The value of repeat kidney biopsy during an atypical course of membranous nephropathy.

BACKGROUND: The clinical trajectory for patients with primary membranous nephropathy ranges widely from spontaneous remission to a rapid decline in kidney function. Etiologies for rapid progression with membranous nephropathy include concurrent bilateral renal vein thrombosis, malignant hypertension, and crescentic membranous nephropathy. Given the wide heterogeneity in prognosis, timing of immunosuppressive therapy is often challenging and centers around an individual patient's perceived risk for rapidly progressive disease. CASE PRESENTATION: Herein, we describe the clinical course of a young patient who initially developed a typical presentation of membranous nephropathy with consistent kidney biopsy findings. Given clinical stability, a six month observation period was undertaken prior to initiating immunosuppression. Within this observation window, the patient developed community acquired pneumonia followed several weeks later by a sudden, rapid decline in kidney function requiring dialysis. Repeat kidney biopsy revealed post-infectious glomerulonephritis superimposed upon a background of membranous nephropathy. Immunosuppressive therapy resulted in a favorable long-term outcome with normalization of kidney function and remission of nephrotic syndrome. To our knowledge, this is the first report of the simultaneous occurrence of these two glomerular disease processes. CONCLUSION: This case illustrates the value of repeat kidney biopsy during an atypical course of membranous nephropathy. Superimposed glomerular disease processes should be considered during a course of rapidly progressive membranous nephropathy.

In vivo Overexpression of Electrogenic Sodium/Bicarbonate Cotransporter (NBCe1) by AAV9 Modifies the Cardiac Action Potential and the QT Interval in Mice.

Cardiac cells depend on specific sarcolemmal ion transporters to assure the correct intracellular pH regulation. The sodium/bicarbonate cotransporter (NBC) is one of the major alkalinizing mechanisms. In the heart two different NBC isoforms have been described: the electroneutral NBCn1 (1Na+:1 HCO 3 - ) and the electrogenic NBCe1 (1Na+:2 HCO 3 - ). NBCe1 generates an anionic repolarizing current that modulates the action potential duration (APD). In addition to regulating the pH, the NBC is a source of sodium influx. It has been postulated that NBC could play a role in the development of hypertrophy. The aim of this research was to study the contribution of NBCe1 in heart electrophysiology and in the development of heart hypertrophy in an in vivo mouse model with overexpression of NBCe1. Heart NBCe1 overexpression was achieved by a recombinant cardiotropic adeno-associated virus (AAV9) and was evidenced by western-blot and qPCR. AAV9-mCherry was used as a transduction control. NBCe1 overexpression fails to increase heart growth. Patch clamp and electrocardiogram were performed. We observed a reduction on both, ventricular myocytes APD and electrocardiogram QT interval corrected by cardiac rate, emphasizing for the first time NBCe1 relevance for the electrical activity of the heart.

Doppler ultrasonographic evaluation of medically treated female dogs with cystic endometrial hyperplasia-pyometra complex.

Monitoring the treatment outcome of canine cystic endometrial hyperplasia-pyometra complex (CEH-P) is essential to identify nonresponding patients who might require a rapid intervention to avoid life-threatening conditions. Uterine artery Doppler characterization may contribute to monitoring medically treated CEH-P, but published studies are currently lacking. Therefore, the aim of this longitudinal prospective observational study was to evaluate uterine artery resistance changes in the medical treatment of female dogs with CEH-P. Twelve diestrous female dogs suffering from CEH-P were treated with a combined protocol of cabergoline, cloprostenol, and antibiotics. The animals were clinically and ultrasonographically evaluated before the beginning of treatment (day 0) and on days 3, 7, 14, 21, and 28. The widest transverse diameter and luminal diameter of uterine horns were measured, as well as the peak systolic velocity (PSV) and end diastolic velocity (EDV) of uterine arteries. The resistance index (RI), pulsatility index (PI), and notch deep index (NDI) were calculated. On day 3, nine of 12 animals showed clinical improvement. In all these female dogs, the widest transverse sectional diameter (P < 0.01), luminal diameter (P < 0.01), PSV (P < 0.01), and EDV (P < 0.01) progressively decreased, while RI (P < 0.01), PI (P < 0.01), and NDI (P < 0.01) increased up to day 21. In nonresponding dogs (3/12), Doppler parameters remained unchanged. Although comparisons of PSV, EDV, and NDI were significantly different, these results should be cautiously interpreted due to the low statistical power. female dogs that responded to this treatment showed an increase in uterine artery resistance, along with clinical and ultrasonographic improvement.

Efficacy of bilateral temporal artery biopsies and sectioning of the entire block of tissue for the diagnosis of temporal arteritis.

Giant cell arteritis (GCA) is a systemic vasculitis of medium and large sized blood vessels. The incidence is greater in women as compared to men (3:1) and most often occurs in the elderly. The most common symptoms are unilateral headaches, visual disturbances and scalp tenderness. If untreated, GCA may result in irreversible blindness. Prompt treatment is necessary to prevent progression of the disease, but accurate diagnosis is vital to prevent unwarranted side effects of the therapy. Temporal artery biopsy (TAB) remains the gold standard for diagnosis. TAB is an invasive procedure that can require up to 40 minutes to perform but is important for pathological confirmation. Variation amongst centers and practitioners exists in the type of biopsies performed. In 2013, a survey of over 1000 specialists showed that 37% recommended unilateral biopsy alone, 29% recommended initial unilateral biopsy with biopsy of the contralateral side if the first side is negative, 18% recommended bilateral biopsy in all cases, and 16% stated that their preference depended upon the degree of suspicion. Studies have shown that bilateral TAB can enhance diagnostic accuracy by 3 to 12.7%. Furthermore, temporal arteritis can involve the artery in a discontinuous fashion and there is no standardization of the number of sections or levels that should be examined in a segment of temporal artery. This study aims to shed light on the benefits of a bilateral temporal artery biopsy as well as to determine the optimum level for block sectioning for the diagnosis of temporal arteritis.

Ovarian and uterine two-dimensional and Doppler ultrasonographic changes in the feline peri-estrus period.

OBJECTIVES: The aim of this study was to evaluate two-dimensional and Doppler ultrasonographic changes of the ovary and uterus during estrus and the early post-estrus period in domestic cats. METHODS: Two-dimensional and Doppler ultrasonographic evaluations of the ovaries and uterus were performed in seven queens on days 1, 3 and 5 of estrus, and 5 days after estrus (AE5). RESULTS: On day 1, 5.4 ± 0.5 follicles of 2.1 ± 0.1 mm were detected progressively increasing in number and size up to day 5 and then decreased on AE5 (P <0.05). A maximum follicular diameter of 4.1 ± 0.1 mm was achieved on day 5. Both during and after estrus, the uterus was generally hypoechoic compared with the surrounding tissues and delineated by a thin hyperechoic line corresponding to the serosa. In some animals, the uterine layers were distinguished during and after estrus. The blood flow waveforms of the intraovarian and uterine arteries were characterized by a systolic peak and diastolic flow extending throughout the remainder of the cardiac cycle to the next systole. In the uterine artery waveforms, the early diastolic notch was mild or absent during most estrous observations. The resistance index of the intraovarian arteries decreased up to day 5, and then increased on AE5 (P <0.05). The resistance index of the uterine arteries was lower during estrus than in the post-estrus period (P <0.05). CONCLUSIONS AND RELEVANCE: It is concluded that in the domestic cat, follicular number and diameter as well as ovarian and uterine blood flow changed during and immediately after estrus. Doppler ultrasound proved suitable to evaluate the hemodynamic changes involved in the cyclic remodeling of ovarian and uterine tissues that occurs during and after follicular growth in domestic cats.

CON: Pulmonary artery catheter use should be forgone in modern clinical practice.

The pulmonary artery catheter (PAC) and its role in the practice of modern medicine remains to be questioned and has experienced a substantial decline in its use in the most recent decades. The complications associated to its use, the lack of consistency of the interpretation provided by the PAC among clinicians, the development of new hemodynamic methods, and the deleterious cost profile associated to the PAC are some of the reasons behind the decrease in its use. Since its introduction into clinical practice, the PAC and the data obtained from its use became paramount in the management of critically ill patients as well as for the high-risk/invasive procedures. Initially, many clinicians were under the impression that regardless the clinical setting, acquiring the information provided by the PAC justified its use, until a growing body of evidence demonstrated its lack of mortality and morbidity improvement, as well as several reports of the presence of difficulties-some of them fatal-during its insertion. The authors present an updated review discussing the futility of the PAC in current clinical practice, the complications associated to its insertion, the lack of mortality benefit in critically ill patients and cardiac surgery, as well as present alternative hemodynamic methods to the PAC.

Antimicrobial Peptide Exposure Selects for Resistant and Fit Stenotrophomonas maltophilia Mutants That Show Cross-Resistance to Antibiotics.

Antimicrobial peptides (AMPs) are essential components of the innate immune system and have been proposed as promising therapeutic agents against drug-resistant microbes. AMPs possess a rapid bactericidal mode of action and can interact with different targets, but bacteria can also avoid their effect through a variety of resistance mechanisms. Apart from hampering treatment by the AMP itself, or that by other antibiotics in the case of cross-resistance, AMP resistance might also confer cross-resistance to innate human peptides and impair the anti-infective capability of the human host. A better understanding of how resistance to AMPs is acquired and the genetic mechanisms involved is needed before using these compounds as therapeutic agents. Using experimental evolution and whole-genome sequencing, we determined the genetic causes and the effect of acquired de novo resistance to three different AMPs in the opportunistic pathogen Stenotrophomonas maltophilia, a bacterium that is intrinsically resistant to a wide range of antibiotics. Our results show that AMP exposure selects for high-level resistance, generally without any reduction in bacterial fitness, conferred by mutations in different genes encoding enzymes, transporters, transcriptional regulators, and other functions. Cross-resistance to AMPs and to other antibiotic classes not used for selection, as well as collateral sensitivity, was observed for many of the evolved populations. The relative ease by which high-level AMP resistance is acquired, combined with the occurrence of cross-resistance to conventional antibiotics and the maintained bacterial fitness of the analyzed mutants, highlights the need for careful studies of S. maltophilia resistance evolution to clinically valuable AMPs.IMPORTANCEStenotrophomonas maltophilia is an increasingly relevant multidrug-resistant (MDR) bacterium found, for example, in people with cystic fibrosis and associated with other respiratory infections and underlying pathologies. The infections caused by this nosocomial pathogen are difficult to treat due to the intrinsic resistance of this bacterium against a broad number of antibiotics. Therefore, new treatment options are needed, and considering the growing interest in using AMPs as alternative therapeutic compounds and the restricted number of antibiotics active against S. maltophilia, we addressed the potential for development of AMP resistance, the genetic mechanisms involved, and the physiological effects that acquisition of AMP resistance has on this opportunistic pathogen.

Evaluation of T-Cell Responses Against Shared Melanoma Associated Antigens and Predicted Neoantigens in Cutaneous Melanoma Patients Treated With the CSF-470 Allogeneic Cell Vaccine Plus BCG and GM-CSF.

The CSF-470 vaccine consists of lethally-irradiated allogeneic cells derived from four cutaneous melanoma cell lines administered plus BCG and GM-CSF as adjuvants. In an adjuvant phase II study vs. IFN-α2b, the vaccine significantly prolonged the distant metastasis-free survival (DMFS) of stages IIB-IIC-III melanoma patients with evidence of the induction of immune responses against vaccine cells. Purpose: The aim of this study was to analyze the antigens against which the immune response was induced, as well as the T-helper profile and lytic ability of immune cells after CSF-470 treatment. Methods: HLA-restricted peptides from tumor-associated antigens (TAAs) were selected from TANTIGEN database for 13 evaluable vaccinated patients. In addition, for patient #006 (pt#006), tumor somatic variants were identified by NGS and candidate neoAgs were selected by predicted HLA binding affinity and similarity between wild type (wt) and mutant peptides. The patient's PBMC reactivity against selected peptides was detected by IFNγ-ELISPOT. T-helper transcriptional profile was determined by quantifying GATA-3, T-bet, and FOXP3 mRNA by RT-PCR, and intracellular cytokines were analyzed by flow cytometry. Autologous tumor cell lysis by PBMC was assessed in an in vitro calcein release assay. Results: Vaccinated patient's PBMC reactivity against selected TAAs derived peptides showed a progressive increase in the number of IFNγ-producing cells throughout the 2-yr vaccination protocol. ELISPOT response correlated with delayed type hypersensitivity (DTH) reaction to CSF-470 vaccine cells. Early upregulation of GATA-3 and Foxp3 mRNA, as well as an increase in CD4+IL4+cells, was associated with a low DMFS. Also, IFNγ response against 9/73 predicted neoAgs was evidenced in the case of pt#006; 7/9 emerged after vaccination. We verified in pt# 006 that post-vaccination PBMC boosted in vitro with the vaccine lysate were able to lyse autologous tumor cells. Conclusions: A progressive increase in the immune response against TAAs expressed in the vaccine and in the patient's tumor was induced by CSF-470 vaccination. In pt#006, we demonstrated immune recognition of patient's specific neoAgs, which emerged after vaccination. These results suggest that an initial response against shared TAAs could further stimulate an immune response against autologous tumor neoAgs.

The activation of the G protein-coupled estrogen receptor (GPER) prevents and regresses cardiac hypertrophy.

Ventricular hypertrophy is a risk factors for arrhythmias, ischemia and sudden death. It involves cellular modifications leading to a pathological remodeling and is associated with heart failure. The activation of the G protein-coupled estrogen receptor (GPER) mediates beneficial actions in the cardiovascular system. Our goal was to prevent and regress the hypertrophy by the activation of GPER in neonatal cardiac myocytes (NRCM) and SHR male rats. Aldosterone increased the neonatal cardiomyocytes cell surface area after 48 h of incubation. The aldo-induced hypertrophy was blocked by the mineralocorticoid receptor (MR) inhibitor Eplererone or the reduction of MR expression by siRNA. The activation of GPER by the agonist G-1 totally prevented the increase surface area by Ald. The transfection of neonatal rat cardiac myocytes with a siRNA against GPER or the incubation with GPER blockers G-15 and G-36 inhibited the protection of G-1. The significant increase of cell surface area after 48 h of incubation with Ald was totally regressed in 24 h by the presence of G-1, indicating that the activation of GPER not only prevent the hypertrophy but also regress the hypertrophy when it is already established. In the in vivo model, G-1 or Vehicle was constantly infused via the minipump to SHR. The reduction of the hypertrophy by G-1 was evident by the cross-sectional area, BNP and ANP markers and by echocardiography. In this studied we demonstrated that the activation of GPER prevented and regressed the hypertrophy induced by Ald in NRCM and regressed hypertrophy in SHR rats.

Immunohistochemical analysis of benign and malignant melanocytic lesions of the conjunctiva using double-staining.

OBJECTIVE: To implement a double-staining technique to identify the most sensitive and specific combinations of melanoma antigen recognized by T cells (Melan-A), microphthalmia-associated transcription factor (MITF), human melanoma black 45 (HMB45), and Ki67 aiming to assist in the diagnosis of atypical melanocytic conjunctival lesions that are more prone to malignant progression. METHODS: Eight specimens of conjunctival melanoma and of primary acquired melanosis with moderate to severe atypia were double-immunostained with a combination of a cytoplasmic marker (anti-Melan-A or anti-HMB45), and a nuclear marker (anti-MITF or anti-Ki67). Eight specimens of normal conjunctiva and of conjunctival nevi served as controls. The specimens were processed using 3,3-diaminobenzidine substrate for nuclear stains and the fast-red substrate for cytoplasmic stains. Each slide was analyzed by light microscopy and provided a percent scale and a 0 to 4+ score for each nuclear and cytoplasmic component. RESULTS: Melan-A and MITF were strongly positive markers for all melanocytic cells, whereas Ki67 and HMB45 provided a variable response for identifying potentially proliferative or aggressive cells. HMB45 and MITF proved to be the best combination for differentiating between atypical and benign lesions on a percent scale and a 0 to 4+ scale (p = 0.0004), with the 3 other combinations providing mainly confirmatory diagnostic information (p < 0.05). CONCLUSIONS: Our study used an immunohistochemical double-staining approach to differentiate between atypical and benign melanocytic lesions of the conjunctiva. Our findings should aid in a more complete immunohistopathological diagnosis of conjunctival melanocytic lesions, particularly in diagnostically difficult cases.

Immunization With the CSF-470 Vaccine Plus BCG and rhGM-CSF Induced in a Cutaneous Melanoma Patient a TCRß Repertoire Found at Vaccination Site and Tumor Infiltrating Lymphocytes That Persisted in Blood.

The CSF-470 cellular vaccine plus BCG and rhGM-CSF increased distant metastases-free survival in cutaneous melanoma patients stages IIB-IIC-III relative to medium dose IFN-α2b (CASVAC-0401 study). Patient-045 developed a mature vaccination site (VAC-SITE) and a regional cutaneous metastasis (C-MTS), which were excised during the protocol, remaining disease-free 36 months from vaccination start. CDR3-TCRß repertoire sequencing in PBMC and tissue samples, along with skin-DTH score and IFN-γ ELISPOT assay, were performed to analyze the T-cell immune response dynamics throughout the immunization protocol. Histopathological analysis of the VAC-SITE revealed a highly-inflamed granulomatous structure encircled by CD11c+ nested-clusters, brisk CD8+ and scarce FOXP3+, lymphocytes with numerous Langhans multinucleated-giant-cells and macrophages. A large tumor-regression area fulfilled the C-MTS with brisk lymphocyte infiltration, mainly composed of CD8+PD1+ T-cells, CD20+ B-cells, and scarce FOXP3+ cells. Increasing DTH score and IFN-γ ELISPOT assay signal against the CSF-470 vaccine-lysate was evidenced throughout immunization. TCRß repertoire analysis revealed for the first time the presence of common clonotypes between a VAC-SITE and a C-MTS; most of them persisted in blood by the end of the immunization protocol. In vitro boost with vaccine-lysate revealed the expansion of persistent clones that infiltrated the VAC-SITE and/or the C-MTS; other persistent clones expanded in the patient's blood as well. We propose that expansion of such persistent clonotypes might derive from two different although complementary mechanisms: the proliferation of specific clones as well as the expansion of redundant clones, which increased the number of nucleotide rearrangements per clonotype, suggesting a functional antigenic selection. In this patient, immunization with the CSF-470 vaccine plus BCG and rhGM-CSF induced a T-cell repertoire at the VAC-SITE that was able to infiltrate an emerging C-MTS, which resulted in the expansion of a T-cell repertoire that persisted in blood by the end of the 2-year treatment.

Periadventitial tissue examination in temporal artery biopsies for suspected giant cell arteritis: a case series and literature review.

OBJECTIVE: Giant cell arteritis (GCA) is a systemic vasculitis, affecting medium- and large-sized vessels. Temporal artery biopsies (TABs) are currently the benchmark for diagnosing suspected cases of GCA. Often, the temporal artery is "skeletonized," and surrounding soft tissue is discarded at the time of biopsy. The purpose of this study was to identify cases in which diagnoses were made through examination of periadventitial soft tissue in nonskeletonized TABs. DESIGN: Retrospective observational case series and literature review. PARTICIPANTS: Six patients were recruited on a case-by-case basis. INCLUSION CRITERIA: bilateral TABs for suspected GCA and periadventitial findings leading to appropriate diagnosis. EXCLUSION CRITERIA: none. METHODS: A retrospective chart review was performed to collect patient demographics and clinical information in 2 academic institutions in Ontario, Canada. The primary outcome measure was identification of histopathological diagnoses made through examination of periadventitial soft tissue in TABs performed for suspected GCA. RESULTS: Two patients were diagnosed with GCA, one of which had a concurrent diagnosis of chronic lymphocytic leukemia. Four patients were diagnosed with small vessel vasculitis, 3 of which were antineutrophil cytoplasmic antibody-related vasculitides. All patients had evidence of a disease limited to the periadventitial tissue of the TAB. The results are limited by the study's size. CONCLUSIONS: This case series demonstrates that other serious conditions may declare themselves with symptoms similar to that of GCA. We recommend that surgeons perform a nonskeletonized TAB in all cases of suspected GCA and that pathologists adequately examine the periadventitial tissue in these biopsies to ensure appropriate diagnosis.

Histopathological Study on the Proposed Pathogenesis of Intratarsal Keratinous Cysts.

PURPOSE: Intratarsal keratinous cysts (IKCs) are a recently described entity that is frequently misdiagnosed clinically as chalazia and mislabeled in the literature as "intratarsal epidermal inclusion cysts" or "epidermoid cysts." It is important to accurately diagnose IKCs and distinguish them from chalazia because IKCs require a complete surgical excision and can exhibit multiple recurrences following curettage. The authors performed a retrospective case series to further elucidate the pathogenesis of IKCs and to determine the diagnostically optimal panel of stains for diagnosis. METHODS: A study group of 8 specimens of IKCs and control specimens of epidermal inclusion cysts were obtained from their pathology laboratories. The authors compared the histological and immunohistochemical profile of IKCs and epidermal inclusion cysts by staining sections from each specimen with hematoxylin and eosin, periodic acid-Schiff, Masson trichrome, cytokeratin 5, cytokeratin 17, carcinoembryonic antigen, and epithelial membrane antigen. The immunoreactivity data were then analyzed using a 2-tailed Mann-Whitney test, assuming a nonparametric population (p < 0.05 is significant). RESULTS: Histopathologically, IKCs are embedded in the tarsus lined by stratified squamous epithelium with an inner undulating cuticle filled with a compact keratinous-appearing material. The authors demonstrate that IKCs develop progressively from dilated meibomian ducts to the formation of complete cysts with their markers. The most valuable immunochemical stains to diagnose IKC were cytokeratin 17, carcinoembryonic antigen, and epithelial membrane antigen (p < 0.05 with each). CONCLUSIONS: These findings provide a better understanding of the pathogenesis and the immunohistochemical findings of this relatively new entity allowing for more appropriate diagnosis of IKCs aiming to reduce future complications from their management.

Dissecting the Immune Stimulation Promoted by CSF-470 Vaccine Plus Adjuvants in Cutaneous Melanoma Patients: Long Term Antitumor Immunity and Short Term Release of Acute Inflammatory Reactants.

As cutaneous melanoma (CM) currently remains with a bleak prognosis, thorough investigation of new treatment options are of utmost relevance. In the phase II/III randomized clinical trial (CASVAC-0401), the repeated immunization of stages IIB-III CM patients with the irradiated, allogeneic cellular CSF-470 vaccine plus the adjuvants bacillus Calmette-Guerin (BCG) and recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) demonstrated a significant benefit over IFN-alpha2B treatment in distant metastasis-free survival. Here we present on the short and long term immune monitoring results after completing the 2-year protocol; a continuation of the previous report by Mordoh et al. (1). We demonstrate that the repeated CSF-470 vaccinations stimulated a long term cellular and humoral immunity response directed against the vaccine antigens. In the case of 2 patients, we are able to show that a similar immune response was generated against autologous antigens. Evaluation of inhibitory receptor co-expression on patient's T cells indicates that the vaccination protocol did not stimulate T cell exhaustion. In order to better understand the basis for the efficacious vaccine responses observed, we investigated the short term immune events following vaccine injection. A significant increase in C-reactive protein (CRP) and IL-6 was observed 24 h after vaccination, with in vitro studies suggesting IL-6 production occurs in the vaccine site. We demonstrate that CRP enhances the cytotoxicity of peripheral blood mononuclear cells (PBMC) against melanoma cells in an in vitro model. Additionally, CRP stimulates the release of pro and anti-inflammatory cytokines from PBMC. As our results demonstrate that successive vaccinations with CSF-470 plus adjuvants promoted an increase in both anti-tumor innate and adaptive immunity, we propose a subsequent model of action.

Uterine two-dimensional and Doppler ultrasonographic evaluation of feline pyometra.

The aim of this study was to compare uterine two-dimensional and Doppler ultrasonographic parameters in queens suffering from pyometra from those in early pregnancy. Secondly, the effect of the presence of clinical signs of systemic illness on these parameters was also described. Fourteen post-oestrous queens, with uterine luminal content in the absence of embryos were included. According to their outcome (pyometra surgery or parturition), the queens were retrospectively assigned to one of the following groups: Pyometra (PYO; n = 7) or pregnant (PRG; n = 7). In all the queens, two-dimensional and Doppler ultrasound examinations of the uterus were performed. The presence or absence of clinical signs of systemic illness was recorded. The widest cross-sectional diameter (UD), uterine wall thickness (WT), uterine lumen contents (LC) and uterine artery resistance index (RI) were measured. Uterine horn diameter was higher in PYO group than in PRG group (p < 0.05), while WT (p > 0.1) and LC (p = 0.09) did not differ between groups. Values of RI for PYO and PRG groups were 0.61 ± 0.03 vs 0.53 ± 0.09 (p < 0.05), respectively. PYO cats suffering from clinical signs of systemic illness showed larger UD than those without signs (p < 0.01). It is concluded that two-dimensional and Doppler ultrasound might be useful to distinguish queens suffering from pyometra from those in early pregnancy. Secondly, the clinical signs of systemic illness were associated with a larger UD.

Sickle cell disease: a case report of renal amyloidosis.

BACKGROUND: The development of proteinuria and reduced glomerular filtration rate is associated with higher mortality among patients with sickle cell disease (SCD). AA amyloidosis, also associated with increased mortality, in SCD is rare. We present a case of a woman with homozygous sickle cell disease with nephrotic syndrome and antibodies to double stranded DNA without clinical features of systemic lupus erythematosus. Kidney biopsy reveals AA amyloidosis and is the first report of concomitant AA amyloidosis with antibodies to double stranded DNA in SCD. CASE PRESENTATION: A 40-year-old Central African woman with homozygous sickle cell disease and history of vaso-occlusive pain crises undergoes kidney biopsy for nephrotic-range proteinuria. Kidney biopsy reveals AA type amyloidosis, which is a rare manifestation of SCD in the kidney. Her anemia worsens with an ACE inhibitor, initiated to reduce proteinuria and limit GFR decline, so it was discontinued. Hydroxyurea, shown to decrease the frequency of vaso-occlusive crises and lower proteinuria, was subsequently initiated but then discontinued due to worsening anemia. Unfortunately, her glomerular filtration rate worsens. CONCLUSIONS: AA amyloidosis and antibodies to double stranded DNA can occur in sickle cell disease. ACE inhibition and hydroxyurea decrease proteinuria so they may limit progression of chronic kidney disease. Hydroxyurea also decreases frequency of vaso-occlusive pain crises so it might be helpful in limiting progression of renal AA amyloidosis. However, further studies are needed to determine optimal treatment strategies for AA amyloidosis in sickle cell disease.

Cognitive biases in orbital mass lesions - Lessons learned.

PURPOSE: A patient's presentation and clinical diagnosis can at times be clouded by their past medical history. Clinicians' anchoring bias towards initial information, such as a history of cancer, may lead them astray when creating a differential diagnosis for a patient who presents with new signs and symptoms of a mass lesion, assuming metastatic disease without seeking tissue confirmation. METHODS: The presentation, workup, diagnosis, and treatment of two patients who presented with orbital masses in the context of a primary prostate cancer are presented in this report. RESULTS: In both cases, prostate cancer metastasis to the orbit was top on the differential. Ultimately, histopathological examination of biopsies taken from the orbital masses revealed orbital lymphoma in both patients. CONCLUSION: With mounting rates of patients who have survived a previous cancer, multiple primary cancers within one patient are becoming increasingly common. While prostate cancer metastasis to the orbit is a relatively rare event, orbital lymphoma is a more common diagnosis in orbital masses. Therefore, when patients present with orbital masses in the context of prostate cancer, the conclusion should not immediately be metastasis and a tissue diagnosis should be sought; especially given that the treatment of these entities is different.