The impact of neoadjuvant systemic treatment on postoperative complications in breast cancer surgery.

PURPOSE: The aim of the study was to analyze the impact of neoadjuvant systemic treatment (NST) on postoperative complications and the beginning of adjuvant treatment. METHODS: This study includes data from a prospectively maintained database including patients with breast cancer (BC) stage I-IV with or without NST undergoing breast cancer surgery between January 2010 and September 2021. RESULTS: Out of 517 enrolled patients, 77 received NST, 440 had primary breast surgery. After NST patients underwent surgery after a meantime of 34 days (26.5-40 days). No statistical significance could be found comparing the complication grading according to the Clavien Dindo classification. The complications were most frequently rated as grade 3b. There were no complications with grade 4 or higher. When differentiating into short and long-term, the overall rate of short-term complications was 20.3% with no significant difference between the two groups (20.8% vs. 20.2%). Regarding long-term complications, there was more impairment of shoulder mobility (26.0% vs. 9.5%, p ≤ 0.001) and chronic pain (42.9% vs. 28.6%, p ≤ 0.016) for patients with NST. The beginning of the administration of the adjuvant treatment was comparable in both groups (46.3 days vs. 50.5 days). CONCLUSION: In our cohort, complications between both groups were comparable according to Clavien Dindo. This study shows that NST has no negative impact on postoperative short-term complications and most importantly did not lead to a delay of the beginning of adjuvant treatment. Therefore, NST can be safely admitted, even when followed by extensive breast reconstruction surgery.

Optimizing Quality of Life With Cognitive Impairment: A Study of End-of-Life Care in Assisted Living.

OBJECTIVES: Assisted living (AL) is an expanding site of end-of-life (EOL) care in the United States. Understanding determinants of quality of life (QoL) for AL residents near EOL is vital to optimize care for this growing population, most of whom have some degree of cognitive impairment (CI). This analysis aimed to identify factors associated with QoL in a diverse sample of AL residents with CI approaching EOL. DESIGN: Observational cross-section design. SETTING AND PARTICIPANTS: Data are from a 5-year study funded by the National Institute on Aging examining EOL care of residents in 7 diverse AL communities in metropolitan Atlanta (n = 67). METHODS: CI was assessed with the Montreal Cognitive Assessment (scores ≤ 26) and QoL was determined with the self-reported QoL in Alzheimer's disease survey adapted for use in AL. Psychological distress was assessed using the Patient Health Questionnaire-4 and fatigue was assessed using the 13-item Functional Assessment of Chronic Illness Therapy Fatigue Scale. Initial descriptive analyses were followed by backward stepwise regression analyses to select a best-fitting model of QoL. RESULTS: The final model predicted 27% of the variance in QoL. CI was not significantly correlated with QoL and was not retained in the final model. Pain and functional limitation also did not meet inclusion criteria (P ≤ .10) and were sequentially removed, producing a final model of QoL in terms of psychological distress (ß = -0.28, P = .032), fatigue (ß = -0.26, P = .048), and race (ß = 0.21, P = .063). CONCLUSIONS AND IMPLICATIONS: The lack of a significant correlation between degree of CI and self-reported QoL suggests that AL residents have the potential to experience high QoL, despite CI. Interventions to reduce psychological distress and manage fatigue could be implemented during EOL care to attempt to improve QoL for AL residents with CI. The correlation between race and QoL warrants investigation into possible racial disparities in AL and EOL care.

Pretransplant and protocol biopsies may help in defining short and mid-term kidney transplant outcome.

Although many variables may affect long-term graft survival no biomarker is available to identify donor kidney with poor quality and with inadequate short and long-term outcome. While in marginal donors pre-transplant renal biopsies are commonly performed to establish if donor kidneys are suitable for transplantation they are not performed in standard donors. In this study we assessed the relevance of pre-transplant morphological features on post-transplant renal function and evaluated the association between perioperative parameters with posttransplant histological and clinical findings. Kidney transplant recipients undergone pre-transplant and post transplant protocol biopsies at 1, 6, and 12 months were enrolled in the study. Perioperative and posttransplant clinical and biochemical parameters were recorded. Semiquantitative analysis of PAS stained kidney sections was used to determine the degree of lesions. Glomerular volume was measured by computed morphometry. A strong inverse correlation was found between donor age and renal graft function at 1, 6, and 12 months after transplantation. A prompt functional recovery was associated with a better renal function at 6 months and one year. Kidneys with higher glomerular volume demonstrated a lower serum creatinine at 1 month. Higher tubulo-interstitial grading at protocol biopsies was associated with a poor renal function at 1 month. Our findings confirm the importance of donor age in kidney transplant long-term outcome and demonstrate that pretransplant and protocol biopsies are valid options to determine graft outcome and to define therapeutic strategies and tailor immunosuppressive regimen for each patient.

Effects of continuous erythropoietin receptor activator (CERA) in kidney transplant recipients.

Erythropoietin-stimulating agents (ESAs) are commonly used to treat anemia in kidney transplant recipients (KTRs). Since 2007, continuous erythropoietin receptor activator (CERA) has been one of the newest recombinant ESAs to treat anemia in dialysis and nondialysis patients with chronic kidney disease. The efficacy of CERA to manage anemia has not been extensively evaluated in KTRs. We evaluated safety, efficacy, and satisfaction among KTRs treated with CERA. We enrolled 19 anemic KTRs (60 ± 9.3 y) who were treated with short-acting ESA for ≥24 weeks. They were shifted to the equivalent dose of CERA and followed for 24 weeks. We measured serum hemoglobin, hematocrit, creatinine, iron, ferritin, and transferrin. To investigate tolerance to and satisfaction with short-acting ESA and CERA, questionnaires were administered to the patients before shifting to CERA and at the end of the follow-up. After 6 months, CERA induced an increase in hemoglobin levels (12.3 ± 0.8 vs 11.2 ± 1.1 g/dL; P = .002, CERA vs short-acting ESA, respectively). In 2 patients treatment was discontinued because the hemoglobin increased to >13 g/dL. No significant differences were observed in serum iron and creatinine between short-acting ESA and CERA throughout the study. The questionnaires showed better compliance to CERA treatment with reduced pain at the injection site, which led subjects to prefer CERA to short-acting ESA. In summary, CERA showed better control of anemia compared with short-acting ESA. It was preferred by the majority of patients, mainly because of the reduced number of monthly injections. Our results demonstrated CERA to be effective, safe, and well tolerated in the management of anemia in KTRs.

Effects of sirolimus on human mesangial cells.

Mesangial cell (MC) proliferation and production of extracellular matrix or loss of MC are both central findings in a number of renal proteinuric diseases. However, the role of MC as components of the glomerular filtration barrier and whether MC alterations induce changes in the glomerular filtration barrier leading to proteinuria are still matters of debate. The effects of Sirolimus (SRL) in proteinuric nephropathies is controversial: some papers have indicated a reduction and others, an increase in proteinuria after sirolimus treatment. Considering the pivotal role of MC in the pathogenesis of many chronic nephropathies, we evaluated the effect of SRL on cultured human MC. We treated primary human MC cultures with SRL, or platelet-derived growth factor (PDGF) or SRL + PDGF, or dimethylsulfoxide, the SRL vehicle, as a control. PDGF was used to activate MC. After 48 hours treatment, MC showed a significant growth increase that was significantly reduced by SRL (P < .01). Apoptosis, determined by the TUNEL assay and flow cytometry, was not modified by the treatments at 24 hours. SRL treatment increased significantly the number of alpha-smooth muscle actin-positive cells compared with controls (P < .05). Cells treated with SRL and SRL + PDGF showed significant changes in morphology with increased mean cell surface, perimeter, and maximum diameter (P < .01) but not protein content. Furthermore, MC treated with SRL showed decreased migration through polycarbonate membranes. The changes induced by SRL may help to explain some of the in vivo effects observed in SRL-treated patients.

Increased asymmetric dimethylarginine serum levels are associated with acute rejection in kidney transplant recipients.

Asymmetric dimethylarginine (ADMA) has been identified as a marker of endothelial dysfunction and an independent risk factor for cardiovascular events in uremic subjects. This study evaluated ADMA plasma levels in kidney transplant recipients. ADMA levels were serially measured during the first year posttransplantation in 41 recipients treated with cyclosporine regimen (CY), sirolimus (SIR), or low-dose cyclosporine plus everolimus (E). Homocysteine, C reactive protein (CRP), nitric oxide (NO), and standard routine laboratory analyses were determined serially. ADMA significantly increased at 6 months posttransplantation, but was significantly lower among patients on SIR or E. NO was only slightly reduced in patients with increased ADMA levels. Interestingly, ADMA was significantly increased during the first 4 days posttransplantation in patients who experienced acute rejection during the first 6 months after transplantation. The same group of patients demonstrated higher levels of CRP and systolic blood pressure before transplantation. Our results demonstrated that ADMA was increased in patients on CY at 6 months. When increased soon after transplantation ADMA may be associated with episodes of acute rejection in kidney transplant recipients. The presence of elevated systolic blood pressure, as well as CRP and ADMA levels, suggested a role for endothelial dysfunction in the development of acute rejection episodes among deceased donor kidney transplant recipients.

Rapamycin reduces proteinuria and renal damage in the rat remnant kidney model.

Rapamycin is an immunosuppressive drug used to prevent acute allograft rejection in solid organ transplantation. It shows less nephrotoxicity than calcineurin inhibitors. We evaluated the effect of rapamycin in rats undergoing 5/6 nephrectomy, a model of proteinuric and progressive renal failure. Fourteen days after surgery rats were randomized either to receive rapamycin or to remain untreated (control). Rats were humanely killed on day 91; serum creatinine, creatinine clearance, and proteinuria were assessed. Renal sections were stained with periodic acid-Schiff to evaluate glomerular volume (Gv), glomerulosclerosis (GS) and tubulointerstitial damage (TIS); we evaluated GS and TIS by Sirius red staining (SR). Epithelial-to-mesenchymal transition (EMT) was assessed by immunohistochemistry. Rapamycin affected neither serum creatinine nor creatinine clearance; it reduced Gv (controls, 5.9 +/- 3.1 x 10(6); rapamycin, 1.3 +/- 0.7 x 10(6) microm(3)) and proteinuria (control, 349 +/- 146; rapamycin, 56 +/- 27 mg/24 h; P < .05); rapamycin ameliorated GS (control, 78 +/- 7; rapamycin, 36 +/- 7%; P < .05; SR: control, 13.2 +/- 3.5; rapamycin, 3.8 +/- 1.0%; P < .05), and TIS (control, 3.25 +/- 0.5; rapamycin, 1.0 +/- 0.1; P < .05; SR: control, 29 +/- 3; rapamycin, 11 +/- 3%; P < .05). Rapamycin reduced alphaSMA (control, 3.25 +/- 0.5; rapamycin, 1.0 +/- 0.1; P < .05), VIM (control, 3.5 +/- 0.6; rapamycin, 1.0 +/- 1.4; P < .05), and CD68(+) cells infiltration (control, 110 +/- 43; rapamycin, 24 +/- 1 cells; P < .05). Rapamycin slows the progression of renal damage in the rat remnant kidney and may represent a novel approach to the treatment of chronic kidney disease.