Concordant care in sentinel lymph node omission following Choosing Wisely® recommendations at a comprehensive cancer center.

BACKGROUND: In 2016, the SSO and ABIM released a Choosing Wisely® guideline stating SLNB can be safely omitted in women ≥70 with HR â€‹+ â€‹HER-invasive breast cancer. No study evaluating concordance of care with this guideline has been performed within a comprehensive cancer center. METHODS: From 2005 to 2020, there were 382 patients with cT1-2N0 invasive carcinoma ER+/PR+ and HER2-identified as having undergone SLNB. These patients were then separated into two groups; those in the pre-guideline concordance cohort (2005-2015) and those in the post-guideline concordance (2016-2020) cohort. Axillary management concordance was trended over time. RESULTS: 382 patients from 2005 to 2020 with HR â€‹+ â€‹HER- IBC were identified. No difference was seen in SLNB pre-versus post-guidelines (p â€‹= â€‹0.35). Increased concordance was noted as age increased (p â€‹= â€‹0.0068) and adjuvant radiation therapy exclusion (p â€‹< â€‹0.0001) post-guideline release. Concordance improved over the years post-guideline release (R2 â€‹= â€‹0.45). CONCLUSIONS: Surgical guideline adoption occurs over time but may also be affected by outside decisions and factors. Further study into patterns of guideline adoption may facilitate improving adherence to guidelines.

Luminal A Versus B After Choosing Wisely: Does Lymph Node Surgery Affect Oncologic Outcomes?

BACKGROUND: In 2016, the Choosing Wisely campaign recommended against routine sentinel lymph node biopsy (SLNB) in women ≥ 70 years old diagnosed with early-stage hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer. No distinction is made between luminal A and luminal B phenotypes, despite luminal B being considered more aggressive. This study evaluates the effect of SLNB on oncologic outcomes in HER2- luminal B versus luminal A breast cancer. PATIENTS AND METHODS: We performed an IRB-approved, single institution, retrospective cohort study from 2010 to 2020 of women aged ≥ 70 years with clinically node negative, HR+ breast cancer undergoing definitive surgical treatment. Luminal status was defined by gene expression panel testing, Ki67%, and/or pathologic grading. Primary endpoints included locoregional recurrence (LRR), disease free survival (DFS), and overall survival (OS). RESULTS: SLNB did not correlate with significant differences in LRR in luminal A (p = 0.92) or luminal B (p = 0.96) disease. SLNB correlated with improved DFS (p < 0.01) and OS (p < 0.001) in luminal A disease, but not in luminal B disease (DFS p = 0.73; OS p = 0.36). On multivariate analysis, age (HR = 1.17; p < 0.01) and tumor size (HR = 1.03; p < 0.05) were associated with DFS, while SLNB was not (p = 0.71). Luminal status (HR = 0.52, p < 0.05), age (HR = 1.15, p < 0.01), and comorbidities (HR = 1.35, p < 0.05) were associated with OS, but not SLNB (p = 0.71). CONCLUSIONS: Our results suggest that SLNB may be safely omitted in patients aged ≥ 70 years with luminal B disease given similar LRR in luminal A disease. Our findings suggest that DFS and OS are driven by tumor biology, patient age, and comorbidities rather than receipt of SLNB.

In silico designing of multiepitope-based-peptide (MBP) vaccine against MAPK protein express for Alzheimer's disease in Zebrafish.

Understanding the role of the mitogen-activated protein kinases (MAPKs) signalling pathway is essential in advancing treatments for neurodegenerative disorders like Alzheimer's. In this study, we investigate in-silico techniques involving computer-based methods to extract the MAPK1 sequence. Our applied methods enable us to analyze the protein's structure, evaluate its properties, establish its evolutionary relationships, and assess its prevalence in populations. We also predict epitopes, assess their ability to trigger immune responses, and check for allergenicity using advanced computational tools to understand their immunological properties comprehensively. We apply virtual screening, docking, and structure modelling to identify promising drug candidates, analyze their interactions, and enhance drug design processes. We identified a total of 30 cell-targeting molecules against the MAPK1 protein, where we selected top 10 CTL epitopes (PAGGGPNPG, GGGPNPGSG, SAPAGGGPN, AVSAPAGGG, AGGGPNPGS, ATAAVSAPA, TAAVSAPAG, ENIIGINDI, INDIIRTPT, and NDIIRTPTI) for further evaluation to determine their potential efficacy, safety, and suitability for vaccine design based on strong binding potential. The potential to cover a large portion of the world's population with these vaccines is substantial-88.5 % for one type and 99.99 % for another. In exploring the molecular docking analyses, we examined a library of compounds from the ZINC database. Among them, we identified twelve compounds with the lowest binding energy. Critical residues in the MAPK1 protein, such as VAL48, LYS63, CYS175, ASP176, LYS160, ALA61, LEU165, TYR45, SER162, ARG33, PRO365, PHE363, ILE40, ASN163, and GLU42, are pivotal for interactions with these compounds. Our result suggests that these compounds could influence the protein's behaviour. Moreover, our docking analyses revealed that the predicted peptides have a strong affinity for the MAPK1 protein. These peptides form stable complexes, indicating their potential as potent inhibitors. This study contributes to the identification of new drug compounds and the screening of their desired properties. These compounds could potentially help reduce the excessive activity of MAPK1, which is linked to Alzheimer's disease.

Bilateral versus single internal mammary artery in diabetic patients: systematic review and meta-analysis.

OBJECTIVES: Data on bilateral internal mammary artery (BIMA) versus single internal mammary artery (SIMA) on diabetics were analyzed; This is the only meta-analysis, the last 7 years. METHODS: Medline through PubMed/EMBASE/CINHAL and the Cochrane Central Register of Controlled Trials; 179 articles were studied; 19 studies deemed suitable and were included in the analysis. RESULTS: The mortality was 2.41% for BIMA versus 1.71% for SIMA (odds ratio [OR] = 0.95; 95% confidence interval [CI]: 0.74-1.22). Postoperative reopening for bleeding was higher at 3.75% for BIMA versus 2.91% for SIMA (OR = 1.49; 95% CI: 1.15-1.93). The incidence of MI was 0.87% for BIMA versus 0.83% for SIMA (OR = 0.73; 95% CI: 0.37-1.44). Deep sternal wound infection was 3.02% for BIMA and 1.95% for SIMA (OR = 1.57; 95% CI: 1.26-1.95). When skeletonized, the incidence of DSWI was 2.5% for BIMA versus 2.41% for SIMA. There was a significant difference at 5-year survival favoring the BIMA, 85.15% BIMA versus 80.77% SIMA (OR = 1.79; 95% CI: 1.60-2.01). The 10-year overall survival was 74.04% BIMA versus 61.57% SIMA (OR = 1.79; 95% CI: 1.61-1.98). The 15-year survival was 47.08% for BIMA versus 37.06% for SIMA (OR = 1.69; 95% CI: 1.52-1.88). CONCLUSIONS: Postoperative bleeding was higher in BIMA group. Bilateral internal mammary artery in diabetic patients should be carried out in a skeletonize fashion, to reduce DSWI. There is a survival benefit of using BIMA in diabetics within 5 years of surgery; it remains significant up to 15 years.

Comparison of Clinical Characteristics and Outcome of COVID-19 Patients Between the 4th and 5th Wave in a Tertiary Care Hospital in Karachi, Pakistan.

ABSTRACT       Objective: To compare the clinical parameters of 4th and 5th COVID waves in Karachi, Pakistan. STUDY DESIGN: Descriptive study. Place and Duration of the Study: PNS Shifa Hospital, Karachi, from July 2021 to February 2022. METHODOLOGY: All patients with COVID-19 in PNS Shifa Hospital were included in the study. The patients were divided into two groups, those who had COVID-19 during the 4th wave, and others who had it during the 5th wave. The patients' demographic details, comorbidities, vaccination status, initial presentation, the severity of disease, clinical progress, and final disposal from the hospital were noted. A comparison of severity, length of hospital stays, and mortality was made between the groups. RESULTS: There were 747 patients admitted during the Delta variant-dominated 4th wave of COVID-19, and 490 patients during the 5th wave, dominated by the Omicron variant. A vast majority of fifth-wave patients had the mild disease (87.35% vs. 49.39%), with significantly lower critical patients (2.04% vs. 7.09%). Vaccination was effective against both the Delta and the Omicron variant of the SARS-CoV-2 virus. The mean length of stay in the hospital for patients was significantly lesser (p < 0.001) during the 5th wave as compared to the 4th wave (6.43 ± 3.37 vs. 9.56 ± 5.45 days). The mortality rate was 7.09% among patients admitted in the 4th wave and 2.04% in the 5th wave. This difference was statistically significant (p < 0.001). CONCLUSION: The severity of disease, length of hospital stays, and mortality were higher in the Delta variant-dominated 4th wave of COVID-19 as compared to the Omicron variant-dominated 5th wave in Pakistan. The vaccination was effective against both the Delta and the Omicron variant of COVID 19, as the mortality rate among the vaccinated patients during the two waves was not significantly different. KEY WORDS: COVID 19, Vaccination, Disease outcome, Mortality.

Ag2Se Nanorod Arrays with Ultrahigh Room Temperature Thermoelectric Performance and Superior Mechanical Properties.

Ag2Se is an intriguing material for room-temperature energy harvesting. Herein, we report the fabrication of Ag2Se nanorod arrays by glancing angle deposition technique (GLAD) followed by simple selenization in a two-zone furnace. Ag2Se planar films of different thickness were also prepared. The unique tilted Ag2Se nanorod arrays show excellent zT = 1.14 ± 0.09 and a power factor of 3229.21 ± 149.01 µW/m-K2, respectively, at 300 K. The superior thermoelectric performance of Ag2Se nanorod arrays compared to planar Ag2Se films could be ascribed to the unique nanocolumnar architecture that not only facilitates efficient electron transport but also significantly scatters phonons at the interfaces. Furthermore, the nanoindentation measurements were performed to explore mechanical properties of the as-prepared films. The Ag2Se nanorod arrays showed hardness values of 116.51 ± 4.25 MPa and elastic modulus of 10,966.01 ± 529.61 MPa, which are lowered by 51.8 and 45.6%, compared to Ag2Se films, respectively. The synergetic dependence between the tilt structure and thermoelectric properties accompanied with the simultaneous improvement in mechanical properties opens a new avenue for the practical applications of Ag2Se in next-generation flexible thermoelectric devices.

Artificial microRNA-mediated resistance against Oman strain of tomato yellow leaf curl virus.

Tomato yellow leaf curl virus (TYLCV) is a global spreading begomovirus that is exerting a major restraint on global tomato production. In this transgenic approach, an RNA interference (RNAi)-based construct consisting of sequences of an artificial microRNA (amiRNA), a group of small RNA molecules necessary for plant cell development, signal transduction, and stimulus to biotic and abiotic disease was engineered targeting the AC1/Rep gene of the Oman strain of TYLCV-OM. The Rep-amiRNA constructs presented an effective approach in regulating the expression of the Rep gene against TYLCV as a silencing target to create transgenic Solanum lycopersicum L. plant tolerance against TYLCV infection. Molecular diagnosis by PCR followed by a Southern hybridization analysis were performed to confirm the effectiveness of agrobacterium-mediated transformation in T0/T1-transformed plants. A substantial decrease in virus replication was observed when T1 transgenic tomato plants were challenged with the TYLCV-OM infectious construct. Although natural resistance options against TYLCV infection are not accessible, the current study proposes that genetically transformed tomato plants expressing amiRNA could be a potential approach for engineering tolerance in plants against TYLCV infection and conceivably for the inhibition of viral diseases against different strains of whitefly-transmitted begomoviruses in Oman.

Complicated jejunal diverticulitis: A case report and review of literature.

Jejunal diverticulitis is an uncommon pathology wherein a delay in diagnosis can lead to significant morbidity and mortality. We report a case of such diverticula requiring operative management, after patient failed non-operative management, likely due to advanced jejunal inflammation from a delay in diagnosis and subsequent management.

Understanding the effect of organizational innovation environment and customer participation in virtual communities on customer creativity: A study of mediating and moderating influences.

The importance of enterprises significantly improving their innovation performance by working closely with customers throughout the innovation process has been emphasized in recent literature. However, the role of organizational innovation environment in customer creativity and the impact of customer knowledge matching on the innovation environment are not sufficiently explored. Based on the Social cognitive theory and Flow theory, his investigate the factors that influence enterprise innovation performance in the context of customer participation in innovation, as well as how businesses can foster an online innovation environment that fosters customer creativity. The mixed-methods study, which combines qualitative and quantitative research, is used to create the scale item that measures the study's main variables. Structural equation modeling and bootstrapping estimation was performed on survey data collected via questionnaire from 392 consumers who participated in online service innovation in an online virtual brand community between June 2018 and May 2019. The study obtain the following main results. First, the innovative environment of customer online participation in service innovation fosters customer creativity. Second, two mediation interactions exist: creative self-efficacy and positive emotions, both of which partially mediate the relationship between customer creativity and the innovation environment. Third, while customer knowledge matching influences the intermediary effect of creative self-efficacy on innovation environment and customer creativity, it has no effect on the intermediary effect of positive emotion on innovation environment and customer creativity.

Comparison of Clinical Characteristics and Outcome Between Vaccinated and Non-Vaccinated Patients of Covid-19 During the Delta Variant-Dominated Fourth Wave in a Tertiary Care Hospital in Karachi, Pakistan.

Introduction In Pakistan, the fourth wave of coronavirus disease 2019 (Covid-19) started around July 2021, which was dominated by the Delta variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The vaccination drive to immunize the people of Pakistan against Covid-19 was also going on during this period. There were multiple types of vaccines being administered to the people of Pakistan, as the vaccines had been procured from multiple sources. Some people had apprehensions about different vaccines being administered in the country. The purpose of this study was to compare the clinical characteristics and outcome of the patients vaccinated against Covid-19 with those of the non-vaccinated patients during the fourth wave of Covid-19 in Pakistan Naval Ship (PNS) Shifa Hospital. Methods The cross-sectional descriptive study was performed at PNS Shifa Hospital Karachi, from July to October 2021. All the Covid-19 patients treated in PNS Shifa Hospital during the "fourth Covid-19 wave" were interviewed. Their medical records were accessed, and they were followed up till their discharge from the hospital. The vaccinated and non-vaccinated patients were compared for differences in their age or gender distribution, the severity of illness, comorbidities, and mortality. Results There were 884 participants in the study: 664 (75.11%) men and 220 (24.89%) women. There were 493 patients below 40 years of age, 233 were 40-59 years old, and 158 were aged 60 and above. One hundred and sixty-nine patients had one or more comorbidities, including hypertension, diabetes mellitus, ischemic heart disease, various malignancies, bronchial asthma, and chronic kidney disease. There were 63 (7.13%) obese patients, 28 of whom developed severe disease. Five hundred and four (57%) patients were vaccinated and 380 (47%) were non-vaccinated. Among the vaccinated patients, the effect of Covid-19 was mild in 58.37%, moderate in 36.11%, severe in 0.79%, and critical in 4.37%. Among the non-vaccinated patients, the effect of Covid-19 was mild in 40.26%, moderate in 46.58%, severe in 3.16%, and critical in 10%. The difference in disease severity between the two groups was statistically significant (p<0.05). Conclusion Vaccinated Covid-19 patients had significantly lower severity of disease and displayed better outcomes when compared to non-vaccinated patients during the fourth Covid-19 wave dominated by the Delta variant of the SARS-CoV-2 virus.

Effects of late, repetitive remote ischaemic conditioning on myocardial strain in patients with acute myocardial infarction.

Late, repetitive or chronic remote ischaemic conditioning (CRIC) is a potential cardioprotective strategy against adverse remodelling following ST-segment elevation myocardial infarction (STEMI). In the randomised Daily Remote Ischaemic Conditioning Following Acute Myocardial Infarction (DREAM) trial, CRIC following primary percutaneous coronary intervention (P-PCI) did not improve global left ventricular (LV) systolic function. A post-hoc analysis was performed to determine whether CRIC improved regional strain. All 73 patients completing the original trial were studied (38 receiving 4 weeks' daily CRIC, 35 controls receiving sham conditioning). Patients underwent cardiovascular magnetic resonance at baseline (5-7 days post-STEMI) and after 4 months, with assessment of LV systolic function, infarct size and strain (longitudinal/circumferential, in infarct-related and remote territories). At both timepoints, there were no significant between-group differences in global indices (LV ejection fraction, infarct size, longitudinal/circumferential strain). However, regional analysis revealed a significant improvement in longitudinal strain in the infarcted segments of the CRIC group (from - 16.2 ± 5.2 at baseline to - 18.7 ± 6.3 at follow up, p = 0.0006) but not in corresponding segments of the control group (from - 15.5 ± 4.0 to - 15.2 ± 4.7, p = 0.81; for change: - 2.5 ± 3.6 versus + 0.3 ± 5.6, respectively, p = 0.027). In remote territories, there was a lower increment in subendocardial circumferential strain in the CRIC group than in controls (- 1.2 ± 4.4 versus - 2.5 ± 4.0, p = 0.038). In summary, CRIC following P-PCI for STEMI is associated with improved longitudinal strain in infarct-related segments, and an attenuated increase in circumferential strain in remote segments. Further work is needed to establish whether these changes may translate into a reduced incidence of adverse remodelling and clinical events. Clinical Trial Registration: http://clinicaltrials.gov/show/NCT01664611 .

Definition, prevalence, and clinical significance of mitral annular disjunction in different patient cohorts: A systematic review.

BACKGROUND: Mitral annular disjunction (MAD) is a structural abnormality involving a distinct separation of the left atrium/mitral valve annulus and myocardium continuum. The literature around MAD has increased over recent years, thus we sought to review the current data on the definition, prevalence, and clinical outcomes of MAD. METHODS: A search of MEDLINE and EMBASE was conducted to identify studies which evaluated MAD in any patient cohort. The study results were synthesized narratively. RESULTS: A total of 12 studies were included with 3925 patients (average age 62 years, 63% male). The pooled prevalence of MAD in patients with mitral valve prolapse and/or Barlow's disease was 30.1%. In a general population, MAD prevalence was 8.7%. The definition of MAD was not consistent across all studies. In terms of clinical outcomes, only one study reported MAD to be associated with ventricular arrhythmias. CONCLUSIONS: MAD is an increasingly recognized finding amongst patients undergoing cardiac imaging. This review highlights the need for agreed definitions for clinically significant MAD and how identified MAD should be managed. At present, there is insufficient evidence that MAD is associated adverse clinical outcomes.

Complementary role of cardiac CT in the diagnosis and management of mechanical aortic valve thrombosis with a novel low-dose, ultraslow thrombolysis treatment strategy.

A 31-year-old man presented to our emergency department with a 3-day history of progressive breathlessness, fatigue and exertional angina. His history included a mechanical aortic valve replacement (mAVR) for rheumatic heart disease at age 19 years. He could no longer afford medication prescription costs and consequently had not taken oral anticoagulation for 2 months. Transthoracic echocardiography (TTE) demonstrated mechanical prosthetic valve obstruction (PVO) and severe left ventricular (LV) systolic dysfunction; however, valve visualisation was limited by mAVR-related artefact. The patient declined transoesophageal echocardiography. Valve haemodynamics failed to improve despite a prolonged course of parenteral anticoagulation. Multidetector cardiac CT scan was performed which confirmed prosthetic valve thrombosis. A novel low-dose, ultraslow thrombolysis regimen was administered to mitigate the associated bleeding and embolic stroke risk. The patient made an excellent recovery and was discharged on day 30, with repeat cardiac CT scan showing complete resolution of mechanical PVO and normalisation of valve and LV function on TTE.

Prevalence and Prognostic Significance of Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The pathophysiological and clinical significance of microvascular dysfunction (MVD) in patients with heart failure with preserved ejection fraction (HFpEF) remains uncertain. OBJECTIVES: The aim of this study was to use cardiovascular magnetic resonance to: 1) quantify coronary microvascular function; 2) examine the relationship between perfusion and fibrosis; and 3) evaluate the impact of MVD and fibrosis on long-term clinical outcomes. METHODS: In a prospective, observational study, patients with HFpEF and control subjects underwent multiparametric cardiovascular magnetic resonance (comprising assessment of left ventricular volumetry, perfusion, and fibrosis [focal by late gadolinium enhancement and diffuse by extracellular volume]). The primary endpoint was the composite of death or hospitalization with heart failure. RESULTS: One hundred and one patients with HFpEF (mean age 73 ± 9 years, mean ejection fraction 56% ± 5%) and 43 control subjects (mean age 73 ± 5 years, mean ejection fraction 58% ± 5%) were studied. Myocardial perfusion reserve (MPR) was lower in patients with HFpEF versus control subjects (1.74 ± 0.76 vs 2.22 ± 0.76; P = 0.001). MVD (defined as MPR <2.0) was present in 70% of patients with HFpEF (vs 48% of control subjects; P = 0.014). There was no significant linear correlation between MPR and diffuse fibrosis (r = -0.10; P = 0.473) and no difference in MPR between those with and without focal fibrosis (mean difference -0.03; 95% CI: -0.37 to 0.30). In the HFpEF group, during median follow-up of 3.1 years, there were 45 composite events. MPR was independently predictive of clinical outcome following adjustment for clinical, blood, and imaging parameters (1 SD increase: HR: 0.673 [95% CI: 0.463 to 0.978; P = 0.038]; HR: 0.694 [95% CI: 0.491 to 0.982; P = 0.039]; and HR: 0.690 [95% CI: 0.489 to 0.973; P = 0.034], respectively). CONCLUSIONS: MVD is highly prevalent among patients with HFpEF and is an independent predictor of prognosis. The lack of correlation between MVD and fibrosis may challenge the assertion of a direct causal link between these entities. (Developing Imaging and Plasma Biomarkers in Describing Heart Failure With Preserved Ejection Fraction [DIAMONDHFpEF]; NCT03050593).

Does sustainable environmental agenda matter in the era of globalization? The relationship among financial development, energy consumption, and sustainable environmental-economic growth.

The purpose of this research is to explore the connection of financial development, sustainable environmental-economic growth, and energy consumption among the South Asian Nations. This research examines a combine influence on energy consumption, financial development on sustainable environmental economic growth regarding south Asian economies. This study has used autoregressive distributive lag (ARDL) and panel data set from World Development Indicators (WDI) start from 1980 to 2018. The findings of this study indicate a significant and positive effect of financial development toward economic growth of selected south Asian economies. However, energy consumption has also positive impact toward sustainable environmental-economic growth, which further leads toward sustainable environmental agenda progress. Finally, energy consumption results have positive effect on sustainable economic growth among mean group (MG), pooled mean group (PMG), and common correlated effect mean group (CMEMG) results.