The changing face of chronic autoimmune atrophic gastritis: an updated comprehensive perspective

Chronic autoimmune atrophic gastritis (CAAG) is an organ-specific autoimmune disease, which affects the corpus–fundus gastric mucosa. Although it has been described for several years, the real pathophysiological mechanisms, the natural history and the possible neoplastic complications are not completely known. Atrophy of the gastric mucosa is the endpoint of the chronic processes, with the loss of glandular cells and their replacement by intestinal-type epithelium, pyloric-type glands, and fibrous tissue. As a consequence, hydrochloric acid, pepsin and intrinsic-factor is impaired resulting in pernicious anemia. The exact causal agent is not yet known, but both genetic and environmental factors seem to play a decisive role.Moreover, the clinical onset may assume different characteristics; differently from what previously observed, recent evidence has reported the onset of CAAG at a younger age, frequently with iron deficiency anemia or upper gastro-intestinal symptoms.The diagnosis of CAAG might be challenging and usually requires the combination of clinical, serological and histopathologic data; moreover, CAAG patients are often misdiagnosed as refractory to HP eradication therapy, probably because achlorhydria might allow urease-positive bacteria other than H pylori to colonize the stomach, causing positive ¹³C-urea breath test results.However, biopsy is the most reliable method to evaluate the presence of metaplastic atrophic gastritis. In order to assess the severity of gastric atrophy and intestinal metaplasia, OLGA and OLGIM staging systems have been proposed and seem to correlate with the risk of developing gastric adenocarcinoma. Indeed, CAAG represents a pre-neoplastic condition, as patients with CAAG are very likely to develop either type-1 gastric neuroendocrine tumors and gastric adenocarcinomas, as well as several other neoplastic diseases. To date, the need, the intervals and cost-effectiveness of endoscopic/histological surveillance for patients with CAAG/pernicious anemia are yet to be established.     

The SLC6A3 3′-UTR VNTR and intron 8 VNTR polymorphisms association in the time estimation

Objective

The present study investigated the association of 3′-UTR VNTR and intron 8 VNTR polymorphisms with a time estimation task performance.

Materials and methods

One hundred and eight men in a Brazilian Northeast population (18–32 years old) participated in the experiment. The 3′-UTR VNTR and intron 8 VNTR polymorphisms were associated alone and combined to absolute error (AE) and relative error (RE) in a time estimation task (target duration: 1 s, 4 s, 7 s and 9 s).

Results

We found an association of the behavioral variable with intron 8 VNTR for the time intervals of 1 s and 9 s (p < 0.001) and polymorphisms combinatorial effect for 1 s (p ≤ 0.05).

Conclusion

The intron 8 VNTR polymorphism and the combinatorial effect can modulate the time estimate in the domain of supra seconds, and thus our study indicates a role of the dopamine transporter in the neurobiological areas related to the time intervals judgment.

     

Severe Herpes Zoster Requiring Intravenous Antiviral Treatment in Allogeneic Hematopoietic Cell Transplantation Recipients on Standard Acyclovir Prophylaxis

Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. The incidence, timing, and risk factors for severe herpes zoster (HZ) are not well described in the era of acyclovir (ACV) prophylaxis. We performed a retrospective cohort study of all patients who underwent first allogeneic HCT between October 2006 and December 2015 at our institution. Patients were followed until December 2017 for the development of severe HZ, defined as necessitating administration of i.v. antiviral medication. Out of 2163 patients who underwent allogeneic HCT, 22 (1.0%) developed severe HZ at a rate of 1 per 228 person-years, including dermatomal/multidermatomal disease (n = 5), disseminated skin disease (n = 5), HZ ophthalmicus (n = 4), meningitis/encephalitis (n = 4), pneumonia (n = 2), viremia (n = 1), and erythema multiforme (n = 1). Severe HZ infection occurred in a bimodal distribution during the early peri-HCT period and at 12 to 24 months post-HCT (median, 12.7 months). Twelve patients (54.5%) were compliant with ACV prophylaxis at the time of HZ diagnosis. Eleven patients (50%) died during the study period, only 2 of whom (9.1%) with active VZV infection. Mortality was higher in patients on immunosuppressive therapy (62.5% versus 16.7%; P = .045) and with concurrent graft-versus-host disease (75.0% versus 35.7%; P= .044). These data suggest that severe HZ remains an important consideration despite ACV prophylaxis.     

Who Is a Better Donor for Recipients of Allogeneic Hematopoietic Cell Transplantation: A Young HLA-Mismatched Haploidentical Relative or an Older Fully HLA-Matched Sibling or Unrelated Donor?

T cell replete HLA-mismatched haploidentical transplantation (HIDT) with post-transplant cyclophosphamide is increasingly becoming an acceptable treatment approach for patients lacking timely access to a suitably matched related donor transplant (MRDT) or matched unrelated donor transplant (MUDT). Multiple recent registry and single-center studies have shown comparable overall survival (OS) and disease-free survival (DFS) rates among HIDT, MRDT, and MUDT with a significantly lower risk of acute and chronic graft-versus-host disease (GVHD) among HIDT recipients. Candidates for allogeneic hematopoietic stem cell transplantation (HSCT) often have access to multiple donor sources, and a relevant question is whether outcomes can be improved with a younger HLA-mismatched haploidentical donor (≤35 years) rather than an older matched related donor (≥35 years) or matched unrelated donor (≥35 years). We analyzed 406 consecutive allogenic HSCT recipients, with a median age of 54 years (range, 19 to 77), after a MRDT with a donor age of ≥35 years (n = 222), MUDT with a donor age of ≥35 years (n = 91), and HIDT with a donor age of ≤35 years (n = 93). Median follow-up time for survivors was 51.5 months. Compared with MRDT and MUDT, HIDT recipients had a similar median age at time of HSCT, hematopoietic cell transplant comorbidity index, disease risk index distribution, and donor recipient sex matching. The survival estimates and relapse incidence at 3 years post-HSCT were OS (64% for MRDT, 54% for MUDT, and 62% for HIDT), DFS (55% for MRDT, 44% for MUDT, and 58% for HIDT), Transplant related mortality (TRM) (19% for MRDT, 16% for MUDT, and 18% for HIDT), and relapse (26% for MRDT, 37% for MUDT, and 24% for HIDT). HIDT recipients had better 3-year relapse rates compared with MUDT recipients (24% versus 37%, P= .048), with similar DFS and OS in a univariate analysis. MRDT recipients had a better relapse rate (26% versus 37%, P = .042) compared with MUDT recipients. Recipients of HIDT also had significantly lower rates of moderate to severe chronic GVHD compared with MRDT and MUDT recipients (P = .01). Multivariable analysis showed no effect of donor on OS, DFS, relapse, and TRM. Recipients of HIDT from a young donor ≤35 years had similar OS, lower rates of chronic GVHD, and better chronic GVHD-free, relapse-free survival compared with patients undergoing transplantation with an MRD or a MUD donor ≥35 years. This study suggests that given a situation where a choice between a young haploidentical relative and an older matched unrelated donor is to be made, one can achieve similar survival with a haploidentical donor and significantly lower rates of chronic GVHD.