Induction of remission with tacrolimus in a patient with severe acute, cortisone refractory ulcerative colitis and severe Covid-19 pneumonia: a case report

Background Therapy regimens used in patients with inflammatory Bowel Disease (IBD) have been associated with enhanced risk of viral infections or viral reactivation. Moreover, it is uncertain whether IBD patients have increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or infected patients may have an increased risk for severe coronavirus disease 2019 (Covid-19). Managing severe acute flare in ulcerative colitis during the Covid-19 pandemic is a challenge for clinicians and their patients. The results of the published studies mainly report on the role of the prior medication, but not how to treat severe acute flare of IBD patients with severe Covid-19 pneumonia. Case presentation We report the case of a 68-year-old patient with a long history of ulcerative colitis. He was initially admitted to an external hospital because of severe acute flare. The initiation of a high-dose oral cortisone therapy did not improve the clinical symptoms. During the inpatient treatment, he was tested positive for SARS-CoV-2. At admission to our hospital the patient showed severe flare of his ulcerative colitis and increased Covid-19 symptoms. A cortisone-refractory course was noticed. After detailed multidisciplinary risk–benefit assessment, we initiated an intravenous tacrolimus therapy and dose of prednisolone was tapered gradually. After clinical response, the therapy was adjusted to infliximab. Additionally, the Covid-19 pneumonia was kept under control despite immunosuppression and the patient could be discharged in clinical remission. Conclusions This case suggest the use of tacrolimus as a bridging therapeutic option for severe acute, cortisone refractory ulcerative colitis in Covid-19 patients. Nevertheless, the best treatment strategy for IBD patients presenting a flare during the outbreak has yet to be defined. Further data for IBD patients under calcineurin inhibitor therapy are urgently needed.

Optimization of pineapple juice amount used as a negative oral contrast agent in magnetic resonance cholangiopancreatography

To evaluate the potential variability of Manganese (Mn2+) in commercial pineapple juice (PJ) produced in different years and to identify the optimal Mn2+ concentration in the correct amount of PJ to be administered prior to Magnetic Resonance Cholangiopancreatography (MRCP) in order to suppress the gastroduodenal (GD) liquid signal. The Mn2+ concentration in PJ produced in different years was defined using Atomic Absorption Spectrometry. The optimal Mn2+ concentration and the amount of PJ, were estimated in an in-vitro analysis, and were then prospectively tested in a population of patients who underwent MRCP. The results were compared with those achieved with the previous standard amount of PJ used in a similar population. The concentrations of Mn2+ in commercial PJ produced in different years did not differ. A total amount of 150 ml (one glass) of PJ having a high Mn2+ content (2.37 mg/dl) was sufficient for the suppression of the GD liquid signal, despite the additional dilution caused by GD liquids since it led to a final concentration of Mn2+ of 0.5–1.00 mg/dl. The optimized single-dose oral administration of 150 ml (approximately one glass) of PJ having a high Mn2+ concentration prior to MRCP was adequate to guarantee the correct amount of Mn2+ to suppress the GD signal.

Periocular capillary hemangioma treated with low dose oral propranolol - presentation and outcome of 30 patients

Purpose: To evaluate the presentation and outcome of periocular capillary hemangioma treated with low-dose oral propranolol. Method: Thirty cases of periocular capillary hemangioma prospectively studied from 1st June 2015 to 31st May 2017 who received oral propranolol on an outpatient basis. Hemangioma causing any threat to vision or disfigurement was included and age below 3 months and multiple lesions were excluded. Starting dose of propranolol was 1 mg/kg and increased to 2 mg/kg after 2 weeks as a maintenance dose. The tapering dose was 1 mg/kg of body weight before discontinuing the medication. Treatment was continued till the child is 1 year of age or no further change in color or size of the lesion in two successive follow-ups. Results: Presenting age was 6.36 ± 3.36 months (ranged 3–24 months) with female predominance (70%). In 86.6% of cases, the vision was Central Steady and Maintained and cycloplegic refraction showed marked astigmatism in 3 children which resolved after treatment. Forty-six percent of children showed color change as an initial response to treatment. Most children (33.3%) responded completely within 5 months after starting the treatment. One third patients (33.3%) showed 100% resolution, 50% showed 90% to 70% resolution. Pretreatment and post-treatment lesion size was1.60 ± 0.86 cm2 and 0.30 ± 0.40 cm2 respectively (p - value < 0.0005). None showed any significant adverse effect of oral propranolol. Conclusion: Low-dose oral propranolol is an effective and cost-effective treatment modality for periocular capillary hemangioma and is safe as an outpatient basis.

A Phase II Multicenter Trial on High-Dose Vitamin D Supplementation for the Correction of Vitamin D Insufficiency in Patients with Breast Cancer Receiving Adjuvant Chemotherapy

Breast cancer (BC) treatments induce vitamin D (VD) insufficiency and bone metabolism changes, resulting in osteoporosis and skeletal morbidity risk. We report the results of a bicentric phase II trial (ClinicalTrials.gov Identifier: NCT04091178) on the safety and efficacy of high-dose oral VD supplementation for VD deficiency correction in 44 patients with early BC treated with adjuvant chemotherapies. Patients received one dose of 100,000 IU 25-OH VD every 3 weeks from day 1 of cycle 1 to day 1 of cycle 5. The primary endpoint was the percentage of patients achieving serum 25-OH VD concentration normalization on day 1 of cycle 6 (D1C6). Secondary endpoints were safety, VD and calcium parameters at baseline and during chemotherapy, and identification of predictive biomarkers of VD normalization on D1C6. On D1C6, 21 patients (47.7%, 95% CI: 33.0–62.8) achieved VD normalization. No VD-related clinical toxicity was reported. However, 13 patients (29.5%) presented asymptomatic grade 1 hypercalciuria, leading to interruption of the high-dose oral VD supplementation in 10, followed by a rapid reduction in serum VD concentration. No baseline clinical factor was predictive of VD normalization on D1C6. This high-dose VD supplementation appears safe and efficient in patients with early BC receiving adjuvant chemotherapy.

Repeated, low-dose oral esketamine in patients with treatment-resistant depression: pilot study

Background Intravenous infusion of ketamine can produce rapid and large symptom reduction in patients with treatment-resistant depression (TRD) but presents major obstacles to clinical applicability, especially in community settings. Oral esketamine may be a promising addition to our TRD treatment armamentarium. Aims To explore the safety, tolerability and potential clinical effectiveness of a 3-week treatment with repeated, low-dose oral esketamine. Method Seven patients with chronic and severe TRD received 1.25 mg/kg generic oral esketamine daily, over 21 consecutive days. Scores on the Systematic Assessment for Treatment Emergent Events (SAFTEE), Community Assessment of Psychic Experiences (CAPE), Clinician Administered Dissociative States Scale (CADSS) and Hamilton Rating Scale for Depression (HRSD) instruments, as well as blood pressure and heart rate, were repeatedly assessed. Results Treatment with oral esketamine was well-tolerated. No serious side-effects occurred, and none of the participants discontinued treatment prematurely. Psychotomimetic effects were the most frequently reported adverse events. Mean HDRS score decreased by 16.5%, from 23.6 to 19.7. Three participants showed reductions in HDRS scores above the minimum clinically important difference (eight-point change), of whom two showed partial response. No participants showed full response or remission. Conclusions These results strengthen the idea that oral esketamine is a safe and well-tolerated treatment for patients with chronic and severe TRD, but therapeutic effects were modest. Results were used to design a randomised controlled trial that is currently in progress.

Assessment of the Gastrointestinal Fate of Bacterial Cellulose and Its Toxicological Effects After Repeated-dose Oral Administration

BackgroundBacterial cellulose (BC) is a nanofibrillar polysaccharide produced by certain acetic acid bacteria. BC may be used in food, pharma and many other applications. However, detailed studies of the oral toxicology of BC are limited. Controversial data is published regarding this topic, specially when it comes to answering the question on whether cellulose is absorbed at the intestine.MethodsFollowing the European Food Safety Authority guidelines (EFSA), this work presents the results of a 21-day repeated dose oral toxicity of BC in male and female Wistar Han rats (Wistar rats). In parallel, microcrystalline cellulose Avicel LM310 (commercially available as a food additive) was used. Wistar rats were subjected to daily oral gavage of 0.75 mL of an aqueous suspension 1% (m/v) BC or of its counterpart of plant origin, Avicel LM310. Rats not submitted to gavage were included in the experiment as controls. Clinical observations, such as body weight measurements, food consumption and ophthalmologic evaluations were performed during the assay. After occision, serum chemistry, necropsic examination and histopathological analyses of the liver, kidneys, spleen and small and large intestines were performed. The presence of BC fibers along the gastrointestinal tract was assessed histologically using a Green Fluorescence Protein coupled to a Cellulose Carbohydrate Binding Module (GFP-CBM) from Clostridium cellulolyticum.ResultsNo adverse clinical observations related to BC administration were noticed, nor appreciable differences in the toxicological endpoints evaluated were detected. No evidence of BC persorption was found. Particularly, no BC was detected in the Peyer´s patches or in the mesenteric lymphatic nodules. Moreover, the histopathological analyses revealed that the global architecture and morphology of the organs and tissues was preserved, among the different experimental groups, with no significant pathological changes among them. Regarding serum biochemistry, no significant differences were recorded, for both sexes.ConclusionsThese results demonstrate that BC nanofibers can be considered safe and, as the vegetal cellulose, can be used as a food additive.