Radical Resection for Second EGFR-mutated Primary Lung Cancer Following Immune Checkpoint Inhibitor Monotherapy for Stage IV Lung Adenocarcinoma

A 78-year-old woman with multiple lung nodules, epithelial growth factor receptor (EGFR) exon 20 insertion mutations, and diagnosed with advanced lung adenocarcinoma (cT4N3M1a, stage IVA), was referred to our hospital. She received immune checkpoint inhibitor (ICI) therapy. The therapy showed remarkable antitumor effects; only a single nodule remained in the right upper lobe. The nodule was diagnosed as adenocarcinoma through a biopsy. We subsequently performed right upper lobectomy for multiple primary lung cancer (MPLC). The surgical specimen contained EGFR exon 19 deletion mutations and not exon 20 insertion mutations.     

Neurocognitive and psychiatric disorders-related axonal degeneration in Parkinson's disease

Neurocognitive and psychiatric disorders have significant consequences for quality of life in patients with Parkinson's disease (PD). In the current study, we evaluated microstructural white matter (WM) alterations associated with neurocognitive and psychiatric disorders in PD using neurite orientation dispersion and density imaging (NODDI) and linked independent component analysis (LICA). The indices of NODDI were compared between 20 and 19 patients with PD with and without neurocognitive and psychiatric disorders, respectively, and 25 healthy controls using tract-based spatial statistics and tract-of-interest analyses. LICA was applied to model inter-subject variability across measures. A widespread reduction in axonal density (indexed by intracellular volume fraction [ICVF]) was demonstrated in PD patients with and without neurocognitive and psychiatric disorders, as compared with healthy controls. Compared with patients without neurocognitive and psychiatric disorders, patients with neurocognitive and psychiatric disorders exhibited more extensive (posterior predominant) decreases in axonal density. Using LICA, ICVF demonstrated the highest contribution (59% weight) to the main effects of diagnosis that reflected widespread decreases in axonal density. These findings suggest that axonal loss is a major factor underlying WM pathology related to neurocognitive and psychiatric disorders in PD, whereas patients with neurocognitive and psychiatric disorders had broader axonal pathology, as compared with those without. LICA suggested that the ICVF can be used as a useful biomarker of microstructural changes in the WM related to neurocognitive and psychiatric disorders in PD.     

Identification of CD157-Positive Vascular Endothelial Stem Cells in Mouse Retinal and Choroidal Vessels: Fluorescence-Activated Cell Sorting Analysis

PurposeCD157 (also known as Bst1) positive vascular endothelial stem cells (VESCs), which contribute to vascular regeneration, have been recently identified in mouse organs, including the retinas, brain, liver, lungs, heart, and skin. However, VESCs have not been identified in the choroid. The purpose of this study was to identify VESCs in choroidal vessels and to establish the protocol to isolate retinal and choroidal VESCs.MethodsWe established an efficient protocol to create single-cell suspensions from freshly isolated mouse retina and choroid by enzymatic digestion using dispase, collagenase, and type II collagenase. CD157-positive VESCs, defined as CD31⁺CD45⁻CD157⁺ cells, were sorted using fluorescence-activated cell sorting (FACS).ResultsIn mouse retina, among CD31⁺CD45⁻ endothelial cells (ECs), 1.6 ± 0.2% were CD157-positive VESCs, based on FACS analysis. In mouse choroid, among CD31⁺CD45⁻ ECs, 4.5 ± 0.4% were VESCs. The CD157-positive VESCs generated a higher number of EC networks compared with CD157-negative non-VESCs under vascular endothelial growth factor (VEGF) in vitro cultures. The EC network area, defined as the ratio of the CD31-positive area to the total area in each field, was 4.21 ± 0.39% (retinal VESCs) and 0.27 ± 0.12% (retinal non-VESCs), respectively (P < 0.01). The EC network area was 8.59 ± 0.78% (choroidal VESCs) and 0.14 ± 0.04% (choroidal non-VESCs), respectively (P < 0.01). The VESCs were located in large blood vessels but not in the capillaries.ConclusionsWe confirmed distinct populations of CD157-positive VESCs in both mouse retina and choroid. VESCs are located in large vessels and have the proliferative potential. The current results may open new avenues for the research and treatment of ocular vascular diseases.     

Successful treatment of unresectable recurrent cutaneous squamous cell carcinoma of the scalp with meningeal invasion with nivolumab monotherapy

Although the number of cutaneous squamous cell carcinoma (cSCC) cases is increasing, the effectiveness of systemic therapy for the treatment of advanced cSCC is limited. Since cSCC possesses a high tumor mutation burden (TMB) compared to other cancer species, and since high TMB correlated with increased neoantigens and the efficacy of anti‐PD1 antibodies (Abs) in various cancers, cSCC could be a target for anti‐PD1 Abs monotherapy. In this report, we describe a case of unresectable recurrent cSCC of the scalp with meningeal invasion, but highly expressed programmed death‐ligand 1 (PD‐L1), treated with nivolumab monotherapy.     

Inhibitory effect of angiotensin Ⅱ receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis

AIM: To investigate the efficacy of angiotensin II receptor antagonist on hepatic stellate cells (HSCs) activation in the patients with non-alcoholic steatohepatitis (NASH). METHODS: Seven patients with NASH were prescribed losartan, a selective angiotensin II type 1 receptor antagonist (50 mg/d) for 48 wk. Liver biopsies were performed both at the entry and end of the study in all patients. Quiescent and activated HSCs were identified by double immunostaining using anti-p75 and -smooth muscle actin antibodies, and the number of each phenotype was counted. Similarly, the liver specimens obtained from the eight patients with non-alcoholic fatty liver (NAFL) were also examined as controls. RESULTS: In NASH hepatic tissues, activated HSCs were dominantly distributed as compared with those in NAFL. The 48-wk losartan treatment induced a remarkable decrease in activated HSCs and a mild increase in quiescent phenotypes. CONCLUSION: Our data suggest the crucial involvement of HSCs in anti-fibrotic effect of angiotensin II receptor antagonist on patients with NASH.     

Global Health and Emergency Care: A Resuscitation Research Agenda—Part 2

At the 2013 Academic Emergency Medicine global health consensus conference, a breakout session to develop a research agenda for resuscitation was held. Two articles are the result of that discussion. This second article addresses data collection, management, and analysis and regionalization of postresuscitation care, resuscitation programs, and research examples around the world and proposes a strategy to strengthen resuscitation research globally. There is a need for reliable global statistics on resuscitation, international standardization of data, and development of an electronic standard for reporting data. Regionalization of postresuscitation care is a priority area for future research. Large resuscitation clinical research networks are feasible and can give valuable data for improvement of service and outcomes. Low‐cost models of population‐based research, and emphasis on interventional and implementation studies that assess the clinical effects of programs and interventions, are needed to determine the most cost‐effective strategies to improve outcomes. The global challenge is how to adapt research findings to a developing world situation to have an effect internationally.     

Hip dysplasia in Charcot-Marie-Tooth disease: report of a family

Charcot-Marie-Tooth disease is classified into hereditary motor and sensory neuropathy (HMSN) types I and II, and affected patients present with progressive peripheral neuropathy. Some previous orthopedic studies have revealed the association of hip dysplasia with HMSN, in addition to pes cavovarus, scoliosis, and recurrent dislocation of the patella. We describe three patients from the same family who were each diagnosed as having HMSN type I with associated bilateral severe hip dysplasia, borderline abnormalities of both acetabula, and dysplastic osteoarthritis. Based on our experience with these patients and a review of previous reports, we concluded that routine screening of hip joints, especially for those with a family history of HMSN, is necessary for early diagnosis.     

AFP, AFP-L3, DCP, and GP73 as markers for monitoring treatment response and recurrence and as surrogate markers of clinicopathological variables of HCC

Background

Alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxy prothrombin (DCP), and Golgi protein-73 (GP73) have been used or proposed as tumor markers for hepatocellular carcinoma (HCC).

Methods

They were measured in 96 patients undergoing hepatectomy for HCC to investigate their treatment response and association with variables linked with tumor invasiveness and/or prognosis. Values at 1 month post-surgery in the 77 patients without recurrence within 6 postoperative months were adopted as those after surgery.

Results

GP73 levels did not change after hepatectomy, but levels of other markers decreased and areas under receiver operating characteristic curves (95% CI) were: 0.64 (0.56–0.72), 0.63 (0.55–0.71), 0.79 (0.73–0.86), and 0.63 (0.55–0.71) for AFP, AFP-L3, DCP, and combination of AFP and AFP-L3, respectively. Cutoff points giving specificities of 96.1% (sensitivities at these points) were: 124 ng/mL (28.1%), 10% (21.9%), and 60 mAU/mL (52.1%), for AFP, AFP-L3, and DCP, respectively. The combination of AFP and AFP-L3 provided a sensitivity of 26.0% at a specificity of 96.1%. The increased DCP value was, or tended to be, associated with a larger tumor, vascular invasion, intrahepatic metastases, and a lower grade of tumor cell differentiation. Although similar associations were found between AFP and vascular invasion as well as a lower grade of tumor cell differentiation, no such relationship was found with AFP-L3.

Conclusions

DCP is a more effective tumor marker than AFP and AFP-L3. AFP-L3 showed comparable accuracy to AFP but no benefit was found in their combination. GP73 did not play a significant role in this context. Indices of tumor invasiveness were most closely associated with DCP.