Geriatric nutritional risk index as an easy-to-use assessment tool for nutritional status in hepatocellular carcinoma treated with atezolizumab plus bevacizumab

Aim

The present study focused on Geriatric Nutritional Risk Index (GNRI), which is based on bodyweight and serum albumin, and known as an easy-to-use nutritional assessment tool in clinical settings, to elucidate the prognostic predictive ability of GNRI in patients treated with atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC).

Methods

A total of 525 HCC patients treated with Atez/Bev, based on their classification of unsuitable status for curative treatments and/or transarterial catheter chemoembolization, were enrolled (Child–Pugh A:B:C = 484:40:1, Barcelona Clinic Liver Cancer stage 0:A:B:C:D = 7:25:192:283:18). Prognosis was evaluated retrospectively using GNRI.

Results

Atez/Bev was used in 338 of the present cohort as first-line systemic chemotherapy (64.4%). Median progression-free survival based on GNRI indicating normal, mild decline, moderate decline, and severe decline was 8.3, 6.7, 5.3, and 2.4 months, respectively, whereas median overall survival was 21.4, 17.0, 11.5. and 7.3 months, respectively (both p < 0.001). The concordance index (c-index) values of GNRI for predicting prognosis (progression-free survival/overall survival) were superior to those of Child–Pugh class and albumin-bilirubin grade (0.574/0.632 vs. 0.527/0.570 vs. 0.565/0.629). As a subanalysis, muscle volume loss was observed in 37.5% of 256 patients with computed tomography data available. Along with GNRI decline, frequency of muscle volume loss became progressively larger (normal vs. mild vs. moderate vs. severe = 17.6% vs. 29.2% vs. 41.2% vs. 57.9%, p < 0.001), and a GNRI value of 97.8 was predictive of its occurrence (AUC 0.715, 95% CI 0.649–0.781; specificity/sensitivity = 0.644/0.688).

Conclusion

These findings indicate that GNRI is an effective nutritional prognostic tool for predicting prognosis and muscle volume loss complication in HCC patients treated with Atez/Bev.     

N-terminus of Etanercept is Proteolytically Processed by Dipeptidyl Peptidase-4

Pharmaceutical Research - Biologics are structurally heterogeneous and can undergo biotransformation in the body. Etanercept (ETN) is a fusion protein composed of a soluble tumor necrosis factor...     

An autopsy case of ornithine transcarbamylase deficiency

We present an autopsy case of ornithine transcarbamylase (OTC) deficiency with grumose degeneration in the dentate nucleus of the cerebellum. The patient had intractable neonatal convulsions and hyperammonemia from the 3rd day after birth. Diagnosis of OTC deficiency was made based on null activity of the enzyme and four-base deletions in exon 9 of the OTC gene. Death was due to sepsis as well as disseminated intravascular coagulation at 1 year and 2 months of age. Neuropathology showed multiple cystic changes and ulegyria in the bilateral frontal and parietal lobes. Multiple cysts were associated with the region, which was infiltrated with macrophages surrounded by astroglia showing palisading pattern. Ferrugination was marked in the thalamus and severe neuronal loss with astrogliotic change in the CA1-2 area of the hippocampus. Grumose degeneration was noted in the dentate nucleus of the cerebellum. This is the first report of grumose degeneration in OTC deficiency.     

Contribution of sarcoplasmic reticulum Ca²+ release and Ca²+ transporters on sarcolemmal channels to Ca²+ transient in fetal mouse heart

Sarcoplasmic reticulum (SR) Ca release has been shown not to be the predominant mechanism responsible for excitation-contraction (E-C) coupling in fetal myocytes. However, most of the studies have been conducted either on primary cultures or acutely isolated cells, in which an apparent reduction of ryanodine receptor density have been reported. We aimed to elucidate the contribution of SR Ca release and Ca transporters on sarcolemmal channels to Ca transients in fetal mouse whole hearts. On embryonic day 13.5, ryanodine significantly reduced the amplitude of the Ca transient to 27.2 ± 4.4% of the control, and both nickel and SEA0400 significantly prolonged the time to peak from 84 ± 2 ms to 140 ± 5 ms and 129 ± 6 ms, respectively, whereas nifedipine did not alter it. Therefore, at early fetal stages, SR Ca release should be an important component of E-C coupling, and T-type Ca channel and reverse mode sodium-calcium exchanger (NCX)-mediated SR Ca release could be the predominant contributors. Using embryonic mouse cultured cardiomyocytes, we showed that both nifedipine and nickel inhibited the ability of NCX to extrude Ca from the cytosol. From these results, we propose a novel idea concerning E-C coupling in immature heart.     

A case of nodular cutaneous lupus mucinosis

The patient was a 44-year-old female. She was diagnosed as having systemic lupus erythematosus at the age of 21 years and had been receiving systemic steroid treatment (5 mg prednisolone/day). Nodules began to appear on her neck, chest and back from June in 2000, and she was referred to our clinic for examination and treatment. Examination of a biopsy sample of an eruption on the neck revealed mucin deposition in the dermis. Based on the clinical and histopathological findings, she was diagnosed as having typical nodular cutaneous lupus mucinosis. The dose of steroid was increased, and the eruptions gradually disappeared.     

Activated and mature CD83-positive dendritic cells and interferon-gamma-positive cells in skin eruptions of secondary syphilis

Dendritic cells are considered to be the most potent antigen-presenting cells, and CD83 is expressed at a high level in immunocompetent, activated and mature dendritic cells. Various pathogens can activate and modulate the function of dendritic cells. The presence of activated and mature dendritic cells in skin lesions of secondary syphilis has never been reported. In the present study, an immunohistochemical technique was used to determine the exact tissue distributions of CD83+ dendritic cells and interferon-gamma+ cells in skin lesions of patients with secondary syphilis. Immunohistochemical staining was performed by using formalin-fixed, paraffin-embedded sections. A small but significant subpopulation of CD83+ dendritic cells was found in the dermis. CD83+ dendritic cells were in close contact with lymphocytes. High-intensity staining of CD83 antigens was detected not only on the surface but also in the cytoplasm of dendritic cells. Infiltrating mononuclear cells were stained positively for CD4 or CD8, with CD8+ cells always being in the majority. A small number of interferon-gamma+ cells resembling mononuclear lymphoid cells were detected in all samples. These results provide in vivo support for the hypothesis that dendritic cells are activated by Treponema pallidum and that thus activated and mature CD83+ dendritic cells may play a role in the Th1 response in secondary syphilis.     

Perceptions of specialized inpatient palliative care: a population-based survey in Japan

This study aimed to clarify and compare the awareness and perceptions of the specialized inpatient palliative care service. A cross-sectional questionnaire survey was performed on the general population selected by stratified two-stage random sampling (n=2,548) and bereaved families who actually received specialized inpatient palliative care at 12 palliative care units (PCUs) in Japan (n=513). The respondents reported their awareness and perceptions of PCUs. Thirty-eight percent of the general population answered that they had "considerable" or "moderate" knowledge of PCUs, but 24% answered that they had "no" knowledge. Bereaved families who received PCU care (PCU-bereaved families) were likely to have better perceptions of PCUs than the general population: "alleviates pain" (68% of the general population and 87% of PCU-bereaved families agreed), "provides care for families" (67% and 86%, respectively), and "provides compassionate care" (67% and 87%, respectively). Both groups, however, expressed concerns about PCUs: "a place where people only wait to die" (30% and 40%, respectively) and "shortens the patient's life" (8% and 17%, respectively). These perceptions were associated with overall satisfaction with received care, and differed among the 12 PCUs. In conclusion, public awareness of PCUs was insufficient in Japan. Although PCU-bereaved families were generally likely to have better perceptions of PCUs than the general population, both groups shared concerns that a PCU was a place where people only wait to die. To facilitate appropriate use of specialized palliative care services, more efforts to inform the general population about the actual palliative care system are needed. In addition, the role of PCUs might be reconsidered in terms of the continuum of cancer care.