Fractional excretion of electrolytes and neutrophil gelatinase-associated lipocalin as early biomarkers of acute kidney injury in dogs with acute pancreatitis.

OBJECTIVES: To determine if fractional excretion of urinary electrolytes and neutrophil gelatinase-associated lipocalin could detect different degrees of kidney injury in dogs with naturally occurring acute pancreatitis. MATERIALS AND METHODS: We included dogs with acute pancreatitis. Dogs with a history of kidney disease, urinary tract infection, dogs which received potentially nephrotoxic drugs and dogs managed with haemodialysis were excluded. Acute kidney injury was diagnosed if there was an acute onset of clinical signs, haemato-chemical results compatible with acute kidney injury. Students or staff-owned dogs were selected to build the healthy group. RESULTS: The study population was composed of 53 dogs: acute pancreatitis with AKI (n=15), acute pancreatitis alone (n=23), and healthy dogs (n=15). In dogs with acute pancreatitis and AKI, all the FEs of urine electrolytes were significantly higher than dogs with acute pancreatitis alone and healthy ones. Dogs with acute pancreatitis alone had higher uNGAL/uCr than healthy dogs (median 54 ng/mg vs. 0.1 ng/mg) and lower compared to AP-AKI patients (54 ng/mg vs 209 ng/mg). CLINICAL SIGNIFICANCE: Some fractional excretion of electrolytes are increased acute kidney injury dogs, however their role in the early detection of renal injury in acute pancreatitis dogs remains doubtful. On the contrary, urinary neutrophil gelatinase-associated lipocalin had higher concentrations in dogs with acute pancreatitis with or without acute kidney injury compared to healthy controls, suggesting that it may be used as an early marker of renal tubular damage in acute pancreatitis dogs.

HLA-haploidentical hematopoietic stem cells transplantation with regulatory and conventional T-cell adoptive immunotherapy in pediatric patients with very high-risk acute leukemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) is still needed for many children with very high-risk acute leukemia. An HLA-haploidentical family donor is a suitable option for those without an HLA-matched donor. Here we present outcomes of a novel HLA-haploidentical HSCT (haplo-HSCT) strategy with adoptive immunotherapy with thymic-derived CD4+CD25+ FoxP3+ regulatory T cells (Tregs) and conventional T cells (Tcons) performed between January 2017 and July 2021 in 20 children with high-risk leukemia. Median age was 14.5 years (range, 4-21), 15 had acute lymphoblastic leukemia, 5 acute myeloid leukemia. The conditioning regimen included total body irradiation (TBI), thiotepa, fludarabine, cyclophosphamide. Grafts contained a megadose of CD34+ cells (mean 12.4 × 106/Kg), Tregs (2 × 106/Kg) and Tcons (0.5-1 × 106/Kg). All patients achieved primary, sustained full-donor engraftment. Only one patient relapsed (5%). The incidence of non-relapse mortality was 15% (3/20 patients). Five/20 patients developed ≥ grade 2 acute Graft versus Host Disease (aGvHD). It resolved in 4 who are alive and disease-free; 1 patient developed chronic GvHD (cGvHD). The probability of GRFS was 60 ± 0.5% (95% CI: 2.1-4.2) (Fig. 6), CRFS was 79 ± 0.9% (95% CI: 3.2-4.9) as 16/20 patients are alive and leukemia-free. The median follow-up was 2.1 years (range 0.5 months-5.1 years). This innovative approach was associated with very promising outcomes of HSCT strategy in pediatric patients.

The erythrocyte sedimentation rate (ESR) in canine inflammation.

The clinical application of the erythrocyte sedimentation rate (ESR) assay is challenging due to its long processing time. However, in 2020 a new automated instrument for veterinary ESR was released and validated. This study sought: (1) to refine the proposed reference range (reference interval, RI) for canine ESR; (2) to compare the ESR values of healthy and sick dogs; and (3) to correlate ESR with other inflammatory markers such as C-reactive protein (CRP), fibrinogen, albumin:globulin ratio (A/G), and neutrophil-to-lymphocyte ratio (NLR); and also (4) to study ESR behavior across illnesses of varying durations. A prospective cohort study of 396 client-owned dogs (n = 120 healthy and n = 276 sick dogs) was conducted. Animals with a full clinical evaluation, complete hematobiochemical profile and a final diagnosis were included. ESR was performed according to manufacturer's instructions using the same 1 mL K3-EDTA tube used for the complete blood count. The RI was established at 1-8 mm/h in 14 min. Sick dogs had a significantly faster ESR (median 10 mm/h) than healthy dogs (median 1 mm/h; P < 0.0001). ESR was positively correlated with NLR (r = 0.36), CRP (r = 0.18) and fibrinogen (r = 0.56) and negatively correlated with A/G (r = -0.37). Dogs with an acute-on-chronic disease had the highest ESR values (median 17 mm/h) compared with either acute (median 11 mm/h; P < 0.001) or chronic diseases (median 7 mm/h; P = 0.001). ESR was confirmed as a reliable canine inflammatory marker, positively correlating with the main inflammatory markers in dogs and significantly different between sick and healthy dogs. The ESR assay appears useful especially in dogs with an acute clinical presentation, with or without an underlying chronic condition.

Critical illness-related corticosteroid insufficiency in dogs with systemic inflammatory response syndrome: A pilot study in 21 dogs.

Critical illness-related corticosteroid insufficiency (CIRCI) refers to a lack of adequate corticosteroid activity, which occurs in up to 48% of dogs with sepsis. However, data regarding the occurrence of CIRCI in critically-ill dogs are still scarce. This study aimed to assess: (1) the relationship between CIRCI and clinicopathological inflammatory markers, hypotension and mortality; and (2) the impact of low-dose hydrocortisone treatment on survival. Twenty-one dogs diagnosed with systemic inflammatory response syndrome (SIRS) were enrolled in a prospective case-control study. All dogs were initially evaluated for adrenal function with an ACTH stimulation test and dogs with Δcortisol ≤ 3 µg/dL were diagnosed with CIRCI. Mean arterial pressure (MAP), white blood cell (WBC), band neutrophils (bNs), c-reactive protein (CRP), and 28-day mortality rate were assessed. Fourteen dogs were treated with low-dose hydrocortisone. The relationships between CIRCI and MAP, WBC, bN, CRP, basal cortisol and mortality were investigated, as was the association between mortality and hydrocortisone treatment. Ten of 21 (48%) dogs were diagnosed with CIRCI. Increased bNs were associated with the presence of CIRCI (P = 0.0075). CRP was higher in dogs with CIRCI (P = 0.02). Fourteen of 21 (66%) dogs died during the study (6/14 had CIRCI). Basal hypercortisolemia (>5 µg/dL) was associated with increased risk of mortality (P = 0.025). Based on our diagnostic criteria, CIRCI occurs frequently in dogs with SIRS and was associated with increased bNs and increased CRP. In this study, CIRCI and low-dose hydrocortisone treatment were not significantly associated with mortality, but basal hypercortisolemia was associated with increased mortality.

Druggable targets meet oncogenic drivers: opportunities and limitations of target-based classification of tumors and the role of Molecular Tumor Boards.

The therapeutic landscape of cancer is changing rapidly due to the growing number of approved drugs capable of targeting specific genetic alterations. This aspect, together with the development of noninvasive methods for the assessment of somatic mutations in the peripheral blood of patients, generated a growing interest toward a new tumor-agnostic classification system based on 'predictive' biomarkers. The current review article discusses this emerging alternative approach to the classification of cancer and its implications for the selection of treatments. It is suggested that different types of cancers sharing the same molecular profiles could benefit from the same targeted drugs. Although recent clinical trials have demonstrated that this approach cannot be generalized, there are also specific examples that demonstrate the clinical utility of this alternative vision. In this rapidly evolving scenario, a multidisciplinary approach managed by institutional Molecular Tumor Boards is fundamental to interpret the biological and clinical relevance of genetic alterations and the complexity of their relationship with treatment response.

Oesophagostomy tube complications in azotaemic dogs: 139 cases (2015 to 2019).

OBJECTIVES: To retrospectively assess the rate of oesophagostomy tube-related complications in azotaemic dogs, the influence of the oesophagostomy tube (o-tube) duration and the therapeutic approach (medical versus haemodialysis) on the complication rate. MATERIALS AND METHODS: Medical records were retrospectively reviewed in order to identify azotaemic dogswhich underwent o-tube placement. o-Tube duration (short-term versus long-term), time of o-tube change, therapeutic approach (medical versus haemodialysis), prevalence of minor (malposition, suture related, inflammation, muco-purulent discharge, abscess) and major (haemorrhage, malposition, obstruction, dislodgement, vomiting of the tube, food coming from the stoma) o-tube-related complications were extracted. Univariate and multivariate logistic regression analysis were performed to identify the risk factors for o-tube-related complications. RESULTS: Tube-related complications were reported in 74 of 139 dogs (53%). Minor complications were reported in 66 of 74 (89%) and major complications in eight of 74 (11%). In azotaemic dogs, o-tube indwelling time (odds ratio (OR) 1.03; 95% confidence interval (CI) 1.01 to 1.05), and the use of haemodialysis (OR 40.12; 95% CI 9.18 to 175.20) were risk factors for o-tube-related complications. CLINICAL SIGNIFICANCE: The majority of o-tube-related complications were minor, and easily manageable, with no need of hospitalisation, tube-removal or euthanasia. In azotaemic dogs, the use of haemodialysis was strongly associated with a higher risk of o-tube-related complications, possibly as a consequence of the presence of the neck bandage.

Evaluation of C-reactive protein/albumin ratio and its relationship with survival in dogs with acute pancreatitis.

Aims: To evaluate the association between the C-reactive protein (CRP)/albumin (ALB) ratio and survival in dogs with acute pancreatitis and its use as a prognostic marker for survival. Methods: Medical records of a veterinary referral hospital in Italy were retrospectively searched for dogs that were admitted with acute pancreatitis between January 2015 and April 2019, in which the concentrations of CRP and ALB in serum were measured at admission. The CRP/ALB ratio was calculated and the time between admission and discharge or death was recorded. Mortality rates overall and for dogs that died within 2 days of admission were calculated. A univariable Cox proportional hazard model was used to assess the relationship between survival time and CRP/ALB ratio. Results: Seventy-one dogs were included in the study. Of these, 19 died within 2 days of presentation; an early mortality rate of 26.8%, while 27 died before discharge for an overall mortality rated of 38%. Dogs with higher CRP/ALB ratio had a significantly greater mortality rate than dogs with lower CRP/ALB ratio: for every 1-unit increase in CRP/ALB ratio, the hazard of death over the study period increased by 130% (hazard ratio = 2.34; 95% CI = 1.53-3.58; p < 0.001). The optimal CRP/ALB ratio cut-off point for predicting mortality was 0.56, with a sensitivity and specificity of 88.9% and 68.2%, respectively (AUC = 0.82; p < 0.001). Conclusions: As in humans, the CRP/ALB ratio, may be a promising, though not particularly specific, prognostic marker for increased risk of death in dogs with acute pancreatitis.

Neutrophil-to-lymphocyte ratio, nucleated red blood cells and erythrocyte abnormalities in canine systemic inflammatory response syndrome.

Systemic inflammatory response syndrome (SIRS) is the manifestation of the systemic response to an infectious or non-infectious disease. We evaluated the association between erythrocyte parameters, including nucleated red blood cells (NRBCs) and leukocyte ratios (NLR, neutrophil-to-lymphocyte ratio; BLR, band neutrophil-to-lymphocyte ratio; BLNR, band neutrophil-to-neutrophil-to-lymphocyte ratio). A review of the medical records was conducted searching SIRS dogs among those admitted to our intensive care unit and a SIRS grading was obtained based on how many criteria were fulfilled. The Acute Patient Physiology and Laboratory Evaluation (APPLEfast) score was assessed in each dog. Survival rate was assessed 15 days after admission. Dogs with clinical and/or clinicopathological signs of hemolytic or hemorrhagic disorders were excluded. Dogs with ≥2 criteria of SIRS along with a documented underlying infectious cause were recorded as septic (32/90, 35%). A SIRS grading >2 (p = .001) and an APPLEfast score > 25 (p = .03) were associated with mortality. Twenty-two of SIRS dogs (24%) showed circulating NRBCs. The occurrence of circulating NRBCs was associated with the mortality in SIRS groups (p = .0025). The median NLR was 11.69 and NLR was lower in septic dogs compared to non-septic ones (p = .0272). APPLEfast, SIRS grading and circulating NRBCs may be considered as negative prognostic factors in canine SIRS. NLR could be a useful tool in dogs with SIRS, which was significantly lower in the septic group. Further prospective, large-scale studies investigating BLR and BNLR in canine SIRS are warranted.

Acute pancreatitis and acute kidney injury in dogs.

Acute pancreatitis and acute kidney injury are well-documented comorbidities in human medicine. Dogs that develop acute kidney injury during hospitalization have significantly higher mortality rates than those that do not. The aim of this study was to evaluate the prevalence of acute kidney injury in dogs with acute pancreatitis and the prognostic value of various clinicopathological parameters. Cases of acute pancreatitis presented between January 2012 and June 2016 were identified. The diagnosis of acute pancreatitis was based on two or more of the following clinical signs: abdominal pain, diarrhea, vomiting or anorexia/hyporexia, no other abdominal extra-pancreatic diseases at abdominal ultrasound, and abnormal SNAP cPL test. Diagnosis of acute kidney injury was based on the guidelines of the International Renal Interest Society. Dogs were classified into survivors and non-survivors. Serum creatinine, urea, amylase, total calcium, total cholesterol, C-reactive protein, WBC and band neutrophils were evaluated at admission. Clinical severity index was calculated at admission. Clinical and clinicopathological data were compared between survivors and non-survivors. Sixty-five dogs with acute pancreatitis were assessed. Clinical severity index≥6.5 were associated with poor outcome (P=0.0011). Serum urea and creatinine concentrations at admission were significantly lower in survivors than non-survivors (P<0.0001 and P=0.0002, respectively). Acute kidney injury was diagnosed in 17/65 dogs (26.2%) and was associated with poor outcome (P<0.0001). Oligo-anuria was associated with poor outcome (P=0.0294). Increased clinical severity index and azotemia in dogs with acute pancreatitis were associated with an increased risk of mortality. Acute kidney injury may be a comorbidity of canine acute pancreatitis. The presence of oligo-anuria is associated with poor outcome.

The limitations of some European healthcare databases for monitoring the effectiveness of pregnancy prevention programmes as risk minimisation measures.

PURPOSE: Pregnancy prevention programmes (PPPs) exist for some medicines known to be highly teratogenic. It is increasingly recognised that the impact of these risk minimisation measures requires periodic evaluation. This study aimed to assess the extent to which some of the data needed to monitor the effectiveness of PPPs may be present in European healthcare databases. METHODS: An inventory was completed for databases contributing to EUROmediCAT capturing pregnancy and prescription data in Denmark, Norway, the Netherlands, Italy (Tuscany/Emilia Romagna), Wales and the rest of the UK, to determine the extent of data collected that could be used to evaluate the impact of PPPs. RESULTS: Data availability varied between databases. All databases could be used to identify the frequency and duration of prescriptions to women of childbearing age from primary care, but there were specific issues with availability of data from secondary care and private care. To estimate the frequency of exposed pregnancies, all databases could be linked to pregnancy data, but the accuracy of timing of the start of pregnancy was variable, and data on pregnancies ending in induced abortions were often not available. Data availability on contraception to estimate compliance with contraception requirements was variable and no data were available on pregnancy tests. CONCLUSION: Current electronic healthcare databases do not contain all the data necessary to fully monitor the effectiveness of PPP implementation, and thus, special data collection measures need to be instituted.

Elevated serum creatinine and hyponatraemia as prognostic factors in canine acute pancreatitis.

OBJECTIVE: To evaluate prognostic factors for canine acute pancreatitis (AP) based on clinical and laboratory data that can be easily assessed in veterinary practice. DESIGN: Retrospective study between January 2010 and December 2013. METHODS: The diagnosis of AP was based on clinical signs and an abnormal SNAP® cPL™ test result, concurrently with an ultrasound pattern suggestive of pancreatitis. Dogs were divided into survivors and non-survivors. We evaluated 12 clinical and laboratory parameters: respiratory rate, rectal temperature, white blood cells, haematocrit, total serum proteins, albumin, creatinine, cholesterol, total and ionised calcium, sodium and potassium. Clinical and clinicopathological data were statistically compared between survivors and non-survivors. A value of P < 0.05 was considered significant and P < 0.01 as highly significant. The odds ratio (OR) was calculated. RESULTS: The study enrolled 50 client-owned dogs with a diagnosis of AP. Serum creatinine (P = 0.017) and sodium (P = 0.004) correlated significantly with the outcome. Serum sodium < 139.0 mmol/L (139.0 mEq/L) and serum creatinine > 212 µmol/L (2.4 mg/dL) were associated significantly with poor prognosis. Azotaemia (OR 12.5; 95% confidence interval (CI) 1.32-118.48) and hyponatraemia (OR 4.9; 95% CI 1.36-17.64) were associated with increased risk of death. CONCLUSIONS: In dogs with AP, hyponatraemia and azotaemia seem to be significantly associated with an increased risk of death.

Canine indolent and aggressive lymphoma: clinical spectrum with histologic correlation.

Sixty-three dogs with newly diagnosed lymphoma underwent complete staging and received the same chemotherapy. Diffuse large B-cell lymphoma was the leading histotype (44.4%), followed by peripheral T-cell lymphoma (20.6%). Indolent lymphomas accounted for 30.2% of cases. Most dogs with aggressive B-cell lymphoma had stage IV disease. Dogs with indolent and aggressive T-cell lymphoma had more often stage V disease and were symptomatic. Liver and bone marrow were predominantly involved in B-cell and T-cell lymphoma, respectively. The clinical stage was significantly related to substage, sex and total lactic dehydrogenase (LDH) levels. Aggressive B-cell lymphomas were more likely to achieve remission. Median survival was 55 days for aggressive and indolent T-cell lymphoma, 200 and 256 days for indolent and aggressive B-cell lymphoma, respectively. The prognosis of advanced indolent lymphoma does not appear to be appreciably different from that of aggressive disease. Familiarity with the various histotypes is critical to make the correct diagnosis and drive therapy.

Selective serotonin reuptake inhibitor prescribing before, during and after pregnancy: a population-based study in six European regions.

OBJECTIVE: To explore the prescribing patterns of selective serotonin reuptake inhibitors (SSRIs) before, during and after pregnancy in six European population-based databases. DESIGN: Descriptive drug utilisation study. SETTING: Six electronic healthcare databases in Denmark, the Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the rest of the UK. POPULATION: All women with a pregnancy ending in a live or stillbirth starting and ending between 2004 and 2010. METHODS: A common protocol was implemented across databases to identify SSRI prescriptions issued (UK) or dispensed (non-UK) in the year before, during or in the year following pregnancy. MAIN OUTCOME MEASURES: The percentage of deliveries in which the woman received an SSRI prescription in the year before, during or in the year following pregnancy. We also compared the choice of SSRIs and changes in prescribing over the study period. RESULTS: In total, 721 632 women and 862,943 deliveries were identified. In the year preceding pregnancy, the prevalence of SSRI prescribing was highest in Wales [9.6%; 95% confidence interval (CI95 ), 9.4-9.8%] and lowest in Emilia Romagna (3.3%; CI95 , 3.2-3.4%). During pregnancy, SSRI prescribing had dropped to between 1.2% (CI95 , 1.1-1.3%) in Emilia Romagna and 4.5% (CI95 , 4.3-4.6%) in Wales. The higher UK pre-pregnancy prescribing rates resulted in higher first trimester exposures. After pregnancy, SSRI prescribing increased most rapidly in the UK. Paroxetine was more commonly prescribed in the Netherlands and Italian regions than in Denmark and the UK. CONCLUSIONS: The higher SSRI prescribing rates in the UK, compared with other European regions, raise questions about differences in the prevalence and severity of depression and its management in pregnancy across Europe.

Vibrational and structural behavior of (L)-cysteine ethyl ester hydrochloride in the solid state and in aqueous solution.

The aim of this work is to evaluate the vibrational and structural properties of l-cysteine ethyl ester hydrochloride (CE), and its electronic behavior mainly in relation to the action of the thiol and amine groups at different degrees of solvation. The crystal structure of CE was determined at room temperature by X-ray diffraction methods. Infrared and Raman spectra were collected to compare the behavior of different functional groups in the molecule, both in the solid phase and in aqueous solution. Its UV and circular dichroism spectra were also measured in aqueous solution. The influence of an aqueous environment on the CE spectra was simulated by means of implicit (polarizable continuum model) and explicit (molecular dynamics, solute-solvent clusters) methods. Calculations in explicit and continuous solvent are of interest to explain the behavior of bioavailable sites in this medium. The study was completed by natural bond orbital analysis to determine the presence of hyperconjugative interactions.

Nevoid basal cell carcinoma syndrome: our experience in a pediatric hospital.

Nevoid basal cell carcinoma (BCC) syndrome, or Gorlin syndrome, is a rare autosomal dominant disorder associated with mutations in the patched 1 gene, PTCH1. It is characterized by the presence of multiple BCCs in association with disorders affecting the bones, the skin, the eyes, and the nervous system. We describe 6 cases of nevoid BCC syndrome evaluated in our department. Palmoplantar pitting was observed in all 6 patients, multiple BCCs in 5 patients (83%), skeletal anomalies in 3 patients (50%), and odontogenic keratocysts in 1 patient (17%). We would like to stress the importance of early diagnosis and treatment in nevoid BCC syndrome and the need for continuous, long-term follow-up by a multidisciplinary team.

Trends in the prevalence, risk and pregnancy outcome of multiple births with congenital anomaly: a registry-based study in 14 European countries 1984-2007.

OBJECTIVE: To assess the public health consequences of the rise in multiple births with respect to congenital anomalies. DESIGN: Descriptive epidemiological analysis of data from population-based congenital anomaly registries. SETTING: Fourteen European countries. POPULATION: A total of 5.4 million births 1984-2007, of which 3% were multiple births. METHODS: Cases of congenital anomaly included live births, fetal deaths from 20 weeks of gestation and terminations of pregnancy for fetal anomaly. MAIN OUTCOME MEASURES: Prevalence rates per 10,000 births and relative risk of congenital anomaly in multiple versus singleton births (1984-2007); proportion prenatally diagnosed, proportion by pregnancy outcome (2000-07). Proportion of pairs where both co-twins were cases. RESULTS: Prevalence of congenital anomalies from multiple births increased from 5.9 (1984-87) to 10.7 per 10,000 births (2004-07). Relative risk of nonchromosomal anomaly in multiple births was 1.35 (95% CI 1.31-1.39), increasing over time, and of chromosomal anomalies was 0.72 (95% CI 0.65-0.80), decreasing over time. In 11.4% of affected twin pairs both babies had congenital anomalies (2000-07). The prenatal diagnosis rate was similar for multiple and singleton pregnancies. Cases from multiple pregnancies were less likely to be terminations of pregnancy for fetal anomaly, odds ratio 0.41 (95% CI 0.35-0.48) and more likely to be stillbirths and neonatal deaths. CONCLUSIONS: The increase in babies who are both from a multiple pregnancy and affected by a congenital anomaly has implications for prenatal and postnatal service provision. The contribution of assisted reproductive technologies to the increase in risk needs further research. The deficit of chromosomal anomalies among multiple births has relevance for prenatal risk counselling.

Haga su diagnóstico / Make your diagnosis

El diagnóstico es Pitiriasis liquenoide crónica

Perianal ulcers on a segmental hemangioma with minimal or arrested growth.

Hemangiomas with minimal or arrested growth are a type of infantile hemangioma in which the proliferative component characteristic of such lesions is not observed or accounts for less than 25% of the surface area of the hemangioma. For this reason, these lesions are frequently confused with capillary vascular malformations or may even go undetected. Awareness of these lesions is, however, important because they can become ulcerated, as occurs with typical infantile hemangiomas. A proper diagnosis is therefore important to enable administration of appropriate treatment. We present the case of a 3-month-old girl with slowly progressing perianal ulcers first detected when she was 20 days old. She had received many different therapies without any response. A pathology study of the ulcer showed a GLUT-1-positive infantile hemangioma. Response to treatment with propranolol 2mg/kg/d and local wound care was excellent.