Given the associated risks with transcatheter aortic valve replacement (TAVR), it is crucial to determine how the implant will affect the valve dynamics and cardiac function, and if TAVR will improve ...or worsen the outcome of the patient. Effective treatment strategies, indeed, rely heavily on the complete understanding of the valve dynamics. We developed an innovative Doppler-exclusive non-invasive computational framework that can function as a diagnostic tool to assess valve dynamics in patients with aortic stenosis in both pre- and post-TAVR status. Clinical Doppler pressure was reduced by TAVR (52.2 ± 20.4 vs. 17.3 ± 13.8 mmHg, p < 0.001), but it was not always accompanied by improvements in valve dynamics and left ventricle (LV) hemodynamics metrics. TAVR had no effect on LV workload in 4 patients, and LV workload post-TAVR significantly rose in 4 other patients. Despite the group level improvements in maximum LV pressure (166.4 ± 32.2 vs 131.4 ± 16.9 mmHg, p < 0.05), only 5 of the 12 patients (41%) had a decrease in LV pressure. Moreover, TAVR did not always improve valve dynamics. TAVR did not necessarily result in a decrease (in 9 out of 12 patients investigated in this study) in major principal stress on the aortic valve leaflets which is one of the main contributors in valve degeneration and, consequently, failure of heart valves. Diastolic stresses increased significantly post-TAVR (34%, 109% and 81%, p < 0.001) for each left, right and non-coronary leaflets respectively. Moreover, we quantified the stiffness and material properties of aortic valve leaflets which correspond with the reduced calcified region average stiffness among leaflets (66%, 74% and 62%; p < 0.001; N = 12). Valve dynamics post-intervention should be quantified and monitored to ensure the improvement of patient conditions and prevent any further complications. Improper evaluation of biomechanical valve features pre-intervention as well as post-intervention may result in harmful effects post-TAVR in patients including paravalvular leaks, valve degeneration, failure of TAVR and heart failure.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
The aim of this study was to describe the clinical characteristics and outcome of patients with coronavirus disease-2019 (COVID-19) pneumonia admitted to an intensive care unit (ICU) of a ...tertiary care center in the United Arab Emirates (UAE) and to identify early risk factors for in-hospital mortality in these patients.
Methods
A total of 371 adult patients (>18 years) admitted to the ICU of Al Ain Hospital between March 16 and July 19, 2020 with SARS-CoV-2 infection confirmed using real-time reverse transcription polymerase chain reaction (rt-PCR) on nasopharyngeal swabs were included.
Results
The mean patient age was 53 years (standard deviation = 13). Patients were mostly male (n = 314 84.6%) and of South Asian origin (n = 231 62.3%). Invasive mechanical ventilation was required in 182 (49.1%) patients for a median of 11 days (25–75% interquartile range: 6–17). During the ICU stay, renal replacement therapy was required in 87 (23.5%) and vasopressor therapy in 190 (51.2%) patients. ICU and hospital lengths of stay were 9 (IQ: 5–17) and 18 (IQ: 13–29) days, respectively and ICU and hospital mortality rates were both 20.2%. In a multivariable analysis with in-hospital mortality as the dependent variable, greater Acute Physiology and Chronic Health Evaluation II score on ICU admission, diarrhea prior to hospital admission, greater, admission from hospital ward, and higher lactate dehydrogenase levels and neutrophil:lymphocyte ratio on admission to the ICU were independently associated with higher risk of in-hospital mortality.
Conclusion
In this cohort of patients admitted to the ICU of a tertiary hospital in the UAE, COVID-19 pneumonia was associated with high morbidity and mortality rates. Identifying patients at high risk of death may help detect future therapeutic targets.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) ...may maximize the WL benefits of surgery.
This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification.
In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.47±2.23), at 6 months (18.29 ±1.74 vs. 15.58 ±1.65), and at 12 months 24.15±2.35 versus 22.70±2.13 (all P <0.001). For %EWL, this was also significantly higher in the liraglutide group at all time points. A %TWL of greater than 20% at 6 months of treatment was recorded in six (15.8%) patients in the liraglutide group and none in the placebo group ( P =0.029). Both groups had comparable changes in metabolic biomarkers. Adverse events were recorded in 11 (27.5%) patients in the liraglutide, with no adverse events in the placebo group ( P <0.001). Both groups had Clavien-Dindo scores I and II (5.0 and 2.5%), and GOB values indicated that 90.0 and 97.5% were low-risk patients.
Adjunctive use of liraglutide with cRYGB gives significantly higher WL and resolution of associated medical problems.
Vaginal pessaries are widely considered to be a safe and effective non-surgical management option for women with pelvic organ prolapse. Complications may occur, and are more frequent with improper ...care and certain device designs and materials. It is imperative to provide information to patients about potential complications. We present the case of a woman in her 70s who presented to the Emergency Department with increasing groin and abdominal pain following a vaginal pessary insertion 2 days prior for grade 3 vaginal vault prolapse. On presentation, her abdomen was markedly distended with guarding. Laboratory investigations showed a significant acute kidney injury with a metabolic acidosis. An initial non-contrast CT showed fluid and inflammatory changes surrounding the bladder, and bladder perforation was suspected. A subsequent CT cystogram showed extravasation of contrast from the bladder into the peritoneal cavity, in keeping with an intraperitoneal bladder rupture. The patient underwent an emergency bladder repair in theatre.
In May 2015 in United Arab Emirates, asymptomatic Middle East respiratory syndrome coronavirus infection was identified through active case finding in 2 men with exposure to infected dromedaries. ...Epidemiologic and virologic findings suggested zoonotic transmission. Genetic sequences for viruses from the men and camels were similar to those for viruses recently detected in other countries.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although cytochromes P450 2C9 (CYP2C9) and 2C19 (CYP2C19) have 91% amino acid identity, they have different substrate specificities. Previous studies have suggested that several amino acid residues ...may be involved in substrate specificity. In this study, we focused on the roles of two amino acids, residues 72 and 241. The amino acids in these positions have opposite charges in CYP2C9 and 2C19; the former has lysines in both positions (Lys72 and Lys241), and the latter has glutamic acids (Glu72 and Glu241). Reciprocal mutants for both CYP2C19 and 2C9 were produced, and their metabolic activities and spectroscopic properties were examined using three tricyclic antidepressant (TCA) drugs: amitriptyline, imipramine, and dothiepin. Although CYP2C19 wild-type (WT) had a high metabolic activity for all three drugs, the E72K mutation decreased enzymatic activity by 29–37%, while binding affinities were diminished 2.5- to 20-fold. On the other hand, low activity and low affinity of CYP2C9 WT were recovered notably by K72E mutation. The metabolic activities and binding affinities were minimally affected by CYP2C19 E241K and CYP2C9 K241E mutations. We could also show linear correlations between metabolic activities and binding affinities, and hence we conclude that amino acid residue 72 plays a key role in TCA drug metabolism by limiting the binding affinities of CYP2C19 and CYP2C9.
Abstract
Stomas are essential for colorectal surgery and are widely used not only for selected cases for bowel obstructions but also in rectal cancer operations to divert stool away from low rectal ...anastomosis. On the other hand, complications with stomas/ stomas reversal are not uncommon. In this study, we aimed at studying the frequency and the predictors of temporary stomas being permanent, and the contributing factors of surgical stoma/stoma closure related complications. In our cohort, only about 40% of the patient closed their initially planned temporary stomas. The occurrence of intestinal leak, wound sepsis, or any type of morbidity with 30 days of operation were significant predictors of permanent stomas. In addition, alarmingly although Hartmann's procedure was uncommon in our practice, only 9% of those who underwent Hartmann's have had it reversed. Moreover, the only factor that significantly increased stoma related complications was having an end colostomy. There was a tendency toward late closure of stomas with median 8.2 months, however early closure did not correlate to complications. In conclusion, further studies are needed to delineate the low rate of stoma closure. Patients who develop postoperative complications, even wound sepsis, would be at a higher risk of living with permanent stomas. Hartmann's procedures are commonly associated with stoma problems, and reluctance to reverse the stomas.
Today there is increasing evidence concerning the association between individual genetic polymorphisms within proinflammatory cytokines and chronic hepatitis C (CHC) severity. It has been ...demonstrated that polymorphisms in some genes may significantly predict HCV infected patients' susceptibility to developing liver cirrhosis or their responsiveness to the treatment.
We investigated the influence of single nucleotide polymorphisms (SNPs) in Interferon (IFN-γ) and Interferon Gamma-Inducible Protein 10 (IP-10) genes on cirrhosis risk in HCV-infected patients and their association with response to various direct-acting antiviral drugs (DAAs).
IFN-γ (+874T/A, +2109A/G) and IP-10 (−135G/A, −1447A/G) genotypes were determined in 175 CHC Egyptian HCV patients (69 liver cirrhotic and 106 non-cirrhotic patients) using either single-stranded polymorphism polymerase chain reaction (SSP-PCR) or Restriction fragment length-PCR (RFLP-PCR) methods.
IFN-γ + 874 TA, IP-10 − 135AA, and IP-10 − 1447AA and IP-10 − 1447GG genotypes are increased in patients developing liver cirrhosis compared to non-cirrhotic ones. Although, no statistical significance in their distribution was demonstrated, indicating the lack of association between these SNPs and liver cirrhosis susceptibility in HCV-infected patients. Haplotypes analysis between different loci on all selected genes showed a significant increase in AGGA and TAGA and a significant decrease in TGGA haplotypes in cirrhotic patients. Genotype frequencies at loci −135 and −1447 of IP-10 appeared to be in complete Linkage disequilibrium (LD) (D' = 0.999, r
2
= 0.689).
Our data support the concept that IFN-γ and IP-10 gene polymorphisms are not predictors of disease progression among Egyptian patients with HCV infection.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background Despite the proven benefits of transcatheter aortic valve replacement (TAVR) and its recent expansion toward the whole risk spectrum, coronary artery disease is present in more than half ...of the candidates for TAVR. Many previous studies do not focus on the longer-term impact of TAVR on coronary arteries, and hemodynamic changes to the circulatory system in response to the anatomical changes caused by TAVR are not fully understood. Methods and Results We developed a multiscale patient-specific computational framework to examine the effect of TAVR on coronary and cardiac hemodynamics noninvasively. Based on our findings, TAVR might have an adverse impact on coronary hemodynamics due to the lack of sufficient coronary blood flow during diastole phase (eg, maximum coronary flow rate reduced by 8.98%, 16.83%, and 22.73% in the left anterior descending, left circumflex coronary artery, and right coronary artery, respectively N=31). Moreover, TAVR may increase the left ventricle workload (eg, left ventricle workload increased by 2.52% N=31) and decrease the coronary wall shear stress (eg, maximum time averaged wall shear stress reduced by 9.47%, 7.75%, 6.94%, 8.07%, and 6.28% for bifurcation, left main coronary artery, left anterior descending, left circumflex coronary artery, and right coronary artery branches, respectively). Conclusions The transvalvular pressure gradient relief after TAVR might not result in coronary flow improvement and reduced cardiac load. Optimal revascularization strategy pre-TAVR and progression of coronary artery disease after TAVR could be determined by noninvasive personalized computational modeling.
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