Is the skin microbiota a modifiable risk factor for breast disease?: A systematic review

PurposeHigh prevalence, unreliable risk discrimination and poor clinical outcomes are observed in malignant and benign breast diseases (BD). The involvement of microbial communities in the development of BD has become topical, and distal influences of microbial dysregulation in the breast have been well established. Despite advances, the role of the breast skin microbiota in BD remains unclear. Interactions between the skin microbiota and the underlying mucosal immune system are complex. In homeostasis, the skin offers a physical barrier protecting underlying breast tissue from skin commensals and noxious environmental triggers. Our review aims to illuminate the role of the skin microbiota in the development of BD.MethodsAdhering to the PRISMA protocol, a systematic review was conducted utilising the Medline and Embase search engines.ResultsThrough a comprehensive search of the last ten years, twenty-two studies satisfied the inclusion criteria. Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes were identified as the most prevalent phyla of both breast tissue and skin in healthy controls and BD. High abundance of skin commensals, specifically some species of Staphylococcus, have been linked in breast cancer and metastases. Similarly, dysregulated microbial abundance is also seen in inflammatory and implant-associated BD. These findings raise the hypothesis that the skin microbiota plays a role in tissue homeostasis and may contribute to a range of breast pathologies. Several mechanisms of microbial transfer to underlying tissue have been proposed, including retrograde transfer through ductal systems, breakdown of the skin barrier, and migration through nipple-aspirate fluid.ConclusionOur review provides preliminary insights into the skin microbiota as a modifiable risk factor for BD. This raises opportunities for future studies in antimicrobials/probiotics as an adjunct to, or replacement of surgery; a diagnostic and/or prognostic tool for BD; and the possibility of conditioning the microbiota to manage BD.     

Intra-articular injection of culture-expanded adipose tissue-derived stem cells for knee osteoarthritis: Assessments with clinical symptoms and quantitative measurements of articular cartilage volume

BackgroundIntra-articular administration of adipose tissue-derived stem cells (ADSC) is an alternative treatment option for knee osteoarthritis (OA) after conventional treatment fails; however, the clinical results related to the severity of OA grade and changes of cartilage volumes after the administration of ADSC is unknown. This study aimed to determine 1) clinical outcomes after the ADSC administration in knee OA with consideration of radiographic OA grades and 2) changes in cartilage volumes after ADSC administration.MethodsThis observational study included 86 knees from 51 patients who underwent intra-articular administration of cultured ADSC; 47 patients (80 knees) completed follow-up for 6 months (follow-up rate: 93%). The Knee injury and Osteoarthritis Outcome Scores (KOOS) were reported at baseline and 1, 3, and 6 months after the administration. The efficacy rate in the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) was evaluated using the KOOS. Cartilage volume of the knee joint was measured using quantitative 3-dimensional magnetic resonance imaging (3D-MRI) software at baseline and 6 months in 52 knees in 31 patients (follow-up rate: 61%).ResultsAll items on the KOOS except “sports/recreation” improved significantly at 6 months with more significance in knees with a Kellgren–Lawrence (KL) grade 2 or 3 compared with KL grade 4 knees. The OMERACT-OARSI responder at 6 months was significantly greater in knees with KL grade 2 or 3 (64%) than in knees with KL grade 4 (42%, p = 0.045). Cartilage volume changes varied among patients and were not related to the changes in KOOS after ADSC administration.ConclusionsIntra-articular administration of ADSC in knee OA improved KOOS at 6 months. The effects were more significant in knees with KL grade 2 or 3 than with KL grade 4. Changes in KOOS were not related to change in cartilage volumes after ADSC administration.     

Threshold for lateral meniscal body extrusion on MRI in middle-aged and elderly patients with symptomatic knee osteoarthritis

PurposeTo determine the MRI-based threshold of lateral meniscal body extrusion (LMBE) that are associated with meniscal damage, cartilage damage and radiological knee osteoarthritis (OA).Materials and methodsA total of 142 patients (59 men and 83 women) with a mean age of 57.2 ± 7.9 (SD) years (range: 41–77 years) with symptomatic knee OA were included. Radiological assessment was performed using the Kellgren-Lawrence scoring system. Meniscus and cartilage damage were assessed using the whole-organ magnetic resonance imaging score. Meniscal extrusion was quantified on coronal sections of intermediate-weighted MRI sequences. Differences between medial and lateral compartments in meniscal extrusion and incidence of tibiofemoral OA-related structural changes were assessed using Wilcoxon signed rank test and Bowker test. Receiver operating characteristic curves and Youden index were used for determining thresholds for meniscal extrusion.ResultsA total of 142 knees were assessed. Meniscal body extrusion distances between medial and lateral compartments were significantly different in the entire sample, and in subjects with and without radiological knee OA (P < 0.05 for all). The incidence of structural changes between medial and lateral compartments were significantly different (P = 0.003 for meniscal damage; P = 0.001 for femoral cartilage damage). Three mm and 2 mm were determined to be the optimal thresholds for medial and lateral meniscal body extrusion, respectively.ConclusionMedial and lateral meniscal body extrusion were associated with the incidence of OA-related knee structural changes in symptomatic patients with knee OA. A threshold of 2 mm for LMBE with respect to meniscal damage, cartilage damage and radiological knee OA was determined.     

Deep Sternal Wound Infection and Mortality in Cardiac Surgery: A Meta-analysis

BackgroundDeep sternal wound infection (DSWI) is a rare but severe complication after cardiac surgical procedures and has been associated with increased early morbidity and mortality. Studies reporting long-term outcomes in patients with DSWI have shown contradictory results. We performed a study-level meta-analysis evaluating the impact of DSWI on short- and long-term clinical outcomes.MethodsA systematic literature search was conducted to identify studies comparing short- and long-term outcomes of patients submitted to cardiac surgical procedures who developed DSWI and patients who did not. The primary outcome was overall mortality. Secondary outcomes were in-hospital mortality, follow-up mortality, major adverse cardiovascular events, myocardial infarction, and repeat revascularization. Postoperative outcomes were also investigated.ResultsTwenty-four studies totaling 407 829 patients were included. Overall, 6437 (1.6%) patients developed DSWI. Mean follow-up was 3.5 years. DSWI was associated with higher overall mortality (incidence rate ratio [IRR], 1.99; 95% CI, 1.66-2.38; P < .001), in-hospital mortality (odds ratio, 3.30; 95% CI, 1.88-5.81; P < .001), follow-up mortality (IRR, 2.02; 95% CI, 1.39-2.94; P = .001), and major adverse cardiovascular events (IRR, 2.04; 95% CI, 1.60-2.59; P < .001). No differences in myocardial infarction and repeat revascularization were found, but limited studies reported those outcomes. DSWI was associated with longer postoperative hospitalization, stroke, myocardial infarction, and respiratory and renal failure. Sensitivity analyses on isolated coronary artery bypass grafting studies and by adjustment method were consistent with the main analysis.ConclusionsCompared with patients who did not develop DSWI, patients with DSWI after cardiac surgical procedures had increased risk of death as well as short- and long-term adverse clinical outcomes.     

Evaluation of efficacy and safety of PARP inhibitors in breast cancer: A systematic review and meta-analysis

BackgroundMany breast cancer clinical trials with PARPi have been completed or are currently carried out, either by monotherapy or combined with chemotherapy. We aim to assess the efficacy and safety of PARPi in breast cancer patients as compared to chemotherapy.MethodsA comprehensive literature search of PubMed, EMBASE, CENTRAL, conference meetings and clinical trial registry was performed. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR). The secondary outcome was safety profile. The comparative effects were measured using hazard ratio (HR) or relative risk (RR) with 95% confidence interval. Subgroup analyses were conducted based on types of intervention and baseline characteristics of patients.ResultsSix RCTs (n = 1953) were included. Two RCTs were recognized as high risk. PARPi was associated with an improved PFS (HR, 0.65; 95% CI, 0.56–0.74), OS (HR, 0.86; 95% CI, 0.73–1.01), and a higher ORR (RR, 1.38; 95% CI, 1.05–1.82). PARPi, however, significantly increased risk of grade 3–4 thrombocytopenia (RR, 1.63; 95% CI, 1.06–2.52). Monotherapy was observed with lower risk of disease progression and higher ORR rate than combination therapy, 0.56 to 0.65 and 2.21 to 1.05, respectively. For patients without prior platinum treatment, PARPi significantly improved PFS (HR, 0.64; 95% CI, 0.52–0.79).ConclusionsPARPi was observed with a significantly improved efficacy in aspects of PFS and ORR, but also higher risk of grade 3–4 thrombocytopenia as compared to chemotherapy. PARPi was a better choice for patients who had not received previous platinum treatment.     

Colon Cancer in Patients Under 25 Years Old: A Different Disease?

1. Download : Download high-res image (227KB)
2. Download : Download full-size image

     

Development and Validation of a Laboratory Risk Score (LabScore) to Predict Outcomes after Resection for Intrahepatic Cholangiocarcinoma

1. Download : Download high-res image (219KB)
2. Download : Download full-size image

     

Steen solution protects pulmonary microvascular endothelial cells and preserves endothelial barrier after lipopolysaccharide-induced injury

ObjectivesAcute respiratory distress syndrome represents the devastating result of acute lung injury, with high mortality. Limited methods are available for rehabilitation of lungs affected by acute respiratory distress syndrome. Our laboratory has demonstrated rehabilitation of sepsis-injured lungs via normothermic ex vivo and in vivo perfusion with Steen solution (Steen). However, mechanisms responsible for the protective effects of Steen remain unclear. This study tests the hypothesis that Steen directly attenuates pulmonary endothelial barrier dysfunction and inflammation induced by lipopolysaccharide.MethodsPrimary pulmonary microvascular endothelial cells were exposed to lipopolysaccharide for 4 hours and then recovered for 8 hours in complete media (Media), Steen, or Steen followed by complete media (Steen/Media). Oxidative stress, chemokines, permeability, interendothelial junction proteins, and toll-like receptor 4-mediated pathways were assessed in pulmonary microvascular endothelial cells using standard methods.ResultsLipopolysaccharide treatment of pulmonary microvascular endothelial cells and recovery in Media significantly induced reactive oxygen species, lipid peroxidation, expression of chemokines (eg, chemokine [C-X-C motif] ligand 1 and C-C motif chemokine ligand 2) and cell adhesion molecules (P-selectin, E-selectin, and vascular cell adhesion molecule 1), permeability, neutrophil transmigration, p38 mitogen-activated protein kinase and nuclear factor kappa B signaling, and decreased expression of tight and adherens junction proteins (zonula occludens-1, zonula occludens-2, and vascular endothelial-cadherin). All of these inflammatory pathways were significantly attenuated after recovery of pulmonary microvascular endothelial cells in Steen or Steen/Media.ConclusionsSteen solution preserves pulmonary endothelial barrier function after lipopolysaccharide exposure by promoting an anti-inflammatory environment via attenuation of oxidative stress, toll-like receptor 4-mediated signaling, and conservation of interendothelial junctions. These protective mechanisms offer insight into the advancement of methods for in vivo lung perfusion with Steen for the treatment of severe acute respiratory distress syndrome.