effective tool for evaluating structural disease of the koala urogenital tract, most commonly seen with chlamydiosis. The study also illustrates the advances benefiting animal welfare that can be made by wildlife carer groups through using a scientific, evidence-based approach.

Pharmacokinetics of fluconazole following intravenous and oral administration to koalas (Phascolarctos cinereus).

Clinically normal koalas (n = 12) received a single dose of 10 mg/kg fluconazole orally (p.o.; n = 6) or intravenously (i.v.; n = 6). Serial plasma samples were collected over 24 h, and fluconazole concentrations were determined using a validated HPLC assay. A noncompartmental pharmacokinetic analysis was performed. Following i.v. administration, median (range) plasma clearance (CL) and steady-state volume of distribution (Vss ) were 0.31 (0.11-0.55) L/h/kg and 0.92 (0.38-1.40) L/kg, respectively. The elimination half-life (t1/2 ) was much shorter than in many species (i.v.: median 2.25, range 0.98-6.51 h; p.o.: 4.69, range 2.47-8.01 h), and oral bioavailability was low and variable (median 0.53, range 0.20-0.97). Absorption rate-limited disposition was evident. Plasma protein binding was 39.5 ± 3.5%. Although fluconazole volume of distribution (Varea ) displayed an allometric relationship with other mammals, CL and t1/2 did not. Allometrically scaled values were approximately sevenfold lower (CL) and sixfold higher (t1/2 ) than observed values, highlighting flaws associated with this technique in physiologically distinct species. On the basis of fAUC/MIC pharmacodynamic targets, fluconazole is predicted to be ineffective against Cryptococcus gattii in the koala as a sole therapeutic agent administered at 10 mg/kg p.o. every 12 h.

In vitro hepatic microsomal metabolism of meloxicam in koalas (Phascolarctos cinereus), brushtail possums (Trichosurus vulpecula), ringtail possums (Pseudocheirus peregrinus), rats (Rattus norvegicus) and dogs (Canis lupus familiaris).

Quantitative and qualitative aspects of in vitro metabolism of the non-steroidal anti-inflammatory drug meloxicam, mediated via hepatic microsomes of specialized foliage (Eucalyptus) eating marsupials (koalas and ringtail possums), a generalized foliage eating marsupial (brushtail possum), rats, and dogs, are described. Using a substrate depletion method, intrinsic hepatic clearance (in vitro Clint) was determined. Significantly, rates of oxidative transformation of meloxicam, likely mediated via cytochromes P450 (CYP), were higher in marsupials compared to rats or dogs. The rank order of apparent in vitro Clint was brushtail possums (n=3) (mean: 394µL/min/mg protein), >koalas (n=6) (50), >ringtail possums (n=2) (36) (with no significant difference between koalas and ringtail possums), >pooled rats (3.2)>pooled dogs (in which the rate of depletion, as calculated by the ratio of the substrate remaining was <20% and too slow to determine). During the depletion of meloxicam, at a first-order rate constant, 5-hydroxymethyl metabolite (M1) was identified in the brushtail possums and the rat as the major metabolite. However, multiple hydroxyl metabolites were observed in the koala (M1, M2, and M3) and the ringtail possum (M1 and M3) indicating that these specialized foliage-eating marsupials have diverse oxidation capacity to metabolize meloxicam. Using a well-stirred model, the apparent in vitro Clint of meloxicam for koalas and the rat was further scaled to compare with published in vivo Cl. The closest in vivo Cl prediction from in vitro data of koalas was demonstrated with scaled hepatic Cl(total) (average fold error=1.9) excluding unbound fractions in the blood and microsome values; whereas for rats, the in-vitro scaled hepatic Cl fu(blood, mic), corrected with unbound fractions in the blood and microsome values, provided the best prediction (fold error=1.86). This study indicates that eutherians such as rats or dogs serve as inadequate models for dosage extrapolation of this drug to marsupials due to differences in hepatic turnover rate. Furthermore, as in vivo Cl is one of the pharmacokinetic indexes for determining therapeutic drug dosages, this study demonstrates the utility of in vitro to in vivo scaling as an alternative prediction method of drug Cl in koalas.

Computed tomographic anatomy of the nasal cavity, paranasal sinuses and tympanic cavity of the koala.

OBJECTIVE: To use cross-sectional imaging (helical computed tomography (CT)) combined with conventional anatomical dissection to define the normal anatomy of the nasal cavity and bony cavitations of the koala skull. METHODS: Helical CT scans of the heads of nine adult animals were obtained using a multislice scanner acquiring thin slices reconstructed in the transverse, sagittal and dorsal planes. Subsequent anatomical dissection permitted confirmation of correct identification and further delineation of bony and air-filled structures visible in axial and multiplanar reformatted CT images. RESULTS: The nasal cavity was relatively simple, with little scrolling of nasal conchae, but bony cavitations were complex and extensive. A rostral maxillary recess and ventral conchal, caudal maxillary, frontal and sphenoidal paranasal sinuses were identified and characterised. Extensive temporal bone cavitation was shown to be related to a large epitympanic recess. CONCLUSIONS: The detailed anatomical data provided are applicable to future functional and comparative anatomical studies, as well as providing a preliminary atlas for clinical investigation of conditions such as cryptococcal rhinosinusitis, a condition more common in the koala than in many other species.

Pharmacokinetics of meloxicam in koalas (Phascolarctos cinereus) after intravenous, subcutaneous and oral administration.

The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high-performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (Vz ) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (Vss ) of 0.22 ± 0.12 L/kg. Median plasma terminal half-life (t(1/2)) was 1.19 h (range 0.71-1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (C(max) 0.013 ± 0.001 and 0.014 ± 0.001 µg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 µg/mL] between 4-8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5-hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate.

Severe subacute necrotizing encephalopathy (Leigh-like syndrome) in American Staffordshire bull terrier dogs.

Seventeen American Staffordshire bull terrier puppies, 6-8 weeks of age, from seven closely related litters, presented with rapidly progressive central vestibular neurological signs. Previously reported hereditary ataxias in the breed, including l-2 hydroxyglutaric aciduria and cerebellar cortical degeneration, as well as thiamine deficiency, were excluded. Elevated lactate levels and lactate:pyruvate ratios gave supporting evidence of a defect of the respiratory chain or Leigh-like syndrome. Histopathology in all cases showed a bilaterally symmetrical necrotizing encephalopathy, with malacia of the neuropil centred on the vestibular and olivary nuclei of the brainstem. This is the first documentation of a heritable rapidly progressive lethal necrotizing encephalopathy consistent with Leigh-like syndrome, in American Staffordshire bull terrier dogs.

Pharmacokinetics of chloramphenicol following administration of intravenous and subcutaneous chloramphenicol sodium succinate, and subcutaneous chloramphenicol, to koalas (Phascolarctos cinereus).

Clinically normal koalas (n = 19) received a single dose of intravenous (i.v.) chloramphenicol sodium succinate (SS) (25 mg/kg; n = 6), subcutaneous (s.c.) chloramphenicol SS (60 mg/kg; n = 7) or s.c. chloramphenicol base (60 mg/kg; n = 6). Serial plasma samples were collected over 24-48 h, and chloramphenicol concentrations were determined using a validated high-performance liquid chromatography assay. The median (range) apparent clearance (CL/F) and elimination half-life (t(1/2)) of chloramphenicol after i.v. chloramphenicol SS administration were 0.52 (0.35-0.99) L/h/kg and 1.13 (0.76-1.40) h, respectively. Although the area under the concentration-time curve was comparable for the two s.c. formulations, the absorption rate-limited disposition of chloramphenicol base resulted in a lower median C(max) (2.52; range 0.75-6.80 µg/mL) and longer median tmax (8.00; range 4.00-12.00 h) than chloramphenicol SS (C(max) 20.37, range 13.88-25.15 µg/mL; t(max) 1.25, range 1.00-2.00 h). When these results were compared with susceptibility data for human Chlamydia isolates, the expected efficacy of the current chloramphenicol dosing regimen used in koalas to treat chlamydiosis remains uncertain and at odds with clinical observations.

Cerebral cryptococcomas in a cow.

Cerebral cryptococcomas are described in a 5-year-old mixed-breed cow without manifestations of systemic cryptococcosis. Two cryptococcomas were observed grossly. Microscopical examination revealed accumulations of yeast that were morphologically consistent with Cryptococcus neoformans. Immunohistochemistry characterized the organisms as C. neoformans var. grubii.

Plasma concentrations of chloramphenicol after subcutaneous administration to koalas (Phascolarctos cinereus) with chlamydiosis.

Nine mature koalas with chlamydiosis, typically keratoconjunctivitis and/or urogenital tract infection, were treated with daily subcutaneous injections of chloramphenicol at 60 mg/kg for 45 days (five koalas), or for a shorter duration (four koalas). All koalas were initially positive for Chlamydia pecorum as determined by real-time polymerase chain reaction (qPCR). Plasma chloramphenicol concentrations were determined at t = 0, 1, 2, 4, 8, and 24 h after the day 1 injection (nine koalas) and after the day 15 injection (seven koalas). Chloramphenicol reached a median (and range) maximum plasma concentration of 3.03 (1.32-5.03 µg/mL) at 4 (1-8 h) after the day 1 injection and 4.82 (1.97-27.55 µg/mL) at 1 (1-2 h) after day 15. The median (and range) of AUC(0-24) on day 1 and day 15 were 48.14 (22.37-81.14 µg·h/mL) and 50.83 (28.43-123.99 µg·h/mL), respectively. The area under the moment curve (AUMC)(0-24) median (and range) for day 1 and day 15 were 530.03 (233.05-798.97 h) and 458.15 (291.72-1093.58 h), respectively. Swabs were positive for chlamydial DNA pretreatment, and all koalas except one, produced swabs negative for chlamydial DNA during treatment and which remained so, for 2-63 days after treatment, however whether chloramphenicol treatment prevented long-term recrudescence of infection was not established. At this dose and dosing frequency, chloramphenicol appeared to control mild chlamydial infection and prevent shedding, but severe urogenital disease did not appear to respond to chloramphenicol at this dosage regime. For koalas affected by severe chlamydiosis, antibiotics alone are not sufficient to effect a cure, possibly because of structural or metabolic changes associated with chronic disease and inflammation.

Sinonasal and sino-orbital aspergillosis in 23 cats: aetiology, clinicopathological features and treatment outcomes.

Aetiology, clinicopathological findings and treatment outcomes were documented in 23 cats (1.5-13 years of age) with sinonasal (SNA, n=6) or sino-orbital (SOA, n=17) aspergillosis. Cases recruited retrospectively and prospectively were included if fungal hyphae were identified on cytological or histological examination and the fungal pathogen was identified by PCR and DNA sequencing (ITS1 or ITS1-5.8S-ITS2 regions, rDNA gene cluster). Fungal culture was positive in 22/23 cases. In cases of SNA, the fungal pathogen was Aspergillus fumigatus (n=4), Neosartorya fischeri or A. lentulus (n=1) or a non-speciated Neosartorya spp. (n=1). In all cases of SOA (n=17), the fungal pathogen was identified as Neosartorya spp. Nine cats had brachycephalic conformation. Cats with SNA were more likely to be infected with A. fumigatus and had a better prognosis than cats with SOA.

New erythrocyte and reticulocyte parameters on CELL-DYN Sapphire: analytical and preanalytical aspects.

INTRODUCTION: Extended RBC and reticulocyte parameters are useful in diagnosing functional iron deficiency and various other clinical conditions. The newest software of the CELL-DYN Sapphire measures extended RBC and reticulocyte parameters. The aims of the present communication were to assess the analytical aspects of these parameters compared with the Siemens Advia 120 analyzer, to study the effect of sample aging and to briefly explore their clinical usefulness in patients with anemia. METHODS: Blood samples were obtained from the routine workload of two hospital laboratories and were run on Siemens Advia and Abbott CELL-DYN Sapphire analyzers in parallel. Data analysis was performed using standard statistics. RESULTS: In total, 1416 patient samples were analyzed. There was close correlation in microcytic and macrocytic RBC (r(2) > 0.97) with small bias. The hypo- and hyperchromic RBC showed reasonable correlations, Advia 120 giving higher values. Reticulocyte MCV showed acceptable agreement, with significant proportional bias (Advia 8-9% higher). CELL-DYN Sapphire MCHr correlated rather well with Advia CHr (r(2) > 0.91) with significant absolute bias. Remarkably, the correlation data differed significantly between the two laboratories. It was found that aging of EDTA samples had significant effect on most of the RBC parameters. CONCLUSIONS: The new RBC parameters of CELL-DYN Sapphire generally correlated well with those of Advia 120, although significant systematic differences were present, particularly in reticulocyte MCH and MCV. These differences necessitate instrument-specific reference ranges and clinical decision values. To minimize preanalytical effects, these parameters should be measured in fresh blood samples.