Ketamine subcutaneous continuous infusion for depressive symptoms at home: A case report beyond pain use.

OBJECTIVES: Ketamine has been widely used in refractory pain as an opioid adjuvant. Evidence suggests that ketamine can also have an essential role in easing depressive symptoms. Its rapid onset of action makes it a valuable choice in palliative care. METHODS: We present a case of a 70-year-old man with stage IV renal carcinoma and bone metastasis. The main symptoms included neuropathic pain, depression, and a persistent and severe desire for death. RESULTS: We started continuous subcutaneous infusion with morphine 30 mg and ketamine 100 mg/day. The dose of ketamine was incremented to the maximum of 250 mg/day. During the 28-day treatment, we observed an overall improvement in neuropathic pain, depressive symptoms, and other end-of-life psychological aspects of distress. Only minor psychological side effects were identified, which were controlled by using midazolam in the continuous subcutaneous infusion. SIGNIFICANCE OF RESULTS: Some studies have already demonstrated the benefits of ketamine use in alleviating depression, using parental infusion or oral formulas, which are administered in hospice care. Our report enhances the benefit of the subcutaneous route for palliative patients cared for at home.

An unconventional retrograde approach for self-expanding metallic stent delivery in oesophagus cancer palliation.

Partially covered self-expanding metallic stents (SEMS) are the main recommendation for palliative treatment of malignant dysphagia. Delivering self-expanding metallic stents in stenosing oesophagus neoplasia's are often challenging due to the difficulty on passing a guide wire through the tumour. We describe a case in which the guidewire was only able to franchise the tumour retrogradely, after entering the gastric cavity through the percutaneous endoscopic gastrostomy orifice using an ultra slim scope.

Inflammatory Bowel Disease and Pregnancy: Is It a Marker for Adverse Outcomes? / Doença inflamatória intestinal e gravidez: Será um marcador de desfechos adversos?

Abstract Objective To assess obstetric/puerperal/neonatal outcomes in an inflammatory bowel disease (IBD) population and to analyze disease characteristics that may be associated to adverse outcomes. Methods Retrospective descriptive analysis including 47 pregnant women with IBD (28 with Crohn's disease - CD and 19 with ulcerative colitis - UC) who delivered between March 2012 and July 2018 in a tertiary hospital. We reviewed clinical records to extract demographic information, previous medical history, disease subtype, activity, severity, treatment, and obstetric, puerperal, and neonatal outcome measures. Results Obstetric and neonatal complications (composite outcomes) occurred in 55.3% and 14.6% of the IBD population, respectively, and were more frequent in UC patients. Preterm birth (PTB), preeclampsia, anemia, low birth weight (LBW), and neonatal death were also more frequent in UC patients. The rate of postpartum hemorrhage (PPH) was 14.9%, and it was higher in CD patients. Women with active IBD had more obstetric/neonatal adverse outcomes (fetal growth restriction and LBW in particular) and cesarean sections. Patients with medicated IBD had less obstetric/neonatal complications (PTB and LBW in specific) and cesarean sections but more PPH. Conclusion Women with IBD may have an increased risk of obstetric/puerperal/neonatal adverse outcomes. Ulcerative colitis patients had more obstetric and neonatal complications, whereas PPH was more frequent if CD patients. Other disease characteristics were considered, which allowed a better understanding of their possible influence. Although more research is needed, this work reinforces the importance of adequate surveillance to allow prompt recognition and treatment of complications.

Resumo Objetivo Avaliar os desfechos obstétricos/puerperais/neonatais em uma população com doença inflamatória intestinal (DII) e analisar as características da doença, que podem estar associadas a desfechos adversos. Métodos Análise descritiva retrospectiva incluindo 47 gestantes com DII (28 com doença de Crohn - DC e 19 com retocolite ulcerativa - RCU) que deram à luz entre março de 2012 e julho de 2018 em um hospital terciário. Revisamos os registros clínicos para extrair informações demográficas, histórico médico prévio, subtipo da doença, atividade, gravidade, tratamento e medidas de resultados obstétricos, puerperais e neonatais. Resultados As complicações obstétricas e neonatais (desfechos compostos) ocorreram em 55,3% e 14,6% da população com DII, respectivamente; e foram mais frequentes em pacientes com RCU. Nascimento prematuro (PTB), pré-eclâmpsia, anemia, baixo peso ao nascer (BPN) e óbito neonatal também foram mais frequentes em pacientes com RCU. A taxa de hemorragia pós-parto (HPP) foi de 14,9% e foi maior em pacientes com DC. Mulheres com DII ativa tiveram mais desfechos obstétricos/neonatais adversos (restrição de crescimento fetal e BPN em particular) e cesarianas. Pacientes com DII medicada tiveram menos complicações obstétricas/neonatais (PTB e BPN em específico) e cesarianas, mas mais HPP. Conclusão Mulheres com DII podem ter um risco aumentado de desfechos adversos obstétricos/puerperais/neonatais. As pacientes com RCU apresentaram mais complicações obstétricas e neonatais, enquanto a HPP foi mais frequente em pacientes com DC. Outras características da doença foram consideradas, o que permitiu uma melhor compreensão de sua possível influência. Embora mais pesquisas sejam necessárias, este trabalho reforça a importância de uma vigilância adequada para permitir o reconhecimento e o tratamento imediatos das complicações.

Estimating the attributable fraction of cirrhosis and hepatocellular carcinoma due to hepatitis B and C.

A goal of the WHO strategy on the elimination of hepatitis as a public threat is a 65% reduction in the attributable mortality. Deaths related to hepatitis B and C infections are mostly due to decompensated cirrhosis and hepatocellular carcinoma (HCC) but accurately measuring mortality is challenging as death certificates often do not capture the underlying disease. The aim of this collaborative study between European Centre for Disease Prevention and Control (ECDC) and the European Association for the Study of the Liver (EASL) was to assess a WHO-developed protocol to support countries in implementing studies to collect data on the fraction of cirrhosis and hepatocellular carcinoma attributable to hepatitis B and C. Three sentinel sites (in Bulgaria, Norway and Portugal) collected data for patients first admitted or seen in their centres during 2016. Patients with cirrhosis or HCC were identified through patient files or healthcare databases using ICD-10 codes. The proportion of patients with cirrhosis and HCC who tested positive for HBV and HCV were calculated to estimate the aetiological fractions. After the pilot study was completed, each site was asked about the feasibility and acceptability of the protocol. A total of 1249 patients presenting with cirrhosis and/or HCC were evaluated across the three sites. The prevalence of HBV and HCV among cases of cirrhosis showed that in Norway and Portugal, HCV was responsible for about one-quarter of the cases, whereas in Bulgaria, HBV was more common. For HCC, HCV was responsible for more than one-third of cases in Norway and Portugal, while in Bulgaria HBV was more frequent as the underlying cause. Results obtained during the pilot study were comparable to published estimates obtained through statistical modelling or meta-analyses. Several challenges were reported from the sites involved in the pilot including the considerable time needed for reviewing the hospital records and extracting patient data. The pilot demonstrated the feasibility of collecting data on the prevalence of HBV and HCV infection among patients with cirrhosis and HCC in sentinel sites. This method can be used to estimate mortality attributable to HBV and HCV for elimination monitoring. Where easily implementable, sentinel studies are the best way to empower countries, get up-to date data and closely monitor the changes in the attributable fraction at a country level.

DNA damage repair as a target in pancreatic cancer: state-of-the-art and future perspectives.

Complex rearrangement patterns and mitotic errors are hallmarks of most pancreatic ductal adenocarcinomas (PDAC), a disease with dismal prognosis despite some therapeutic advances in recent years. DNA double-strand breaks (DSB) bear the greatest risk of provoking genomic instability, and DNA damage repair (DDR) pathways are crucial in preserving genomic integrity following a plethora of damage types. Two major repair pathways dominate DSB repair for safeguarding the genome integrity: non-homologous end joining and homologous recombination (HR). Defective HR, but also alterations in other DDR pathways, such as BRCA1, BRCA2, ATM and PALB2, occur frequently in both inherited and sporadic PDAC. Personalised treatment of pancreatic cancer is still in its infancy and predictive biomarkers are lacking. DDR deficiency might render a PDAC vulnerable to a potential new therapeutic intervention that increases the DNA damage load beyond a tolerable threshold, as for example, induced by poly (ADP-ribose) polymerase inhibitors. The Pancreas Cancer Olaparib Ongoing (POLO) trial, in which olaparib as a maintenance treatment improved progression-free survival compared with placebo after platinum-based induction chemotherapy in patients with PDAC and germline BRCA1/2 mutations, raised great hopes of a substantially improved outcome for this patient subgroup. This review summarises the relationship between DDR and PDAC, the prevalence and characteristics of DNA repair mutations and options for the clinical management of patients with PDAC and DNA repair deficiency.

Sexual Quality of Life in Inflammatory Bowel Disease: A Multicenter, National-Level Study.

BACKGROUND: The impact of inflammatory bowel disease (IBD) on sexual health is a leading concern among patients. Most studies focus on sexual dysfunction rather than patient-perceived sexual quality of life (SQoL). We aimed to assess SQoL in IBD patients compared with healthy controls. METHODS: This is a multicenter, cross-sectional study of IBD patients (n = 575 with Crohn's disease and n = 294 with ulcerative colitis), compared with healthy controls (n = 398), that used an anonymous self-administered questionnaire. This multimodal questionnaire included sociodemographic data and 4 validated instruments: Short IBD Questionnaire, Social Desirability Scale, Sexual QoL Questionnaire-Male/Female, Nine-item Patient Health Questionnaire. RESULTS: Inflammatory bowel disease patients reported lower SQoL (men: 77.29 vs 83.83; P < 0.001; women: 70.40 vs 81.63; P < 0.001) compared with controls. Among IBD patients, SQoL was positively correlated with health-related quality of life (HRQoL) and negatively correlated with depression symptoms. Perianal disease was associated with lower HRQoL and higher incidence of depression, but only impacted SQoL in men. In linear regression analysis for men, SQoL was associated with age, marital status, and depression (ß, -2.101; 95% confidence interval [CI], -2.505 to -1.696; P < 0.001). In women, SQoL was associated with depression (ß, -1.973; 95% CI, -2.313 to -1.632; P < 0.001) only. CONCLUSIONS: Patients with IBD had impaired SQoL compared with healthy controls. Age, widow status, and depression were independent predictors of SQoL in men with IBD, whereas in women depression was the only independent predictor. Emotional and self-esteem issues were the main concerns reported by IBD patients regarding sexual health.

Proactive Infliximab Drug Monitoring Is Superior to Conventional Management in Inflammatory Bowel Disease.

BACKGROUND: Increasing evidence supports the use of reactive therapeutic drug monitoring (TDM) in Crohn's disease (CD) and ulcerative colitis (UC) following secondary loss of response. It is still unknown if proactive TDM can improve clinical outcomes. METHODS: Consecutive patients completing infliximab (IFX) induction therapy were prospectively allocated into a proactive TDM protocol (pTDM). Before the fourth infusion and every 2 infusions, IFX trough levels and antidrug antibodies were measured using a drug-sensitive assay (Theradiag, Lisa Tracker). Treatment was proactively escalated aiming at an IFX trough level between 3 and 7 ug/mL (CD) and 5 and 10 ug/mL (UC). A retrospective cohort treated with IFX but without TDM served as the reference group. End points included the need for surgery, hospitalization, treatment discontinuation, and mucosal healing at 2 years of follow-up. RESULTS: Two hundred five patients were included, 56 in the proactive regimen. Treatment escalation was more common in pTDM patients (76.8% vs 25.5%; P < 0.001), who also required less surgery (8.9% vs 20.8%; P = 0.032) and presented higher rates of mucosal healing (73.2% vs 38.9%; P < 0.0001). Proactive TDM significantly decreased the odds of reaching any unfavorable outcome (odds ratio, 0.358; 95% confidence interval, 0.188-0.683; P = 0.002). CONCLUSIONS: Proactive TDM is associated with fewer surgeries and higher rates of mucosal healing than conventional non-TDM-based management.

Lateral Spreading Tumor Arising in an Interposed Colonic Segment.

A 57-year-old woman developed dysphagia 30 years after esophagectomy with partial gastrectomy and colonic interposition due to severe and extensive caustic esophageal stricture. Upper gastrointestinal endoscopy showed a lateral spreading tumor in the colonic tube with a granular surface measuring 40 mm in diameter. The lesion was removed by piecemeal endoscopic mucosal resection. Histology revealed tubular adenoma with low/high-grade dysplasia. Although colonic interposition replacement is a relatively common procedure, especially in the past, the development of adenoma or adenocarcinoma as a late complication is very rare.

Molecular Approaches to Metastatic Colorectal Cancer: Better Diagnosis - Better Treatment?

Molecular diagnostics of metastatic colorectal cancer (mCRC) are coming of age. Whereas for many years RAS mutations were the only relevant molecular alterations examined in mCRC, nowadays the BRAF, HER2, and microsatellite instability status of a given tumor is gaining importance, since it has not only prognostic relevance but opens new avenues for therapeutic approaches. This review summarizes the recent advances in molecular approaches to mCRC and their therapeutic consequences and discusses novel approaches for molecular diagnostics in mCRC.

Validade de construção em testes de equilíbrio: ordenação cronológica na apresentação das tarefas / Construction validity in equilibrium tests: chronological order in tasks presentation

Os testes de equilíbrio da Escala de Desenvolvimento Motor de Rosa Neto1 são constituídos por dez tarefas correspondentes às idades cronológicas de 2 a 11 anos e determinam a Idade Motora dos participantes. A ordem de apresentação dos testes é crescente, partindo da idade cronológica da criança e a idade motora baseia-se no sucesso ou fracasso em cada tarefa. O objetivo deste estudo foi analisar a validade de construção dos testes motores em equilíbrio, observando a ordenação e os graus de dificuldade da tarefa. Participaram 76 crianças, com idade cronológica de 6 a 9 anos, que foram distribuídas em dois grupos: grupo controle, aplicação dos testes em ordem crescente; grupo invertido, aplicação dos testes em ordem decrescente. Os resultados não apresentaram diferenças estatisticamente significativas no desempenho entre os grupos, indicando que a ordem de apresentação dos testes não interferiu no desempenho das crianças, independente da idade cronológica. Baixas taxas de sucesso ocorreram em algumas tarefas específicas, seguidas por sucesso em tarefas posteriores. Como os resultados demonstraram que os participantes conseguem executar tarefas seguintes à tarefa em que houve o fracasso, a idade motora apontada pela Escala de Desenvolvimento Motor pode estar subestimando o desenvolvimento motor dessas crianças. A variação do desempenho das crianças nos testes sugere que o processo de desenvolvimento motor é não linear. As tarefas motoras em equilíbrio propostas na Escala de Desenvolvimento Motor apresentam validade de construção.

The equilibrium tests of the Rosa Neto1 Motor Development Scale are constituted by ten tasks related to the chronological ages from 2 to 11 years and they determine the participants Motor Age. The tests presentation order is crescent from the child chronological age and the motor age is based on the success or failure in each task. The aim of this study was to analyze the construction validity of the equilibrium motor tests observing the ordering the levels of task difficulty. 76 children with 6 to 9 years of chronological age participated and were assigned in two groups: control group, tests presentation in increased order; and inverted group, tests presentation in decreased order. The results did not revealed statistical significant differences between groups, which indicate that the presentation order of the tests did not interfere in the children performance, independently of the chronological age. Low success rates occurred in some specific tasks followed by success in advanced tasks. As the results revealed that the participants could perform the tasks after that in which the failure happened the motor age ascribed by the Motor Development Scale can underestimate the children motor development. The variation of the children performance in the tasks suggests that the motor development process is nonlinear. The equilibrium motor tasks purposed in the Motor Development Scale show construction validity.