A Non-Coronary, Peripheral Arterial Atherosclerotic Disease (Carotid, Renal, Lower Limb) in Elderly Patients-A Review: Part I-Epidemiology, Risk Factors, and Atherosclerosis-Related Diversities in Elderly Patients.

Atherosclerosis is a generalized and progressive disease. Ageing is a key risk factor for atherosclerosis progression that is associated with the increased incidence of ischemic events in supplied organs, including stroke, coronary events, limb ischemia, or renal failure. Cardiovascular disease is the leading cause of death and major disability in adults ≥ 75 years of age. Atherosclerotic occlusive disease affects everyday activity and quality of life, and it is associated with reduced life expectancy. Although there is evidence on coronary artery disease management in the elderly, there is insufficient data on the management in older patients presented with atherosclerotic lesions outside the coronary territory. Despite this, trials and observational studies systematically exclude older patients, particularly those with severe comorbidities, physical or cognitive dysfunctions, frailty, or residence in a nursing home. This results in serious critical gaps in knowledge and a lack of guidance on the appropriate medical treatment and referral for endovascular or surgical interventions. Therefore, we attempted to gather data on the prevalence, risk factors, and management strategies in patients with extra-coronary atherosclerotic lesions.

A Non-Coronary, Peripheral Arterial Atherosclerotic Disease (Carotid, Renal, Lower Limb) in Elderly Patients-A Review PART II-Pharmacological Approach for Management of Elderly Patients with Peripheral Atherosclerotic Lesions outside Coronary Territory.

BACKGROUND: Aging is a key risk factor for atherosclerosis progression that is associated with increased incidence of ischemic events in supplied organs, including stroke, coronary events, limb ischemia, or renal failure. Cardiovascular disease is the leading cause of death and major disability in adults ≥ 75 years of age. Atherosclerotic occlusive disease affects everyday activity, quality of life, and it is associated with reduced life expectancy. As most multicenter randomized trials exclude elderly and very elderly patients, particularly those with severe comorbidities, physical or cognitive dysfunctions, frailty, or residence in a nursing home, there is insufficient data on the management of older patients presenting with atherosclerotic lesions outside coronary territory. This results in serious critical gaps in knowledge and a lack of guidance on the appropriate medical treatment. In addition, due to a variety of severe comorbidities in the elderly, the average daily number of pills taken by octogenarians exceeds nine. Polypharmacy frequently results in drug therapy problems related to interactions, drug toxicity, falls with injury, delirium, and non-adherence. Therefore, we have attempted to gather data on the medical treatment in patients with extra-cardiac atherosclerotic lesions indicating where there is some evidence of the management in elderly patients and where there are gaps in evidence-based medicine. Public PubMed databases were searched to review existing evidence on the effectiveness of lipid-lowering, antithrombotic, and new glucose-lowering medications in patients with extra-cardiac atherosclerotic occlusive disease.

Formation of HopQ1:14-3-3 complex in the host cytoplasm modulates nuclear import rate of Pseudomonas syringae effector in Nicotiana benthamiana cells.

HopQ1, a type three effector from Pseudomonas syringae upon phosphorylation coopts plant 14-3-3 proteins to control its stability and subcellular localization. Mass spectrometry of the cytoplasm-restricted effector revealed that HopQ1 already in this subcellular compartment undergoes phosphorylation at serine 51 within the canonical 14-3-3 binding motif and within the second putative 14-3-3 binding site, 24RTPSES29. Our analyses revealed that the stoichiometry of the HopQ1:14-3-3a complex is 1:2 indicating that both binding sites of HopQ1 are involved in the interaction. Notably, 24RTPSES29 comprises a putative nuclear translocation signal (NTS). Although a peptide containing NTS mediates nuclear import of a Cargo protein suggesting its role in the nuclear trafficking of HopQ1, a deletion of 25TPS27 does not change HopQ1 distribution. In contrast, elimination of 14-3-3 binding site, accelerates nuclear trafficking the effector. Collectively, we show that formation of the HopQ1:14-3-3 complex occurs in the host cytoplasm and slows down the effector translocation into the nucleus. These results provide a mechanism that maintains the proper nucleocytoplasmic partitioning of HopQ1, and at the same time is responsible for the relocation of 14-3-3s from the nucleus to cytoplasm in the presence of the effector.

Is single-catheter technique for coronary angiography an optimal tool for beginners in interventional cardiology?-randomized controlled study TRACT 2: Transradial Coronary Angiography Trial 2.

Background: Transradial coronary angiography can be performed using a dual-catheter technique (DCT) or single-catheter technique (SCT). The current study aimed to compare DxTerity SCT Ultra and the Trapease curve SCT catheters with DCT catheters in procedures performed by young, less experienced, interventional cardiologists. Methods: For this prospective, single-blinded, randomized study 107 were enrolled and assigned to 1 of 3 groups. They underwent planned coronary angiography at the Second Department of Cardiology Jagiellonian University in Kraków. In groups 1 (n=37) and 2 (n=35), DxTerity SCT Ultra catheters and the Trapease curve were used, respectively. In control group 3 (n=35), standard DCT Judkins catheters were applied. One patient was excluded from group 2, bringing the total number of cases analysed to 106. The study endpoints comprised the percentage of optimal stability, proper ostial artery engagement, a good quality angiogram, the duration of each procedure stage, the amount of contrast and the radiation dose. Results: The highest percentage of optimal stability was observed in group 1 for the right coronary artery (RCA): 94%, and in group 3, for the left coronary artery (LCA): 85%. The necessity to change the catheter was most common in group 2. Group 1 was characterised by a shorter total procedural time. The contrast volume was higher in group 2, while there were no differences in radiation dose. Conclusions: SCT is at least as adequate as DCT for young cardiologists. SCT was associated with lower necessity of catheter exchange during RCA visualization. The DxTerity Ultra curve catheter allows shortening the total procedure time.

Culprit plaque location within the left circumflex coronary artery predicts clinical outcomes in patients experiencing acute coronary syndromes with percutaneous coronary intervention: Data from the ORPKI registry.

BACKGROUND: The left circumflex (LCx) artery is the most diagnostically challenging of the coronary branches in terms of diagnostics because the clinical presentation and electrocardiography (ECG) do not always suggest critical occlusion despite its presence. Therefore, it is important to determine the factors contributing to the clinical manifestation and outcome, such as the culprit location. AIMS: To determine the relationship between the location of the culprit plaque and clinical outcomes in the LCx artery. METHODS: Data from the Polish Registry of Invasive Cardiology Procedures (ORPKI) from the years 2019-2020 concerning percutaneous coronary intervention (PCI) procedures were extracted and analyzed using appropriate statistical tests. RESULTS: 97 899 clinical records were analyzed. Patients with proximal occlusion received a worse grade using the Killip classification. Patients with Thrombolysis in Myocardial Infarction (TIMI) score 0 had worse clinical presentation in each of the occlusion locations. The periprocedural cardiac arrest and death rates were the highest among patients with proximal circumflex (Cx) occlusion. The death rate among patients with proximal occlusion and non-ST-segment elevation myocardial infarction (NSTEMI) was greater than among patients with distal occlusion and ST-segment elevation myocardial infarction (STEMI). CONCLUSIONS: Among patients with proximal occlusions of the Cx artery and TIMI 0 grade flow on initial angiogram, a STEMI-like approach should be undertaken apart from initial ECG findings. This is driven by a higher rate of critical and fatal complications such as cardiac arrest and periprocedural death. Fatal complications occur more often in patients with proximal occlusion of Cx than in medial or distal occlusion. Grade IV according to the Killip classification can suggest a proximal culprit location.

Trends in Incidence and Mortality of Gynecological and Breast Cancers in Poland (1980-2018).

BACKGROUND: This study aimed to analyze and determine the incidence and mortality trends in gynecological and breast cancers (BCs) in Poland. The gynecological cancers assessed were cervical cancer (CC), corpus uteri cancer (CUC), ovarian cancer (OC), vaginal cancer (VAC), and vulvar cancer (VUC). PATIENTS AND METHODS: Data concerning the incidence and mortality for the period of 1980-2018 were obtained from the Polish National Cancer Registry (PNCR). Joinpoint regression analysis was performed to identify trends, which were described using the annual percentage change (APC) and the average annual percent change (AAPC). RESULTS: Statistically significant increases were observed in BC incidence (AAPC: 2.3; CI: 1.8 to 2.9; p<0.05), CUC incidence (AAPC: 2.3; CI: 1.9 to 2.7; p<0.05), CUC mortality (AAPC: 0.4; CI: 0.1 to 0.7; p<0.05) and VUC mortality (AAPC: 1.16, CI: 0.1 to 2.2; p<0.05). VAC mortality decreased (AAPC: -3.5, CI: -5.0 to -2.0; p<0.05), as did CC incidence and mortality (AAPC: -2.1, CI: -2.3 to -1.8; p<0.05, AAPC: -2.0, CI: -2.2 to -1.8; p<0.05, respectively). Between 1980 and 1993, OC incidence initially increased and then stabilized (AAPC: 0.9; CI: 0.7 to 1.1; p<0.05). After 2007, OC mortality decreased (AAPC: 0.0; CI: -0.2 to 0.2; p=0.8). Trends in VUC and VAC incidence and BC mortality were not statistically significant. CONCLUSION: The results of this study showed a significant increase in OC, CUC, and BC incidence, and a decrease in the incidence of CC and VAC. The VUC trends were stable. Mortality trends for BC initially fluctuated and, since 2010, has begun to increase. Throughout the observed period, mortality due to VUC and CUC increased, whereas decreased among patients with CC. OC mortality was stable, but not significant. Furthermore, the study showed a correlation between age group and rate of incidence and mortality of each assessed cancer.

Comparison of Access Site-Related Complications and Quality of Life in Patients after Invasive Cardiology Procedures According to the Use of Radial, Femoral, or Brachial Approach.

The radial approach (RA) is the most common in invasive cardiology, but depending on the clinical situation, the femoral approach (FA) and brachial approach (BA) are also used. The BA is associated with the highest odds of complications so it is used mainly if a first-choice approach fails. The aim of the study was to assess clinical outcomes after invasive cardiology procedures stratified by the use of the RA, FA, and BA, with a focus on access site-related complications, quality of life (QoL), and patients' perspective. A total of 250 procedures (RA: 98; FA: 99; BA: 53) performed between 2013 and 2020 were retrospectively analyzed. Puncture site-related complications, vascular events, patient preferences, and QoL were assessed by the analysis of medical records and telephone follow-up using a proprietary questionnaire and the modified EQ-5D-3L questionnaire. Patients from the RA group received the smallest volume of contrast during a percutaneous coronary interventions (PCI) procedure (RA vs. FA vs. BA: 180 (150-240) mL vs. 200 (180-270) mL vs. 190 (100-200) mL, p = 0.045). The access site was changed most frequently in the procedures initiated from the RA (p < 0.04). Overall puncture site-related complications, especially local hematomas, occurred most commonly in the BA group (7.1, 14.1, and 24.5% for RA, FA, and BA, respectively, p = 0.01). During the index procedure, the access site was changed most frequently in procedures initiated from the RA (19.7, 8.5 and 0%, p = 0.04). The RA was indicated as an approach preferred by the patient for a hypothetical next procedure (87.9, 55.4, and 70.0% for subjects preferring the same approach out of patients who underwent a procedure by the RA, FA, and BA, respectively, p < 0.001). For the RA and FA, the prevalence of moderate or extreme access site-related problems in self-care decreased significantly (RA: p < 0.01, FA: p < 0.05) within 1 month after the index procedure (RA: 18.1, 4.2, and 1.4%; FA: 20.7, 11.1, and 9.6% periprocedurally, after 1 and 6 months, respectively). In contrast, for the BA these percentages were higher and a significant improvement (p < 0.05) was delayed until 6 months (54.6, 36.4, and 18.2% periprocedurally, after 1 and 6 months, respectively). In conclusion, compared to the BA and FA, the RA appears to be not only the safest, mainly due to the lowest risk of puncture site-related complications after coronary procedures but also represents a preferable approach from the patient's perspective. Although overall post-procedural QoL outcomes did not differ significantly according to the access site, nevertheless, the BA was associated with more frequent self-care problems whose improvement was delayed until more than one month after the index procedure.

An Engineered Distant Homolog of Pseudomonas syringae TTSS Effector From Physcomitrella patens Can Act as a Bacterial Virulence Factor.

Pseudomonas syringae pv. phaseolicola is the causative agent of halo blight in common bean (Phaseolus vulgaris). Similar to other pathogenic gram-negative bacteria, it secrets a set of type III effectors into host cells to subvert defense mechanisms. HopQ1 (for Hrp outer protein Q) is one of these type III effectors contributing to virulence of bacteria. Upon delivery into a plant cell, HopQ1 undergoes phosphorylation, binds host 14-3-3 proteins and suppresses defense-related signaling. Some plants however, evolved systems to recognize HopQ1 and respond to its presence and thus to prevent infection. HopQ1 shows homology to Nucleoside Hydrolases (NHs), but it contains a modified calcium binding motif not found in the canonical enzymes. CLuster ANalysis of Sequences (CLANS) revealed that HopQ1 and alike proteins make a distinct group of putative NHs located distantly from the classical enzymes. The HopQ1 - like protein (HLP) group comprises sequences from plant pathogenic bacteria, fungi, and lower plants. Our data suggest that the evolution of HopQ1 homologs in bacteria, fungi, and algae was independent. The location of moss HopQ1 homologs inside the fungal clade indicates a possibility of horizontal gene transfer (HGT) between those taxa. We identified a HLP in the moss Physcomitrella patens. Our experiments show that this protein (referred to as PpHLP) extended by a TTSS signal of HopQ1 promoted P. syringae growth in bean and was recognized by Nicotiana benthamiana immune system. Thus, despite the low sequence similarity to HopQ1 the engineered PpHLP acted as a bacterial virulence factor and displayed similar to HopQ1 virulence properties.

Two Strategies of Pseudomonas syringae to Avoid Recognition of the HopQ1 Effector in Nicotiana Species.

Pseudomonas syringae employs a battery of type three secretion effectors to subvert plant immune responses. In turn, plants have developed receptors that recognize some of the bacterial effectors. Two strain-specific HopQ1 effector variants (for Hrp outer protein Q) from the pathovars phaseolicola 1448A (Pph) and tomato DC3000 (Pto) showed considerable differences in their ability to evoke disease symptoms in Nicotiana benthamiana. Surprisingly, the variants differ by only six amino acids located mostly in the N-terminal disordered region of HopQ1. We found that the presence of serine 87 and leucine 91 renders PtoHopQ1 susceptible to N-terminal processing by plant proteases. Substitutions at these two positions did not strongly affect PtoHopQ1 virulence properties in a susceptible host but they reduced bacterial growth and accelerated onset of cell death in a resistant host, suggesting that N-terminal mutations rendered PtoHopQ1 susceptible to processing in planta and, thus, represent a mechanism of recognition avoidance. Furthermore, we found that co-expression of HopR1, another effector encoded within the same gene cluster masks HopQ1 recognition in a strain-dependent manner. Together, these data suggest that HopQ1 is under high host-pathogen co-evolutionary selection pressure and P. syringae may have evolved differential effector processing or masking as two independent strategies to evade HopQ1 recognition, thus revealing another level of complexity in plant - microbe interactions.

Phosphorylation of HopQ1, a type III effector from Pseudomonas syringae, creates a binding site for host 14-3-3 proteins.

HopQ1 (for Hrp outer protein Q), a type III effector secreted by Pseudomonas syringae pv phaseolicola, is widely conserved among diverse genera of plant bacteria. It promotes the development of halo blight in common bean (Phaseolus vulgaris). However, when this same effector is injected into Nicotiana benthamiana cells, it is recognized by the immune system and prevents infection. Although the ability to synthesize HopQ1 determines host specificity, the role it plays inside plant cells remains unexplored. Following transient expression in planta, HopQ1 was shown to copurify with host 14-3-3 proteins. The physical interaction between HopQ1 and 14-3-3a was confirmed in planta using the fluorescence resonance energy transfer-fluorescence lifetime imaging microscopy technique. Moreover, mass spectrometric analyses detected specific phosphorylation of the canonical 14-3-3 binding site (RSXpSXP, where pS denotes phosphoserine) located in the amino-terminal region of HopQ1. Amino acid substitution within this motif abrogated the association and led to altered subcellular localization of HopQ1. In addition, the mutated HopQ1 protein showed reduced stability in planta. These data suggest that the association between host 14-3-3 proteins and HopQ1 is important for modulating the properties of this bacterial effector.