Propofol versus sodium thiopentone for the treatment of status epilepticus and refractory status epilepticus in dogs.

AIMS: To compare the effect on mortality and length of hospital stay of propofol with that of sodium thiopentone for the management of dogs with status epilepticus (SE) and refractory status epilepticus (RSE). METHODS: In this cohort study, medical records of a veterinary referral clinic in Argentina were retrospectively searched for dogs that were hospitalised and required induction of therapeutic coma (TC) with either propofol or sodium thiopentone for the management of SE or RSE of any cause. A logistic regression model was performed to evaluate the association between the type of anaesthetic used and in-hospital mortality adjusting for the type of epilepsy (idiopathic, structural, or reactive). Kaplan-Meier estimated survival curves for the length of hospital stay by the type of anaesthetic drug were compared using the log-rank test (deaths were considered censored events). Cox proportional hazards regression was used to estimate hazard ratios for time to hospital discharge, unadjusted and adjusted for type of epilepsy. RESULTS: A total of 24 dogs with SE were included in the study: eight treated with propofol and 16 treated with sodium thiopentone. Four dogs treated with propofol (proportion = 0.50; 95% CI = 0.15-0.84), and eight treated with sodium thiopentone (proportion = 0.50; 95% CI = 0.50-0.74) died during hospitalisation. The median hospitalisation time was 43 (IQR 24-56) hours for dogs that were treated with propofol and 72 (IQR 64-96) hours for dogs that were treated with sodium thiopentone. There was no evidence of a difference in the median duration of TC in dogs treated with propofol (12 (IQR 8-24) hours) or with sodium thiopentone (12 (IQR 7.5-20) hours; p = 0.946). In the logistic regression model, no evidence of association between the anaesthetic protocol for the management of RSE and in-hospital mortality, adjusted for the type of epilepsy, was found (OR 1.09 (95% CI = 0.17-6.87); p = 0.925). Cox regression analysis revealed a difference in the time to hospital discharge, adjusted by the type of epilepsy, between treatment groups (HR = 0.05 (95% CI = 0.01-0.54); p = 0.013). CONCLUSIONS AND CLINICAL RELEVANCE: The time spent in hospital before discharge was longer in dogs with RSE treated with sodium thiopentone compared to those treated with propofol. However, as the sample size was very small, the results obtained in the present study should be analysed with caution. Further studies including a greater number of dogs are required.

Relationship between tricuspid annular plane systolic excursion, fluid responsiveness and volume status in hospitalised dogs with circulatory abnormalities.

AIMS: To evaluate the echocardiographic variable tricuspid annular plane systolic excursion normalised to body weight (TAPSEnorm) as a predictor of fluid responsiveness in hospitalised dogs with haemodynamic and tissue perfusion alterations and to investigate the association of left ventricular internal diameter in diastole normalised to body weight (LVIDdN) and aortic velocity time integral (VTIAo) with TAPSEnorm. METHODS: A single-centre, prospective study was carried out in a cohort of spontaneously breathing dogs, hospitalised for any reason, with severe haemodynamic and tissue perfusion alterations. The echocardiographic variables TAPSEnorm, LVIDdN, and VTIAO were measured. A bolus of 30 mL/kg of lactated Ringer's solution was administered and then VTIAo was subsequently remeasured. Patients were classified as fluid responsive if VTIAo increased by ≥15% after fluid expansion, or non-responsive if VTIAo increased by <15% after fluid expansion. The area under the receiver operating characteristic (AUROC) curve was generated to evaluate the ability of TAPSE to predict fluid responsiveness. Simple regression models were used to assess the linear relationship between TAPSEnorm and LVIDdN or VTIAO. RESULTS: TAPSEnorm was lower in fluid responsive dogs (mean 0.57 (95% CI = 0.50-0.64) cm/kg) compared to non-responsive dogs (mean 0.76 (95% CI = 0.62-0.90) cm/kg). The AUROC for TAPSEnorm was 0.827 (95% CI = 0.65-1.00). The optimal cut-off point was 0.76 with sensitivity of 80 (95% CI = 28.4-99.5)% and specificity of 86.7 (95% CI = 69.3-99.2)%, positive predictive value of 50 (95% CI = 15.7-84.3)% and negative predictive value of 96.3 (95% CI = 81-99.9)%. A monotonic linear relationship was observed between TAPSEnorm and LVIDdN (p<0.001) and between TAPSEnorm and VTIAo (p=0.001). CONCLUSIONS AND CLINICAL RELEVANCE: TAPSEnorm could be useful in determining those dogs that are likely to respond to a fluid bolus from those that are likely to be non-responsive. Additionally, a positive linear association between the LVIDdN and the TAPSEnorm suggests that TAPSEnorm decreases at lower preload values. The present study results suggest that TAPSEnorm could be a valuable tool for evaluating blood volume status and fluid responsiveness in hospitalised dogs.Abbreviations: AUROC: Area under the receiver operating characteristic; CO: Cardiac output; ICC: Intraclass correlation coefficient; LVIDd: Left ventricular internal diameter in diastole; LVIDdN: Left ventricular internal diameter in diastole normalised to body weight; TAPSE: Tricuspid annular plane systolic excursion; TAPSEnorm: Tricuspid annular plane systolic excursion normalised to body weight; VTIAo: Aortic velocity time integral.

An amyloid beta vaccine that safely drives immunity to a key pathological species in Alzheimer's disease: pyroglutamate amyloid beta.

Pyroglutamate amyloid beta3-42 (pGlu-Abeta3-42), a highly amyloidogenic and neurotoxic form of Abeta, is N-terminally truncated to form a pyroglutamate and has recently been proposed as a key target for immunotherapy. Optimized ACI-24, a vaccine in development for the treatment and prevention of Alzheimer's disease, focuses the antibody response on the first 15 N-terminal amino acids of Abeta (Abeta1-15). Importantly, clinical data with an initial version of ACI-24 incorporating Abeta1-15, established the vaccine's safety and tolerability with evidence of immunogenicity. To explore optimized ACI-24's capacity to generate antibodies to pGlu-Abeta3-42, pre-clinical studies were carried out. Vaccinating mice and non-human primates demonstrated that optimized ACI-24 was well-tolerated and induced an antibody response against Abeta1-42 as expected, as well as high titres of IgG reactive with pyroGlu-Abeta. Epitope mapping of the polyclonal response confirmed these findings revealing broad coverage of epitopes particularly for Abeta peptides mimicking where cleavage occurs to form pGlu-Abeta3-42. These data are in striking contrast to results obtained with other clinically tested Abeta targeting vaccines which generated restricted and limited antibody diversity. Taken together, our findings demonstrate that optimized ACI-24 vaccination represents a breakthrough to provide a safe immune response with a broader Abeta sequence recognition compared to previously tested vaccines, creating binders to pathogenic forms of Abeta important in pathogenesis including pGlu-Abeta3-42.

Angiotensin-converting enzyme inhibitors in preclinical myxomatous mitral valve disease in dogs: systematic review and meta-analysis.

OBJECTIVES: To determine the efficacy and adverse events of the administration of angiotensin--converting enzyme inhibitors for the management of preclinical myxomatous mitral valve disease in dogs. MATERIALS AND METHODS: A compre- hensive search using Pubmed/MEDLINE, LILACS and CAB abstracts databases was performed. Ran- domised clinical trials that assessed efficacy and adverse events of angiotensin-converting enzyme inhibitors for the management of preclinical myxomatous mitral valve disease in dogs were included. Certainty of evidence was rated using GRADE methods. RESULTS: Four randomised clinical trials were included. While safe, angiotensin-converting enzyme inhibitors administration to dogs with myxomatous mitral valve disease and cardiomegaly results in little to no difference in the risk of development congestive heart failure (high certainty of evidence; relative risk: 1.03; 95% confidence interval: 0.87 to 1.23) and may result in little to no difference in cardiovascular-related (low certainty of evidence; relative risk: 1.01; 95% confidence interval: 0.54 to 1.89) and all-cause mortality (low certainty of evidence; relative risk: 0.93; 95% confidence interval: 0.63 to 1.36). Administration of angiotensin-converting enzyme inhibitors to dogs with myxomatous mitral valve disease without cardiomegaly may result in a reduced risk of congestive heart failure development. However, the range in which the actual effect for this outcome may be, the "margin of error," indicates it might also increase the risk of congestive heart failure development (low certainty of evidence; relative risk: 0.86; 95% confidence interval: 0.54 to 1.35). CLINICAL SIGNIFICANCE: Administration of angiotensin-converting enzyme inhibitors to dogs with -preclinical myxoma- tous mitral valve disease and cardiomegaly results in little to no difference in the risk of the develop- ment of congestive heart failure and may result in little to no difference in -cardiovascular-related and all-cause mortality. The certainty of evidence of the efficacy of angiotensin-converting enzyme inhibi- tors administration to dogs without cardiomegaly was low.

Clinicopathological factors associated with the presence of hypercapnia at admission in hospitalised cats with decompensated chronic kidney disease.

AIMS: To evaluate associations between clinicopathological variables and hypercapnia measured in cats with decompensated chronic kidney disease (CKD) on admission to a veterinary hospital. METHODS: This is a retrospective, cross-sectional study of cats (n = 39) that presented to a tertiary veterinary hospital in Argentina between June 2015 and December 2017 with blood creatinine concentrations >140 µmol/L, and abdominal ultrasound results consistent with CKD. Data recorded included venous partial pressure of CO2 (PvCO2), blood pH, haematocrit and concentrations of glucose, potassium, sodium, corrected sodium (Na+c), and ionised calcium in blood. A logistic regression model was used to assess associations between the presence of hypercapnia (PvCO2 ≥ 44.7 mmHg) and the other clinicopathologic variables. The duration of hospitalisation was compared in cats with and without hypercapnia using the Wilcoxon Rank Sum test. RESULTS: The final study population comprised 39 cats. Eleven cats (28.2%) had hypercapnia. In the logistic regression model, two independent variables were associated with the presence of hypercapnia at admission in cats with CKD: the concentration of creatinine in blood (OR = 1.06 (95% CI = 1.016-1.108); p = 0.007) and Na+c (OR = 1.33 (95% CI = 1.08-1.63); p = 0.005). There were no statistically significant differences in the length of hospital stay between the two groups. CONCLUSIONS AND CLINICAL RELEVANCE: There appears to be an association between elevated concentrations of creatinine and Na+c in blood, and hypercapnia in cats with CKD, suggesting careful assessment of blood gas and electrolyte parameters during hospitalisation is required. Further prospective studies are needed to evaluate the mechanisms behind this association and the association of hypercapnia with disease outcome including mortality.

Sildenafil improves clinical signs and radiographic features in dogs with congenital idiopathic megaoesophagus: a randomised controlled trial.

We evaluated the efficacy of oral sildenafil citrate in dogs with congenital idiopathic megaoesophagus (CIM). Twenty-one puppies were randomly assigned to two groups (treatment and control). The dogs were given sildenafil oral suspension 1 mg/kg every 12 hours for 14 days or placebo in a masked fashion. Clinical signs (frequency of regurgitation and weight gain) and oesophagrams (relative oesophageal diameter, ROD) were evaluated in order to assess the efficacy of drug treatment, by examiners who were unaware of the study protocol. In addition, a set of in vitro experiments on isolated samples of canine lower oesophageal sphincter (LOS) was performed, and the effects of increasing concentrations of sildenafil on basal tone and electrically-stimulated motility were assessed. Sildenafil administration significantly reduced the number of regurgitation episodes (0.88±1.40 v 2.65±1.56, P<0.0001) and significantly increased weight gain in the treated dogs compared to controls (79.76±28.30 per cent v 53.40±19.30 per cent, P=0.034). ROD values, at the end of the treatment period, were significantly decreased in the sildenafil group, compared to pre-treatment values (0.97±0.19 v 0.24±0.14, P<0.0001), in contrast to control subjects (0.98±0.17 v 1.10±0.25, P=0.480). In accordance with the in vivo findings, sildenafil dose-dependently reduced basal tone and increased electrically-induced relaxation of dog LOS samples. These results suggest that sildenafil citrate helps ameliorate clinical and radiographic signs in dogs with CIM by reducing LOS tone, and could represent a novel therapeutic tool for the treatment of this disease.

Adenocarcinoma of the cervix associated with a neuroendocrine small cell carcinoma of the cervix in the spectrum of Muir-Torre syndrome.

Muir-Torre syndrome (MTS) is an autosomal genodermatosis that is diagnosed by the presence of at least one sebaceous gland tumor and at least one visceral malignancy. The most frequent visceral malignancies reported in literature are low-grade colon-rectal and genitourinary cancers, with prolonged survival. The authors report the case of a 52-year-old female, with a positive familial history for MTS, who developed a cutaneous sebaceous carcinoma, a synchronous colon-rectal adenocarcinoma, and a metachronous endocervical adenocarcinoma associated with a neuroendocrine small cell carcinoma of the cervix (SCNC), with lymph node metastasis. The rare occurrence in literature of the cervical SCNC and the rarest occurrence of a neuroendocrine carcinoma in the context of a MTS deviate from the usual and low-grade types of cancers normally described with MTS. It should be always appropriate to assess any symptoms that might reveal an underlying malignancy, although not within the spectrum of neoplasms most associated with this rare syndrome.

Dermo Beta Brachytherapy with 188Re in extramammary Paget's disease.

AIM: Extramammary Paget's disease (EMPD) is a rare neoplastic pathology involving the vulva, scrotum, and perianal areas, and it is characterized by a slow and insidious course. EMPD may also be associated with internal malignancy, and its clinical presentation features long-standing pruritic lesions, eczema-like, refractory to any therapy. The pathogenesis is unclear, and univocal standardization of treatment is yet to be determined. As regard to the patients who suffer from it, women are more often affected than men. The therapeutic approach depends on the extent of involvement; wide surgical excision is the first choice among treatments, but other forms of therapy, alone or in combination, include imiquimod 5%, photodynamic therapy, Mohs surgery as well as external beam radiotherapy and Brachytherapy. In the present paper a new therapeutic alternative is proposed: Dermo-Beta-Brachytherapy (DBBT) with 188Re. METHODS: Five patients with EMPD, one secondary and four primary cases, have been treated by Brachytherapy with DBBT. This therapy has been successfully used for non-melanocytic skin tumors and basically consists in the topical application of a specially designed, tailor-made mould containing a radioactive beta-emitting isotope, rhenium-188. RESULTS: The patients healed completely, after one session in one case and after two sessions in four cases, with 34 months mean follow-up. CONCLUSION: Brachyterapy could represent a new alternative therapy, instead than invasive treatments as surgery and conventional radiotherapy, capable to treat EMPD independently of its extension, with aesthetic and functional satisfactory results.

hMena: altered expression in psoriatic skin.

Psoriasis is a chronic inflammatory skin disease, characterized by an enhanced proliferation and a deregulated differentiation of keratinocytes. hMena is an actin regulatory protein involved in the control of cell motility and adhesion. hMena results up-modulated in several human tumors with respect to normal tissues and its expression has been positively correlated to proliferation rate, tumor size and aggressiveness in response to mitogenic stimuli, such as epidermal growth factor. The hyperproliferation of keratinocytes observed in psoriasis prompted us to evaluate hMena expression on biopsies collected from involved and uninvolved skin of 12 patients with active plaque-type psoriasis with respect to healthy skin. We analyzed the expression of hMena at transcript and protein levels by quantitative RT-PCR and immunohistochemistry. We correlated the expression of hMena to Ki67 proliferation index and to keratin 10 (K10) and keratin 16 (K16) used as markers of keratinocyte differentiation and activation. We demonstrated the expression of hMena in a hyperproliferative skin condition not related to neoplastic transformation. Interestingly, we observed that hMena is not expressed in healthy skin, but it becomes detectable in non-lesional areas and it is even more expressed in lesional psoriatic skin. In addition, we found that hMena expression is correlated to the rate of keratinocyte proliferation and activation. Hence, our observations indicate hMena as a new possible player, involved in the development and/or maintenance of the hyperproliferative state of psoriatic keratinocytes.

Visceral leishmaniasis revealed by a squamous cell carcinoma in an HIV-1 infected patient.

We present a case of visceral leishmaniasis confirmed after the histological investigation of an ulcerate lesion of the scalp in an HIV-1-infected patient receiving highly active antiretroviral therapy (HAART). Histological examination of the skin lesion revealed a squamous cell carcinoma superinfected by amastigotes of Leishmania infantum from the bloodstream. Because HIV-1-infected individuals can harbour parasitic infections in normal and neoplastic tissue, it is necessary to examine carefully any skin lesions, particularly those with uncommon aspects or a worsening course, to exclude superinfections by unsuspected pathogens.

Lichen sclerosus and the risk of malignant progression: a case series of 159 patients.

AIM AND METHODS: We analyzed 159 stored specimens of Lichen Sclerosus (LS) collected in the period 1999-2011 from 159 patients, in order to evaluate the histological patterns, clinical outcomes and possible associations with malignancies. The histopathologic analysis revealed 145 cases (males and females) with LS alone, 7 in whom penile LS was associated with spinocellular carcinoma (SCC), and 7 in whom LS was associated with a pseudocarcinomatous-hyperplasia (PCH). Extragenital LS was found in 20% (17/85) of the males and 78% (58/74) of the females. In the cases of SCC, immunohistochemical analyses was performed. RESULTS AND CONCLUSION: The results showed very low positivity to p16INK4A and Ki-67; biomolecular PCR was positive in only two cases, and in both cases the non-oncogenic genotype HPV 100 was detected. No important additional risk factors for malignancies were found (e.g., hormones, infections, other autoimmune diseases).

Clinical, dermoscopic and reflectance confocal microscopy features of sebaceous neoplasms in Muir-Torre syndrome.

BACKGROUND: Muir-Torre syndrome (MTS) is an autosomal-dominant disorder characterized by the association of sebaceous tumors or keratoacanthomas with an early onset visceral cancer in the spectrum of Lynch syndrome. OBSERVATIONS: A total of 20 sebaceous tumors including 18 sebaceous adenoma and two sebaceomas of six patients with MTS were analysed. Two main clinico-dermoscopic features were observed: (1) clinically pink to white papules/nodules with a central crater, dermoscopically characterized by radially arranged, elongated crown vessels surrounding opaque structureless yellow areas at times covered by blood crusts (n = 13) and (2), clinically pink to yellow papules/nodules without a central crater, dermoscopically exhibiting a few, loosely arranged yellow comedo-like globules and branching arborizing vessels (n = 7). Confocal microscopy was available in three sebaceous adenomas and revealed a good histopathologic correlation; sebaceous lobules were composed by clusters of ovoid cells with dark nuclei and bright, highly refractile glistening cytoplasm. They were delimited by a rim of epithelial cells, corresponding to basaloid cells. CONCLUSIONS: A better characterization of clinical, dermoscopic and confocal microscopy features of sebaceous tumors may improve their recognition and consequently, aid to rise the suspect for MTS.

["Dying nevus" or regressing melanoma]. / "Sterbender Nävus" oder regressives Melanom?

Epidemiological studies suggest that the number of acquired melanocytic nevi increases from puberty until midlife and, thereafter, decreases. The latter phenomenon is related to spontaneous involution/apoptosis of nevi. The widespread use of dermoscopy has enriched profoundly our knowledge of the morphological variability of nevi during their evolution. A peripheral symmetric rim of small grown globules represents a clear sign of nevus growth. Instead, nevi in adults often reveal a reticular or reticular-mixed pattern. In patients aged 30 to 40 years clinically vanishing nevi can be noticed, which represent nevi during involution. The important differential diagnoses are melanocytic nevi and melanoma with regression. The life cycle of a nevus is also reflected by the phrase" we are born and we die without nevi".

Elevation of serum gamma-glutamyltranspeptidase activity is frequent in chronic hepatitis C, and is associated with insulin resistance.

BACKGROUND AND AIMS: Serum gamma-glutamyltranspeptidase level is often increased in patients with chronic hepatitis C, and we aimed to identify factors associated with this phenomenon in patients completely abstinent from alcohol (teetotaller). PATIENTS AND METHODS: 71 teetotaller patients have been identified by personal history, questioning of relatives, CAGE questionnaire administration and unscheduled alcoholemia measurements. RESULTS: 39 patients (55%) had elevated (>50IU/L) gamma-glutamyltranspeptidase level. Body mass index, insulin and C-peptide level, insulin resistance, piecemeal necrosis score > or =3, fibrosis score > or =2 and steatosis score > or =1 were significantly higher in these patients than in those (n=32) with normal gamma-glutamyltranspeptidase. At multiple linear regression analysis gamma-glutamyltranspeptidase level was associated with C-peptide level, insulin resistance and histopathologic grading. At multiple logistic regression analysis, C-peptide level (OR=2.13) and piecemeal necrosis score > or =3 (OR=4.59) were the only factors independently associated with elevated gamma-glutamyltranspeptidase. Sustained virological response during pegylated interferon plus ribavirine treatment was achieved by 97% and 49% patients with normal and elevated gamma-glutamyltranspeptidase, respectively (p=0.0001). CONCLUSION: Serum gamma-glutamyltranspeptidase level is often elevated in chronic hepatitis C and is associated with metabolic and inflammatory factors; this phenomenon may contribute to explain and to predict resistance to treatment in this subgroup of patients.

Dermatological high-dose-rate brachytherapy for the treatment of basal and squamous cell carcinoma.

BACKGROUND: Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are among the most common cancers in humans. Various therapies are currently being used to treat these tumours including surgery, topical treatments and radiotherapy. We describe a new treatment for BCC and SCC. This consists of superficial radiotherapy, using synthetic resin containing a radioactive beta-emitting isotope. The resin is applied to the lesion to perform a selective beta-irradiation brachytherapy treatment. METHODS: In total, 53 patients with histologically confirmed diagnosis of BCC and of SCC were enrolled for the treatment. RESULTS: In all treated cases, an apparent clinical remission occurred in approximately 3 months, and complete healing was obtained in 100% of the treated patients; in 82% of the cases, this occurred after a single application. No disfiguring scars or any side-effects were seen. After a follow-up of 20-72 months (mean 51 months), no clinical relapses were observed in the treated patients. Histological examination confirmed complete tumour regression. CONCLUSION: The results indicated that brachytherapy is an effective treatment for BCC and SCC.