Sleep and quality of life in adults with atopic dermatitis: cross sectional study.

Summary: Background.Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease that causes sleep disturbances and worsens quality of life. However, few studies have been conducted on sleep in adults with atopic dermatitis. This study aimed to evaluate sleep and quality of life in adults with AD. Methods. A cross-sectional study was conducted with 36 adults diagnosed with AD and 21 healthy volunteers (controls), who completed questionnaires on sleep, itching, and quality of life. Disease severity was estimated using SCORing Atopic Dermatitis (SCORAD). All participants wore actigraphy watches for one week to objectively assess sleep quality. Results. Adults with AD slept worse than controls as measured by self-report (Global Pittsburgh Sleep Quality Index, mean ± SD, 9.33 ± 3.59 vs 5.00 ± 2.30, p < 0.001) and by actigraphy (sleep efficiency, SE), mean ± SD, 74.48 ± 11.63 vs 85.6 ± 6.53, p < 0.001). Actigraphy showed that adults with AD slept, on average, almost one hour less (p = 0.010), stayed awake during sleep for almost 44 minutes more (p < 0.001), and woke up 25% more than the controls (p = 0.047). In the AD group, SE and total sleep time were significantly inversely correlated with SCORAD (rs = -0.601, p < 0.001 and rs = -0.604, p < 0.001, respectively), but no significant correlation was found between itch and SE. A decreased quality of life was observed in adults with AD (DLQI, mean ± SD, 8.75 ± 6.7). Conclusions. Adults with AD slept worse than the controls and had a diminished quality of life. Actigraphy is a useful tool to objectively measure sleep quality in adults with AD especially those with moderate to severe disease.

Spiritual well-being and quality of life are impaired in chronic urticaria.

SUMMARY: Background. Patients with chronic urticaria (CU) often report an impaired quality of life (QoL). Although a positive effect of addressing spirituality in health care has been proved in several chronic diseases, its potential role in CU has received no attention. Objective. We aim to evaluate spirituality and QoL in CU subjects. Methods. In a single-centre observational study, 100 CU subjects were investigated using Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-12) scale, Chronic Urticaria Quality of life Questionnaire (CU-Q2oL) and Urticaria Control Test (UCT). Results. Of 100 subjects, 82 were female and 18 were male. It was observed that subjects with poorly controlled CU presented FACIT Sp-12 meaning/peace (p = 0.004) significantly lower, and CU-Q2oL (p less than 0.0001) significantly higher (worst QoL) than subjects with controlled CU. There was no difference in the FACIT Sp-12 faith (p = 0.43) between groups. There was moderate direct correlation between FACIT Sp-12 faith and FACIT Sp-12 meaning/peace (r = 0.483; p less than 0.0001; n = 100). There was a significant strong inverse correlation between the CU-Q2oL and the UCT (r = - 0.762; p less than 0.0001; n = 100). No correlation was found between the FACIT Sp-12 faith and CU-Q2oL, neither with UCT. Conclusions. No study has ever investigated the role of spirituality in managing patients with urticaria. Our findings support the impact of poorly controlled urticaria in spiritual well-being and QoL. Therefore, clinicians should pay more attention to spirituality among CU patients. We suggest that urticaria guidelines should include specific recommendations on spirituality assessment.

Outcomes of an enhanced recovery after radical cystectomy program in a prospective multicenter study: compliance and key components for success.

OBJECTIVE: To investigate the effect of an Enhanced Recovery After Surgery (ERAS) program on complications and length of stay (LOS) after radical cystectomy (RC) and to assess if the number and type of components of ERAS play a key role on the decrease of surgical morbidity. MATERIALS AND METHODS: We analyzed the data of 277 patients prospectively recruited in 11 hospitals undergoing RC initially managed according to local practice (Group I) and later within an ERAS program (Group II). Two main outcomes were defined: 90-day complications rate and LOS. As secondary variables we studied 90-day mortality, 30-day readmission and transfusion rate. RESULTS: Patients in Group II had a higher use of ERAS measures (98.6%) than those in Group I (78.2%) (p < 0.05). Patients in Groups I and II experienced similar complications (70.5% vs. 66%, p = 0.42). LOS was not different between Groups I and II (12.5 and 14 days, respectively, p = 0.59). The risk of having any complication decreases for patients having more than 15 ERAS measures adopted [RR = 0.815; 95% confidence interval (CI) 0.667-0.996; p = 0.045]. Avoidance of transfusion and nasogastric tube, prevention of ileus, early ambulation and a fast uptake of a regular diet are independently associated with the absence of complications. CONCLUSIONS: Complications and LOS after RC were not modified by the introduction of an ERAS program. We hypothesize that at least 15 measures should be applied to maximize the benefit of ERAS.

Feasibility and reproducibility of spleen transient elastography and its role in combination with liver transient elastography for predicting the severity of chronic viral hepatitis.

Liver transient elastography (L-TE) is a reliable, noninvasive predictor of disease severity in chronic liver disease of viral aetiology (CLD). Owing to the relationships among severity of CLD, portal hypertension and spleen involvement, the assessment of splenic stiffness (S-TE) may have an added value in staging CLD. Of 132 CLD patients of viral aetiology, 48 with myeloproliferative disorders (MD) and 64 healthy volunteers (HV), were concurrently investigated by both L-TE and S-TE. Liver disease severity was staged by liver biopsy (LB; Metavir) taken concurrently with TE examination and upper gastrointestinal tract endoscopy for gastro-oesophageal varices. The S-TE inter-observer agreement was analysed by an intra-class correlation coefficient (ICC); L-TE and S-TE accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. Logistic regression analysis assessed the independent effect of L-TE and S-TE as predictors of hepatic fibrosis stage. S-TE failed in 22 CLD (16.6%), 12 (25%) MD and 12 (18%) HV. In the three groups, the ICC was 0.89 (0.84-0.92), 0.90 (0.85-0.94) and 0.86(0.80-0.91), respectively. In the CLD group, L-TE and S-TE independently predicted significant fibrosis (OR 5.2 and 4.6) and cirrhosis (OR 7.8 and 9.1), but at variance from L-TE, S-TE was independent from liver necroinflammation and steatosis. The NPV of S-TE for gastro-oesophageal varices was 100% using a 48 kPa cut-off. In CLD, spleen stiffness alone or in combination with hepatic stiffness can be reliably and reproducibly assessed by TE with the added value of improving the noninvasive diagnosis of severe liver disease and excluding the presence of oesophageal varices.

Hereditary angioedema: first report of the Brazilian registry and challenges.

BACKGROUND: Hereditary Angio-oedema (HAE) is a serious medical condition caused by a rare autosomal dominant genetic disorder, in which C1 inhibitor (C1-INH) function is reduced. There is no organized information on the HAE patient population in Brazil. OBJECTIVE: The Brazilian Registry was established to disseminate diagnostic access, and to better understand the main features of the disease in our country and its clinical impact. METHODS: A questionnaire was prepared and sent to specialists. The completed questionnaires were forwarded to the coordinating site and then entered into the Registry. Samples from patients with an unconfirmed diagnosis were tested for C1 inhibitor and C4 levels. RESULTS: From 2006 to 2010, 210 patients (133 females; mean age, 30 ±17 years) were included. The median age of onset of symptoms and age at diagnosis were 6.5 and 21 years, respectively; 80.9% of the patients had subcutaneous oedema, 54% gastrointestinal and 35.7% respiratory symptoms (21% had laryngeal oedema). Laparotomy due to the disease was performed in 6.2% of the patients. The majority of patients had Type I HAE of moderate severity. Twenty-seven per cent did not receive treatment; 53% were treated with danazol alone. CONCLUSION: A paucity of patients with Type II HAE and a high frequency of laparotomy were observed, highlighting the need for better diagnosis in Brazil. HAE related educational activities, improved diagnosis and access to available therapy are needed in Brazil.

Measles outbreak in the Lazio region of Italy: surveillance and impact on emergency departments and hospitalizations.

BACKGROUND: The World Health Organization's (WHO) Regional Office for Europe had committed to 2015 as the year to eliminate measles from the region but several outbreaks have been reported recently from several areas of the continent. Here we describe an outbreak that occurred in 2010-2011 in Lazio region, Central Italy, and its impact on some health care services (i.e., Emergency Departments (EDs) and hospital clinics). METHODS: We analyzed cases of measles reported to the infectious diseases surveillance system and accesses to EDs and hospitalizations for measles in the Lazio Region (central Italy, population of about 5,730,000 people). RESULTS: In 2010-2011, 2,956 cases were reported to the surveillance system (incidence rate: 18.4 and 33.3 per 100,000 in 2010 and 2011, respectively). The incidence rates varied greatly with the territory. The outbreak occurred mainly among children <1 year old and among adolescents, most unvaccinated and did not seem to be related to cases imported from Eastern Europe. Complications were reported in 37.4% of the cases. The epidemic was mainly related to an accumulation of adolescents susceptible to measles due to unsatisfactory vaccination coverage in the early nineties. The outbreak had a strong impact on the health system with 2,881 ED visits and 1,168 hospitalizations. Outbreak-associated costs were considerable. CONCLUSIONS: An additional intervention should be considered aimed at improving routine immunization coverage in children and at planning catch-up vaccination of 6-18 year olds not previously vaccinated. Further, timely surveillance is needed and specific protocols should be implemented to limit secondary cases.

The tubercular disease in immigrants without documents: new diagnostic settings adopted in Milan, Italy.

The tubercular disease (TB) is "the disease of poverty and people in need", spread in the poorest countries and among the less wealthy people of the western world (immigrants). In Italy the health authority has recently defined precise diagnostic and therapeutic patterns for TB. The social and health Association Naga in Milan with the Regional Reference Centre for TB, designed a screening system. In Naga's surgery all the undocumented immigrants, coming to Italy from countries with high TB incidence (> 100/100000) and high immigration rates, are screened by a questionnaire created by the Swiss Lung League; the suspect cases are sent to a designed centre for a second level of investigation. The use of this form allows to set a first selection based on the patients' anamnestic history, thus avoiding the intradermal reaction that, due to its low selectivity, could cause a 4 times higher crowding of the designed secondary centers.

Preoperative coagulation screening tests in pediatric patients: Clinical relevance and hemorrhagic outcomes of abnormal results.

PURPOSE: Coagulation screening tests in children are still frequently performed in many countries to evaluate bleeding risk. The aim of this study was to assess the management of unexpected prolongations of the activated partial thromboplastin time (APTT) and prothrombine time (PT) in children prior to elective surgery, and the perioperative hemorrhagic outcomes. METHODS: Children with prolonged APTT and/or PT who attended a preoperative anesthesia consultation from January 2013 to December 2018 were included. Patients were grouped according to whether they were referred to a Hematologist or were scheduled to undergo surgery without further investigation. The primary endpoint was to compare perioperative bleeding complications. RESULTS: 1835 children were screened for eligibility. 102 presented abnormal results (5.6%). Of them, 45% were referred to a Hematologist. Significant bleeding disorders were associated with a positive bleeding history, odds ratio of 51 (95% CI 4.8-538.5, P=.0011). No difference in perioperative hemorrhagic outcomes were found between the groups. An additional cost of 181 euros per patient and a preoperative median delay of 43 days was observed in patients referred to Hematology. CONCLUSIONS: Our results suggest that hematology referral has limited value in asymptomatic children with a prolonged APTT and/or PT. Hemorrhagic complications were similar among patients referred and not referred to Hematology. A positive personal or family bleeding history can help identify patients with a higher bleeding risk, thus it should guide the need for coagulation testing and hematology referral. Further efforts should be made to standardize preoperative bleeding assessments tools in children.

Immune dysregulation and pathophysiology of alcohol consumption and alcoholic liver disease.

Alcoholic liver disease (ALD) is a clinical-pathologic entity caused by the chronic excessive consumption of alcohol. The disease includes a broad spectrum of anomalies at the cellular and tissual level that can cause acute-on-chronic (alcoholic hepatitis) or chronic (fibrosis, cirrhosis, hepatocellular cancer) injury, having a great impact on morbidity and mortality worldwide. Alcohol is metabolized mainly in the liver. During alcohol metabolism, toxic metabolites, such as acetaldehyde and oxygen reactive species, are produced. At the intestinal level, alcohol consumption can cause dysbiosis and alter intestinal permeability, promoting the translocation of bacterial products and causing the production of inflammatory cytokines in the liver, perpetuating local inflammation during the progression of ALD. Different study groups have reported systemic inflammatory response disturbances, but reports containing a compendium of the cytokines and cells involved in the pathophysiology of the disease, from the early stages, are difficult to find. In the present review article, the role of the inflammatory mediators involved in ALD progression are described, from risky patterns of alcohol consumption to advanced stages of the disease, with the aim of understanding the involvement of immune dysregulation in the pathophysiology of ALD.

Axonal loss and cognitive deficits in term infants with normal umbilical artery Doppler born small-for-gestational age.

OBJECTIVE: To assess cognitive outcomes and structural changes in the central nervous system, the latter using a novel approach to examine changes in neuronal integrity of the optic nerve, in children at 5-6½ years of age who were born small-for-gestational age (SGA) at term having shown normal umbilical artery (UA) Doppler. METHODS: We compared neuronal damage, cognitive deficits and visuospatial perception in two cohorts of infants, one born SGA (n = 40) and one born appropriate-for-gestational age (AGA) (n = 39) in weight. Neuronal damage was evaluated using optical coherence tomography (OCT) of the optic nerve. Cognitive deficits were assessed with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) test. Visuospatial perception was evaluated with Rey-Osterreich Complex Figure (ROCF) tasks. RESULTS: Children from the SGA group had a significantly thinner average retinal nerve fiber layer (RNFL) compared with those from the AGA group (98.2 vs 104.5 µm, P = 0.012). Children from the SGA group exhibited impaired performance in copy tasks on the ROCF (3.27 vs 3.56, P = 0.036) and a higher rate of suboptimal WPPSI test performance intelligence quotient scores (15% vs 0%; P = 0.025) compared with those from the AGA group. CONCLUSION: Term infants with normal UA Doppler born SGA are at increased risk for cognitive deficits and axonal loss in the RNFL at the age of 5-6½ years.

Validation of a novel respiratory rate monitor based on exhaled humidity.

BACKGROUND: Postoperative monitoring of ventilation is largely restricted to the measurement of haemoglobin-oxygen saturation and respiratory rate (RR) derived from the ECG. measurement is inadequate when used with supplemental oxygen and ECG-derived RR is subject to artifacts. A new monitor measures RR by quantifying the humidity of exhaled air (respiR8(®)). METHODS: The accuracy of the system was tested using a breathing simulator. In healthy volunteers, the respiR8(®) monitor was compared with two other methods of measuring RR: capnometry and counting of thoracic breathing movements. The ability of the monitor to track changes in RR resulting from the infusion of 2.5 µg kg(-1) fentanyl was assessed and compared with RR measured from a validated flow measurement system. The RR in 50 postoperative patients measured with the respiR8(®) was compared with that derived from the ECG. RR values were compared by population-based Bland-Altman analyses. RESULTS: The respiR8(®) monitor was accurate in the range required in clinical practice. There was a close agreement between RR from respiR8(®), capnometry, and manual counting of respiratory movements without bias (limits of agreement ±1 bpm). The respiR8(®) monitor was well able to accurately track RR changes from fentanyl. In postoperative patients, RR from respiR8(®) and ECG had a bias of 1.7 (5.7) bpm due to greater RR values observed from the ECG due to artifacts. CONCLUSIONS: The respiR8(®) gives an accurate measurement of RR and is useful in postoperative care.

Risk of misclassification during diagnosis of malnutrition in retroperitoneal sarcoma patients.

BACKGROUND: Retroperitoneal sarcoma (RPS) is a rare tumour that can reach exceptionally large size at diagnosis and affects body weight with its volume. We investigated the risk of nutritional status misclassification based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in RPS patients. METHODS: We retrospectively analyzed the baseline data of patients with primary RPS including anthropometry, Malnutrition Universal Screening Tool (MUST) score and skeletal muscle index (SMI) calculated on preoperative CT scan. Phenotypic GLIM criteria considered were non-volitional weight loss, low-BMI and low muscle mass. MUST score, being inclusive of weight loss, was chosen as its surrogate. Reduced muscle mass was defined with SMI cut-offs <38.5-52.4 cm2/m2 for female and male respectively. RESULTS: From 2018 to 2020, 100 consecutive patients (male/female: 48/52) were included. Median age was 61 (48-68) years, median BMI 24.6 (21.5-27.4) kg/m2. Seven patients (7%) reported MUST score ≥2 and 80 (80%) score 0. Five patients (5%) were underweight, 44 (44%) overweight and obese. Sixty patients (60%) presented low SMI, of those 56 (93%) were normal or overweight, and 46 (77%) not at nutritional risk according to the MUST score. Both underweight BMI and MUST score ≥2 were not correlated with low SMI (p = 0.406, p = 0.612, respectively). No relevant discrepancy was found in the postoperative course of patients with low or normal muscle mass, although SMI was able to better characterize nutritional risk in the proportion of patents with high-grade liposarcoma and predicted worst overall survival. CONCLUSION: GLIM criteria are a useful tool for diagnosis of malnutrition. However, our analysis suggests that phenotypic criteria are not interchangeable with each other. An altered body composition is often hidden in patients with retroperitoneal sarcoma and the use of weight-based classification does not seem to be appropriate, enhancing the role of mass muscle measurement to prevent misdetections of malnourished patient.

Cross-cultural adaptation of the Brazilian-Portuguese version of the chronic urticaria quality-of-life questionnaire - CU-Q2oL.

BACKGROUND: Chronic urticaria (CU) is a debilitating skin disorder that affects patients' health related quality of life and the only questionnaire prepared specifically to CU is the Chronic Urticaria Quality of Life Questionnaire (CU-Q(2)oL). OBJECTIVE: The purpose of this study was to cross-culturally adapt and validate the CU-Q(2)oL Brazilian-Portuguese version. METHODS: Forward and back translation by three bilingual translators followed by pre-test was used to adapt the questionnaire. The CU-Q(2)oL was self-administered along with the Dermatology Life Quality Index (DLQI) in 112 patients with CU. Disease activity was assessed using the Urticaria Activity Score. Factor analysis was used to identify scales of the Brazilian portuguese CU-Q(2)oL. Internal consistency, convergent validity and known-group validity was determined. Reproducibility was evaluated by interclass correlation coefficient (ICC). Multiple linear regression was used to determine the predicting factors of CU-Q(2)oL results. RESULTS: Factor analysis revealed a three-dimensional structure: sleep/mental status/eating (I), pruritus/impact on life activities (II) and swelling/limits/look (III), which explained 52.49% of the total variance. All scales showed excellent internal consistency. External construct validity was supported by correlations between the CU-Q(2)oL and DLQI. The tool was found to be able to differentiate between patients with high and low levels of urticaria activity. Test-retest reliability was good to excellent (ICC = 0.69-0.86). Disease severity and urticaria type were the only factors predicting results. CONCLUSIONS: The CU-Q(2)oL Brazilian portuguese version was easily filled out, well accepted by the patients, demonstrated an acceptable validity and reliability and might be used to evaluate treatment outcomes and in clinical research.

[Serious complications after pulmonary radiofrequency ablation: report of 2 cases]. / Dos casos de complicaciones graves tras radiofrecuencia pulmonar.

Radiofrequency ablation can be used to treat primary or metastatic pulmonary tumors when surgery is not indicated or involves high risk. Although this technique is less invasive than surgical resection, it is not free of risk for complications and adverse events, especially when it is used in patients with serious respiratory disease in whom comorbidity is common. We report 2 cases of serious complications. One was an intractable air leak that led to death. The other was a large hemothorax that was brought under control in the radiology procedure room. We review the literature on this technique as well as recommendations that contribute to making it as safe as possible.

Nutritional status and body composition assessment in patients with a new diagnosis of advanced solid tumour: Exploratory comparison of computed tomography and bioelectrical impedance analysis.

OBJECTIVE: Low skeletal muscle is a common characteristic of cancer-related malnutrition and a predictor of poorer prognosis in oncological patients. In this study we evaluated nutritional status and altered body composition using computed tomography (CT) and bioelectrical impedance analysis (BIA) in newly diagnosed patients. Our purpose was to compare the results of two available techniques to assess body composition suggested by the guidelines and some diagnostic criteria to identify malnutrition. METHODS: In a prospective study, patients with a new diagnosis of advanced solid tumour were enrolled and evaluated before starting first-line chemotherapy. Anthropometric, body composition and systemic inflammation measurements were collected and cut-off points from literature data were used for results classification. Malnutrition was expressed as weight loss (WL) in the previous 6 months >10% and underweight body mass index (BMI). Altered body composition was assessed as low index both skeletal muscle (SMI) derived by CT and fat-free mass by BIA (FFMI). Descriptive statistic was presented. Several statistical correlation analyses were performed. RESULTS: 67 patients were assessed: 40M/27F; average age 59 ± 13 years and BMI 23 ± 4; 43 (64%) upper gastrointestinal, 12 lung, 9 colorectal, 3 other cancers. Fourty-five (67%) were malnourished with WL criteria but only 8 (12%) resulted underweight. From analysis of CT images and BIA, 49 (73%) and 10 (15%) patients respectively reported lower cut-off point. Overall, 35 (52%) had both sarcopenia and WL > 10%. CONCLUSIONS: Our results suggest that prevalence data of malnutrition expressed as WL are more in agreement with those of sarcopenia recognised using CT than BIA method. Further studies are required to confirm these findings and to identify the best and easiest methods for monitoring BC during nutritional intervention and oncological therapies.

Ecophysiological Performance of Proteaceae Species From Southern South America Growing on Substrates Derived From Young Volcanic Materials.

Southern South American Proteaceae thrive on young volcanic substrates, which are extremely low in plant-available phosphorus (P). Most Proteaceae exhibit a nutrient-acquisition strategy based on the release of carboxylates from specialized roots, named cluster roots (CR). Some Proteaceae colonize young volcanic substrates which has been related to CR functioning. However, physiological functioning of other Proteaceae on recent volcanic substrates is unknown. We conducted an experiment with seedlings of five Proteaceae (Gevuina avellana, Embothrium coccineum, Lomatia hirsuta, L. ferruginea, and L. dentata) grown in three volcanic materials. Two of them are substrates with very low nutrient concentrations, collected from the most recent deposits of the volcanoes Choshuenco and Calbuco (Chile). The other volcanic material corresponds to a developed soil that exhibits a high nutrient availability. We assessed morphological responses (i.e., height, biomass, and CR formation), seed and leaf macronutrient and micronutrient concentrations and carboxylates exuded by roots. The results show that G. avellana was less affected by nutrient availability of the volcanic substrate, probably because it had a greater nutrient content in its seeds and produced large CR exuding carboxylates that supported their initial growth. Embothrium coccineum exhibited greater total plant height and leaf P concentration than Lomatia species. In general, in all species leaf macronutrient concentrations were reduced on nutrient-poor volcanic substrates, while leaf micronutrient concentrations were highly variable depending on species and volcanic material. We conclude that Proteaceae from temperate rainforests differ in their capacity to grow and acquire nutrients from young and nutrient-poor volcanic substrates. The greater seed nutrient content, low nutrient requirements (only for G. avellana) and ability to mobilize nutrients help explain why G. avellana and E. coccineum are better colonizers of recent volcanic substrates than Lomatia species.

A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study.

BACKGROUND: Bromelain (Brom) and Acetylcysteine (Ac) have synergistic activity resulting in dissolution of tumour-produced mucin both in vitro and in vivo. The aim of this study was to determine whether treatment of mucinous peritoneal tumour with BromAc can be performed with an acceptable safety profile and to conduct a preliminary assessment of efficacy in a clinical setting. METHODS: Under radiological guidance, a drain was inserted into the tumour mass or intraperitoneally. Each patient could have more than one tumour site treated. Brom 20-60 mg and Ac 1·5-2 g was administered in 5% glucose. At 24 h, the patient was assessed for symptoms including treatment-related adverse events (AEs) and the drain was aspirated. The volume of tumour removed was measured. A repeat dose via the drain was given in most patients. All patients that received at least one dose of BromAc were included in the safety and response analysis. FINDINGS: Between March 2018 and July 2019, 20 patients with mucinous tumours were treated with BromAc. Seventeen (85%) of patients had at least one treatment-emergent AE. The most frequent treatment-related AEs were CRP rise (n = 16, 80%), WCC rise (n = 11, 55%), fever (n = 7, 35%, grade I) and pain (n = 6, 30%, grade II/III). Serious treatment-related AEs accounted for 12·5% of all AEs. There were no anaphylactic reactions. There were no deaths due to treatment-related AEs. An objective response to treatment was seen in 73·2% of treated sites. CONCLUSION: Based on these preliminary results and our preclinical data, injection of BromAc into mucinous tumours had a manageable safety profile. Considerable mucolytic activity was seen by volume of mucin extracted and radiological appearance. These results support further investigation of BromAC for patients with inoperable mucinous tumours and may provide a new and minimally invasive treatment for these patients.

Pyometra-associated insulin resistance assessment by insulin binding assay and tyrosine kinase activity evaluation in canine muscle tissue.

Diestrus is associated with insulin resistance in bitches and pyometra can further impair insulin sensitivity. This study aimed to compare insulin sensitivity, insulin binding, and tyrosine kinase activity in bitches in anestrus, diestrus, or with pyometra. Patients submitted to elective ovariohysterectomy were divided into anestrus (n = 11) or diestrus (n = 13) according to reproductive history, vaginal cytology, and uterine histology. The group pyometra (n = 8) included bitches diagnosed with the disease based on clinical presentation and abdominal ultrasound findings and further confirmed by uterine histopathology. All patients were submitted to an intravenous glucose tolerance test (IVGTT) before ovariohysterectomy, and rectus abdominis muscle samples were collected during surgery for plasmatic membrane suspension preparation. Muscle-membranes were submitted to cold saturation insulin binding assay for dissociation constant (Kd) and maximum binding capacity (Bmax) determination, as well as exogenous substrate Poly (Glu: Tyr 4:1) phosphorylation assay for basal tyrosine kinase evaluation. Bitches with pyometra showed higher basal insulin (P < 0.001) and higher area under the curve (AUC) for insulin (P = 0.01) and glucose (P < 0.001) response during the IVGTT in comparison with bitches in anestrus or diestrus. Diestrus (P < 0.0001) and pyometra (P = 0.001) were associated with reduced tyrosine kinase activity in comparison with anestrus. No differences were documented in Kd and Bmax results for the low-affinity/high-capacity insulin receptors; however, high-affinity/low-capacity insulin receptors showed higher Kd and Bmax results in bitches in diestrus or with pyometra (P < 0.05) in comparison with anestrus. Despite the pyometra group showed the highest Kd values (P < 0.01), its Bmax results did not differ from the diestrus group (P > 0.05). Diestrus' higher Kd values and reduced tyrosine kinase activity in muscle tissue were compensated by increased total insulin binding capacity. Absent differences in IVGTT results between diestrus and anestrus bitches corroborate this finding. However, in bitches with pyometra, the highest Kd values were not compensated by increased total insulin binding capacity. This finding was associated with insulin resistance and glucose intolerance in IVGTT results. Moreover, pyometra resolution restored insulin sensitivity and glucose tolerance. These features can play a key role in pyometra-associated CDM, as well as in diabetic remission after pyometra resolution.