Evolution of the emotional impact in patients with early inflammatory bowel disease during and after Covid-19 lockdown / Evolución del impacto emocional en pacientes con enfermedad inflamatoria intestinal temprana durante y después del bloqueo de COVID-19

Background: Patients with inflammatory bowel disease (IBD) are vulnerable to some psychological disorders. Here we describe the psychological impact of a COVID-19 pandemic lockdown in patients with IBD.Methods: This multicenter prospective cohort study included 145 patients recently diagnosed with IBD. Data on clinical and demographic characteristics, anxiety and depression scales, and IBD activity were collected in two telephone surveys, during and after the first COVID-19 lockdown in Spain. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.Results: During lockdown, 33.1% and 24.1% scored high on the anxiety and depression scales, respectively. Independent factors related to anxiety (all values ORs; 95% CIs) during lockdown were female sex (2; 1.2–5.4) and IBD activity (4.3; 1.8–10.4). Factors related to depression were comorbidity (3.3; 1.1–9.8), IBD activity (6; 1.9–18.1), use of biologics (2.9; 1.1–7.6), and living alone or with one person (3.1; 1.2–8.2). After lockdown, anxiety and depression symptoms showed significant improvement, with 24.8% and 15.2% having high scores for anxiety and depression, respectively. Factors related to post-lockdown anxiety were female sex (2.5; 1.01–6.3), Crohn's disease (3.3; 1.3–8.5), and active IBD (4.1; 1.2–13.7). Factors associated with depression were previous history of mood and/or anxiety disorders (6.3; 1.6–24.9), active IBD (7.5; 2.1–26.8), and steroid use (6.4; 1.4–29).Conclusions: Lockdown during the COVID-19 pandemic had a significant psychological impact in patients with IBD. Disease activity was related to the presence of anxiety and depression symptoms during and after lockdown.

Antecedentes: Los pacientes con enfermedad inflamatoria intestinal (EII) son vulnerables a sufrir trastornos psicológicos. En este estudio describimos el impacto psicológico que ha supuesto el confinamiento durante el COVID-19 en pacientes con EII.Métodos: Este estudio de cohorte prospectivo multicéntrico se incluyeron 145 pacientes con diagnóstico de EII reciente. Los datos sobre las características clínicas y demográficas, las escalas de ansiedad y depresión y la actividad de la EII se recogieron en dos encuestas telefónicas, durante y después del primer confinamiento por COVID-19 en España. Se calcularon las odds ratios (OR) y los intervalos de confianza (IC) al 95%.Resultados: Durante el confinamiento, el 33,1% y el 24,1% puntuaron alto en las escalas de ansiedad y depresión respectivamente. Los factores independientes relacionados con la ansiedad (todos los valores OR; IC del 95%) durante el confinamiento fueron el sexo femenino (2; 1,2-5,4) y la actividad de la EII (4,3; 1,8-10,4). Los factores relacionados con la depresión fueron la comorbilidad (3,3; 1,1-9,8), la actividad de la EII (6; 1,9-18,1), el uso de biológicos (2,9; 1,1-7,6) y el vivir solo o con una persona (3,1; 1,2-8,2). Tras el confinamiento, los síntomas de ansiedad y depresión mostraron una mejoría significativa, ya que el 24,8% y el 15,2% tenían puntuaciones altas en ansiedad y depresión, respectivamente. Los factores relacionados con la ansiedad tras el confinamiento fueron el sexo femenino (2,5; 1,01-6,3), enfermedad de Crohn (3,3; 1,3-8,5) y EII activa (4,1; 1,2-13,7). Los factores asociados con la depresión fueron los antecedentes de trastornos del estado de ánimo y/o de ansiedad (6,3; 1,6-24,9), EII activa (7,5; 2,1-26,8), y el uso de esteroides (6,4; 1,4-29).

Evolution of the emotional impact in patients with early inflammatory bowel disease during and after Covid-19 lockdown.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are vulnerable to some psychological disorders. Here we describe the psychological impact of a COVID-19 pandemic lockdown in patients with IBD. METHODS: This multicenter prospective cohort study included 145 patients recently diagnosed with IBD. Data on clinical and demographic characteristics, anxiety and depression scales, and IBD activity were collected in two telephone surveys, during and after the first COVID-19 lockdown in Spain. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: During lockdown, 33.1% and 24.1% scored high on the anxiety and depression scales, respectively. Independent factors related to anxiety (all values ORs; 95% CIs) during lockdown were female sex (2; 1.2-5.4) and IBD activity (4.3; 1.8-10.4). Factors related to depression were comorbidity (3.3; 1.1-9.8), IBD activity (6; 1.9-18.1), use of biologics (2.9; 1.1-7.6), and living alone or with one person (3.1; 1.2-8.2). After lockdown, anxiety and depression symptoms showed significant improvement, with 24.8% and 15.2% having high scores for anxiety and depression, respectively. Factors related to post-lockdown anxiety were female sex (2.5; 1.01-6.3), Crohn's disease (3.3; 1.3-8.5), and active IBD (4.1; 1.2-13.7). Factors associated with depression were previous history of mood and/or anxiety disorders (6.3; 1.6-24.9), active IBD (7.5; 2.1-26.8), and steroid use (6.4; 1.4-29). CONCLUSIONS: Lockdown during the COVID-19 pandemic had a significant psychological impact in patients with IBD. Disease activity was related to the presence of anxiety and depression symptoms during and after lockdown.

Actual Anti-TNF Trough Levels Relate to Serum IL-10 in Drug-Responding Patients With Crohn's Disease.

BACKGROUND: Patients with Crohn's disease (CD) responding to anti-tumor necrosis factor (anti-TNF) show great variability in serum drug levels, even within the therapeutic range. We aimed at exploring the role of inflammatory, genetic, and bacterial variables in relation to anti-TNF through levels in CD patients. METHODS: Consecutive CD patients receiving stable doses of infliximab or adalimumab were included. Clinical and analytical parameters were recorded. Cytokine response, bacterial DNA translocation, and several immune-related genes' genotypes were evaluated, along with serum through anti-TNF drug levels. A linear regression analysis controlled by weight and drug regimen was performed. RESULTS: One hundred nineteen patients were initially considered. Five patients on infliximab and 2 on adalimumab showed antidrug antibodies in serum and were excluded. One hundred twelve patients were finally included (62 on infliximab, 50 on adalimumab). Fourteen patients on infliximab and 15 on adalimumab (22.6% vs 30%, P = 0.37) were receiving an intensified drug regimen. C-reactive protein (CRP), fecal calprotectin, Crohn's Disease Activity Index, leukocyte count, and albumin levels in plasma were not significantly associated with infliximab or adalimumab levels in the multivariate analysis. Serum interleukin-10 (IL-10) levels were directly related to infliximab (Beta = 0.097, P < 0.0001) and adalimumab levels (Beta = 0.069, P = 0.0241). The best multivariate regression model explaining the variability of serum infliximab and adalimumab levels included IL-10. Predicted drug levels by this model robustly fitted with actual drug levels (R2 = 0.841 for infliximab, R2 = 0.733 for adalimumab). CONCLUSION: Serum IL-10 is significantly related to serum anti-TNF levels in CD patients, showing how the disposition of anti-TNF drugs is significantly influenced by the degree of immunological activation.

Gut Bacterial DNA Translocation is an Independent Risk Factor of Flare at Short Term in Patients With Crohn's Disease.

OBJECTIVES: We aimed at evaluating bacterial DNA (bactDNA) presence in blood of Crohn's disease (CD) patients in remission as an independent risk factor of flare at 6 months. METHODS: This is a prospective, multicenter study on CD patients with Crohn's disease activity index (CDAI)<150. The primary end point was time-to-relapse as evaluated by CDAI>150 in the following 6 months. BactDNA in blood, the nucleotide-binding oligomerization domain containing 2 (NOD2) genotype, and serum cytokine levels were determined at baseline. RESULTS: A total of 288 patients were included. BactDNA was detected in 98 patients (34.0%). A variant-NOD2 genotype was identified in 114 patients (39.6%). Forty patients (14%) relapsed during follow-up. Multivariate survival analysis identified bactDNA as an independent risk factor of flare (hazard ratio (HR) 8.75 (4.02-19.06) 95% confidence interval (CI)). Hospitalization, surgery, switch of treatment, initiation and escalation of anti-tumor necrosis factor (TNF) therapy, steroids initiation, and increased fecal calprotectin levels at 6 months were associated with bactDNA at baseline. A logistic regression analysis showed bactDNA as an independent and significant predictive factor of hospitalization (odds ratio (OR) 11.9 (3.4-42.3); P<0.001), steroids startup (OR 8.5 (2.7-27.1); P<0.001), and switch of treatment (OR 3.5 (1.6-7.7); P=0.002) at 6 months. No relationship was observed between bactDNA and mucosal lesions in patients with colonoscopy at admission. Serum pro-inflammatory cytokines were significantly increased in patients with bactDNA or a variant-NOD2 genotype. The combination of both factors induced decreased anti-TNF-α levels and a higher percentage of patients on intensified anti-TNF therapy. CONCLUSIONS: BactDNA is an independent risk factor of relapse at 6 months in CD patients. BactDNA is also independently associated with an increased risk of hospitalization, switch of treatment, and steroids initiation.

Factors associated with non-attendance at outpatient endoscopy.

OBJECTIVE: Non-attendance at endoscopy procedures leads to wasted resources and increased costs. The purpose of this study was to investigate the factors associated with non-attendance. MATERIAL AND METHODS: All patients who attended the outpatient clinic for gastroscopy or colonoscopy examinations were included in the study. Patients who missed their appointment were identified and their data were collected prospectively. Patients who kept their appointment in the same period of time served as controls. RESULTS: Between August 2002 and February 2003, 1051 gastroscopies and 756 colonoscopies were scheduled. A total of 265 patients (14.7%) missed their appointment. No significant differences were found between attendees and non-attendees for mean age, gender, type of examination and day of the week on which the examination was scheduled. The time on the waiting list was longer in patients who did not keep their appointment than in those who did. Fewer appointments were missed in patients with a preferent referral, and among patients referred by their general practitioner a higher percentage failed to keep their appointment compared with those referred by a specialist. In the multivariate analysis, length of time on the waiting list and the source of referral were the only two independent predictive factors for non-attendance. CONCLUSIONS: A longer time on the waiting list and referral by a general practitioner are factors associated with patients failing to keep their endoscopy appointment.

Different profile of cytokine synthesis according to the severity of acute pancreatitis.

AIM: To evaluate the cellular synthetic ability of cytokines involved in pro- and anti-inflammatory reactions in patients with AP. METHODS: Sixty-seven patients with AP (16 severe, 51 mild) and 10 controls were included in the study. Cultures of whole blood were performed in samples obtained within the first 72 h from the onset of pain. Serum levels of interleukins (IL) 6, 8, 10, and TNF-alpha were measured at baseline and in the supernatant of cultures with (functional reserve) or without stimulation with phytohemaglutinin. RESULTS: Basal levels of cytokines were significantly higher in patients with severe AP. A significant increase of all pro-inflammatory cytokines vs basal levels was observed in the supernatant after 24 h of whole blood cultures in patients, but not in controls. In contrast, IL-10 increased significantly in the supernatant of cultures only in patients with mild AP. Cells showed a statistically significant functional reserve for all IL in patients with mild, but only for pro-inflammatory cytokines in patients with severe AP. CONCLUSION: A marked activation of immune system may be observed in patients with AP, being balanced between pro- and anti-inflammatory cytokines in patients with mild but not severe AP. A reduced functional reserve for the synthesis of IL-10 may be observed in patients with severe AP, which might lead to a worst prognosis.

Clinical value of rapid urine trypsinogen-2 test strip, urinary trypsinogen activation peptide, and serum and urinary activation peptide of carboxypeptidase B in acute pancreatitis.

AIM: To assess the usefulness of urinary trypsinogen-2 test strip, urinary trypsinogen activation peptide (TAP), and serum and urine concentrations of the activation peptide of carboxypeptidase B (CAPAP) in the diagnosis of acute pancreatitis. METHODS: Patients with acute abdominal pain and hospitalized within 24 h after the onset of symptoms were prospectively studied. Urinary trypsinogen-2 was considered positive when a clear blue line was observed (detection limit 50 microg/L). Urinary TAP was measured using a quantitative solid-phase ELISA, and serum and urinary CAPAP by a radioimmunoassay method. RESULTS: Acute abdominal pain was due to acute pancreatitis in 50 patients and turned out to be extrapancreatic in origin in 22 patients. Patients with acute pancreatitis showed significantly higher median levels of serum and urinary CAPAP levels, as well as amylase and lipase than extrapancreatic controls. Median TAP levels were similar in both groups. The urinary trypsinogen-2 test strip was positive in 68% of patients with acute pancreatitis and 13.6% in extrapancreatic controls (P<0.01). Urinary CAPAP was the most reliable test for the diagnosis of acute pancreatitis (sensitivity 66.7%, specificity 95.5%, positive and negative predictive values 96.6% and 56.7%, respectively), with a 14.6 positive likelihood ratio for a cut-off value of 2.32 nmol/L. CONCLUSION: In patients with acute abdominal pain, hospitalized within 24 h of symptom onset, CAPAP in serum and urine was a reliable diagnostic marker of acute pancreatitis. Urinary trypsinogen-2 test strip showed a clinical value similar to amylase and lipase. Urinary TAP was not a useful screening test for the diagnosis of acute pancreatitis.

A study of intestinal permeability in relation to the inflammatory response and plasma endocab IgM levels in patients with acute pancreatitis.

BACKGROUND: There is scarce information regarding intestinal permeability (IP) in patients with acute pancreatitis (AP) and its relationship with systemic inflammatory response and bacterial translocation (BT). AIMS: To study IP in patients with mild and severe forms of AP as compared with controls and the presumed correlations between IP, the inflammatory response, and endotoxin. PATIENTS AND METHODS: Sixty-eight patients with AP and 13 healthy controls were included. IP was assessed by means of the lactulose/mannitol (L/M) test, at admission (LMR1), and at the 15th day (LMR2). The presence of endotoxin was assessed by means of endotoxin-core antibodies type IgM (EndoCab IgM), at admission and 15 days later in patients with severe AP. Plasma levels of interleukins 6, 8, 10, and tumor necrosis factor alpha were tested within the first 72 hours from the onset of pain. RESULTS: Both LMR1 and LMR2 were significantly higher in patients than in controls, and in patients with severe versus mild forms of AP. Plasma levels of Endocab IgM increased significantly in patients with severe AP. Basal plasma levels of pro- and anti-inflammatory cytokines were significantly higher in patients with severe AP. A significant correlation was found between LMR2 and Endocab IgM levels in patients with severe AP (r = 0.73, P = 0.02). CONCLUSIONS: Patients with AP show an increased IP when compared with controls, being more relevant and persistent in severe cases. This seems related to an increase of endotoxemia late in the course of the disease, but not with an exacerbation of the systemic immune response.

Comparison of stool immunoassay with standard methods for detection of Helicobacter pylori infection in patients with upper-gastrointestinal bleeding of peptic origin.

OBJECTIVE: To assess the accuracy of the determination of Helicobacter pylori infection by a stool immunoassay in patients with upper-gastrointestinal bleeding (UGB) of peptic origin, in comparison with the routine histological study, serology, rapid urease and 13C-breath tests. METHODS: Sixty-eight patients with endoscopically proven UGB of peptic origin were included. The presence of H. pylori was considered when observed on histology or, if negative, by the positive indications of two of the remaining tests (serology, rapid urease,13C-breath test). The accuracy of stool immunoassay was estimated according to results obtained with other diagnostic methods. RESULTS: Lesions causing gastrointestinal bleeding were 49 duodenal ulcers, 11 gastric ulcers, six pyloric channel ulcers, 13 acute lesions of the gastric mucosa, and 16 erosive duodenitis. H. pylori infection was present in 59 (86.76%) patients. Forty-one patients had received nonsteroidal anti-inflammatory drugs. The sensitivity and specificity of the diagnostic methods were 47.5% and 100% for the rapid urease test, 93% and 87.5% for the breath test, 86.4% and 77.7% for serology, 89.4% and 100% for histology, and 96.6% and 33.3% for the stool test. CONCLUSIONS: The detection of H. pylori antigen in stools in patients with UGB of peptic origin has a good sensitivity (96.6%) but a low specificity (33.3%) for the diagnosis of H. pylori infection, which probably makes this test an inadequate tool in this setting if utilized alone.

Porphyromonas asaccharolytica liver abscess.

The black pigmented Gram-negative anaerobes, Porphyromonas species, have been isolated from clinical specimens in cases of central nervous system, dental-oral, pleuropulmonary and genitourinary infections and bacteremia. Herein, we report an unusual case of liver abscess caused by Porphyromonas asaccharolytica that has not been previously reported.