Comparison between open and laparoscopic technique in the management of perforated gastroduodenal ulcers

GOALS: The aim of this study was to evaluate our results of laparoscopic treatment of perforated gastroduodenal ulcers during a 5-year period and to compare the outcome of open and laparoscopic surgery. BACKGROUND: The value of laparoscopic treatment of gastroduodenal ulcers is still controversially debated because its superiority to conventional open surgery has not been established. STUDY: From January 1996 to December 2001, 24 patients were treated laparoscopically and 31 patients underwent conventional open suture repair. The results of these patients were retrospectively reviewed. RESULTS: There were 55 patients with a mean age of 55 years (range 18-92 years) who were eligible for the study. Patients with laparoscopic repair had a lower mean ASA score (2 vs. 2.9; P = 0.02) and a less severe Mannheimer peritonitis index (16.5 vs. 21; P = 0.00001) compared with patients with open repair. Three patients who were begun by the laparoscopic approach had to be converted to open surgery (12.5%). Three patients who underwent open repair died postoperatively (5.5%). There was no difference between treatment groups regarding operative time, morbidity, or postoperative hospital stay. The laparoscopic group required significantly fewer analgesics postoperatively (2.2 vs. 4 dosages; P = 0.04). CONCLUSIONS: Laparoscopic treatment of perforated gastroduodenal ulcers is an effective treatment option and should be considered in suited patients for the initial approach.     

Characterization of brain natriuretic peptide in long-term follow-up of pulmonary arterial hypertension

STUDY OBJECTIVES: Pulmonary arterial hypertension (PAH) leads to substantial morbidity and mortality. Noninvasive parameters in the follow-up assessment of PAH could be helpful in clinical decision making. The brain natriuretic peptide (BNP) has been shown to correlate with the functional status and prognosis of these patients and could be a valuable parameter in this respect. The aim of our study was to investigate whether BNP levels could reflect clinical and hemodynamic changes, including the response to therapy during long-term follow-up in patients with PAH. STUDY DESIGN: We measured pulmonary hemodynamics, functional parameters including the 6-min walk distance (6MWD), and plasma BNP levels at baseline and after a mean (+/- SEM) follow-up period of 12.6 +/- 1.5 months in patients with PAH. RESULTS: In group A (n = 18), with decreasing BNP levels mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) decreased (PAP, 60.89 +/- 3.44 to 53.47 +/- 3.24 mm Hg; PVR, 1,207.47 +/- 111.75 to 942.35 +/- 103.15 dyne.s.cm(-5); p < 0.01) and 6MWD increased (408.24 +/- 29.57 to 470 +/- 25.54 m; p < 0.01). In group B (n = 12), with increasing BNP levels mean PAP and PVR increased (PAP, 52 +/- 3.31 to 60.17 +/- 5.03 mm Hg; PVR, 946.13 +/- 115.35 to 1,236.6 +/- 180.23 dyne . s . cm(-5); p < 0.01) and mean 6MWD decreased from 463.64 +/- 27.77 to 367.27 +/- 38.87 m (p < 0.05). Comparing groups revealed statistically significant differences regarding changes in PAP (group A, -11.58 +/- 3.57%; group B, +13.29 +/- 5.44%; p = 0.001) and PVR (group A, -19.21 +/- 5.87%, group B, +30.35 +/- 7.72%; p < 0.001). Correlations existed between the changes in BNP levels and pulmonary hemodynamics. CONCLUSION: We concluded that BNP levels parallel changes in pulmonary hemodynamics and functional parameters, including the 6MWD, in PAH patients. Consequently, we suggest BNP as a parameter for the follow-up assessment of PAH patients.     

Quantitative [(123)I]FP-CIT pinhole SPECT imaging predicts striatal dopamine levels, but not number of nigral neurons in different mouse models of Parkinson's disease

Single photon emission computed tomography (SPECT) using [(123)I]FP-CIT as radioligand for the dopamine transporter has become a widely used tool to monitor the integrity of the nigrostriatal dopaminergic projection in Parkinson's disease (PD). Previous studies with pinhole SPECT in small animals have demonstrated that the striatal [(123)I]FP-CIT binding indeed correlates with the striatal dopamine transporter protein level. It is unclear, however, if there is a stable relationship between the striatal [(123)I]FP-CIT binding and other functionally important parameters of the nigrostriatal system, such as the striatal dopamine levels and the number of dopaminergic neurons in the substantia nigra. To assess this question experimentally, we studied two different mouse models of PD, namely a mild 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication paradigm, to model mild nigrostriatal damage and the intrastriatal 6-hydroxydopamine paradigm to model more advanced nigrostriatal damage. Our data demonstrate that the striatal [(123)I]FP-CIT binding measured by SPECT in vivo precisely predicts the striatal dopamine concentrations, but does not necessarily correlate with the nigral dopaminergic cell number. Thus, the present work underscores that FP-CIT SPECT does only allow judging the integrity of the striatal dopaminergic nerve terminals, but not the nigral dopaminergic cells in PD. This finding may have significant impact on the use of [(123)I]FP-CIT SPECT as a surrogate marker for clinical trials aimed at measuring neuroprotection.     

Short-echo spectroscopic imaging combined with lactate editing in a single scan

A short-echo spectroscopic imaging sequence extended with a frequency-selective multiple-quantum- coherence technique (Sel-MQC) is presented. The method enables acquisition of a complete water-suppressed proton spectrum with a short echo time and filtering of the J-coupling metabolite, lactate, from co-resonant lipids in one scan. The purpose of the study was to validate this combined pulse sequence in vitro and in vivo. Measurements on phantoms confirmed the feasibility of the method, and, for a practical in vivo application, experiments were carried out on eight tumors from two different tumor models [UT-SCC-8 (n = 4) and SAS (n = 4)]. T(1)- and T(2)-weighted metabolite and lipid ratios were calculated, and the tumors showed different values in the central and outer regions. The ratio of the lipid methylene peak area (1.30 ppm) to choline peak area (3.20 ppm) was significantly (p < 0.01) different in the central tumor area between the two models, and lactate was detected in only three out of four tumors in the SAS tumor line. The present approach of combining short-echo spectroscopic imaging and lactate editing allows the characterization of tumor-specific metabolites such as choline, lipid methylene and methyl resonances as well as lactate in a single scan.     

Euploidy in relation to blastocyst sex and morphology

Purpose

The objective of our study is to assess the relationship of embryo ploidy status in relation to embryo sex, morphological characteristics, and transfer parameters.

Methods

This is a retrospective cohort study at an academic medical center of patients who underwent in vitro fertilization with preimplantation genetic screening (PGS) from 2010 to 2015. Embryos were screened with 24-chromosome preimplantation genetic screening with day 5/6 trophectoderm biopsy. We investigated embryo euploidy in relation to morphology (expansion, inner cell mass, trophectoderm), embryo sex, biopsy day, and blastocyst cohort size. We used multivariate logistic regression to calculate odds ratios of euploidy in relation to these parameters.

Results

A total of 1559 embryos from 316 cycles and 233 patients (mean maternal age?=?37.8?±?4.2 years) were included in the analysis. Six hundred and twenty-eight blastocysts (40.3%) were found to be euploid. Expansion (p?<?0.001), inner cell mass (ICM) (p?<?0.01), and trophectoderm grade (p?<?0.001) were significantly associated with embryo ploidy in bivariate models controlling for maternal age, while embryo sex, biopsy day, and blastocyst cohort size were not associated with embryo ploidy. In a multivariate model, we found that maternal age (p?<?0.001), higher grade of expansion (p?<?0.01), and better quality trophectoderm (p?<?0.001 for A compared to C grade) remained significantly associated with increased embryo euploidy, but ICM grade was no longer significant. Embryo sex was not associated with ploidy status, though male embryos were found to be associated with higher trophectoderm scores (p?<?0.02).

Conclusions

This is the largest study to date to investigate PGS-tested embryo sex and ploidy status. While maternal age and some morphological parameters (expansion, trophectoderm grade) are associated with euploidy in our cohort, other parameters such as embryo sex, biopsy day, and cohort size are not. Though embryo sex was not associated with euploidy, male embryos were found to be associated with higher trophectoderm grades. Additional investigation in larger studies is warranted.

     

In vivo delivery of CRISPR-Cas9 therapeutics: Progress and challenges

Within less than a decade since its inception, CRISPR-Cas9-based genome editing has been rapidly advanced to human clinical trials in multiple disease areas. Although it is highly anticipated that this revolutionary technology will bring novel therapeutic modalities to many diseases by precisely manipulating cellular DNA sequences, the low efficiency of in vivo delivery must be enhanced before its therapeutic potential can be fully realized. Here we discuss the most recent progress of in vivo delivery of CRISPR-Cas9 systems, highlight innovative viral and non-viral delivery technologies, emphasize outstanding delivery challenges, and provide the most updated perspectives.KEY WORDS: CRISPR, Cas9, Genome editing therapy, LNP, Nanoparticle, AAV, Lentivirus, In vivo     

Changes in Health-Promoting Behaviors and Their Association with Weight Loss,Retention, and Engagement on a Digital Program: Prospective Study

Health-promoting lifestyle behaviors (e.g., as measured by the HPLP-II) are associated with reductions in lifestyle disease mortality, as well as improved well-being, mental health, and quality of life. However, it is unclear how a weight-management program relates to a broad range of these behaviors (i.e., health responsibility, physical activity, nutrition, spiritual growth, interpersonal relations, and stress management), especially a fully digital program on which individuals have to self-manage their own behaviors in their daily lives (with assistance from a virtual human coach). In the context of a digital setting, this study examined the changes in health-promoting behaviors over 12 months, as well as the associations between health-promoting behaviors and weight loss, retention, and engagement, among participants who self-enrolled in a mobile CBT-based nutritionally focused behavior change weight management program (n = 242). Participants lost a statistically significant amount of weight (M = 6.7 kg; SD = 12.7 kg; t(80) = 9.26, p < 0.001) and reported significantly improved overall health-promoting lifestyle behaviors (i.e., HPLP-II summary scores), as well as, specifically, health responsibility, physical activity, nutrition, spiritual growth, stress management, and interpersonal relations behaviors from baseline to 6 months and from 6 months to 12 months (all ps < 0.008). Health-promoting behaviors at 6 months (i.e., learned health-promoting behaviors) compared to baseline were better predictors of retention and program engagement. A fully digital, mobile weight management intervention can improve HPLP-II scores, which, in turn, has implications for improved retention, program engagement, and better understanding the comprehensive effects of weight management programs, particularly in a digital setting.