Vedolizumab for perianal fistulizing Crohn’s disease: systematic review and meta-analysis

Background/Aims@#Perianal fistulas are a debilitating manifestation of Crohn’s disease (CD). Despite the advent of anti-tumor necrosis factor (anti-TNF) therapy, the medical management of fistulizing CD continues to be challenged by unmet needs. We conducted a systematic review and meta-analysis of the effectiveness of vedolizumab for the management of perianal fistulizing CD. @*Methods@#A search of PubMed, EMBASE and the Cochrane Library was performed from inception to June 2020 for studies reporting rates of perianal fistula healing in CD patients treated with vedolizumab. The primary outcome of interest was complete healing of perianal fistulas and the secondary outcome was partial healing. The pooled fistula healing rates with 95% confidence intervals (CI) were calculated utilizing a random effects model. @*Results@#A total of 74 studies were initially identified, 4 of which met the inclusion criteria. A total of 198 patients with active perianal fistulas were included, 87% of whom had failed previous anti-TNF therapy. The pooled complete healing rate was 27.6% (95% CI, 18.9%–37.3%) with moderate heterogeneity (I2=49.4%) and the pooled partial healing rate was 34.9% (95% CI, 23.2%–47.7%) with high heterogeneity (I2=67.1%). @*Conclusions@#In a meta-analysis of 4 studies that included 198 patients with perianal fistulizing CD, the majority of whom had failed previous anti-TNF therapy, vedolizumab treatment led to healing of perianal fistulas in nearly one-third of the patients. The lack of high-quality data and significant study heterogeneity underscores the need for future prospective studies of fistula healing in patients receiving anti-integrin therapy.

Factors associated with anti-tumor necrosis factor effectiveness to prevent postoperative recurrence in Crohn’s disease

Background/Aims@#We assessed the effectiveness of anti-TNF agents and its associated factors to prevent endoscopic and clinical postoperative recurrence (POR) in Crohn’s disease (CD). @*Methods@#From a prospectively-maintained database, we retrieved 316 CD patients who underwent intestinal resection (2011–2017). Endoscopic (Rutgeerts index ≥ i2 at 6 months) and clinical (recurrence of symptoms leading to hospitalization or therapeutic escalation) POR were assessed. @*Results@#In 117 anti-TNF-naïve patients, anti-TNF therapy was more effective than immunosuppressive agents (odds ratio [OR], 8.8; 95% confidence interval [CI], 1.8–43.9; P= 0.008) and no medication/5-aminosalicylates (OR, 5.2; 95% CI, 1.0–27.9; P= 0.05) to prevent endoscopic POR. In 199 patients exposed to anti-TNF prior to the surgery, combination with anti-TNF and immunosuppressive agents was more effective than anti-TNF monotherapy (OR, 2.32; 95% CI, 1.02–5.31; P= 0.046) to prevent endoscopic POR. Primary failure to anti-TNF agent prior to surgery was predictive of anti-TNF failure to prevent endoscopic POR (OR, 2.41; 95% CI, 1.10–5.32; P= 0.03). When endoscopic POR despite anti-TNF prophylactic medication (n = 55), optimizing anti-TNF and adding an immunosuppressive drug was the most effective option to prevent clinical POR (hazard ratio, 7.38; 95% CI, 1.54–35.30; P= 0.012). Anti-TNF therapy was the best option to prevent clinical POR (hazard ratio, 3.10; 95% CI, 1.09–8.83; P= 0.034) in patients with endoscopic POR who did not receive any biologic to prevent endoscopic POR (n = 55). @*Conclusions@#Anti-TNF was the most effective medication to prevent endoscopic and clinical POR. Combination with anti-TNF and immunosuppressive agents should be considered in patients previously exposed to anti-TNF.

Effect of contrast and gaps between Vernier stimulus elements on sweep visual evoked potential measurements of human cortical Vernier responses

The present paper focuses on a classic hyperacuity, Vernier acuity-the ability to discriminate breaks in the collinearity of lines or edges on the order of only arcseconds of visual angle. We measured steady-state sweep visual evoked potentials (sVEPs) in response to 6 Hz periodic breaks in collinearity (Vernier offsets) in horizontal squarewave gratings. Vernier thresholds, estimated by extrapolating the amplitude of the first harmonic (1F) to 0 µV, were measured for gratings with 4%, 8%, 16%, 32%, 64%, and 80% contrast, with gaps of 0, 2, or 5 arcmin introduced between neighboring bar elements that formed the Vernier offsets. Thresholds for the 2F response component provided an estimate of motion thresholds. The data confirmed and extended evidence that the odd- and even-harmonic components reflect cortical activity of different neurons (i.e., neurons that respond asymmetrically to the periodic breaks in alignment and neurons that respond symmetrically to the local relative motion cue of the stimulus). Suprathreshold data (peak amplitude, response slope, and response phase at the peak amplitude) provided additional independent evidence of this notion. Vernier thresholds decreased linearly as contrast increased, with a slope of approximately -0.5 on log-log axes, similar to prior psychophysical results. The form of contrast dependence showed more similarity to measures of magnocellular ganglion cell spatial precision than measures from parvocellular ganglion cells. Our data thus support the hypothesis that magnocellular ganglion cell output from the retina has the requisite properties to support cortical calculation of Vernier offsets at a hyperacuity level...

The Jitter Spatial Frequency Sweep VEP: a new paradigm to study spatiotemporal development of pattern - and motion - processing mechanisms in human infants

We introduce a new VEP paradigm - the Jitter Spatial Frequency (JSF) Sweep VEP - that permits efficient mapping of the spatiotemporal tuning of the developmental motion asymmetry (DMA). Vertical sinewave gratings undergoing 90º horizontal oscillatory displacements (6 or 10 Hz) were presented while their SF was swept over 2 to 5 octaves during each VEP trial. JSF sweep VEPs were recorded from 28 infants (8-43 weeks), and symmetric (second-harmonic, F2) and asymmetric (F1) components of the VEP were measured. JSF sweeps can provide four useful estimates: (1,2) the high-SF cutoff of F1 and F2 responses estimates the spatial resolution of direction-selective (DS) and non-DS mechanisms, respectively; (3) the low-SF cutoff for F1 estimate the SF-boundary between mature (F1 absent) and immature (F1 present) DS mechanisms; and (4) the F1 high-SF cutoff estimates the lower velocity limit of cortical DS cells. For 6 Hz, the low-SF F1 cutoffs increased two times faster than traditional (contrast-reversal) VEP grating acuity (0.5 vs ~0.25 octaves/month), and twice that of the high-SF F1 and F2 cutoffs. This implies that no single mechanism can account for the DMA at both low and high SFs. At 10 Hz, the DMA exhibited no significant development, consistent with slower maturation of DS mechanisms at higher ST frequencies. The F2 high-SF cutoffs were higher than F1 at both 6 and 10 Hz, suggesting higher spatial resolution for non-DS (pattern) vs DS (motion) mechanisms. Finally, the lower velocity limit of the DS mechanisms decreased from ~2 deg/sec at 8 weeks, to 0.75 deg/sec at 33 weeks, similar to analogous limits for direction-of-motion identification in adults (~0.5 - 1 deg/sec), and close to prior VEP estimates in infants (0.6 deg/sec).

Fluxo coronário desregulado durante reperfusäo pós cardioplegia / Coronary flow response is impaired during post-cardioplegia

Estudaram-se a demanda metabólica e a distribuiçäo do fluxo coronariano na presneça de fibrilaçäo ventricular (FV), durante a reperfusäo pós-cardioplegia. Foram colocados 15 suínos em circulaçäo extracorpórea e submetidos a parada cardíaca cardioplégica sangüínea anterógrada hipotérmica intermitente, durante uma hora, seguida por reperfusäo miocárdica controlada. Os animais foram divididos em três grupos (n=5), conforme estivessem em assistolia (Grupo 1) ou em FV de curta (grupo 2) ou longa duraçäo (Grupo 3), durante os dez primeiros minutos de reperfusäo. Os valores do consumo miocárdico de oxigênio (MVO2), em ml O2/min/g (média + erro padräo) durante a reperfusäo foram de 1,325 + 0,144 (grupo 1); 2,472 + 0,208 (Grupo 2) e 2,469 + 0,228 (Grupo 3). A diferença entre o MVO2 dos coraçöes em assistolia e o dos coraçöes em FV, quer de curta ou longa duraçäo, foi significante (p<0,001). A relaçäo entre os fluxos sangüíneos endo e epicárdico, bem como o fluxo sangüíneo coronário global (ml/mim/100g) foram semelhantes nos 3 grupos. Os valores dessa última variável, em ml/mim/100g, corresponderam a, respectivamente, 169,3 + 11,7; 185,0 + 15,7 e 179,9 + 13,2. Os resultados demonstram que a auto-regulaçäo coronária está alterada durante a fase inicial de reperfusäo pós criocardioplegia, pois a perfusäo miocárdica näo aumentou em resposta à elevaçäo do consumo de oxigênio imposta pela FV. Essa constataçäo, de grande interesse clínico, sugere que a ocorrência de FV durante a fase inicial da reperfusäo possa contribuir para o desenvolvimento de lesöes teciduais em coraçöes cujo fluxo coronário já esteja previamente comprometido, por obstruçäo coronária, distensäo ou hipertrofia ventricular.

Serological study of amoebiasis and toxoplasmosis in the Malili area, South Sulawesi, Indonesia.

Results of a serology survey in September 1972 for Entamoeba histolytica and Toxoplasma gondii antibodies among 915 volunteers from the Malili area of South Sulawesi (Celebes), Indonesia are presented. Indirect hemagglutination antibody titers for amoebiasis were found in 22.7% of the sampled population while 9.5% demonstrated antibody titers greater than or equal to 1:128. The frequency distribution of antibody titers were similar by sex and age. There was no significant correlation between stool positivity and seropositivity. Indirect hemagglutination antibody titers for T. gondii were detected in 62% of the population sampled, and titers greater than or equal to 1:32 were demonstrated in 29% of the samples tested. The distribution of antibody titers was similar in males and females. In both sexes the prevalence of IHA antibody titer against T. gondii increased with age. There was no consistent association between altitude and prevalence of seropositive samples.

Human parasitoses of the Malili area, South Sulawesi (Celebes) province, Indonesia.

A biomedical survey was conducted in 9 villages in the Malili area of South Sulawesi, Indonesia. Blood specimens were examined for malaria and microfilariae; stool specimens were examined for intestinal parasites. Malaria parasitemias were rare; Plasmodium falciparum was detected in 10 and P. vivax in 11 of 985 blood smears. Malayan filariasis was endemic to all villages surveyed. The overall prevalence of detectable microfilaremias was 15%, varying from 34% in Kawata to 1% in Nuha. Microfilarial densities, expressed as MfD50 averaged 8.0 and varied from 1.1 in Timampu to 16.0 in Karabbe. Intestinal parasites were common. Although Schistosoma japonicum was not found, 97% of the examined had one or more intestinal parasites as follows: Ascaris lumbricoides (74%), Trichuris trichiura (65%), hookworm (62%), Entamoeba coli (38%), Endolimax nana (10%), Entamoeba histolytica (6%), Iodamoeba bütschlii (4%), Entamoeba hartmanni (3%), Giardia lamblia (2%) Chilomastix mesnili (1%) and Enterobius vermicularis (1%). Strongyloides stercoralis larvae and Hymenolepis nana eggs were detected once each and heterophyid-like eggs were detected twice.