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.

Repeated Filling of Elastomeric Pumps for Home-Based Subcutaneous Infusions: A Cost Analysis of 240 Devices.

BACKGROUND: The use of continuous subcutaneous infusion of drugs using the repeated filling of elastomeric infuser pumps (EIP) has gained clinical recognition for palliative care at home. However, to date, there has been a notable absence of research examining the cost implications associated with the repeated EIP filling procedure. We aimed to evaluate the cost associated to the repeated filling of EIP used in a home-based palliative care team. METHODS: We conducted an analysis of the cost associated to the repeated filling of 240 EIP (1-day, n = 136; 2-day, n = 102; 7-day, n = 2) (110 patients). RESULTS: The refilling procedure led to a reduction in the utilization of 409 devices, resulting in savings of €4.031. EIP refilling did not result in a decrease in the number of home visits, the duration of each visit, the expenses associated with transportation to patients' residences, or the nurse-to-hour cost. CONCLUSION: Refilling EIPs reduces costs by reducing the number of devices purchased. No additional cost savings were noted in nursing time, number of home visits and duration, and expenses with transportation. Further cost savings could be realized by training laycarers to refill EIP at home independently. Future research should assess the feasibility of laycarers training programs on performing EIP filling 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.

Alpha-1 Antitrypsin Augmentation and the Liver Phenotype of Adults With Alpha-1 Antitrypsin Deficiency (Genotype Pi∗ZZ).

BACKGROUND & AIMS: α1-Antitrypsin (AAT) is a major protease inhibitor produced by hepatocytes. The most relevant AAT mutation giving rise to AAT deficiency (AATD), the 'Pi∗Z' variant, causes harmful AAT protein accumulation in the liver, shortage of AAT in the systemic circulation, and thereby predisposes to liver and lung injury. Although intravenous AAT augmentation constitutes an established treatment of AATD-associated lung disease, its impact on the liver is unknown. METHODS: Liver-related parameters were assessed in a multinational cohort of 760 adults with severe AATD (Pi∗ZZ genotype) and available liver phenotyping, of whom 344 received augmentation therapy and 416 did not. Liver fibrosis was evaluated noninvasively via the serum test AST-to-platelet ratio index and via transient elastography-based liver stiffness measurement. Histologic parameters were compared in 15 Pi∗ZZ adults with and 35 without augmentation. RESULTS: Compared with nonaugmented subjects, augmented Pi∗ZZ individuals displayed lower serum liver enzyme levels (AST 71% vs 75% upper limit of normal, P < .001; bilirubin 49% vs 58% upper limit of normal, P = .019) and lower surrogate markers of fibrosis (AST-to-platelet ratio index 0.34 vs 0.38, P < .001; liver stiffness measurement 6.5 vs 7.2 kPa, P = .005). Among biopsied participants, augmented individuals had less pronounced liver fibrosis and less inflammatory foci but no differences in AAT accumulation were noted. CONCLUSIONS: The first evaluation of AAT augmentation on the Pi∗ZZ-related liver disease indicates liver safety of a widely used treatment for AATD-associated lung disease. Prospective studies are needed to confirm the beneficial effects and to demonstrate the potential efficacy of exogenous AAT in patients with Pi∗ZZ-associated liver disease.

Counselling treatment versus counselling associated with jaw exercises in patients with disc displacement with reduction-a single-blinded, randomized, controlled clinical trial.

OBJECTIVE: To compare effectiveness of counselling program versus counselling program plus jaw exercises to reduce pain and click in patients with temporomandibular joint disc displacement with reduction (DDWR). MATERIALS AND METHODS: Patients were divided into two groups: instructions for temporomandibular disorders (TMD) plus jaw exercises (test, n = 34), only TMD instructions (control, n = 34). Pain was analyzed by palpation (RDC/TMD). It was investigated if the click caused discomfort. Both groups were evaluated at baseline, 24 h, 7 days, and 30 days' post treatment. RESULTS: The click was present in 85.7% (n = 60). In 30-day evaluation, there was a statistically significant difference between groups in the right median temporal muscle (p = 0.041); and there was a statistically significant difference in treatment self-perception (p = 0.002) and click's discomfort (p < 0.001). CONCLUSION: The exercise with recommendations showed better results, resolution of the click, and self-perception of the treatment effectiveness. CLINICAL RELEVANCE: This study presents therapeutic approaches that are easy to perform and that can be monitored remotely. In view of the current stage of the global pandemic, these treatment options become even more valid and useful. CLINICAL TRIAL REGISTER: This clinical trial was registered at Brazilian Clinical Trials Registry (ReBec) under protocol RBR-7t6ycp ( http://www.ensaiosclinicos.gov.br/rg/RBR-7t6ycp/ ), Date of registration: 26/06/2020.

A 7-Week Summer Camp in Antarctica Induces Fluctuations on Human Oral Microbiome, Pro-Inflammatory Markers and Metabolic Hormones Profile.

Antarctic camps pose psychophysiological challenges related to isolated, confined, and extreme (ICE) conditions, including meals composed of sealed food. ICE conditions can influence the microbiome and inflammatory responses. Seven expeditioners took part in a 7-week Antarctic summer camp (Nelson Island) and were evaluated at Pre-Camp (i.e., at the beginning of the ship travel), Camp-Initial (i.e., 4th and 5th day in camp), Camp-Middle (i.e., 19th-20th, and 33rd-34th days), Camp-Final (i.e., 45th-46th day), and at the Post-Camp (on the ship). At the Pre-Camp, Camp-Initial, and Camp-Final, we assessed microbiome and inflammatory markers. Catecholamines were accessed Pre- and Post-Camp. Heart rate variability (HRV), leptin, thyroid stimulating hormone (TSH), and thyroxine (T4) were accessed at all time points. Students' t-tests or repeated-measures analysis of variance (one or two-way ANOVA) followed by Student-Newman-Keuls (post hoc) were used for parametric analysis. Kruskal-Wallis test was applied for non-parametric analysis. Microbiome analysis showed a predominance of Pseudomonadota (34.01%), Bacillota (29.82%), and Bacteroidota (18.54%), followed by Actinomycetota (5.85%), and Fusobacteria (5.74%). Staying in a long-term Antarctic camp resulted in microbiome fluctuations with a reduction in Pseudomonadota-a "microbial signature" of disease. However, the pro-inflammatory marker leptin and IL-8 tended to increase, and the angiogenic factor VEGF was reduced during camp. These results suggest that distinct Antarctic natural environments and behavioral factors modulate oral microbiome and inflammation.

Inflammatory Bowel Disease and Pregnancy: Is It a Marker for Adverse Outcomes?

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.

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.

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.

Human Herpesvirus 6 Reactivation Associated With Intestinal Pseudo-Obstruction in a Renal Transplant Recipient.

Human herpesvirus 6 infection is common after organ transplant. Generally, infection is asymptomatic or is associated with a mild illness. However, human herpesvirus 6 infection in these patients may as well be life threatening as a result of severe end-stage organ disease. Here, we have reported a case of a severe human herpesvirus 6 infection with cerebral, hepatic, and gastrointestinal involvement, which presented as intestinal pseudo-obstruction. The patient was a renal transplant recipient who was successfully treated with ganciclovir. We also reviewed the literature on human herpesvirus 6 diagnosis and the associated colitis and encephalitis with its infection in solid-organ transplant recipients.

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.

Oral health-related quality of life in patients with disc displacement with reduction after counselling treatment versus counselling associated with jaw exercises.

OBJECTIVE: The aim of this study was to compare the effectiveness of two types of treatment (counselling programme versus counselling programme plus jaw exercises) to improve the quality of life of patients with disc displacement with reduction (DDWR). MATERIALS AND METHODS: Patients were divided into two groups. The test group received guidelines for temporomandibular disorders (TMD) plus jaw exercises for DDWR, and the control group received only guidelines for TMD. The total number of investigated patients was 70, thus 35 per group. The oral health-related quality of life was assessed by the OHIP-14 questionnaire. Both groups were evaluated at the baseline and 30 days post-treatment. RESULTS: In the counselling group, there was statistically significant decrease in pain (P = .015) and social disability (P = .046) subscales. In the counselling plus jaw exercise group, there was statistically significant decrease in all subscales (P < .05). At 30 days follow-up, there was a statically significant difference between the two groups in pain (P = .004), psychological discomfort (P < .001), psychological disability (P < .001) and social disability (P = .029) subscales. CONCLUSION: The counselling programme plus jaw exercise protocol showed greater improvement in oral health-related quality of life than the group performing only the counselling programme in patients with DDWR.

Prevalence, risk factors and global impact of musculoskeletal injuries among endoscopists: a nationwide European study.

Background and study aims Previous studies have suggested a high prevalence of musculoskeletal injuries (MI) in endoscopists. Little evidence has come from European countries. Our main aim was to evaluate the prevalence, type, and impact of MI among Portuguese endoscopists. We also sought to identify risk factors for the development, severity and number of endoscopy-related MI. Material and methods A 48-question electronic survey was developed by a multidisciplinary group. The electronic survey was sent to all members of Portuguese Society of Gastroenterology (n = 705) during May 2019. Study data were collected and managed using REDCap electronic data capture tools hosted at SPG - CEREGA. Results The survey was completed by 171 endoscopists (response rate of 24.3 %), 55.0 % female with a median age of 36 years (range 26-78). The prevalence of at least one MI related to endoscopy was 69.6 % (n = 119), the most frequent being neck pain (30.4 %) and thumb pain (29.2 %). The median time for MI development was 6 years (range 2 months-30 years). Severe pain was reported by 19.3 %. Change in endoscopic technique was undertaken by 61.3 % and reduction in endoscopic caseload was undertaken by 22.7 %. Missing work was reported by 10.1 %, with the median time off from work being 30 days (range 1-90). Female gender and ≥ 15 years in practice were independently associated with MI and severe pain. Years in practice, weekly-time performing endoscopy, and gender were significant predictors of the number of MI. Conclusions Prevalence of MI was significant among Portuguese endoscopists and had a relevant impact on regular and professional activities.

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.

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.

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.

Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation.

BACKGROUND & AIMS: Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation-associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form of AATD. METHODS: We collected data from 554 Pi*ZZ adults (403 in an exploratory cohort, 151 in a confirmatory cohort), in 9 European countries, with AATD who were homozygous for the Pi*Z mutation, and 234 adults without the Pi*Z mutation (controls), all without pre-existing liver disease. We collected data on demographic parameters, comorbidities, lung- and liver-related health, and blood samples for laboratory analysis. Liver fibrosis was assessed non-invasively via the serum tests Aspartate Aminotransferase to Platelet Ratio Index and HepaScore and via transient elastography. Liver steatosis was determined via transient elastography-based controlled attenuation parameter. We performed histologic analyses of livers from transgenic mice that overexpress the AATD-associated Pi*Z variant. RESULTS: Serum levels of liver enzymes were significantly higher in Pi*ZZ carriers vs controls. Based on non-invasive tests for liver fibrosis, significant fibrosis was suspected in 20%-36% of Pi*ZZ carriers, whereas signs of advanced fibrosis were 9- to 20-fold more common in Pi*ZZ carriers compared to non-carriers. Male sex; age older than 50 years; increased levels of alanine aminotransferase, aspartate aminotransferase, or γ-glutamyl transferase; and low numbers of platelets were associated with higher liver fibrosis burden. We did not find evidence for a relationship between lung function and liver fibrosis. Controlled attenuation parameter ≥280 dB/m, suggesting severe steatosis, was detected in 39% of Pi*ZZ carriers vs 31% of controls. Carriers of Pi*ZZ had lower serum concentrations of triglyceride and low- and very-low-density lipoprotein cholesterol than controls, suggesting impaired hepatic secretion of lipid. Livers from Pi*Z-overexpressing mice had steatosis and down-regulation of genes involved in lipid secretion. CONCLUSIONS: In studies of AATD adults with the Pi*ZZ mutation, and of Pi*Z-overexpressing mice, we found evidence of liver steatosis and impaired lipid secretion. We identified factors associated with significant liver fibrosis in patients, which could facilitate hepatologic assessment and counseling of individuals who carry the Pi*ZZ mutation. ClinicalTrials.gov Number NCT02929940.