Combining Analysis of Tumor-infiltrating Lymphocytes (TIL) and PD-L1 Refined the Prognostication of Breast Cancer Subtypes

BackgroundPD-L1 has been used as a biomarker to select patients for treatment of PD-1/PD-L1 inhibitors.Materials and MethodsIn this study, we assessed the clinicopathological features of breast cancers that are associated with PD-L1 expression, as well as its relationship with other immune components and its prognostic significance.ResultsTotally 1752 cases were included in this cohort. PD-L1 expression in tumor-infiltrating immune cells (PD-L1-IC) expression and in tumor cells (PD-L1-TC) expression were identified in 34.2% and 10.1% of cases, respectively, and they showed a positive correlation with higher tumor grade, morphological apocrine features, presence of necrosis, and higher stromal tumor-infiltrating lymphocytes (sTIL). PD-L1-IC and PD-L1-TC expression correlated positively with each other, and both of them were negatively associated with estrogen receptor and progesterone receptor and positively associated with Ki67, HER2, EGFR, p63, and p-cadherin. In survival analysis, PD-L1-IC expression was associated with better disease-free survival (DFS) and breast cancer-specific survival (BCSS) in HER2-overexpressed (HER2-OE) cancers and high–grade luminal B cancers. In triple–negative breast cancers (TNBC) and HER2–OE cancers, compared with sTIL low PD-L1-IC negative cases, sTIL high cases showed significantly better DFS independent of PD-L1-IC status. sTIL low PD-L1-IC positive cases also demonstrated a better DFS in HER2–OE cancers. In high–grade luminal B cancers, sTIL high PD-L1-IC positive cases showed the best BCSS.ConclusionThe data suggested that the combining analysis of sTIL and PD-L1-IC expression refined the prognostication of breast cancer subtypes. Cases with high TIL and PD-LI-IC expression appear to be more immune active.     

Remnant liver regeneration and spleen volume changes after living liver donation: influence of the middle hepatic vein

BACKGROUND AND OBJECTIVES: Graft harvest with or without the middle hepatic vein (MHV) affects venous return and function of the remaining liver. The aims of this study are to compare the remnant liver volume and spleen changes in the donors of different types of graft harvest and to evaluate the influence of resection with or without the MHV on the remnant liver volume regeneration, spleen volume change and serum total bilirubin. PATIENTS AND METHODS: A total of 165 donors were grouped according to the type of graft harvest: 88 donors underwent left lateral segmentectomy (LLS), 10 donors underwent extend LLS or left lobectomy (LL), and 67 donors underwent right lobectomy (RL). Groups LLS and LL were later combined as group LH (left hepatectomy, n = 98). There were 68 men and 97 women. The mean age was 32.9 +/- 8.1 yr. The total liver volume (LV) and spleen volume (S1) before graft harvest, graft weight (GW), regenerated liver volume (LV(6m)) and spleen volume (S2) six months post-donation were calculated. RESULTS: There were no significant differences in the regenerated liver volume six months postoperation (LV(6m)) and recovery ratio (LV(6m)/LV x 100%) among the different groups, albeit significant smaller LV(6m) in both groups compared with the initial liver volume was noted. Postoperative spleen volume (S2), average spleen ratio (S2/S1) and spleen change ratio were significantly larger and higher in group RL than in group LH. A significant increase in spleen volume was noted in both groups six months after graft harvest. A significantly higher TB in group RL (4.1 +/- 1.7 mg/dL, range: 1.4-8.5 mg/dL) was noted compared with that of group LH (1.6 +/- 1.0 mg/dL, range: 0.7-6.2 mg/dL). CONCLUSION: There was a significant increase in the regenerated remnant liver and splenic volumes six months postoperation in all types of hepatectomy following living donor hepatectomy, and there was no difference in the mean TB levels among donors whether the MHV was included or not in the graft.     

A case report of tumor lysis syndrome after stage-one ALPPS

Rationale:Tumor lysis syndrome is a potentially lethal condition caused by rapid cell death, releasing a high level of toxic cytokines. It is common in patients with hematological malignancy but rare in solid tumors.Patient concerns:A 64-year-old patient presented to our unit with a 17.3-cm hepatocellular carcinoma and marginal liver reserve. The first-stage operation of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was performed.Diagnosis:The patient was found to be anuric with grossly deranged electrolytes after the first-stage operation. Tumor lysis syndrome was diagnosed.Interventions:The patient was transferred to the intensive care unit for aggressive fluid administration and continuous venovenous hemofiltration for the management of tumor lysis syndrome.Outcomes:The patient recovered and then underwent the second-stage operation of ALPPS with extended right hepatectomy 8 days after the initial operation without any long-term sequelae.Lessons:ALPPS is a relatively new technique in liver surgery, entailing an increased risk of tumor lysis syndrome due to an in situ tumor after the first-stage operation. Clinicians should have a high index of suspicion regarding this potentially lethal complication with prompt management.     

Focused Cardiac Ultrasonography: Current Applications and Future Directions

Focused cardiac ultrasonography is performed by clinicians at the bedside and is used in time‐sensitive scenarios to evaluate a patient's cardiovascular status when comprehensive echocardiography is not immediately available. This simplified cardiac ultrasonography is often performed by noncardiologists using small, portable devices to augment the physical examination, triage patients, and direct management in both critical care and outpatient settings. However, as the use of focused cardiac ultrasonography continues to expand, careful consideration is required regarding training, scope of practice, impact on patient outcomes, and medicolegal implications. In this review, we examine some of the challenges with rapid uptake of this technique and explore the benefits and potential risk of focused cardiac ultrasonography. We propose possible mechanisms for cross‐specialty collaboration, quality improvement, and oversight.     

Effect of Aqueous Cream BP on human stratum corneum in vivo

Background Aqueous Cream BP is widely prescribed to patients with eczema to relieve skin dryness. The formulation contains sodium lauryl sulphate (SLS), a chemical that is a known skin irritant and a commonly used excipient in personal care and household products. The chronic effects of Aqueous Cream BP application on skin barrier function have not been determined. Objectives To characterize and assess skin barrier function of healthy skin after application of Aqueous Cream BP and to study the physical effects of the formulation on the stratum corneum (SC). Methods The left and right volar forearms of six human volunteers were each separated into treated and control sides. The treated sides of each forearm were subjected to twice daily applications of Aqueous Cream BP for 4 weeks at the end of which concomitant tape stripping and transepidermal water loss (TEWL) measurements were made. The untreated sides of the forearms were not exposed to any products containing SLS during the study period. Results Changes in SC thickness, baseline TEWL and rate of increase in TEWL during tape stripping were observed in skin treated with Aqueous Cream BP. The mean decrease in SC thickness was 1·1 μm (12%) (P = 0·0015) and the mean increase in baseline TEWL was 2·5 g m^?2 h^?1 (20%) (P < 0·0001). Reduced SC thickness and an increase in baseline TEWL, as well as a faster rate of increase in TEWL during tape stripping, were observed in 16 out of 27 treated skin sites. Conclusions The application of Aqueous Cream BP, containing ～1% SLS, reduced the SC thickness of healthy skin and increased its permeability to water loss. These observations call into question the continued use of this emollient on the already compromised barrier of eczematous skin.     

Ciliary central microtubular orientation is of no clinical significance in bronchiectasis

It has been suggested that patients with bronchiectasis might have increased central microtubular orientation angle (CMOA), which leads to poor coordination of ciliary beating, and consequently impairment of airway defence. We have employed transmission electron microscopy to assess CMOA of ciliated nasal mucosa in a cohort of 133 (81F, 56.8+/-16.1yr) stable bronchiectasis and 59 healthy subjects (30F, 49.3+/-22.1yr). There was no significant difference in CMOA between bronchiectasis (13.2 degree) and control subjects (13.0 degree, P=0.82). There was no significant difference in CMOA among patients according to the etiology of bronchiectasis, presence of nasal symptoms, or sputum status of Pseudomonas aeruginosa infection. Patients with more severe bronchiectasis, i.e. those with FEV(1) <60%, FVC <60%, or more than 4 bronchiectatic lung lobes, had significantly lower CMOA than their counterparts (P<0.05). There was no correlation between CMOA with age, 24h sputum volume, exacerbation frequency, FEV(1), FVC, or the number of bronchiectatic lung lobes (P>0.05). CMOA correlated with ciliary beat frequency (negative), and the percent of cilia showing ultrastructural or microtubular defects (P<0.05). Central microtubular orientation angle does not correlate with clinically important parameters, in contrary to the results reported by previously published smaller scale studies.     

Blood donation behavior of Hispanics in the lower Rio Grande Valley

This study was designed to determine the blood donation behavior and attitudes of Hispanic residents of the Lower Rio Grande Valley for the purpose of developing promotional and educational approaches to enhance levels of donor participation. Personal interviews of 545 respondents were conducted in English and Spanish using quota sampling and standard intercept techniques at lower- and middle-income supermarkets in five cities during a payday weekend. A number of research hypotheses were established to test for demographic, behavioral, and attitudinal differences that were observed in donors and nondonors using chi-square analysis and multiple discriminant analysis. After analyzing the difference between Hispanics and non-Hispanics for blood donation rates, all non-Hispanics were eliminated from analysis, and the remaining 419 Hispanics were evaluated on the basis of their donor behavior. Donation among Hispanics was most likely to be by better- educated, English-speaking, higher-job-status individuals who had participated in a blood donation drive. Donors tend to have parent(s) who were donors, and they were also more likely to carry an organ donor card. Donors were found to vary in their behaviors as well as their attitudes and beliefs. Perceptions of a lack of safety in donating, the risk of contracting acquired immune deficiency syndrome, and the financial motivation of donors were most pronounced among Hispanics, which indicated a need for improved education on these issues.     

Disrupted muscarinic M1 receptor signaling correlates with loss of protein kinase C activity and glutamatergic deficit in Alzheimer's disease

There are few studies on the clinical and neurochemical correlates of postsynaptic cholinergic dysfunction in Alzheimer's disease (AD). We have previously found that attenuation of guanine nucleotide-binding (G-) protein coupling to muscarinic M(1) receptors in the neocortex was associated with dementia severity. The present study aims to study whether this loss of M(1)/G-protein coupling is related to alterations in signaling kinases and NMDA receptors. Postmortem frontal cortices of 22 AD subjects and 12 elderly controls were obtained to measure M(1) receptors, M(1)/G-protein coupling, NMDA receptors as well as protein kinase C (PKC) and Src kinase activities. We found that the extent of M(1)/G-protein coupling loss was correlated with reductions in PKC activity and NMDA receptor density. In contrast, Src kinase activity was neither altered nor associated with M(1)/G-protein coupling. Given the well established roles of neuronal PKC signaling and NMDA receptor function in cognitive processes, our results lend further insight into the mechanisms by which postsynaptic cholinergic dysfunction may underlie the cognitive features of AD, and suggest alternative therapeutic targets to cholinergic replacement.     

Stromal CD10 expression in mammary fibroadenomas and phyllodes tumours

BACKGROUND/AIMS: CD10 (CALLA) has recently been reported to be expressed in spindle cell neoplasia, and has been used to differentiate endometrial stromal sarcoma from leiomyoma and leiomyosarcoma. In the breast, myoepithelial cells express CD10, but there are few studies of the expression of CD10 in mammary fibroepithelial lesions. METHODS: Stromal CD10 expression was studied in 181 mammary phyllodes tumours (102 benign, 51 borderline malignant, and 28 frankly malignant) and 33 fibroadenomas using immunohistochemistry, to evaluate whether differences in expression correlated with the degree of malignancy. RESULTS: There was a progressive increase in the patients' age and tumour size, from fibroadenoma to phyllodes tumours with an increasing degree of malignancy (p < 0.001). Stromal CD10 expression was positive in one of 33 fibroadenomas, six of 102 benign phyllodes tumours, 16 of 51 borderline malignant phyllodes tumours, and 14 of 28 frankly malignant phyllodes tumours. The difference was significant (p < 0.001) and an increasing trend was established. Strong staining was seen in subepithelial areas with higher stromal cellularity and activity. Stromal CD10 expression had a high specificity (95%) for differentiating between benign lesions (fibroadenomas and benign phyllodes tumours) and malignant (borderline and frankly malignant) phyllodes tumours. CONCLUSIONS: CD10 may be a useful adjunct in assessing malignancy in mammary fibroepithelial lesions.