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HER2 is an actionable target in metastatic colorectal cancer. We assessed the activity of tucatinib plus trastuzumab in patients with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer. MOUNTAINEER is a global, open-label, phase 2 study that enrolled patients aged 18 years and older with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer at 34 sites (clinics and hospitals) in five countries (Belgium, France, Italy, Spain, and the USA). Initially, the study was designed as a single-cohort study, which was expanded following an interim analysis to include more patients. Initially, patients were given tucatinib (300 mg orally twice daily) plus intravenous trastuzumab (8 mg/kg as an initial loading dose, then 6 mg/kg every 21 days; cohort A) for the duration of treatment (until progression), and after expansion, patients were randomly assigned (4:3), using an interactive web response system and stratified by primary tumour location, to either tucatinib plus trastuzumab (cohort B) or tucatinib monotherapy (cohort C). The primary endpoint was confirmed objective response rate per blinded independent central review (BICR) for cohorts A and B combined and was assessed in patients in the full analysis set (ie, patients with HER2-positive disease who received at least one dose of study treatment). Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov , NCT03043313 , and is ongoing. Between Aug 8, 2017, and Sept 22, 2021, 117 patients were enrolled (45 in cohort A, 41 in cohort B, and 31 in cohort C), of whom 114 patients had locally assessed HER2-positive disease and received treatment (45 in cohort A, 39 in cohort B, and 30 in cohort C; full analysis set), and 116 patients received at least one dose of study treatment (45 in cohort A, 41 in cohort B, and 30 in cohort C; safety population). In the full analysis set, median age was 56·0 years (IQR 47–64), 66 (58%) were male, 48 (42%) were female, 88 (77%) were White, and six (5%) were Black or African American. As of data cutoff (March 28, 2022), in 84 patients from cohorts A and B in the full analysis set, the confirmed objective response rate per BICR was 38·1% (95% CI 27·7–49·3; three patients had a complete response and 29 had a partial response). In cohorts A and B, the most common adverse event was diarrhoea (55 [64%] of 86), the most common grade 3 or worse adverse event was hypertension (six [7%] of 86), and three (3%) patients had tucatinib-related serious adverse events (acute kidney injury, colitis, and fatigue). In cohort C, the most common adverse event was diarrhoea (ten [33%] of 30), the most common grade 3 or worse adverse events were increased alanine aminotransferase and aspartate aminotransferase (both two [7%]), and one (3%) patient had a tucatinib-related serious adverse event (overdose). No deaths were attributed to adverse events. All deaths in treated patients were due to disease progression. Tucatinib plus trastuzumab had clinically meaningful anti-tumour activity and favourable tolerability. This treatment is the first US Food and Drug Administration-approved anti-HER2 regimen for metastatic colorectal cancer and is an important new treatment option for chemotherapy-refractory HER2-positive metastatic colorectal cancer. Seagen and Merck & Co. [ABSTRACT FROM AUTHOR]

The article evaluates the efficacy of neoadjuvant dual immune checkpoint blockade in early-stage colon cancer with mismatch repair deficiency (dMMR), emphasizing significant pathological responses observed in patients. It discusses the challenges of staging dMMR tumors accurately, the potential risks and benefits of neoadjuvant immunotherapy, and the need for randomized trials to establish its impact on long-term patient outcomes and treatment standards.

Background: Neoadjuvant chemotherapy and radiation followed by surgical resection of the rectum is a standard treatment for locally advanced rectal cancer. A subset of rectal cancer is caused by a deficiency in mismatch repair. Because mismatch repair-deficient colorectal cancer is responsive to programmed death 1 (PD-1) blockade in the context of metastatic disease, it was hypothesized that checkpoint blockade could be effective in patients with mismatch repair-deficient, locally advanced rectal cancer.Methods: We initiated a prospective phase 2 study in which single-agent dostarlimab, an anti-PD-1 monoclonal antibody, was administered every 3 weeks for 6 months in patients with mismatch repair-deficient stage II or III rectal adenocarcinoma. This treatment was to be followed by standard chemoradiotherapy and surgery. Patients who had a clinical complete response after completion of dostarlimab therapy would proceed without chemoradiotherapy and surgery. The primary end points are sustained clinical complete response 12 months after completion of dostarlimab therapy or pathological complete response after completion of dostarlimab therapy with or without chemoradiotherapy and overall response to neoadjuvant dostarlimab therapy with or without chemoradiotherapy.Results: A total of 12 patients have completed treatment with dostarlimab and have undergone at least 6 months of follow-up. All 12 patients (100%; 95% confidence interval, 74 to 100) had a clinical complete response, with no evidence of tumor on magnetic resonance imaging, 18F-fluorodeoxyglucose-positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy. At the time of this report, no patients had received chemoradiotherapy or undergone surgery, and no cases of progression or recurrence had been reported during follow-up (range, 6 to 25 months). No adverse events of grade 3 or higher have been reported.Conclusions: Mismatch repair-deficient, locally advanced rectal cancer was highly sensitive to single-agent PD-1 blockade. Longer follow-up is needed to assess the duration of response. (Funded by the Simon and Eve Colin Foundation and others; ClinicalTrials.gov number, NCT04165772.). [ABSTRACT FROM AUTHOR]

Background: The causative factors for the recent increase in early-onset colorectal cancer (EO-CRC) incidence are unknown. We sought to determine if early-onset disease is clinically or genomically distinct from average-onset colorectal cancer (AO-CRC).Methods: Clinical, histopathologic, and genomic characteristics of EO-CRC patients (2014-2019), divided into age 35 years and younger and 36-49 years at diagnosis, were compared with AO-CRC (50 years and older). Patients with mismatch repair deficient tumors, CRC-related hereditary syndromes, and inflammatory bowel disease were excluded from all but the germline analysis. All statistical tests were 2-sided.Results: In total, 759 patients with EO-CRC (35 years, n = 151; 36-49 years, n = 608) and AO-CRC (n = 687) were included. Left-sided tumors (35 years and younger = 80.8%; 36-49 years = 83.7%; AO = 63.9%; P < .001 for both comparisons), rectal bleeding (35 years and younger = 41.1%; 36-49 years = 41.0%; AO = 25.9%; P = .001 and P < .001, respectively), and abdominal pain (35 years and younger = 37.1%; 36-49 years = 34.0%; AO = 26.8%; P = .01 and P = .005, respectively) were more common in EO-CRC. Among microsatellite stable tumors, we found no differences in histopathologic tumor characteristics. Initially, differences in TP53 and Receptor Tyrosine Kinase signaling pathway (RTK-RAS)alterations were noted by age. However, on multivariate analysis including somatic gene analysis and tumor sidedness, no statistically significant differences at the gene or pathway level were demonstrated. Among advanced microsatellite stable CRCs, chemotherapy response and survival were equivalent by age cohorts. Pathogenic germline variants were identified in 23.3% of patients 35 years and younger vs 14.1% of AO-CRC (P = .01).Conclusions: EO-CRCs are more commonly left-sided and present with rectal bleeding and abdominal pain but are otherwise clinically and genomically indistinguishable from AO-CRCs. Aggressive treatment regimens based solely on the age at CRC diagnosis are not warranted. [ABSTRACT FROM AUTHOR]

Background: It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes–ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19. Methods: The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality. Results: A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73–0.85, p < 0.0001) and without diabetes (IRR 0.81 (95% CI: 0.78–0.85, p < 0.0001) (p int = 0.40). We observed a significant heterogeneity among centers in the population with and without diabetes (p < 0.001, respectively). The heterogeneity among centers was not related to the incidence of death due to COVID-19 in both groups of patients. Interaction was observed for Hypertension (p = 0.024) only in absence of diabetes. Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients. Conclusions: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a similar reduction in primary PCI procedures in both patients with and without diabetes. Hypertension had a significant impact on PCI reduction only among patients without diabetes. We observed a significant increase in ischemia time and door-to-balloon time mainly in absence of diabetes, that contributed to explain the increased mortality observed in this group of patients during the pandemic. Trial registration number: NCT 04412655. [ABSTRACT FROM AUTHOR]

Purpose Oxaliplatin at a dose of 85 mg/m² traditionally has been administered over 120 min in the standard FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) regimen. CapeOx (capecitabine plus oxaliplatin), in which the dose of oxaliplatin is 130 mg/m², has also been infused over 120 min. Maintenance of a prolonged infusion time has been largely based on the concern for a potential hypersensitivity reaction (HSR) if administered too quickly. Methods We first performed a retrospective review of our institutional experience to assess whether HSR rates were similar in FOLFOX and CapeOx by using computerized pharmacy records between January 1, 2011, and December 31, 2013. We then instituted a new policy to infuse all nonresearch doses of oxaliplatin at a set rate of 1 mg/m²/min (85 mg/m² given over 85 min; 68 mg/m² over 68 min, etc). The incidence of HSRs with the new infusion rate was actively monitored. Results Of 2,097 patients who previously received oxaliplatin over 120 min, 1,936 received a dose of 85 mg/m² (6 10%), and 161 received a dose of 130 mg/m². The incidence of HSRs in the 85 mg/m² group was 11% versus 7% in the 130 mg/m² group (P = .13). Then between December 1,2014, and June 4,2015,667 patients received oxaliplatin at a rate of 1 mg/m²/min for all doses. The incidence of HSRs in patients treated at this fixed infusion rate was 8%. Conclusion Infusing oxaliplatin at a rate of 1 mg/m²/min does not increase the rate of HSRs and does not compromise patient safety. This infusion rate is safe for use in routine practice. [ABSTRACT FROM AUTHOR]

To date, there are no data on the feasibility and accuracy of bedside pacing stress echocardiography in patients admitted to the hospital with new-onset chest pain or unstable angina. We evaluated the feasibility of pacing stress echocardiography and examined its correlation with myocardial perfusion stress scintigraphy (rest thallium-201/stress technetium-99m sestamibi dual-isotope myocardial perfusion single-photon emission computerized tomography) performed within 24 hours of the pacing stress echocardiography test. We studied 70 consecutive patients after acute myocardial infarction had been excluded. The bedside pacing stress echocardiography test was performed with 10Fr transesophageal pacing catheters. We found pacing stress echocardiography to be feasible and safe (3% minor adverse event rate) at the patients' bedside. Target heart rate of >85% of the age-predicted heart rate was achieved in 96% of patients, and the mean rate-pressure product was 22,644 +/- 4,520 beats/min/mm Hg. The mean duration of the bedside pacing stress echocardiography test including technical preparations and image interpretation was 41 +/- 7 minutes. Pacing stress echocardiography and myocardial perfusion stress scintigraphy correlated well for identification or exclusion of inducible myocardial ischemia in 63 of 70 patients (90%) (kappa 0.81, p <0.001). The extent of inducible myocardial ischemia by vascular territories correlated with myocardial perfusion stress scintigraphy in 52 of 70 patients (74%) (kappa 0.6, p <0.001). We conclude that bedside pacing stress echocardiography is feasible and safe, and highly correlates with myocardial perfusion stress scintigraphy for identifying inducible myocardial ischemia in patients with new onset of chest pain or unstable angina. [ABSTRACT FROM AUTHOR]

The article describes the case of a 52-year-old male patient with a history of dilated cardiomyopathy and heart failure (HF), and was subjected to echocardiography to measure hemodynamic parameters, central venous pressure (CVP) and blood volume status. Several factors are considered to ascertain the diagnosis including the use of pulmonary artery flotation catheter, echo-Doppler, and assessment of pulmonary artery pressure (PAP). The formula used in measuring the cardiac output is given.

BACKGROUND BRAF mutations occur in 5% to 11% of patients with metastatic colorectal cancer (mCRC) and have been associated with poor prognosis. The current study was undertaken to determine the clinicopathologic characteristics, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) mutation frequency, and outcomes after metastasectomy in patients with BRAF-mutant mCRC. METHODS Data from 1941 consecutive patients with mCRC who underwent KRAS/BRAF mutation testing between 2009 and 2012 at a single institution were identified to identify BRAF-mutant mCRC cases (92 cases). BRAF wild-type mCRC cases from 2011 (423 cases) served as a control group. RESULTS BRAF-mutated mCRC was found to be significantly associated with older age at diagnosis, female sex, right-sided location, poorly differentiated morphology, and mucinous histology compared with wild-type cases. BRAF-mutant cases more frequently progressed from stage III disease (32% vs 17%; P = .003) and among those patients with stage III disease, T4 disease was more common (48% vs 27%; P = .05). PIK3CA was found to be co-mutated in 5% of BRAF-mutant tumors versus 17% of KRAS-mutant tumors ( P < .01) and 4% of BRAF/KRAS wild-type cases. Patients with BRAF-mutated mCRC presented more frequently with peritoneal involvement (26% vs 14%; P < 0.01) and less frequently with liver-limited metastases (41% vs 63%; P < .01). Patients with BRAF-mutated mCRC were less likely to undergo metastasectomy (41% vs 26% at 2 years from diagnosis of metastatic disease; P < .01) and were found to have lower overall survival ( P < .01) after metastasectomy. CONCLUSIONS BRAF-mutant mCRC is associated with worse clinical outcome. Patients with BRAF-mutant tumors more commonly develop peritoneal metastases, less frequently present with disease limited to the liver, and have shorter survival after metastasectomy compared with patients with BRAF wild-type tumors. Cancer 2014;120:2316-2324. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

The specificity and cross-species activity of thymic extracts and some non-specific agents on some alleged properties of T cells and their precursors in the bone marrow cells of normal, nude and thymectomized mice was studied in vitro. The phenomenon of changes in the structuredness of cytoplasmic matrix (SCM) was used to assess the maturation and responses of cells treated with the extracts to mitogens, i.e. phytohaemagglutinin and concanavalin A. We found that thymic extracts of calf and mouse origin induce functional ‘maturation’ which can be abrogated by cycloheximide, an inhibitor of protein synthesis. The non-specific agents used (spleen extracts, PPD, dBcAMP and endotoxin) had no effect on bone marrow cells, as measured by changes in the SCM. The method of measuring SCM using the technique of fluorescence polarization is described. [ABSTRACT FROM AUTHOR]

Transradial (TR) access is increasingly being used in percutaneous coronary intervention (PCI). However, its role in PCI for ST-segment elevation myocardial infarction remains controversial because of concerns of procedural complexity adversely affecting the promptness of reperfusion. In this study, 150 consecutive patients who underwent PCI for acute ST-segment elevation myocardial infarction over a period of 24 months were prospectively evaluated; 46 had TR access (31%) and 104 (69%) had transfemoral (TF) access. All patients received thienopyridines, aspirin, and heparin per routine management. There were no significant differences between the TR access and TF access groups with respect to age (62.2 ± 11.6 vs 64.7 ± 14.1, p = 0.28), gender (76.1% vs 72.1% men, p = 0.69), or incidence of diabetes (23.9% vs 26.9%, p = 0.84). The TR and TF access groups were comparable with respect to door-to-balloon time (79.2 ± 32.3 vs 86.8 ± 51.8 minutes, p = 0.67) and amount of contrast used (190.5 ± 101.5 vs 172.2 ± 81.7 ml, p = 0.24). Total fluoroscopy time was longer in the TR access group compared to the TF access group (21.7 ± 12.7 vs 14.4 ± 10.4 minutes, p <0.0001). Postprocedural Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow was comparable for the 2 groups (87% for the TF group and 96% for the TR group, p = 0.15). There were no vascular complications in the TR access group compared to the TF access group (0% vs 5.8%, p = 0.18). In conclusion, this single-center observational study shows that TR access for PCI in STEMI is feasible and that it has fewer vascular complications and shorter length of hospital stay than the TF approach. [ABSTRACT FROM AUTHOR]

Abstract: Interleukin 15 (IL-15) is a pro-inflammatory cytokine that modulates T cell recruitment and activation, independent of antigen. It has been detected in human atherosclerotic plaques and atherosclerotic plaques of apoE−/− mice. IL-15 regulates fractalkine (FKN)–CX3CR1 chemokine signaling which is involved in atherogenesis and promotes SMC proliferation. We investigated the role of IL-15 in intimal thickening after arterial injury. Treatment of serum-stimulated SMC with IL-15 in vitro attenuated proliferation and suppressed CX3CR1 and FKN mRNA expression. The role of endogenous IL-15 in vivo was investigated in injured carotid arteries of mice. Periadventitial arterial injury resulted in increased IL-15 expression in the media and neointima, paralleled by increased IL-15 receptor α expression. Blockade of endogenous IL-15 increased intimal thickening. FKN and CX3CR1 expression increased after injury and were further augmented after IL-15 blockade. These data suggest that endogenous IL-15 attenuated intimal thickening after arterial injury. The potential mechanism of action is suppression of CX3CR1 signaling. [Copyright &y& Elsevier]

One hundred fifty patients with their first acute myocardial infarctions (AMIs) were studied. AMIs were confirmed by troponin levels, ST-segment elevation, or angiographic coronary occlusion. In 36% of patients (16 of 45) with left ventricular (LV) hypertrophy, the wall motion score index was normal, whereas in patients with no LV hypertrophy, only 18% (19 of 105) had no segmental wall motion abnormalities (p = 0.03). When adjusting for troponin level, the odds ratio for normal wall motion of patients with LV hypertrophy was 2.86 (95% confidence interval 1.26 to 6.50) compared with those with normal wall thickness. Consequently, normal LV wall motion by echocardiography in the setting of LV hypertrophy does not exclude AMI. [Copyright &y& Elsevier]

Summary: Background: There is serological and epidemiological evidence of an association between Chlamydia pneumoniae infection and coronary artery disease. Results of previous smaller studies have indicated a reduction of recurrent ischaemic events in patients with acute coronary syndrome when given macrolide antibiotics. We aimed to assess whether short-term treatment with the macrolide antibiotic azithromycin reduces recurrent ischaemic events in patients admitted for unstable angina or myocardial infarction. Methods: We assessed the effect of azithromycin in a multicentre, double-blind randomised trial in 1439 patients with unstable angina or acute myocardial infarction. Patients were randomly allocated to receive 500 mg azithromycin on the first day after randomisation, followed by 250 mg daily for 4 days or placebo. Patients were followed up for 6 months. The primary endpoints were death, recurrent myocardial infarction, or recurrent ischaemia necessitating revascularisation. Analysis was done by intention to treat. Findings: Treatment with azithromycin did not result in reduction of either individual endpoints or any of the primary endpoints. Of the 716 patients in the azithromycin group, 23 (3%) died, 17 (2%) developed myocardial infarction, 65 (9%) had recurrent ischaemia needing revascularisation, and 100 (14%) had one or more of these endpoints. In the placebo group (n=723) the corresponding numbers of patients were 24 (4%), 22 (3%), 59 (8%), and 106 (15%), respectively (p=0.664, 95% CI 0.72-1.24). 62 (9%) of patients in the azithromycin group and 59 (8%) in the placebo group reached the secondary endpoint of ischaemia or congestive heart failure necessitating admission (difference 0.5%, 95% CI 0.75-1.53; p=0.707). We recorded few side-effects. Interpretation: Short-term treatment with azithromycin does not reduce development of recurrent events in patients with acute coronary syndrome. [ABSTRACT FROM AUTHOR]

Focuses on the feasibility and accuracy of bedside pacing stress echocardiagraphy in patients admitted to the hospital with new-onset chest pain or unstable angina. Correlation with myocardial perfusion stress scintigraphy; Achievement of target heart rate; Extent of inducible myocardial ischemia in patients.

Concerns have been raised on a potential interaction between renin-angiotensin system inhibitors (RASI) and the susceptibility to coronavirus disease 2019 (COVID-19). No data have been so far reported on the prognostic impact of RASI in patients suffering from ST-elevation myocardial infarction (STEMI) during COVID-19 pandemic, which was the aim of the present study. STEMI patients treated with primary percutaneous coronary intervention (PPCI) and enrolled in the ISACS-STEMI COVID-19 registry were included in the present sub-analysis and divided according to RASI therapy at admission. Our population is represented by 6095 patients, of whom 3654 admitted in 2019 and 2441 in 2020. No difference in the prevalence of SARSCoV2 infection was observed according to RASI therapy at admission (2.5% vs 2.1%, p = 0.5), which was associated with a significantly lower mortality (adjusted OR [95% CI]=0.68 [0.51–0.90], P = 0.006), confirmed in the analysis restricted to 2020 (adjusted OR [95% CI]=0.5[0.33–0.74], P = 0.001). Among the 5388 patients in whom data on in-hospital medication were available, in-hospital RASI therapy was associated with a significantly lower mortality (2.1% vs 16.7%, OR [95% CI]=0.11 [0.084–0.14], p < 0.0001), confirmed after adjustment in both periods. Among the 62 SARSCoV-2 positive patients, RASI therapy, both at admission or in-hospital, showed no prognostic effect. This is the first study to investigate the impact of RASI therapy on the prognosis and SARSCoV2 infection of STEMI patients undergoing PPCI during the COVID-19 pandemic. Both pre-admission and in-hospital RASI were associated with lower mortality. Among SARSCoV2-positive patients, both chronic and in-hospital RASI therapy showed no impact on survival. [ABSTRACT FROM AUTHOR]

POLE and POLD1 proofreading deficiency (POLE/D1pd) define a rare subtype of ultramutated metastatic colorectal cancer (mCRC; over 100 mut/Mb). Disease-specific data about the activity and efficacy of immune checkpoint inhibitors (ICIs) in POLE/D1pd mCRC are lacking and it is unknown whether outcomes may be different from mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRCs treated with ICIs. In this global study, we collected 27 patients with mCRC harboring POLE/D1 mutations leading to proofreading deficiency and treated with anti-programmed cell death-ligand 1 alone +/− anti-cytotoxic T-lymphocyte antigen-4 agents. We collected clinicopathological and genomic characteristics, response, and survival outcomes after ICIs of POLE/D1pd mCRC and compared them with a cohort of 610 dMMR/MSI-H mCRC patients treated with ICIs. Further genomic analyses were carried out in an independent cohort of 7241 CRCs to define POLE and POLD1pd molecular profiles and mutational signatures. POLE/D1pd was associated with younger age, male sex, fewer RAS/BRAF driver mutations, and predominance of right-sided colon cancers. Patients with POLE/D1pd mCRC showed a significantly higher overall response rate (ORR) compared to dMMR/MSI-H mCRC (89% versus 54%; P = 0.01). After a median follow-up of 24.9 months (interquartile range: 11.3-43.0 months), patients with POLE/D1pd showed a significantly superior progression-free survival (PFS) compared to dMMR/MSI-H mCRC [hazard ratio (HR) = 0.24, 95% confidence interval (CI) 0.08-0.74, P = 0.01] and superior overall survival (OS) (HR = 0.38, 95% CI 0.12-1.18, P = 0.09). In multivariable analyses including the type of DNA repair defect, POLE/D1pd was associated with significantly improved PFS (HR = 0.17, 95% CI 0.04-0.69, P = 0.013) and OS (HR = 0.24, 95% CI 0.06-0.98, P = 0.047). Molecular profiling showed that POLE/D1pd tumors have higher tumor mutational burden (TMB). Responses were observed in both subtypes and were associated with the intensity of POLE/D1pd signature. Patients with POLE/D1pd mCRC showed more favorable outcomes compared to dMMR/MSI-H mCRC to treatment with ICIs in terms of tumor response and survival. • POLE/D1pd is associated with male sex, younger age, right-sided primary tumor, and uncommon KRAS mutations in mCRC. • A significantly higher ORR is observed for POLE/D1pd compared to dMMR/MSI-H mCRC treated with ICIs. • POLE/D1pd mCRC exposed to ICIs have a higher PFS and OS than dMMR/MSI-H. • POLE/D1pd mCRCs are enriched in single nucleotide variant while dMMR/MSI-H are enriched in frameshift mutations. • Non-responder POLEpd mCRCs have lower TMB than responders and lower intensity of the POLE signature. [ABSTRACT FROM AUTHOR]

Background: Palmar-plantar erythrodysesthesia (PPE) is a slowly developing cutaneous reaction commonly experienced by patients treated with fluoropyrimidines. While erythrodysesthesia normally presents in a palmar-plantar distribution, it can also present with genital involvement, but this presentation is likely underreported and incorrectly attributed to an acute reaction from radiation therapy. This article aims to define erythrodysesthesia of the penis and scrotum as a rare but significant side effect of capecitabine. Case presentation: We identified five cases of moderate to severe penis and scrotal erythrodysesthesia over a 2-year period at a large tertiary cancer center, representing an estimated incidence of 3.6% among male patients with rectal cancer who were treated with fluoropyrimidine-based chemoradiation within our institution. Conclusions: Improved understanding of erythrodysesthesia involving the penis and scrotum can facilitate early identification and treatment of symptoms, and possibly prevent the discontinuation or delay of cancer treatment in patients treated with capecitabine and similar drugs. These clinical advances would improve and prolong patient quality of life during cancer treatment and prevent complications that result in hospitalization. [ABSTRACT FROM AUTHOR]

The healing events of 7 patients with generalized chronic periodontitis were monitored clinically during 3 consecutive phases of treatment: 1) tooth brushing and flossing, 2) subgingival use of the Perio-Aid®, and 3) supra and subgingival instrumentation. The clinical parameters evaluated were plaque score, bleeding score, probing pocket depth, probing attachment level, and gingival recession. Each phase continued until maximum effects were achieved (5, 3, and 9 months respectively) determined by minimal or no changes in bleeding scores and probing pocket depths between 3 successive examinations. The results showed limited improvement in the bleeding scores and probing pocket depths with tooth brushing and flossing only (Phase 1). During use of the Perio-Aid (Phase 2), there was no additional improvement, but the initial limited gains made during Phase 1 were maintained. By the end of Phase 2, however, a slight loss of probing attachment level was noticeable. After instrumentation (Phase 3), there was further and more pronounced improvement in bleeding scores and probing pocket depths, as well as a reversal of the probing attachment loss. The results of this study indicate that significant improvement in periodontal pockets should not be expected following home care procedures alone, and that instrumentation may account for the bulk of improvement seen following a combined therapy of plaque control and instrumentation. [ABSTRACT FROM AUTHOR]

The author comments on the study on the increased mortality after antibiotic treatment in patients with coronary artery disease. He argues that the facts are hard to reconcile and do not direct to a common mechanism on the negative effects of antibiotic treatment in patients with coronary artery disease. He states that the study need to be considered as hypothesis generating only until further studies on the increased risk of death with clarithromycin or other antibiotics are obtained.

Background: Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center. Methods: A retrospective review of all patients who underwent APR for biopsy-proven persistent or recurrent anal SCC between 1 January 2007 and 31 December 2020 was performed. Patients with stage IV disease at the time of initial diagnosis and patients with missing data were excluded. Univariate analysis was used with a chi-square test for categorical variables, and non-parametric tests were used for continuous variables. Kaplan–Meier survival analysis was performed to evaluate disease-specific (DSS), post-APR local recurrence-free (RFS), and disease-free survival (DFS). Results: A total of 96 patients were included in the analysis: 39 (41%) with persistent disease and 57 (59%) with recurrent SCC after chemoradiation had been completed. The median follow-up was 22 months (IQR 11–47). Forty-nine patients (51%) underwent extended APR and/or pelvic exenteration. Eight (8%) patients developed local recurrence, 30 (31%) developed local and distant recurrences, and 16 (17%) developed distant recurrences alone. The 3-year DSS, post-APR local recurrence-free survival, and disease-free survival were 53.8% (95% CI 43.5–66.5%), 54.5% (95% CI 44.4–66.8%), and 26.8% (95% CI 18.6–38.7%), respectively. In multivariate logistic regression analysis, positive microscopic margin (OR 10.0, 95% CI 2.16–46.12, p = 0.003), positive nodes in the surgical specimen (OR 9.19, 95% CI 1.99–42.52, p = 0.005), and lymphovascular invasion (OR 2.61 95% CI 1.05–6.51, p = 0.04) were associated with recurrence of disease. Gender, indication for APR (recurrent vs. persistent disease), HIV status, extent of surgery, or type of reconstruction did not influence survival outcomes. Twenty patients had targeted tumor-sequencing data available. Nine patients had PIK3CA mutations, seven of whom experienced a recurrence. Conclusions: Salvage APR for anal SCC after failed CRT was associated with poor disease-specific survival and low recurrence-free survival. Anal SCC patients undergoing salvage APR should be counseled that microscopic positive margins, positive lymph nodes, or the presence of lymphovascular invasion in the APR specimen are prognosticators for disease relapse. Our results accentuate the necessity for additional treatment strategies for the ongoing treatment challenge of persistent or recurrent anal SCC after failed CRT. [ABSTRACT FROM AUTHOR]

PURPOSE: Intrahepatic cholangiocarcinoma (ICCA) is characterized by significant phenotypic and clinical heterogeneities and poor response to systemic therapy, potentially related to underlying heterogeneity in oncogenic alterations. We aimed to characterize the genomic heterogeneity between primary tumors and advanced disease in patients with ICCA. METHODS: Biopsy-proven CCA specimens (primary tumor and paired advanced disease [metastatic disease, progressive disease on systemic therapy, or postoperative recurrence]) from two institutions were subjected to targeted next-generation sequencing. Overall concordance (oncogenic driver mutations, copy number alterations, and fusion events) and mutational concordance (only oncogenic mutations) were compared across paired samples. A subgroup analysis was performed on the basis of exposure to systemic therapy. Patients with extrahepatic CCA (ECCA) were included as a comparison group. RESULTS: Sample pairs from 65 patients with ICCA (n = 54) and ECCA (n = 11) were analyzed. The median time between sample collection was 19.6 months (range, 2.7-122.9). For the entire cohort, the overall oncogenic concordance was 49% and the mutational concordance was 62% between primary and advanced disease samples. Subgroup analyses of ICCA and ECCA revealed overall/mutational concordance rates of 47%/58% and 60%/84%, respectively. Oncogenic concordance was similarly low for pairs exposed to systemic therapy between sample collections (n = 50, 53% overall, 68% mutational). In patients treated with targeted therapy for IDH1/2 alterations (n = 6) or FGFR2 fusions (n = 3), there was 100% concordance between the primary and advanced disease specimens. In two patients, FGFR2 (n = 1) and IDH1 (n = 1) alterations were detected de novo in the advanced disease specimens. CONCLUSION: The results reflect a high degree of heterogeneity in ICCA and argue for reassessment of the dominant driver mutations with change in disease status. The low concordance between primary and recurrent/metastatic IHC reflects a high degree of genomic heterogeneity. [ABSTRACT FROM AUTHOR]

SARS-Cov-2 predisposes patients to thrombotic complications, due to excessive inflammation, endothelial dysfunction, platelet activation, and coagulation/fibrinolysis disturbances. The aim of the present study was to evaluate clinical characteristics and prognostic impact of SARS-CoV-2 positivity among STEMI patients undergoing primary percutaneous coronary intervention (PPCI). We selected SARS-CoV-2 positive patients included in the ISACS-STEMI COVID-19, a retrospective multicenter European registry including 6609 STEMI patients treated with PPCI from March 1st until April 30th, in 2019 and 2020. As a reference group, we randomly sampled 5 SARS-Cov-2 negative patients per each SARS-CoV-2 positive patient, individually matched for age, sex, and hospital/geographic area. Study endpoints were in-hospital mortality, definite stent thrombosis, heart failure. Our population is represented by 62 positive SARS-CoV-2 positive patients who were compared with a matched population of 310 STEMI patients. No significant difference was observed in baseline characteristics or the modality of access to the PCI center. In the SARS-CoV-2 positive patients, the culprit lesion was more often located in the RCA (p < 0.001). Despite similar pre and postprocedural TIMI flow, we observed a trend in higher use of GP IIb-IIIa inhibitors and a significantly higher use of thrombectomy in the SARS-CoV-2 positive patients. SARS-CoV-2 positivity was associated with a remarkably higher in hospital mortality (29% vs 5.5%, p < 0.001), definite in-stent thrombosis (8.1% vs 1.6%, p = 0.004) and heart failure (22.6% vs 10.6%, p = 0.001) that was confirmed after adjustment for confounding factors. Our study showed that among STEMI patients, SARS-CoV-2 positivity is associated with larger thrombus burden, a remarkably higher mortality but also higher rates of in-stent thrombosis and heart failure. [Display omitted] • SARS-Cov-2 enhances thrombosis through inflammation, endothelial dysfunction and platelet activation. • SARS-CoV-2 positivity is associated with larger use of GP IIb-IIIa inhibitors and thrombectomy during primary percutaneous coronary intervention. • SARS-CoV-2 positivity increased hospital mortality, definite in-stent thrombosis and heart failure. [ABSTRACT FROM AUTHOR]

SARS-Cov-2 has been suggested to promote thrombotic complications and higher mortality. The aim of the present study was to evaluate the impact of SARS-CoV-2 positivity on in-hospital outcome and 30-day mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) enrolled in the International Survey on Acute Coronary Syndromes ST-segment elevation Myocardial Infarction (ISACS-STEMI COVID-19 registry. The 109 SARS-CoV-2 positive patients were compared with 2005 SARS-CoV-2 negative patients. Positive patients were older (P =.002), less often active smokers (P =.002), and hypercholesterolemic (P =.006), they presented more often later than 12 h (P =.037), more often to the hub and were more often in cardiogenic shock (P =.02), or requiring rescue percutaneous coronary intervention after failed thrombolysis (P <.0001). Lower postprocedural Thrombolysis in Myocardial Infarction 3 flow (P =.029) and more thrombectomy (P =.046) were observed. SARS-CoV-2 was associated with a significantly higher in-hospital mortality (25.7 vs 7%, adjusted Odds Ratio (OR) [95% Confidence Interval] = 3.2 [1.71-5.99], P <.001) in-hospital definite in-stent thrombosis (6.4 vs 1.1%, adjusted Odds Ratio [95% CI] = 6.26 [2.41-16.25], P <.001) and 30-day mortality (34.4 vs 8.5%, adjusted Hazard Ratio [95% CI] = 2.16 [1.45-3.23], P <.001), confirming that SARS-CoV-2 positivity is associated with impaired reperfusion, with negative prognostic consequences. [ABSTRACT FROM AUTHOR]

Background: The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality.Objectives: The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of "at-risk" patient cohorts for failure to present or delays to treatment.Methods: This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality.Results: A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p < 0.0001). The heterogeneity among centers was not related to the incidence of death due to COVID-19. A significant interaction was observed for patients with arterial hypertension, who were less frequently admitted in 2020 than in 2019. Furthermore, the pandemic was associated with a significant increase in door-to-balloon and total ischemia times, which may have contributed to the higher mortality during the pandemic.Conclusions: The COVID-19 pandemic had significant impact on the treatment of patients with STEMI, with a 19% reduction in PPCI procedures, especially among patients suffering from hypertension, and a longer delay to treatment, which may have contributed to the increased mortality during the pandemic. (Primary Angioplasty for STEMI During COVID-19 Pandemic [ISACS-STEMI COVID-19] Registry; NCT04412655). [ABSTRACT FROM AUTHOR]

The investigators describe 2 cases of intestinopericardial fistula. The patients presented with cardiac tamponade and underwent pericardiocentesis, followed by surgical intervention. Both patients survived and were discharged in stable condition. In conclusion, intestinopericardial fistula is a rare and life-threatening disorder that can present in a variety of manners, including pneumopericardium, cardiac tamponade, and pericarditis. Early identification of the disease coupled with prompt surgical intervention maximizes a patient''s chance of survival and reduced morbidity. [Copyright &y& Elsevier]

Purpose: The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy. Patients and Methods: In this single‐institution retrospective analysis, patients with biopsy‐proven IHC treated with either curative‐intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver‐limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver‐limited recurrence was analyzed in the resection cohort. Results: From 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34–0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50–0.65 vs. HR 0.63, 95% CI 0.57–0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver‐only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29–0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression‐free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46–0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43–0.80; p < 0.001). Conclusion: In patients with liver‐limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver‐directed therapy. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact on acute toxicity of replacing 5-fluorouracil (5-FU) with capecitabine in definitive chemoradiation for patients with anal squamous cell carcinoma (ASCC).Methods and Materials: We retrospectively reviewed the records of 107 consecutive patients with nonmetastatic ASCC treated with definitive chemoradiation from January 2009 to May 2014. In 2011, based on the noninferiority of capecitabine versus 5-FU, our institutional practice shifted to use capecitabine instead of 5-FU for ASCC. Of 107 patients, 63 were treated with infusional 5-FU (1000 mg/m2/day for 4 days) and mitomycin C (MMC) (10 mg/m2) during weeks 1 and 5, and 44 patients were treated with capecitabine (825 mg/m2 twice daily) Monday through Friday throughout radiation therapy (RT) and MMC (10 mg/m2) during weeks 1 and 5. The incidence of grade 3 to 4 acute toxicity was compared between the 2 groups.Results: The median age at diagnosis was 59 years, and 78 patients (73%) were female. The patient characteristics were similar between the 2 treatment groups. All patients in both groups were treated with intensity modulated RT (median dose, 56 Gy). In the 5-FU group, 52% experienced grade 3 to 4 neutropenia compared with 20% in the capecitabine group (P=.001). Treatment breaks resulting from toxicity, primarily related to grade 3+ hematologic toxicity, were necessary for 42% of patients treated with 5-FU versus 16% of those treated with capecitabine (P=.006).Conclusions: Pelvic radiation therapy with MMC plus capecitabine was well tolerated and appeared to have less grade 3+ acute hematologic toxicity and fewer treatment interruptions than in a population of ASCC patients undergoing definitive chemoradiation with MMC and 5-FU. [ABSTRACT FROM AUTHOR]

Background: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19. Methods: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March–June 2019 and 2020. Patients were divided according to age (< or ≥75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality. Results: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825–0.861, p < 0.0001). We found a significant age-related reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24–1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05–1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic. Conclusions: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic. [ABSTRACT FROM AUTHOR]

Summary of the article: First patient with metastatic rectal cancer + DPD deficiency treated with floxuridine via HAIP without toxicity. [ABSTRACT FROM AUTHOR]

Background. Several reports have demonstrated the impact of the COVID-19 pandemic on the management and outcome of patients with ST-segment elevation myocardial infarction (STEMI). The aim of the current analysis is to investigate the potential gender difference in the effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI patients within the ISACS-STEMI COVID-19 Registry. Methods. This retrospective multicenter registry was performed in high-volume primary percutaneous coronary intervention (PPCI) centers on four continents and included STEMI patients undergoing PPCIs in March–June 2019 and 2020. Patients were divided according to gender. The main outcomes were the incidence and timing of the PPCI, (ischemia time ≥ 12 h and door-to-balloon ≥ 30 min) and in-hospital or 30-day mortality. Results. We included 16683 STEMI patients undergoing PPCIs in 109 centers. In 2020 during the pandemic, there was a significant reduction in PPCIs compared to 2019 (IRR 0.843 (95% CI: 0.825–0.861, p < 0.0001). We did not find a significant gender difference in the effects of the COVID-19 pandemic on the numbers of STEMI patients, which were similarly reduced from 2019 to 2020 in both groups, or in the mortality rates. Compared to prepandemia, 30-day mortality was significantly higher during the pandemic period among female (12.1% vs. 8.7%; adjusted HR [95% CI] = 1.66 [1.31–2.11], p < 0.001) but not male patients (5.8% vs. 6.7%; adjusted HR [95% CI] = 1.14 [0.96–1.34], p = 0.12). Conclusions. The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures similarly observed in both genders. Furthermore, we observed significantly increased in-hospital and 30-day mortality rates during the pandemic only among females. Trial registration number: NCT 04412655. [ABSTRACT FROM AUTHOR]

Widespread implementation of HAI pump chemotherapy has been limited by logistic and feasibility concerns. Recent studies demonstrating excellent outcomes have fueled renewed enthusiasm and multiple new programs have emerged. This survey aims to identify barriers critical to establish a successful HAI program. Using SurveyMonkey™, a 17-question survey assessing factors required for establishing a successful program was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses. Frequency of categories and average rank scores for each choice were calculated. Twenty-eight HCRN members responded to the survey. Implementation time varied, with 15 institutions requiring less than a year. Most programs (n = 17) became active in the past 5 years. Medical and surgical oncology were ranked most important for building a program (average ranking scores: 7.96 and 6.59/8). Administrative or regulatory approval was required at half of the institutions. The top 3 challenges faced when building a program were related to regulatory approval (6.65/9), device/equipment access (6.33/9), and drug (FUDR) access (6.25/9). Development of successful programs outside of historically established centers is feasible and requires a multidisciplinary team. Future collaborative efforts are critical for sustainability of safe/effective new programs. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to describe the demographics and clinical features of patients with young onset (YO) CRC. Methods: A retrospective review of patients with CRC diagnosed between ages 20 and 49 years was evaluated at the Memorial Sloan Kettering Cancer Center from 1/2004 to 6/2019. We excluded those with a hereditary CRC syndrome, inflammatory bowel disease, or prior CRC diagnosis. Patient demographics; presenting symptoms; medical, surgical, and smoking history; family history of cancer; tumor characteristics; and pathology were obtained from the electronic medical record. Results: We identified 3856 YO CRC patients (median age CRC diagnosis 43; 52.5% male). A total of 59.1% were overweight or obese (32.2% and 26.9%, respectively). Most (90.1%) had no family history of CRC in a first-degree relative; 56.3% of patients reported being never smokers; 5.2% had diabetes. The most common presenting symptoms were rectal bleeding (47.7%), abdominal pain/bloating (33.1%), and change in bowel habits (24.7%). The majority presented with left-sided cancers (77.3%), at late-stage disease (68.4% at stages 3 or 4). Conclusion: Most YO CRC patients presented with rectal bleeding or abdominal pain, left-sided cancers, and later-stage disease and had no family history of CRC in a first-degree relative. Over half were overweight and obese and were more likely to have never smoked. More data are needed to better understand YO CRC risk factors and to help identify high-risk populations who may benefit from earlier screening. [ABSTRACT FROM AUTHOR]

The so-called "smoking paradox", conditioning lower mortality in smokers among STEMI patients, has seldom been addressed in the settings of modern primary PCI protocols. The ISACS–STEMI COVID-19 is a large-scale retrospective multicenter registry addressing in-hospital mortality, reperfusion, and 30-day mortality among primary PCI patients in the era of the COVID-19 pandemic. Among the 16,083 STEMI patients, 6819 (42.3%) patients were active smokers, 2099 (13.1%) previous smokers, and 7165 (44.6%) non-smokers. Despite the impaired preprocedural recanalization (p < 0.001), active smokers had a significantly better postprocedural TIMI flow compared with non-smokers (p < 0.001); this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. Active smokers had a significantly lower in-hospital (p < 0.001) and 30-day (p < 0.001) mortality compared with non-smokers and previous smokers; this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. In conclusion, in our population, active smoking was significantly associated with improved epicardial recanalization and lower in-hospital and 30-day mortality compared with previous and non-smoking history. [ABSTRACT FROM AUTHOR]

Presents an overview of a study to determine if azithromycin given to patients with acute coronary syndromes can prevent recurrent ischemia. Synopsis of the research methodology; Opinion that the research was well done and found that azithromycin did not prevent recurrent coronary events in the subsequent six months.

Background: Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study.Methods: In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents.Results: A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups.Conclusion: This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity.Trial Registration Number: NCT04412655 (2nd June 2020). [ABSTRACT FROM AUTHOR]