Postoperative Outcomes and One-Year Mortality of Patients on Chronic Anticoagulation Medications Undergoing Infrainguinal Bypass.

BACKGROUND: Patients requiring open infrainguinal bypass (IIB) frequently are taking chronic anticoagulation (AC) medications. Taking these medications in the preoperative setting may affect the outcomes of surgery. This study aims to evaluate postoperative outcomes and 1-year mortality of patients taking chronic AC medications that undergo IIB. METHODS: Using data obtained from the Vascular Quality Initiative from January 2011 to October 2021, patients on warfarin or any direct oral anticoagulants (DOAC) within 30 days of IIB were compared with patients not taking chronic AC medications. The primary outcomes were in-hospital, 30-day, and 1-year mortality. The secondary outcomes included total procedure time, need for perioperative packed red blood cell transfusion, prolonged length of hospital stay, postoperative myocardial infarction or stroke, and graft patency at discharge. A subgroup analysis was performed comparing patients taking warfarin with those taking DOACs. Univariate analyses and multivariate logistic regression, Kaplan Meier survival, and Cox regression analyses were used to analyze the data for postoperative and 1-year outcomes, respectively. RESULTS: A total of 55,076 patients underwent IIB during the study period, and 11,547 (20.97%) were on chronic AC prior to surgery. The 2 cohorts differed significantly in almost every demographic and clinical characteristic. Multivariate analyses adjusting for 45 potential confounders revealed that there was no significant difference in in-hospital, 30-day, and 1-year mortality. The total procedure time for the chronic AC cohort was on average 11.46 ± 2.16 min longer (P ≤ 0.001) and there was a greater risk of prolonged length of stay in the hospital (adjusted odds ratio [aOR]: 1.19, 95% confidence interval [CI]: 1.13-1.26, P < 0.001). These patients also returned to the operating room (OR) at a greater rate (aOR: 1.12, 95% CI: 1.05-1.19; P = 0.016) and demonstrated a significantly lower rate of graft patency at discharge (aOR: 0.73, 95% CI: 0.62-0.86, P = 0.001). On subgroup analysis, multivariate analysis demonstrated lower 30-day mortality for the DOAC group in comparison to the warfarin group (aOR: 0.74, 95% CI: 0.57-0.94, P = 0.015), but no significant differences in in-hospital and 1-year mortality. CONCLUSIONS: Patients taking AC medications within 30 days prior to IIBs may require more perioperative red blood cell transfusions, longer hospitalizations, and return to the OR at a greater rate. They are also at an increased risk for loss of graft patency at discharge. However, these patients are not at increased risk of in-hospital, 30-day, or 1-year mortality. IIB can, therefore, be performed safely in patients taking chronic AC medications.

Outcomes of elective peripheral endovascular interventions for peripheral arterial disease performed in hospital outpatient departments, ambulatory surgical centers and office-based labs.

BACKGROUND: A recent shift in the location where peripheral endovascular interventions (PVI) are performed has occurred, from traditional settings such as hospital outpatient departments (HOPD), to ambulatory surgical centers (ASC) and outpatient-based laboratories (OBL). Different settings may influence the safety and efficacy of the PVI, as well as how it is done. This study aims to compare the postprocedural outcomes and intraprocedural details between the three settings. METHODS: The Vascular Quality Initiative database was queried for all elective infrainguinal PVIs for occlusive peripheral arterial disease between January 2016 and December 2021. The primary outcomes were rates of postprocedural hospital admissions, postprocedural medical complications, and access site complications. Secondary outcomes included technical success and intraprocedural details, such as types and number of devices used, amount of contrast, and fluoroscopy time. The χ2 test, analysis of variance, and multivariate logistic regression were used to analyze the outcomes. RESULTS: A total of 66,101 PVI cases (HOPD, 57,062 [83.33%]; ASC, 4591 [6.95%]; OBL, 4448 [6.73%]) were included in the study. There were 445 cases requiring hospital admission (HOPD, 398 [0.70%]; ASC, 26 [0.57%]; OBL, 21 [0.47%]; P = .126). There were no significant differences in cardiac, pulmonary, or renal complications. Access site complications occurred in less than 1.7% of all cases and were significantly higher in OBLs when compared with ASCs (adjusted odds ratio [aOR], 3.70; 95% confidence interval [CI], 1.70-8.03; P = .001) and significantly lower in ASCs in comparison to HOPDs (aOR, 0.27; 95% CI, 0.18-0.41; P < .001). Technical success occurred in at least 92% of all cases, regardless of setting. There was a 16-fold increase in the use of atherectomy devices in an OBL vs HOPD setting (aOR, 16.79; 95% CI, 11.77-23.95; P < .001) and a five-fold increase in the use of atherectomy devices in an ASC vs HOPD setting (aOR, 5.37; 95% CI, 2.47-11.65; P < .001). There was a five-fold decrease in the use of special balloons in an OBL vs HOPD setting (aOR, 0.20; 95% CI, 0.10-0.39; P < .001) and a four-fold decrease when comparing ASCs with HOPDs (aOR, 0.25; 95% CI, 0.12-0.51; P < .001). CONCLUSIONS: Elective PVIs performed in any outpatient setting proved to be safe and technically successful. However, there are significant differences in the way PVIs are performed in each setting, such as the greater use of atherectomy devices in OBLs and greater use of special balloons in HOPDs. Long-term studies are needed to evaluate the durability and reintervention outcomes and understand factors associated with practice pattern variability across these different settings.

Clinical implication of genetic composition and molecular mechanism on treatment strategies of HER2-positive breast cancers.

The current clinical management model of HER2-positive breast cancers is commonly based on guidelines, which in turn are based on the design and outcome of clinical trials. While this model is useful to most practicing clinicians, the treatment outcome of individual patient is not certain at the start of treatment. As the understanding of the translational research of carcinogenesis and the related changes in cancer genetics and tumor microenvironment during treatment is critical in the selection of right choice of treatment to maximize the successful clinical outcome for the patient, this review article intends to discuss the latest developments in the genetic and molecular mechanisms of cancer progression and treatment resistance, and how they influence the planning of the treatment strategies of HER2-positive breast cancers.

Innominate Artery Ligation: A History From Mott to Matas.

Innominate artery ligation emerged in the 19th century as an early operation for right subclavian aneurysm. Clinical outcomes were often dire, but undeterred surgeons believed that ligation represented an opportunity that outweighed the risks of nonoperative aneurysm management. Valentine Mott of New York performed the procedure in 1818; his patient died 26 days later. Variations on Mott's approach were undertaken 13 more times from 1822 to 1861 by surgeons in the United States and abroad, all of which proved fatal. Andrew Woods Smyth of New Orleans was the first to successfully control a subclavian artery aneurysm with innominate ligation in 1864. The Charity Hospital house surgeon used a series of ligations on the innominate, common carotid, vertebral, and internal mammary arteries to prevent collateral and recurrent blood flow to the aneurysmal sac. These physiologically-oriented operations kept Smyth's patient alive and functional for ten years. New Orleans became an internationally-recognized hub for advancements in aneurysm surgery. One of Smyth's students, Rudolph Matas, went on to revolutionize vascular surgery. Along his path to becoming the Father of modern vascular surgery, Matas documented his own performance of Smyth's operation at Charity 4 times over the course of his career. Although later supplanted by primary vascular anastomosis and grafting, the first successful innominate ligation was a collaborative effort between New York and New Orleans that served as a foundation for the development of modern aneurysm repair.

Neoadjuvant palbociclib on ER+ breast cancer (N007): clinical response and EndoPredict's value.

The purpose of the study was to test the efficacy of neoadjuvant palbociclib therapy and to evaluate its impact on cell cycle arrest and changes in EndoPredict (EP) scores before and after treatment. Postmenopausal women with histologically proven ER+ve, HER2-ve invasive breast cancer, 2 cm or greater, were enrolled in an open-label, single-arm study. Twenty eligible patients were given letrozole 2.5 mg per day together with palbociclib 125 mg per day for 3 out of 4 weeks in repeated cycles for 16 weeks (4 cycles) before surgery. The primary end points were clinical response rates (cRR) and preoperative endocrine prognostic index (PEPI). The secondary end points were pathologic response and gene expression testing with EP test on collected tumor samples. The following results were obtained. 17 patients showed a clinical response of 50% or more, including 8 complete responses and 9 partial responses. There was significant reduction in area (P < 0.0001) and volume (P = 0.017) of the cancer. Pathologic complete response (pCR) was achieved in one patient; all cancers were downgraded after treatment. Ki67 (P = 0.044) and EP scores (P < 0.0001) were significantly reduced after treatment. Analysis of the relative gene expression levels showed that all proliferative genes, IL6ST and RBBP8 were decreased after palbociclib treatment. 6 patients with intermediate and three patients with high PEPI risk scores were found to have low EPclin scores. All patients with high PEPI relapse risk score had high EPclin score. In conclusion, effective clinical response was demonstrated by neoadjuvant letrozole in combination with palbociclib. Compared with PEPI, EPclin might be a better parameter to estimate prognosis after neoadjuvant therapy.

Outcomes of adjuvant endocrine therapy and hormone receptor status change following neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: This retrospective study investigated the therapeutic benefit of adjuvant endocrine therapy (ET) in breast cancer patients with hormone receptor (HR) status change from positive to negative after neoadjuvant chemotherapy (NAC). METHODS: From December 2000 to November 2010, 97 eligible patients with a positive-to-negative switch of HR status after NAC were identified. All patients were categorized into 2 groups on the basis of the administration of ET: 57 ET-administered patients and 40 ET-naïve patients. Survival analyses were performed to examine the prognostic value of ET administration as well as other clinical and pathologic variables. RESULTS: The administration of ET was significantly associated with improved disease-free survival (p=0.018) in patients with a positive-to-negative switch of HR status. The 5-year disease-free survival rates were 77.0% and 55.5%, respectively, in ET-administered patients and ET-naïve patients. The 5-year overall survival rate for ET-administered patients was also higher than that of ET-naïve patients (81.3% vs. 72.7%, p=0.053), albeit this was statistically insignificant. CONCLUSIONS: This study revealed that patients with HR altered from positive to negative after NAC still benefit from ET. The HR status should be evaluated not only in specimens obtained during post-NAC surgery but also in specimens biopsied before NAC.

Epigenetic changes of TIMP-3, GSTP-1 and 14-3-3 sigma genes as indication of status of chronic inflammation and cancer.

OBJECTIVES: This study aimed to compare the epigenetic changes via hypermethylation status of TIMP-3, GSTP-1 and 14-3-3σ genes, between healthy subjects and patients with reversible chronic inflammatory disease, and between healthy subjects and patients with irreversible malignant disease, to highlight the genetic changes that occur in the progression from an inflammatory condition to irreversible genetic changes commonly observed in cancer patients. METHODS: DNA was extracted from the blood of 680 healthy subjects, and tissues and blood of 110 patients with chronic inflammation disease of the gums, as well as neoplastic tissues of 108 breast cancer patients. Methylation-specific polymerase chain reaction (PCR) for TIMP-3, GSTP-1 and 14-3-3σ was performed, and hypermethylation status was analyzed and compared between the 3 groups. RESULTS: The hypermethylation frequencies of TIMP-3 and GSTP-1 of reversible chronic inflammatory gum disease and the control group were similar, but both were significantly lower than those for malignant disease patients (p<0.0001). The methylation frequency of 14-3-3σ in chronic inflammatory gum disease was higher than in the cancer and control groups (p<0.0001). The methylation of CpG islands in TIMP-3 and GSTP-1 in chronic inflammation patients occurred as frequently as in the control group, but less frequently than in breast cancer patients. However, the epigenetic silencing of 14-3-3σ occurred more frequently in the chronic inflammation group than in cancer patients and healthy controls. CONCLUSIONS: The epigenetic silencing of 14-3-3σ might be essential for chronic inflammatory gum disease. The epigenetic changes presented in chronic inflammation patients might demonstrate an irreversible destruction in the tissues or organs similar to cancer.

New developments in breast cancer prognosis: molecular predictors of treatment response and survival.

AIM: This study aimed to assess the molecular subtypes of breast cancer for patients attending a dedicated breast care center and examine the association with clinicopathological features, treatment and survival outcomes. METHODS: Demographic, clinicopathological and treatment details were collected from women with primary breast cancer. Immunohistochemical subtypes were also collected. The association between breast cancer subtypes and clinicopathological features was assessed using the chi-square or Fisher's exact test. Survival outcomes were compared among subtypes with the log-rank test. RESULTS: Immunohistochemical subtypes were not associated with tumor size, lymphovascular invasion or lymph node involvement but differed by histological grade (p=0.014) and nuclear grade of tumors (p=0.001). The 5-year overall survival estimates for luminal A, luminal B, HER-2-positive and triple-negative tumors were 100%, 96.2%, 71.4% and 92.3% respectively. Compared to luminal A tumors (93.4%), luminal B (80.8%), HER-2-positive (71.4%) and triple-negative (76.9%) tumors exhibited a reduced disease-free survival (DFS). Patients with ER-positive tumors had a higher DFS than their ER-negative counterparts (p=0.036). Patients with tumors expressing a low Ki-67 level had a more favorable prognosis (p=0.02). CONCLUSIONS: The most prevalent luminal A subtype is associated with relatively better prognosis, whereas HER-2-positive and triple-negative tumors are prone to early relapse with diminished survival.

Association of cytokines, high sensitive C-reactive protein, VEGF and beta-defensin-1 gene polymorphisms and their protein expressions with chronic periodontitis in the Chinese population.

PURPOSES: This study aimed at investigating the association between interleukin-6 (IL-6), interleukin-12 (IL-12), C-reactive protein (CRP), vascular endothelial growth factor (VEGF) and ß-defensin-1 polymorphisms and the susceptibility to periodontitis in the Chinese population. METHODS: DNA was extracted from the blood samples of 532 healthy individuals and 122 chronic periodontitis (CP) patients enrolled in the study. The genes encoding IL-6, IL-12, CRP, VEGF and ß-defensin-1 were amplified using PCR and digested with restriction enzymes. The protein expression of the abovementioned genes was determined by ELISA. Differences in the allele/genotype frequencies were assessed with the chi-square test. RESULTS: The frequencies of the C/C genotypes of IL-6, IL-12, and VEGF were higher in CP patients than healthy controls (66.3% vs 25.9%; 27.8% vs 19.9%; and 64.8% vs 52.1%, respectively). In the patients' group we also recorded frequencies of the A/A genotypes of CRP and VEGF higher than in healthy controls (63.1% vs 58.1% and 64.8% vs 35.2%, respectively). Protein production evaluated by ELISA demonstrated significant differences between CP patients and healthy controls for IL-6, IL-12, CRP, VEGF and ß-defensin-1. CONCLUSIONS: The genotypes of IL-6, IL-12, VEGF and ß-defensin-1 and their protein productions were associated with CP in a Chinese population. Genotypes and serum levels of CRP were associated with CP, but alleles frequency showed no difference between CP patients and healthy controls.

Treatment of chronic nonhealing neurotrophic corneal epithelial defects with thymosin beta4.

Neurotrophic corneal defects are difficult to heal and all too often lead to scarring and vision loss. Medical management is often of limited success. We describe the results of nine patients (ages 37-84) with chronic nonhealing neurotrophic corneal epithelial defects who were treated with thymosin beta 4 (Tbeta4) sterile eye drops for 28 or 49 days with a follow-up period of 30 days. Those with geographic defects (six patients) showed dramatic healing without clinically significant neovascularization. Stromal thinning was observed in one patient. Three patients with punctate epithelial defects did not have a demonstrable change in their clinical findings. Reduced ocular irritation was reported by all patients soon after treatment initiation. Results from these compassionate use cases indicate that Tbeta4 may provide a novel, topical approach to wound healing in chronic nonhealing neurotrophic corneal ulcers.

Comparison of deep lamellar endothelial keratoplasty and penetrating keratoplasty in patients with Fuchs endothelial dystrophy.

PURPOSE: To evaluate and compare 1-year postoperative visual acuity, refractive results, endothelial cell density (ECD), and complications in a consecutive group of patients who underwent deep lamellar endothelial keratoplasty (DLEK) with those who underwent penetrating keratoplasty (PK) performed by 1 surgeon. METHODS: We prospectively analyzed results of 20 consecutive patients with Fuchs dystrophy and pseudophakia who underwent small-incision DLEK surgery and retrospectively compared these results with those of 23 consecutive patients with Fuchs dystrophy and pseudophakia who underwent standard PK surgery during the same period. Main outcome measurements were best spectacle-corrected visual acuity (BSCVA); refractive, keratometric, and topographic astigmatism; topographic irregular astigmatism; absolute change in spherical equivalent; and ECD. Postoperative complications in the 2 groups were also analyzed. RESULTS: Preoperative BSCVA was significantly better in the DLEK group than the PK group (P = 0.013). Postoperative BSCVA was significantly better in the DLEK group than the PK group at 6 months (P = 0.025) and similar in each group at 12 months. Twelve-month postoperative refractive, keratometric, and topographic astigmatism was significantly less in the DLEK group than the PK group (P < 0.001). Surface asymmetry index and change in keratometric spherical equivalent was significantly less in the DLEK group than the PK group at 12 months postoperatively (P < 0.001). Preoperative ECD was significantly higher in the DLEK group (3072 +/- 307 cells/mm) than the PK group (2779 +/- 413 cells/mm). Twelve-month postoperative ECD was similar in the DLEK group (1293 +/- 469 cells/mm) compared with the PK group (1303 +/- 454 cells/mm; P = 0.949, not significant). Twelve-month percent endothelial cell loss was higher than reported in previous studies but was similar in the DLEK group (57.9%) compared with the PK group (53.1%). Twelve months postoperatively, all grafts were clear in the DLEK and PK groups. CONCLUSIONS: DLEK surgery resulted in more rapid vision recovery, significantly less regular and irregular astigmatism, and less change in spherical equivalent than PK surgery. Endothelial cell loss was significant in both groups but was not significantly different in the DLEK group from the PK group. DLEK surgery has significant advantages over PK surgery, but long-term ECD and graft survival in DLEK surgery should be studied.