The Impact of Homogeneous Versus Heterogeneous Emphysema on Dynamic Hyperinflation in Patients With Severe COPD Assessed for Lung Volume Reduction

Dynamic hyperinflation (DH) is a pathophysiologic hallmark of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to investigate the impact of emphysema distribution on DH during a maximal cardiopulmonary exercise test (CPET) in patients with severe COPD.

This was a retrospective analysis of prospectively collected data among severe COPD patients who underwent thoracic high-resolution computed tomography, full lung function measurements and maximal CPET with inspiratory manouvers as assessment for a lung volume reduction procedure. ΔIC was calculated by subtracting the end-exercise inspiratory capacity (eIC) from resting IC (rIC) and expressed as a percentage of rIC (ΔIC %). Emphysema quantification was conducted at 3 predefined levels using the syngo PULMO-CT (Siemens AG); a difference >25% between best and worse slice was defined as heterogeneous emphysema.

Fifty patients with heterogeneous (62.7% male; 60.9 ± 7.5 years old; FEV₁% = 32.4 ± 11.4) and 14 with homogeneous emphysema (61.5% male; 62.5 ± 5.9 years old; FEV₁% = 28.1 ± 10.3) fulfilled the enrolment criteria. The groups were matched for all baseline variables. ΔIC% was significantly higher in homogeneous emphysema (39.8% ± 9.8% vs.31.2% ± 13%, p = 0.031), while no other CPET parameter differed between the groups. Upper lobe predominance of emphysema correlated positively with peak oxygen pulse, peak oxygen uptake and peak respiratory rate, and negatively with ΔIC%. Homogeneous emphysema is associated with more DH during maximum exercise in COPD patients.     

Adverse Pathology After Neoadjuvant Chemotherapy and Radical Cystectomy: The Role of Adjuvant Chemotherapy

Background

The current guidelines do not recommend adjuvant chemotherapy (AC) for patients with adverse pathologic findings after neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for bladder cancer. We sought to evaluate the association of AC with overall survival (OS) in these patients.

Robotic salvage lymph node dissection for nodal-only recurrences after radical prostatectomy: Perioperative and early oncological outcomes

Background

Salvage lymph node dissection (sLND) – performed open or minimally-invasive - is a treatment modality that can be offered to patients with nodal recurrence after radical prostatectomy (RP), especially in times where modern imaging methods like choline- or PSMA-PET/CT are available. Yet, there are only very limited data on the safety and oncological effectiveness of robotic sLND.

Effects of strenuous exercise on blood coagulation activity in sickle cell trait carriers

We compared routine coagulation markers in six sickle cell trait carriers ((SCT, or AS hemoglobinopathy)--the heterozygous form of sickle cell anemia) and six subjects with normal hemoglobin before and after a prolonged and intense exercise. Blood was sampled at rest and at the end of the entire exercise test to measure coagulation markers (prothrombin time, activated partial thromboplastin time, plasma fibrinogen and antithrombin III activity), hematocrit (Hct) and yield stress (tau(y)). Results obtained at the end of exercise were corrected by the percent change in plasma volume. Blood coagulation markers, Hct and tau(y) were not different between the two groups at rest. Exercise did not change prothrombin time, antithrombin III activity and plasma fibrinogen, decreased activated partial thromboplastin time and increased Hct and tau(y) in the two groups. These parameters were not significantly different between the two groups at the end of exercise, except for plasma fibrinogen which was slightly higher in SCT carriers but in the normal range values. The results have been discussed in relation with some cases of exercise-related sudden death in SCT carriers, reported in several studies. Therefore our results show that the increased risk for clinical complications in certain SCT carriers during exercise seems to be unrelated to higher blood coagulation activity.     

The unreported morbidity of suicidal poisonings during an insurgency: a 16-year Kashmir experience

Around a million people commit suicide, and at least 10 times this number attempt suicide, worldwide every year. No nationwide epidemiological studies have been undertaken in India but a significant rise in suicides has been observed in Kashmir in recent years. This study was carried out on patients reporting to the Government SMHS Hospital in Srinagar with a history of suicidal poisoning.     

Ranking dental aesthetics and thresholds of treatment need: a comparison between patients, parents, and dentists

The aims of the present study were to compare rankings of dental aesthetics and the threshold at which orthodontic treatment would be sought among patients, parents, and dentists. A prospective cross-sectional study was designed to address these aims. The study sample comprised 100 patients and parents and 23 dental specialists. The patients were equally divided between males and females and their mean age was 14.7 years (standard deviation 2.3 years). The aesthetic component (AC) of the Index of Orthodontic Treatment Need (IOTN) represented impairment of dental aesthetics. The 10 numbered photographs of the AC were cut into equal-sized rectangles and subjects were asked to arrange them from 'the one that looks best' to 'the one that looks worst'. The subjects were then presented with the 10 photographs of AC in sequence and asked to identify the cut-off point between 'teeth that need orthodontic treatment' and 'no treatment'. Statistical analysis was undertaken with a Mann-Whitney test. The results showed that median rankings of dental aesthetics were similar among the three groups (P > 0.05). The median ranking of photographs 1, 2, 3, 4, and 10 were identical to the AC of IOTN. The photographs representing IOTN AC 7 and 8 were allocated the same median rank of 7 and AC 5 and 9 were allocated corresponding median ranks of 6 and 8, respectively. There were no significant differences in median cut-off points for treatment need among the three groups of subjects (P > 0.05), indicating that the mean threshold at which treatment would be sought was AC 4.     

The Promotion of Genomic Instability in Human Fibroblasts by Adenovirus 12 Early Region 1B 55K Protein in the Absence of Viral Infection

The adenovirus 12 early region 1B55K (Ad12E1B55K) protein has long been known to cause non-random damage to chromosomes 1 and 17 in human cells. These sites, referred to as Ad12 modification sites, have marked similarities to classic fragile sites. In the present report we have investigated the effects of Ad12E1B55K on the cellular DNA damage response and on DNA replication, considering our increased understanding of the pathways involved. We have compared human skin fibroblasts expressing Ad12E1B55K (55K⁺HSF), but no other viral proteins, with the parental cells. Appreciable chromosomal damage was observed in 55K⁺HSFs compared to parental cells. Similarly, an increased number of micronuclei was observed in 55K⁺HSFs, both in cycling cells and after DNA damage. We compared DNA replication in the two cell populations; 55K⁺HSFs showed increased fork stalling and a decrease in fork speed. When replication stress was introduced with hydroxyurea the percentage of stalled forks and replication speeds were broadly similar, but efficiency of fork restart was significantly reduced in 55K⁺HSFs. After DNA damage, appreciably more foci were formed in 55K⁺HSFs up to 48 h post treatment. In addition, phosphorylation of ATM substrates was greater in Ad12E1B55K-expressing cells following DNA damage. Following DNA damage, 55K⁺HSFs showed an inability to arrest in cell cycle, probably due to the association of Ad12E1B55K with p53. To confirm that Ad12E1B55K was targeting components of the double-strand break repair pathways, co-immunoprecipitation experiments were performed which showed an association of the viral protein with ATM, MRE11, NBS1, DNA-PK, BLM, TOPBP1 and p53, as well as with components of the replisome, MCM3, MCM7, ORC1, DNA polymerase δ, TICRR and cdc45, which may account for some of the observed effects on DNA replication. We conclude that Ad12E1B55K impacts the cellular DNA damage response pathways and the replisome at multiple points through protein–protein interactions, causing genomic instability.     

Novel Mapping Strategies for Ventricular Tachycardia Ablation

Despite advances in antiarrhythmic and device therapy, ventricular tachycardia (VT) continues to be a major cause of increased morbidity and mortality. During scar-mediated monomorphic ventricular tachycardia ablation, the search for critical isthmus sites continues to be the primary goal during successful ablative procedures. However, given the overwhelming hemodynamic instability of most ventricular arrhythmias (>?70%), VT ablation is increasingly performed during sinus rhythm. This technique requires either a greater reliance on isthmus surrogates, or more extensive ablation techniques and is a more probabilistic approach to substrate modification. We believe that a better understanding of scar physiology and activation during sinus rhythm has important implications for clinical workflow and mechanistic improvements with current ablation strategies. With advancements in high-density mapping and multi-electrode catheter technology, mapping of VT substrates is performed with higher resolution, with improved visualization of local abnormal ventricular activities (LAVA), and with a more nuanced functional understanding of late potentials. As a prerequisite, our practice for VT ablation starts with a high-density structural map to identify voltage abnormalities as well as an isochronal functional map of sinus rhythm activation to identify region of discontinuous wavefront propagation. As the era of increased automation has emerged, there continues to be vast array of customizable features, and we have adopted the use of multiple wavefront mapping to further elucidate possible arrhythmogenic substrate. Our emerging understanding of how scar propagation patterns relate to areas of abnormal signals and critical isthmuses may greatly improve the ability to identify surrogates during sinus rhythm and help localize the most arrhythmogenic regions within a given scar. In the hemodynamically unstable patients, we routinely integrate isochronal late activation mapping (ILAM) to identify areas of slow conduction to initiate our targeted ablation and substrate modification. Multi-electrode delineation of the entire reentrant VT circuit has value in understanding the size of the circuit, rotational nature, and transmural extent of human reentry. Correlative studies between the activation of the complete VT circuit and sinus rhythm are likely to provide important mechanistic insights on where fixed and/or functional block occurs within a complex scar substrate.