Background
Liver functional reserve is a major prognostic determinant in patients with hepatocellular carcinoma (HCC). The albumin–bilirubin (ALBI) score is an objective method to assess the severity ...of cirrhosis in this setting. However, calculation of the ALBI score is complex and difficult to access in clinical practice. Recently, the EZ (easy)‐ALBI score was proposed as an alternative biomarker of liver injury. We aimed to evaluate the prognostic role of the EZ‐ALBI score in HCC from early to advanced stages.
Methods
A total of 3794 newly diagnosed HCC patients were prospectively enrolled and retrospectively analyzed. Independent prognostic predictors were determined by using the multivariate Cox proportional hazards model.
Results
The EZ‐ALBI score showed good correlation with the ALBI score (correlation coefficient, 0.965; p < 0.001). The correlation of the EZ‐ALBI score was highly preserved in different Child–Turcotte–Pugh (CTP) classifications, treatment methods, and Barcelona Clinic Liver Cancer (BCLC) stages (correlation coefficients, 0.90–0.97). In the Cox multivariate analysis, age >65 years, male sex, serum α‐fetoprotein >20 ng/ml, large or multiple tumors, total tumor volume >100 cm3, vascular invasion or distant metastasis, ascites, poor performance status, EZ‐ALBI grade 2 and 3, and noncurative treatments were independently associated with increased mortality (all p < 0.05). Moreover, EZ‐ALBI grade can stratify long‐term survival in patients with different CTP class, treatment strategy, and BCLC stage.
Conclusions
The EZ‐ALBI score is an easy and feasible method to evaluate liver functional reserve. As a new prognostic biomarker in HCC, the predictive power of the EZ‐ALBI grade is independent across different cancer stages and treatments.
Laparoscopic distal gastrectomy is gaining popularity over open distal gastrectomy for gastric cancer because of better early postoperative outcomes. However, to our knowledge, no studies have proved ...whether laparoscopic distal gastrectomy is oncologically equivalent to open distal gastrectomy.
To examine whether the long-term survival among patients with stage I gastric cancer undergoing laparoscopic distal gastrectomy is noninferior to that among patients undergoing open distal gastrectomy.
The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) group, which includes 15 surgeons from 13 institutes, conducted a phase 3, multicenter, open-label, noninferiority, prospective randomized clinical trial (KLASS-01) of patients with histologically proven, preoperative clinical stage I gastric adenocarcinoma from January 5, 2006, to August 23, 2010. Survival and recurrence status of the patients was determined in December 2016.
Patients were randomly assigned (1:1) to laparoscopic distal gastrectomy (n = 705) or open distal gastrectomy (n = 711). Of these patients, 85 received a surgical approach opposite the one to which they were randomized (63 randomized to the open surgery group and 22 to the laparoscopic group).
Difference in 5-year overall survival between the laparoscopic and open distal gastrectomy groups. The noninferiority margin was prespecified as -5% (corresponding hazard ratio of 1.54), with an assumed survival of 90% after 5 years in the open surgery group.
Among the 1416 patients (mean SD age, 57.3 11.1 years; 940 66.4% male) included in the study, the 5-year overall survival rates were 94.2% in the laparoscopic group and 93.3% in the open surgery group (log-rank P = .64). Intention-to-treat analysis confirmed the noninferiority of the laparoscopic approach compared with the open approach (difference, 0.9 percentage points; 1-sided 97.5% CI, -1.6 to infinity). The 5-year cancer-specific survival rates were similar between the 2 groups (97.1% in the laparoscopic group and 97.2% in the open surgery group, log-rank P = .91; difference, -0.03 percentage points; 1-sided 97.5% CI, -1.8 to infinity). Per-protocol analysis results were consistent with the intention-to-treat results for overall and cancer-specific survival rates.
The KLASS-01 trial revealed similar overall and cancer-specific survival rates between patients receiving laparoscopic and open distal gastrectomy. Laparoscopic distal gastrectomy is an oncologically safe alternative to open surgery for stage I gastric cancer.
ClinicalTrials.gov identifier: NCT00452751.
Purpose It has often been hypothesized that mandibular setback surgery causes narrowing of the pharyngeal airway. We examined whether the pharyngeal airway narrowed after orthognathic surgery in ...patients undergoing either mandibular setback surgery or bimaxillary surgery and whether the amount of narrowing of the pharyngeal airway was any different after mandibular setback surgery or bimaxillary surgery. Materials and Methods Cone-beam computed tomography scans were obtained for 21 patients who were assigned to either mandibular setback surgery or bimaxillary surgery. The anteroposterior dimension, lateral width, cross-sectional area, and volume of each subject's pharyngeal airway were measured before and after surgery. Results The pharyngeal airway showed significant narrowing after both mandibular setback surgery and bimaxillary surgery. The amount of change in the anteroposterior dimension and cross-sectional area on the posterior nasal spine plane and the length of the pharyngeal airway showed significant differences between the 2 groups. Conclusion The amount of narrowing of the pharyngeal airway was smaller in patients undergoing bimaxillary surgery than in the patients undergoing mandibular setback surgery.
The design principle of establishing an intracellular protein gradient for asymmetric cell division is a long-standing fundamental question. While the major molecular players and their interactions ...have been elucidated via genetic approaches, the diversity and redundancy of natural systems complicate the extraction of critical underlying features. Here, we take a synthetic cell biology approach to construct intracellular asymmetry and asymmetric division in Escherichia coli, in which division is normally symmetric. We demonstrate that the oligomeric PopZ from Caulobacter crescentus can serve as a robust polarized scaffold to functionalize RNA polymerase. Furthermore, by using another oligomeric pole-targeting DivIVA from Bacillus subtilis, the newly synthesized protein can be constrained to further establish intracellular asymmetry, leading to asymmetric division and differentiation. Our findings suggest that the coupled oligomerization and restriction in diffusion may be a strategy for generating a spatial gradient for asymmetric cell division.
Background and Aim
Size and number are major determinants of tumor burden in hepatocellular carcinoma (HCC). Patients with HCC undergoing transarterial chemoembolization (TACE) have variable outcomes ...due to heterogeneity of tumor burden. Recently, tumor burden score (TBS) was proposed to evaluate the extent of tumor involvement. However, the prognostic accuracy of TBS has not been well evaluated in HCC. This study aimed to assess its prognostic role in HCC patients undergoing TACE.
Methods
A total of 935 treatment‐naïve HCC patients receiving TACE were retrospectively analyzed. Multivariate Cox proportional hazards model was used to determine independent prognostic predictors.
Results
Tumor burden score tended to increase with increasing size and number of tumors in study patients. The Cox model showed that serum creatinine ≥ 1.2 mg/dL (hazard ratio HR: 1.296, 95% confidence interval CI: 1.077–1.559, P = 0.006), serum α‐fetoprotein ≥ 400 ng/dL (HR: 2.245, 95% CI: 1.905–2.645, P < 0.001), vascular invasion (HR: 1.870, 95% CI: 1.520–2.301, P < 0.001), medium TBS (HR: 1.489, 95% CI: 1.206–1.839, P < 0.001) and high TBS (HR: 2.563, 95% CI: 1.823–3.602, P < 0.001), albumin–bilirubin (ALBI) grade 2–3 (HR: 1.521, 95% CI: 1.291–1.792, P < 0.001), and performance status 1 (HR: 1.362, 95% CI: 1.127–1.647, P < 0.001) and status 2 (HR: 1.553, 95% CI: 1.237–1.948, P < 0.001) were associated with increased mortality. Patients with high TBS had poor overall survival in Barcelona Clinic Liver Cancer stage B/C and different ALBI grades.
Conclusions
Tumor burden score is a feasible new prognostic surrogate marker of tumor burden in HCC and can well discriminate survival in patients undergoing TACE across different baseline characteristics.
For the effective application of surface‐enhanced Raman scattering (SERS) nanoprobes for in vivo targeting, the tissue transparency of the probe signals should be as high as it can be in order to ...increase detection sensitivity and signal reproducibility. Here, near‐infrared (NIR)‐sensitive SERS nanoprobes (NIR SERS dots) are demonstrated for in vivo multiplex detection. The NIR SERS dots consist of plasmonic Au/Ag hollow‐shell (HS) assemblies on the surface of silica nanospheres and simple aromatic Raman labels. The diameter of the HS interior is adjusted from 3 to 11 nm by varying the amount of Au3+ added, which results in a red‐shift of the plasmonic extinction of the Au/Ag nanoparticles toward the NIR (700–900 nm). The red‐shifted plasmonic extinction of NIR SERS dots causes enhanced SERS signals in the NIR optical window where endogenous tissue absorption coefficients are more than two orders of magnitude lower than those for ultraviolet and visible light. The signals from NIR SERS dots are detectable from 8‐mm deep in animal tissues. Three kinds of NIR SERS dots, which are injected into live animal tissues, produce strong SERS signals from deep tissues without spectral overlap, demonstrating their potential for in vivo multiplex detection of specific target molecules.
Near‐infrared‐sensitive surface‐enhanced Raman scattering nanoprobes (NIR SERS dots) are fabricated by forming plasmonic Au/Ag hollow‐shells, which assemble on silica nanospheres. A single NIR SERS dot is capable of generating a strong SERS signal (average SERS enhancement factor value 2.8 × 105) with high reproducibility. In addition, the signals from NIR SERS dots are effectively detected from deep tissues of up to 8 mm depth and have exhibited a capability for in vivo multiplex detection in a live animal study.
In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol ...(LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease.
To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease.
A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022).
Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg.
Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points.
Among 4400 patients, 4341 patients (98.7%) completed the trial (mean SD age, 65.1 9.9 years; 1228 females 27.9%). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, -0.6 percentage points upper boundary of the 1-sided 97.5% CI, 1.1 percentage points; P < .001 for noninferiority).
Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy.
ClinicalTrials.gov Identifier: NCT02579499.
Summary Background D2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient ...outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II–IIIB gastric cancer. Methods The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II–IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m2 twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m2 on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov ( NCT00411229 ). Findings 1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4–41·7) in the chemotherapy and surgery group and 34·3 months (25·6–41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69–79) in the chemotherapy and surgery group and 59% (53–64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44–0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294). Interpretation Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer. Funding F Hoffmann-La Roche and Sanofi-Aventis.
Although the incidence of inflammatory bowel disease IBD is increasing in Asia, data on long-term epidemiological trends are limited. We performed a 30-year longitudinal study to investigate temporal ...trends in the epidemiology of Crohn's disease CD and ulcerative colitis UC in Seoul, Korea.
This population-based study included 1431 IBD patients 418 CD, 1013 UC diagnosed between 1986 and 2015 in the Songpa-Kangdong district of Seoul, Korea. Temporal trends in incidence, prevalence, and disease phenotype at diagnosis were analysed.
The adjusted mean annual incidence rates of CD and UC per 100 000 inhabitants increased from 0.06 (95% confidence interval CI, 0.05-0.07) and 0.29 95% CI, 0.27-0.31, respectively, in 1986-1990 to 2.44 95% CI, 2.38-2.50 and 5.82 95% CI, 5.73-5.92, respectively, in 2011-2015. Average annual percentage change in IBD incidence was 12.3% in 1986-1995, 12.3% in 1996-2005, and 3.3% in 2006-2015. The male-to-female ratio of the adjusted incidence rate was 3.3:1 for CD and 1.2:1 for UC. Perianal fistula/abscess was present in 43.3% of patients before or at CD diagnosis. At diagnosis, 54.3% of UC patients presented only with proctitis. The adjusted prevalence rate in 2015 was 31.59/100 000 95% CI, 31.10-32.07 for CD and 76.66/100 000 95% CI, 75.91-77.42 for UC.
The incidence and prevalence of IBD in Korea have continued to increase over the past three decades. Korean patients have distinct demographic and phenotypic characteristics, including a male predominance and high frequency of perianal fistula/abscess in CD and high proportion of proctitis in UC.
Viral pathogens have not generally been regarded as important causes of severe hospital-acquired pneumonia (HAP), except in patients with hematologic malignancy or transplant recipients. We ...investigated the role and distribution of viruses in adult with severe HAP who required intensive care.
From March 2010 to February 2012, adult patients with severe HAP required admission to the intensive care unit (ICU), 28-bed medical ICU in a tertiary care hospital, were prospectively enrolled. Respiratory viruses were detected using multiplex reverse-transcription polymerase chain reaction and/or shell vial culture.
A total of 262 patients were enrolled and 107 patients (40.8%) underwent bronchoscopic BAL for etiologic diagnosis. One hundred and fifty-six patients (59.5%) had bacterial infections and 59 patients (22.5%) had viral infections. Viruses were detected in BAL fluid specimens of 37 patients (62.7%, 37/59). The most commonly identified viruses were respiratory syncytial virus and parainfluenza virus (both 27.1%, 16/59), followed by rhinovirus (25.4%, 15/59), and influenza virus (16.9%, 10/59). Twenty-one patients (8.0%, 21/262) had bacterial-viral coinfections and Staphylococcus aureus was the most commonly coexisting bacteria (n = 10). Viral infection in non-immunocompromised patients was not uncommon (11.1%, 16/143), although it was not as frequent as that in immunocompromised patients (36.4%, 43/119). Non-immunocompromised patients were significantly older than immunocompromised patients and had significantly higher rates of underlying chronic obstructive pulmonary disease, tuberculous destroyed lung and chronic kidney disease. The 28 day mortalities of patients with bacterial infections, viral infections and bacterial-viral coinfections were not significantly different (29.5%, 35.6% and 19.0%, respectively; p = 0.321).
Viral pathogens are not uncommon in adult patients with severe HAP who required ICU admission. Since viral pathogens may cause severe HAP and could be a potential source of viral transmission, further investigation is required to delineate the role of viral pathogens in severe HAP.
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