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Although percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) is currently indicated in a variety of conditions, limited data are available regarding its safety and the best timing for its replacement. We herein describe a single-centre cohort of patients who underwent PEG-J placement or replacement to assess the short- and long-term safety of the procedure.Demographic and procedure-related data regarding all patients undergoing a PEG-J procedure between March 2010 and 2020, either first placement or any replacement, at the Endoscopy Unit of a University Hospital in Northern Italy (IRCCS Policlinico San Matteo, Pavia, Italy), were retrospectively collected. Data were collected until last available follow-up.We included 73 patients (mean age 70 ± 9.7, 60.3% female) who underwent a PEG-J procedure. Data on a total of 215 procedures were gathered with a median follow up time of 21 months (IQR 9.3-39.5). No immediate adverse events (AEs) were reported. Short-term (within 30 days) AEs, including jejunal extension dislocations, accidental removal, obstruction and kinking occurred in 12 patients (5.6% of the total procedures), whilst long-term AEs (obstruction, tube malfunctions, inner tube dislocation, pyloric ulcer, hypergranulation tissue, wear, buried bumper syndrome and accidental removal) were reported in 40 patients. The risk of developing an AE was not reduced if tube replacement was performed electively. The median duration of the PEG-J before replacement was 12 months (IQR 6-16 months).PEG-J placement and replacement are safe procedures. Although PEG-J durability is variable an elective procedure might be indicated to reduce urgent replacements.

Highlights • UGIB has a prevalence of 0.47% in non-ICU COVID-19 patients and peptic disease is the most common finding • Half of patients were managed conservatively or with delayed endoscopy • This is the first report that evaluates incidence of UGIB in COVID-19 patients • Conservative management and delayed endoscopy could be a successful option in patients with significant respiratory impairment, Background COVID-19 patients have an increased susceptibility to develop thrombotic complications, thus thromboprophylaxis is warranted which may increase risk of upper gastrointestinal bleeding (UGIB). Our aim was to evaluate incidence of UGIB and use of upper GI endoscopy in COVID-19 inpatients. Methods the medical and endoscopic management of UGIB in non-ICU COVID-19 patients has been retrospectively evaluated. Glasgow Blatchford score was calculated at onset of signs of GI bleeding. Timing between onset of signs of GI bleeding and execution, if performed, of upper GI endoscopy was evaluated. Endoscopic characteristics and outcome of patients were evaluated overall or according to the execution or not of an upper GI endoscopy before and after 24 hr. Results Out of 4871 COVID-19 positive patients, 23 presented signs of UGIB and were included in the study (incidence 0.47%). The majority (78%) were on anticoagulant therapy or thromboprophylaxis. In 11 patients (48%) upper GI endoscopy was performed within 24hr, whereas it was not performed in 5. Peptic ulcer was the most common finding (8/18). Mortality rate was 21.7% for worsening of COVID-19 infection. Mortality and rebleeding were not different between patients having upper GI endoscopy before or after 24 hr/not performed. Glasgow Blatchford score was similar between the two groups (13;12-16 vs 12;9-15). Conclusion Upper GI bleeding complicated hospital stay in almost 0.5% of COVID-19 patients and peptic ulcer disease is the most common finding. Conservative management could be an option in patients that are at high risk of respiratory complications.

Colorectal cancer (CRC) diagnosed before the age of 50, known as early-onset CRC (eoCRC), is considered uncommon. We aimed at analysing the incidence of preneoplastic and neoplastic lesions of the colon and rectum in patients under 50 years old and to identify possible predictors Methods: We retrospectively collected data from 1778 patients under 50 years old (mean age 39.9±7.8) referred for colonoscopy between 2015-2018. Cumulative incidence of adenomas and eoCRC was assessed. Multivariable regression models were fitted Results: The cumulative incidence for adenomas was 11.0% (95% CI 9-12), while it was 1.5% (95% CI 1-2) for eoCRC (metastatic disease in 13/27 patients). Age as a continuous variable was associated with the presence of adenomas (incidence rate ratio 1.06; 95% CI 1.03-1.09; p0.001). EoCRC arose in most cases in the rectum (13/27, 48.1%). Age ≥40 was the main risk factor (OR 2.25; 95% CI 1.35-3.73; p=0.002) for both adenomas (160/196 patients, 81.6%) and eoCRC (20/27 patients, 74.1%), while smoking seemed to have no role (p=0.772). The presence of alarm symptoms was statistically significant at bivariable analysis for eoCRC only (OR 3.70; 95% CI 1.49-9.22; p=0.005), as well as having multiple gastrointestinal symptoms (OR 19.85; 95% CI 2.64-149.42; p=0.004). Only 3/27 (11.1%) patients with eoCRC had a family history for CRC Conclusions: A high cumulative incidence rate of both adenomas and eoCRC was found, this latter occurring more common in patients aged 40-49, without apparent risk factors. The presence of alarm symptoms or multiple gastrointestinal symptoms led to a late diagnosis.

Purpose In DR mammography, comparison of the Entrance Skin Dose (ESD) and the Average Glandular Dose (AGD) data provided by the structured dose report (SR) with the measures performed on phantom and on patient. Methods Two identical mammography systems, Amulet (Fujifilm), working in AEC with W/Rh spectrum and voltage range of 26–32 kV, were taken into account. For a PMMA phantom (18 × 24 cm2, thickness of 20–70 mm) and for a sample of 21 patients, both ESD and AGD were estimated. The X-ray output was measured, while Compressed Breast Thickness (CBT), age, tube loading and voltage were taken from the SR. The analysed images are 83, grouped by patient age and CBT. The backscatter factor for the ESD is 1.08. The AGD was estimated according to the “European guidelines for quality assurance in breast cancer screening and diagnosis” (2006 and updates) [1] . In the phantom case, the breast equivalent thickness was considered. In the patient case, the average output of the two systems was used. Results The table summarises estimated mean, SD and average percentage difference between SR and estimated values for ESD and AGD by patient age and CBT. In the graph, the percentage differences are reported as a function of CBT for both PMMA and patients. In the latter case, the data were separated by age range. Conclusions Both PMMA and patient ESD from the SR are an overestimation of the calculated value of at least 20% for all the CBT considered. Percentage differences of AGD are comprised within ±15% for CBT greater than 40 mm, while for smaller thicknesses an overestimation results in the range of 15%-25%. The split of the patient AGD curve may come from the mammography systems, which may not consider the patient age in the dose calculation (hypothesis to verify with the systems producer). Download : Download high-res image (161KB) Download : Download full-size image

To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD).A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated.All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/10(5) cells) than in non-refractory (HCMV 0 and EBV 6 copies/10(5) cells; P0.05 and0.001) IBD patients and controls (HCMV and EBV 0 copies/10(5) cells; P0.001 for both). Refractory patients showed DNA peak values ≥ 10(3) copies/10(5) cells in diseased mucosa in comparison to non-diseased mucosa (P0.0121 for HCMV and0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications.Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specimens.

Pheochromocytomas are adrenal medullary tumors which arise from the transformation of neural crest-derived cells. In the course of studies of mice transgenic for an SV40 T-gene ectopically expressed in the adrenal medulla, we observed the occurrence of large, mainly bilateral tumors in a high proportion of transgenic animals. From these tumors we established immortalized cell lines which grow in vitro at 32 degrees C (the permissive temperature for the tsA58 T-protein encoded by the transgene), but not at 38 C. These cells demonstrate characteristics of both neuronal (160 kd neurofilament) and endocrine (chromogranins) cells. The expression of Mash-1 and ret supports their initial characterization as early bipotential neuro-endocrine progenitors.

The transcription factor GATA-1 is required for the normal development of erythroid cells. GATA-1 is also expressed in other hemopoietic cells, suggesting that it might be initially activated in a multipotent progenitor. To immortalize GATA-1-expressing progenitors, we generated mice transgenic for a thermosensitive SV40 T gene, driven by the GATA-1 promoter-enhancer. Immortalized marrow cells grow in culture at 32 degrees C but not at 38 degrees C, and are dependent on erythropoietin (Epo) or interleukin 3 (IL-3). Epo dependent cells express hemoglobin, high levels of GATA-1, GATA-2 and NF-E2 p45 mRNAs, and are positive for stem cell antigen 2 (Sca-2) and the early myeloid marker ER-MP12. IL-3 dependent cells can be derived from Epo dependent lines, and are hemoglobin-, Sca-2- and ER-MP12-negative, have low GATA-1 and NF-E2 p45 mRNA levels, and express myeloid markers Mac-1, F4/80 and Gr-1. Brief treatment of Epo dependent cells with myeloid growth factors (plus Epo) leads to the induction of Mac-1, F4/80 and Gr-1, concomitant with the disappearance from most cells of Sca-2, ER-MP12 and GATA-1 driven T antigen nuclear expression. Thus, the immortalized Epo dependent cells have the property of a progenitor capable of differentiation towards either the erythroid or myeloid lineages. These cells initiate transcription of a proportion of GATA-1 RNA molecules at an upstream promoter, previously known to be expressed only in testis cells.

A new calibration method for an amorphous silicon (a-Si) electronic portal imaging device (EPID) used for dose measurements in pretreatment verification (field-related) of intensity-modulated radiation therapy (IMRT) with sliding-window technique. The method is independent of data contained in the multileaf collimator (MLC) leaf-motion files and of any calculations made by the treatment planning system (TPS).Sensitivity of the EPID is dependent on radiation energy. For fluence-modulated fields, different dose/reading calibration factors are associated with each pixel of the image acquired by calculating equivalent areas representing the exact ratio between primary and scatter components. The dose measured in the detector plane was compared with that calculated with TPS by using gamma-analysis. Each calibration factor was compared with that calculated by considering the individual contributions of primary and secondary radiation obtained using the convolution method with analytical kernel for homogeneous media.In 837/854 (98%) of the clinical fields analysed, the proportion of irradiated area in which the gamma-index was1.0 exceeded 95%. The overall average gamma-index was 0.39. There was good agreement between the dose/reading calibration factors obtained with the empirical algorithm and with the convolution method.The proposed calibration method is suitable for routine clinical pretreatment verification in IMRT.

On the basis of the encouraging results achieved in several clinical trials and its proven therapeutic efficacy, 153Sm-ethylene diamine tetramethylene phosphonic acid (EDTMP) has become widely used to palliate pain from bone metastases. The results reported in the literature have led the product suppliers (QUADRAMET®, Schering) to suggest administering a fixed activity per kilogram (37 MBq/kg). However, considering the observed extreme inter-patient variability of skeletal uptake of 153Sm-EDTMP, a real therapy optimization would require the individualization of the activity to be administered on a dosimetric basis. This should be planned taking into account the generally accepted 2-Gy dose constraint to the haematopoietic red marrow, the critical organ in palliative treatments with beta-emitting, bone-seeking radiopharmaceuticals. Seven to 14 days before treatment with 153Sm-EDTMP, 44 patients underwent 99mTc-methylene diphosphonate (MDP) total-body bone scan with two scans (the first within 10 min of injection, the second after 6 h). The percentage bone uptake (Tc%) was evaluated as the ratio between total counts at 6 h, adjusted for decay, and total counts at the first scan. Tc% was then compared to Sm% similarly derived from 10-min and 24-h whole-body scans. Tc% and Sm% were compared both with and without Brenner’s method for soft tissue uptake. The correlation between Tc% and Sm% was R 2 = 0.81 and R 2 = 0.88 with and without soft tissue correction, respectively. The difference between their average values was statistically significant (Sm% = 64.3 ± 15.2, Tc% = 56.2 ± 16.0; p = 0.017) with soft tissue correction, while was not statistically significant (Sm% = 68.2 ± 15.5, Tc% = 66.9 ± 14.0; p = 0.670) without soft tissue correction. The rate of retention of 99mTc-MDP in bone provides a reliable estimate of the 153Sm-EDTMP rate of retention. The proposed method can be usefully adopted for prospective dosimetry seeing its extreme simplicity, and it requires no special investment in terms of human or instrumental resources. This allows an optimization of administered 153Sm-EDTMP activity.

International audience; The influx of calcium into the postsynaptic neuron is likely to be an important event in memory formation. Among the mechanisms that nerve cells may use to alter the time course or size of a spike of intracellular calcium are cytosolic calcium binding or "buffering" proteins. To consider the role in memory formation of one of these proteins, calbindin D28K, which is abundant in many neurons, including the CA1 pyramidal cells of the hippocampus, transgenic mice deficient in calbindin D28K have been created. These mice show selective impairments in spatial learning paradigms and fail to maintain long-term potentiation. These results suggest a role for calbindin D28K protein in temporally extending a neuronal calcium signal, allowing the activation of calcium-dependent intracellular signaling pathways underlying memory function.

We have attempted to produce a transgenic mouse model of the neonatal liver disease associated with the human PIZ allele. Analysis of a number of transgenic mouse lines carrying either a normal human PIM gene construct or the mutant Z is reported. Using isoelectric focusing analysis of plasma from transgenic mice, we have shown that the human AAT proteins produced in mice are processed in a similar way to their counterparts in humans. By comparing the level of M and Z mRNA in liver with the levels of M and Z proteins in plasma we have inferred that, as in humans, the mutant protein tends to accumulate within the hepatocyte. Accumulation of Z protein has also been demonstrated by immunocytochemistry. Two of the M transgenic lines produce such high levels of the human protein that it, like the Z protein, accumulates as globules. Histological features of livers from 116 mice of different ages and genotypes were examined: 37 non-transgenic, 62 Z transgenic (23 low expressing and 39 high expressing) and 17 M transgenic mice, all high expressing. Cirrhosis or fibrosis was not seen in any animal and we were unable to find any evidence for neonatal liver disease. Some necrosis was seen in all genotypes and this increased significantly with age with one Z line showing significantly more frequent necrosis than any other group. This line, the highest expressing Z line, was back crossed onto 7 different genetic backgrounds but no major differences between the back crosses with respect to liver disease were observed. The mouse model we have developed is compared with other transgenic Z mouse models; none of these is representative of human neonatal liver disease. Our view is that the transgenic animals generated in these experiments may be most useful for investigating the liver manifestations that almost invariably occur in ZZ adults. Alteration of additional factors other than accumulation of Z protein, for example inactivation of the endogenous mouse genes or some environmental challenge, might produce a mouse model with more relevance to neonatal liver disease.