Outcomes of a bladder preservation technique in female patients undergoing pelvic exenteration surgery for advanced gynaecological tumours

Introduction and hypothesis

The purpose of the study was to report the feasibility of the bladder preservation technique (BPT) during pelvic exenteration for primary advanced gynaecological pelvic tumours (PRSGT) as an alternative for continent urinary diversion.

Methods

Sixteen consecutive female patients underwent BPT during PRSGT. Median age was 50.8 years (range 37–65). Tumours included cervical (5 patients), corpus/vaginal (9), and ovarian (2) carcinomas. In resectable tumours, the excision of the distal ureters and the posterior bladder wall with an inverted “V” incision into the trigone down to the vaginal wall was performed with bladder blood and nerve supply preservation. The remaining mobilized leaflets were fixed to the psoas muscle/sacral promontory. Average follow-up was 34 months (range 24–108). Follow-up parameters included postoperative continence grade (full [no pads], stress incontinence grade I [1–2 pads], and grade II [>2 pads]), urinary tract infections, micturation problems/residual urine, ureteric reflux as well as patients’ global satisfaction (PGS).

Results

All surgeries were done successfully. One patient developed a vesicovaginal fistula 4 weeks postoperatively and was managed conservatively. Fifteen patients (94 %) were able to empty their bladders postoperatively. Prolonged full continence was reported from 8 patients (50 %), incontinence grade I in 3 (18.8 %), and grade II in 5 (31.3 %). Two patients (incontinence grade II) developed cystoceles necessitating transvaginal bladder neck suspension with a fascia lata sling and were continent postoperatively. Another patient (6 %) underwent re-excision of a recurrent pelvic tumour necessitating intermittent self-catheterization. Postoperative hydronephrosis (grade I–II) was observed in 4 patients (25 %) and vesico-ureteral reflux (grade IV) in 4 (25 %) without the need for intervention. PGS and willingness to recommend their procedure to others were favourable.

Conclusions

In patients for whom complete bladder resection is not indicated for oncological reasons, BPT during PRSGT with ureteric reimplantation is feasible and safe and provides good functional results as well as patient global satisfaction. Lower tract surgeries could be safely carried out afterward. Long-term functional results support durable good PGS.     

Genetic basis of neurodevelopmental disorders in 103 Jordanian families

We recruited 103 families from Jordan with neurodevelopmental disorders (NDD) and patterns of inheritance mostly suggestive of autosomal recessive inheritance. In each family, we investigated at least one affected individual using exome sequencing and an in-house diagnostic variant interpretation pipeline including a search for copy number variation. This approach led us to identify the likely molecular defect in established disease genes in 37 families. We could identify 25 pathogenic nonsense and 11 missense variants as well as 3 pathogenic copy number variants and 1 repeat expansion. Notably, 11 of the disease-causal variants occurred de novo. In addition, we prioritized a homozygous frameshift variant in PUS3 in two sisters with intellectual disability. To our knowledge, PUS3 has been postulated only recently as a candidate disease gene for intellectual disability in a single family with three affected siblings. Our findings provide additional evidence to establish loss of PUS3 function as a cause of intellectual disability.     

The influence of physiological matrix conditions on permanent culture of induced pluripotent stem cell-derived cardiomyocytes

Cardiomyocytes (CMs) from induced pluripotent stem (iPS) cells mark an important achievement in the development of in vitro pharmacological, toxicological and developmental assays and in the establishment of protocols for cardiac cell replacement therapy. Using CMs generated from murine embryonic stem cells and iPS cells we found increased cell–matrix interaction and more matured embryoid body (EB) structures in iPS cell-derived EBs. However, neither suspension-culture in form of purified cardiac clusters nor adherence-culture on traditional cell culture plastic allowed for extended culture of CMs. CMs grown for five weeks on polystyrene exhibit signs of massive mechanical stress as indicated by α-smooth muscle actin expression and loss of sarcomere integrity. Hydrogels from polyacrylamide allow adapting of the matrix stiffness to that of cardiac tissue. We were able to eliminate the bottleneck of low cell adhesion using 2,5-Dioxopyrrolidin-1-yl-6-acrylamidohexanoate as a crosslinker to immobilize matrix proteins on the gels surface. Finally we present an easy method to generate polyacrylamide gels with a physiological Young's modulus of 55 kPa and defined surface ligand, facilitating the culture of murine and human iPS-CMs, removing excess mechanical stresses and reducing the risk of tissue culture artifacts exerted by stiff substrates.     

Comparative characteristics of endothelial-like cells derived from human adipose mesenchymal stem cells and umbilical cord blood-derived endothelial cells

Adult peripheral blood contains a limited number of endothelial progenitor cells that can be isolated for treatment of ischemic diseases. The adipose tissue became an interesting source of stem cells for regenerative medicine. This study aimed to investigate the phenotype of cells obtained by culturing adipose-derived mesenchymal stem cells (ad-MSCs) in the presence of endothelial growth supplements compared to endothelial cells obtained from umbilical cord blood (UCB). Passage 3 ad-MSCs and mononuclear layer from UCB were cultured in presence of endothelial growth media for 3 weeks followed by their characterization by flow cytometry and polymerase chain reaction. After culture in endothelial inductive media, ad-MSCs expressed endothelial genes and some endothelial marker proteins as CD31 and CD34, respectively. Adipose tissue could be a reliable source for easy obtaining, expanding and differentiating MSCs into endothelial-like cells for autologous cell-based therapy.     

Acute-phase proteins and oxidative stress biomarkers in water buffalo calves subjected to transportation stress

The objective of the present study was to determine the effect of the transportation stress on water buffalo calves. A total of 50 buffalo calves (8?±?1 months old, 165?±?13 kg) were assigned to one of two equal groups; the first group represented clinically healthy non-transported calves (control non-transported group; n?=?25) whereas calves of the second group were subjected to transportation (transported group; n?=?25). Blood samples were collected from control non-transported calves and from transported calves immediately after unloading (post-transportation). The present findings indicated that the examined hematological and biochemical parameters were not significantly (P?≤?0.05) changed in transported calves when compared with the control non-transported group. Furthermore, serum concentration of the investigated acute-phase proteins (APP) namely, haptoglobin (0.37?±?0.01), serum amyloid A (75.43?±?2.11), and fibrinogen (7.51?±?0.25) were significantly (P?≤?0.05) higher in transported calves when compared with control calves (0.1?±?0.01 g/l, 23.9?±?0.56 mg/l, and 4.2?±?0.16 g/l), respectively. Lipid peroxidation represented as malonaldhyde (56.78?±?3.42) was higher significantly (P?≤?0.05), whereas antioxidant biomarkers in the form of nitric oxide (17.68?±?0.89) levels, and activities of superoxide dismutase (7.37?±?0.53) and reduced glutathione (5.25?±?0.95) were lower significantly (P?≤?0.05) in the serum of transported calves when all were compared with the control group (24.68?±?0.19 nmol/g Hb, 21.80?±?0.24 mmol/ml, 9.24?±?0.1 U/g Hb, and 7.23?±?0.21 mmol/l), respectively. Conclusively, the present study demonstrated that transportation were significantly enough to trigger changes in APP and oxidative stress biomarkers in buffalo calves.     

Synthesis of new oxadiazol-phthalazinone derivatives with anti-proliferative activity; molecular docking,pro-apoptotic,and enzyme inhibition profile

Background and aim: The current study reports the synthesis and biological evaluation of two novel series of 4-(5-mercapto-1,3,4-oxadiazol-2-yl)phthalazin-1(2H)-one derivatives. Methods: The synthetic reactions were carried out under both conventional and ultrasonic irradiation conditions. The anti-proliferative activity of the newly synthesized compounds against two human epithelial cell lines; liver (HepG2) and breast (MCF-7) in addition to normal fibroblasts (WI-38) was investigated. In addition to molecular docking studies, the possible mechanism(s) of action were also explored. Results: In general, an improvement in synthetic rates and yields was observed when reactions were carried out under sonication compared with classical conditions. The structures of the products were established based on analytical and spectral data. Derivatives 2e and 7d, in addition to compound 1, had significant and selective anti-proliferative activity against liver and breast cancer cell lines without harming normal fibroblasts. These derivatives arrested the cell cycle progression and/or induced apoptosis. This has been manifested by the elevation in the expression of p53 and caspase 3, down-regulation of cdk1, and a reduction in the concentrations of MAPK and Topo II at submicromolar concentrations. The latter results confirmed the molecular docking study. Conclusions: Compound 1 had the best profile on the gene and protein levels (arresting cell cycle and inducing apoptosis). The ability of compounds 1 and 2e to inhibit both MAPK and Topo II nominates these derivatives as potential candidates for further anticancer and antitumor studies.

The current study reports the synthesis and biological evaluation of two novel series of 4-(5-mercapto-1,3,4-oxadiazol-2-yl)phthalazin-1(2H)-one derivatives.     

Flow cytometric DNA analysis of fresh prostatic resections: Correlation with conventional prognostic parameters in patients with prostate cancer

Background. DNA ploidy analysis has been investigated as a prognostic indicator in prostate cancer. Most of the data is derived from retrospective studies using paraffin-embedded tissue. This method has drawbacks related to the quality of DNA histograms and uncontrolled data collection. Methods. DNA ploidy analysis of freshly resected prostatic tissue was prospectively compared with conventional prognostic variables in 97 men treated with radical prostatectomy for localized prostate cancer. Results. Regarding the patients, 31.9% were African American and 66% had pathologic Stages C or D1 disease. Only 9.6% of patients with Stages A2 and B had a prostate-specific antigen (PSA) value greater than 10 ng/ml, whereas 97% of patients with PSA values greater than 20 ng/ml had pathologic Stages C and D1. PSA levels correlated with Gleason score (P = < 0.05); 51% and 100% of patients with Gleason score 5–7 and 8–10, respectively, had PSA values greater than 10 ng/ml. Twenty-two patients (23%) had DNA aneuploid tumors. Comparisons of mechanical to enzymatic cell suspensions indicated that DNA aneuploidy was better preserved in mechanical cell preparations. DNA ploidy correlated with pathologic stage (P = < 0.05) and Gleason score (P = < 0.05). Fifteen of 79 patients (18.9%) with Gleason score 5–7 had DNA aneuploid tumors versus 71.4% of patients with Gleason score 8–10. PSA groups correlated with ploidy status (P = 0.01). Although the majority of patients (19 of 22) with DNA aneuploid tumors had elevated preoperative PSA levels, none had a PSA value greater than 50 ng/ml. Conclusions. DNA ploidy analysis correlated with established prognostic indicators in prostate cancer; however, its independent correlation with natural history and treatment outcome must be established for it to have an effect on therapeutic decisions.     

In‐hospital mortality in SARS‐CoV‐2 stratified by gamma‐glutamyl transferase levels

BackgroundThis study investigates in‐hospital mortality amongst patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and its relation to serum levels of gamma‐glutamyl transferase (GGT).MethodsPatients were stratified according to serum levels of gamma‐glutamyl transferase (GGT) (GGT<50 IU/L or GGT≥50 IU/L).ResultsA total of 802 participants were considered, amongst whom 486 had GGT<50 IU/L and a mean age of 48.1 (16.5) years, whilst 316 had GGT≥50 IU/L and a mean age of 53.8 (14.7) years. The chief sources of SARS‐CoV‐2 transmission were contact (366, 45.7%) and community (320, 40%). Most patients with GGT≥50 IU/L had either pneumonia (247, 78.2%) or acute respiratory distress syndrome (ARDS) (85, 26.9%), whilst those with GGT<50 IU/L had hypertension (141, 29%) or diabetes mellitus (DM) (147, 30.2%). Mortality was higher amongst patients with GGT≥50 IU/L (54, 17.1%) than amongst those with GGT<50 IU/L (29, 5.9%). More patients with GGT≥50 required high (83, 27.6%) or low (104, 34.6%) levels of oxygen, whereas most of those with GGT<50 had no requirement of oxygen (306, 71.2%). Multivariable logistic regression analysis indicated that GGT≥50 IU/L (odds ratio [OR]: 2.02, 95% confidence interval [CI]: 1.20–3.45, p=0.009), age (OR: 1.05, 95% CI: 1.03–1.07, p<0.001), hypertension (OR: 2.06, 95% CI: 1.19–3.63, p=0.011), methylprednisolone (OR: 2.96, 95% CI: 1.74–5.01, p<0.001) and fever (OR: 2.03, 95% CI: 1.15–3.68, p=0.016) were significant predictors of all‐cause cumulative mortality. A Cox proportional hazards regression model (B = −0.68, SE =0.24, HR =0.51, p = 0.004) showed that patients with GGT<50 IU/L had a 0.51‐times lower risk of all‐cause cumulative mortality than patients with GGT≥50 IU/L.ConclusionHigher levels of serum GGT were found to be an independent predictor of in‐hospital mortality.