Analyzing Survival Rate of Leukemia Patients Applying Long Term Exponential Model

Background: Making progressin treatment of all branches of cancers has increasedthe percent of patients that never experience the event of interest. These cases are called immune or cure and models for handling the data included cure fraction rate, are referred to as cure model or long-term survival models. Methods:The data for this historical cohort study, were collected from leukemia patients diagnosed between 2007 to 2014 and followed up until 2016 in Taleghani hospital and received BMT (Bone Marrow Transplant). Some data had to be excluded because of incomplete information. Using recorded files mostly and phone calls rarely, were made to confirm whether the patients were still alive or not. Death due to leukemia was regarded as interested event. Analysis were performed by R version 3.4.1and Stata version 14. Results: Number of recurrents after receiving BMT, pre-transplant Hb and age at diagnosis were found as significant prognostics of survival time. HD patients had the highest 5-years overall survival in category of diagnosis type with 81.3%. Cure fraction was estimated to be 64.1%. Conclusion: According to high percentage of censoring, using long-term model had better fit.     

Prognostic factors in patients with active non-variceal upper gastrointestinal bleeding

Background and study aims

Acute upper gastrointestinal bleeding is one of the main causes of hospitalisation. The purpose of this study was to determine the prognostic factors in non-variceal upper gastrointestinal bleeding.

Three-year efficacy and patency follow-up of decellularized human internal mammary artery as a novel vascular graft in animal models

Background

Various investigations have reported that the internal mammary artery (IMA) is an efficient and functional choice of conduit for vascular graft surgeries, especially for coronary artery bypass grafts; however, the quest to find an ideal vascular substitute remains. We hypothesized that acellular IMA could be an appropriate graft for small-diameter vascular bypasses that could be used in various surgeries including coronary artery bypass grafting.

Cognitive rehabilitation for individuals with opioid use disorder: A randomized controlled trial*

Aim: To examine the efficacy of cognitive rehabilitation treatment (CRT) for people with opioid use disorder who were recruited into a methadone maintenance treatment (MMT) programme.

Method: 120 male subjects were randomly assigned to (1) MMT plus CRT in two months or (2) MMT plus a control intervention. Subjects were assessed at the beginning, mid-point and post-intervention as well as at 1-, 3- and 6-month follow-up time points.

Results: Analysis with repeated measure ANOVA showed that the CRT group performed significantly better in tests of learning, switching, processing speed, working memory and memory span. Moreover, the CRT group had significantly lower opiate use over the control group during 3-months follow-up. Analysis including only those with a history of methamphetamine use showed that the CRT group had significantly lower amphetamine use. No group differences were observed for treatment retention.

Conclusions: Our findings provide evidence that adding CRT as an adjunct intervention to MMT can improve cognitive performance as well as abstinence from both opiates and stimulants.     

Sex and smoking differences in the association between gastroesophageal reflux and risk of esophageal squamous cell carcinoma in a high-incidence area: Golestan Cohort Study

Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in-person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66-1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post-hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27-0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08-0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.     

Dual nature of human ACE2 glycosylation in binding to SARS-CoV-2 spike

Binding of the spike protein of SARS-CoV-2 to the human angiotensin-converting enzyme 2 (ACE2) receptor triggers translocation of the virus into cells. Both the ACE2 receptor and the spike protein are heavily glycosylated, including at sites near their binding interface. We built fully glycosylated models of the ACE2 receptor bound to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Using atomistic molecular dynamics (MD) simulations, we found that the glycosylation of the human ACE2 receptor contributes substantially to the binding of the virus. Interestingly, the glycans at two glycosylation sites, N90 and N322, have opposite effects on spike protein binding. The glycan at the N90 site partly covers the binding interface of the spike RBD. Therefore, this glycan can interfere with the binding of the spike protein and protect against docking of the virus to the cell. By contrast, the glycan at the N322 site interacts tightly with the RBD of the ACE2-bound spike protein and strengthens the complex. Remarkably, the N322 glycan binds to a conserved region of the spike protein identified previously as a cryptic epitope for a neutralizing antibody. By mapping the glycan binding sites, our MD simulations aid in the targeted development of neutralizing antibodies and SARS-CoV-2 fusion inhibitors.

Angiotensin-converting enzyme 2 (ACE2) is an enzyme that catalyzes the hydrolysis of angiotensin II into angiotensin (1–7) to counterbalance the ACE receptor in blood pressure control (1). A single transmembrane helix anchors ACE2 into the plasma membrane of cells in the lungs, arteries, heart, kidney, and intestines (2). The vasodilatory effect of ACE2 has made it a promising target for drugs treating cardiovascular diseases (3).ACE2 also serves as the entry point for several coronaviruses into cells, including SARS-CoV and SARS-CoV-2 (4–6). The binding of the spike protein of SARS-CoV and SARS-CoV-2 to the peptidase domain (PD) of ACE2 triggers endocytosis and translocation of both the virus and the ACE2 receptor into endosomes within cells (4). The human transmembrane serine protease 2, TMPRSS2, primes spike for efficient cell entry by cleaving its backbone at the boundary between the S1 and S2 subunits or within the S2 subunit (4). The structure of the ACE2 receptor in complex with the SARS-CoV-2 spike receptor binding domain (RBD) (7–9) reveals the major RBD interaction regions as helix H1 (Q24–Q42), a loop in a beta sheet (K353–R357), and the end of helix H2 (L79–Y83). With a 4-Å heavy-atom distance cutoff, 20 residues of ACE2 interact with 17 residues of the RBD, forming a buried interface of ∼1,700 Ų (7).The structure of full-length ACE2 has been resolved in complex with B⁰AT1 (also known as SLC6A19) (9). B⁰AT1 is a sodium-dependent neutral amino acid transporter (10). ACE2 functions as chaperone for B⁰AT1 and is responsible for its trafficking to the plasma membrane of kidney and intestine epithelial cells (11). Although it was speculated that B⁰AT1 prevents ACE2 cleavage by TMPRSS2 and thus could suppress SARS-CoV-2 infection (9, 12), other studies showed that SARS-CoV-2 can infect human small intestinal enterocytes where ACE2 is expected to be in complex with B⁰AT1 (13).Both the ACE2 receptor and the spike protein are heavily glycosylated. Several glycosylation sites are near the binding interface (7, 9, 14, 15). Whereas the focus has largely been on amino acid interactions in the ACE2–spike binding interface (16, 17), the role of glycosylation in binding has been recognized (7, 18–20). The extracellular domain of the ACE2 receptor has seven N-glycosylation sites (N53, N90, N103, N322, N432, N546, and N690) and several O-glycosylation sites (e.g., T730) (9, 14). Among ACE2 glycosylation sites, the only well-characterized position regarding the effect on the spike binding and viral infectivity is N90. It is known from earlier SARS-CoV studies that glycosylation at the N90 position might interfere with virus binding and infectivity (21). Also, recent genetic and biochemical studies showed that mutations of N90, which remove the glycosylation site directly, or of T92, which remove the glycosylation site indirectly by eliminating the glycosylation motif (NXT), increase the susceptibility to SARS-CoV-2 infection (22, 23).We use extensive molecular dynamics (MD) simulations to gain a detailed molecular-level understanding of how ACE2 glycosylation impacts the host–virus interactions. Glycosylation sites N90 and N322 of human ACE2 emerge as major determinants of its binding to SARS-CoV-2 spike. Remarkably, glycans at these sites have opposite effects, interfering with spike binding in one case, and strengthening binding in the other. Our findings provide direct guidance for the design of targeted antibodies and therapeutic inhibitors of viral entry.     

Resuming Breast Imaging Services in the Aftermath of the COVID-19 Pandemic: Safety and Beyond

As the Coronavirus disease 2019 (COVID-19) epidemic begins to stabilize, different medical imaging facilities not directly involved in the COVID-19 epidemic face the dilemma of how to return to regular operation. We hereby discuss various fields of concern in resuming breast imaging services. We examine the concerns for resuming functions of breast imaging services in 2 broad categories, including safety aspects of operating a breast clinic and addressing potential modifications needed in managing common clinical scenarios in the COVID-19 aftermath. Using a stepwise approach in harmony with the relative states of the epidemic, health care system capacity, and the current state of performing breast surgeries (and in compliance with the recommended surgical guidelines) can ensure avoiding pointless procedures and ensure a smooth transition to a fully operational breast imaging facility.