Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

Videolaryngoscopy vs. flexible fibrescopy for tracheal intubation in patients with cervical spine immobilisation: a randomised controlled trial.

In patients with cervical spine immobilisation, tracheal intubation devices other than a direct laryngoscope are frequently used to facilitate tracheal intubation and avoid related complications. In this randomised controlled trial, we compared videolaryngoscopic and fibrescopic tracheal intubation in patients with a cervical collar. Tracheal intubation was performed using either a videolaryngoscope with a non-channelled Macintosh blade (n = 166) or a flexible fibrescope (n = 164) in patients having elective cervical spine surgery whose neck was immobilised with a cervical collar to simulate a difficult airway. The primary outcome was the first attempt success rate of tracheal intubation. Secondary outcomes were the overall success rate of tracheal intubation; time to tracheal intubation; use of additional airway manoeuvres; and incidence and severity of tracheal intubation-related airway complications. First attempt success rate was higher in the videolaryngoscope group than in the fibrescope group (164/166 (98.8%) vs. 149/164 (90.9%), p = 0.003). Tracheal intubation was successful within three attempts in all patients. Median (IQR [range]) time to tracheal intubation was shorter (50.0 (41.0-72.0 [25.0-170.0]) s vs. 81.0 (65.0-107.0 [24.0-178.0]) s, p < 0.001) and additional airway manoeuvres were less frequent (30/166 (18.1%) vs. 91/164 (55.5%), p < 0.001) in the videolaryngoscope group compared with the fibrescope group. The incidence and severity of intubation-related airway complications were not different between the two groups. When performing tracheal intubation in patients with a cervical collar, videolaryngoscopy with a non-channelled Macintosh blade was superior to flexible fibrescopy.

A phase II open-label trial of avelumab plus axitinib in previously treated non-small-cell lung cancer or treatment-naïve, cisplatin-ineligible urothelial cancer.

BACKGROUND: We hypothesized that avelumab plus axitinib could improve clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC) or urothelial carcinoma (UC). PATIENTS AND METHODS: We enrolled previously treated patients with advanced or metastatic NSCLC, or untreated, cisplatin-ineligible patients with advanced or metastatic UC. Patients received avelumab 800 mg every 2 weeks (Q2W) and axitinib 5 mg orally two times daily. The primary endpoint was objective response rate (ORR). Immunohistochemistry was used to assess programmed death-ligand 1 (PD-L1) expression (SP263 assay) and the presence of CD8+ T cells (clone C8/144B). Tumor mutational burden (TMB) was assessed by whole-exome sequencing. RESULTS: A total of 61 patients were enrolled and treated (NSCLC, n = 41; UC, n = 20); 5 remained on treatment at data cut-off (26 February 2021). The confirmed ORR was 31.7% in the NSCLC cohort and 10.0% in the UC cohort (all partial responses). Antitumor activity was observed irrespective of PD-L1 expression. In exploratory subgroups, ORRs were higher in patients with higher (≥median) CD8+ T cells in the tumor. ORRs were higher in patients with lower TMB (

Risk factors for delirium among patients with advanced cancer in palliative care: a multicenter, patient-based registry cohort in South Korea.

OBJECTIVE: Previous studies have comprehensively investigated the prevalence and various potential risk factors for delirium among patients with advanced cancer admitted to the acute palliative care unit (APCU). Our objective was to evaluate the comprehensive association between delirium and various risk factors among patients with advanced cancer in an acute palliative care setting using a patient-based multicenter registry cohort. PATIENTS AND METHODS: We performed a multicenter, patient-based registry cohort study collected in South Korea between January 1, 2019, and December 31, 2020. Delirium was identified using a medical record review based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. RESULTS: In total, 2,124 eligible patients with advanced cancer in the APCU met the inclusion criteria. There were 127 out of 2,124 patients (prevalence, 6.0%; 95% CI, 5.0 to 7.1) with delirium during admission. Delirium in patients with advanced cancer was associated with age >70 years (OR, 1.793; 95% CI, 1.246 to 2.581), male sex (OR, 1.675; 95% CI, 1.131 to 2.479), no chemotherapy during hospitalization (OR, 2.019; 95% CI, 1.236 to 3.298), hearing impairment (OR, 3.566; 95% CI, 1.176 to 10.810), underweight (OR, 1.826; 95% CI, 1.067 to 3.124), current use of opioid medication (OR, 1.942; 95% CI, 1.264 to 2.982), previous history of delirium (OR, 12.497; 95% CI, 6.920 to 22.568), and mental illness (OR, 2.333; 95% CI, 1.251 to 4.352). CONCLUSIONS: In a large-scale multicenter patient-based registry cohort, delirium was associated with old age, male sex, no chemotherapy during hospitalization, hearing impairment, underweight, current use of opioid medication, and a history of delirium and mental illness. Our findings suggest physicians should pay attention to delirium in patients with advanced cancer admitted to the APCU with the above risk factors.

Precision hormone therapy: identification of positive responders.

Since the introduction of menopausal hormone therapy (MHT) in the 1940s, randomized clinical trials and observational studies have been performed to determine the benefits and risks of MHT. However, MHT therapeutic impact remains under debate as multiple factors including genetic biomarkers and medical history contribute to inter-individual variations in neurodegenerative diseases. Herein, we review the characteristics of women who participated in clinical studies and methodological approaches for study analyses to assess the critical variables influencing an association between MHT and risk of neurodegenerative diseases. Outcomes of the review indicated that: (1) observational studies assessed outcomes of MHT in symptomatic women whereas MHT clinical trials were conducted in asymptomatic postmenopausal women not treated for menopausal symptoms, (2) in asymptomatic postmenopausal women, late MHT intervention was of no benefit, (3) different MHT treatments and regimens between observational studies and clinical trials may impact outcomes, and (4) observational studies may provide greater predictive validity for long-term neurological health outcomes as MHT was introduced in symptomatic women and administered over a long period of time. Going forward, achieving precision hormone therapy will require a priori identification of symptomatic women appropriate for MHT and the type and dose of MHT appropriate for their genetic profile and health risks.

Enhanced antimicrobial stewardship based on rapid phenotypic antimicrobial susceptibility testing for bacteraemia in patients with haematological malignancies: a randomized controlled trial.

OBJECTIVES: Recently, rapid phenotypic antimicrobial susceptibility testing (AST) based on microscopic imaging analysis has been developed. The aim of this study was to determine whether implementation of antimicrobial stewardship programmes (ASP) based on rapid phenotypic AST can increase the proportion of patients with haematological malignancies who receive optimal targeted antibiotics during early periods of bacteraemia. METHODS: This randomized controlled trial enrolled patients with haematological malignancies and at least one positive blood culture. Patients were randomly assigned 1:1 to conventional (n = 60) or rapid phenotypic (n = 56) AST. The primary outcome was the proportion of patients receiving optimal targeted antibiotics 72 hr after blood collection for culture. RESULTS: The percentage receiving optimal targeted antibiotics at 72 hr was significantly higher in the rapid phenotypic AST group (45/56, 80.4%) than in conventional AST group (34/60, 56.7%) (relative risk (RR) 1.42, 95% confidence interval (CI) 1.09-1.83). The percentage receiving unnecessary broad-spectrum antibiotics at 72 hr was significantly lower (7/26, 12.5% vs 18/60, 30.0%; RR 0.42, 95% CI 0.19-0.92) and the mean time to optimal targeted antibiotic treatment was significantly shorter (38.1, standard deviation (SD) 38.2 vs 72.8, SD 93.0 hr; p < 0.001) in the rapid phenotypic AST group. The mean time from blood collection to the AST result was significantly shorter in the rapid phenotypic AST group (48.3, SD 17.6 vs 83.1, SD 22.2 hr). DISCUSSION: ASP based on rapid phenotypic AST can rapidly optimize antibiotic treatment for bacteraemia in patients with haematological malignancy. Rapid phenotypic AST can improve antimicrobial stewardship in immunocompromised patients.

Impact of COVID-19 Pandemic on Ambulatory and Operating Room Rhinology Practice in the US.

INTRODUCTION: The pandemic caused by the novel coronavirus virus has altered all facets of clinical practice in the United States. The goal of this study is to better understand the impact of COVID-19 on rhinologic ambulatory and operative practice. METHODS: A 27-item survey to assess these objectives was created and approved by the Division of Rhinology faculty at Rush University Medical Center in April 2020. The survey was then distributed to rhinologists in a web based format via www.surveymonkey.com from April 10 through April 23, 2020. RESULTS: A total of 277 U.S based rhinologists responded to the survey (23.04%). The most common practice types were single specialty private (44.9%) and academic (24.6%). 90.2% practice in a state under a shelter in place order. Comparing pre-COVID baseline to during-COVID, there was statistically significant reduction in the number of patients of seen daily in clinic (p < 0.001). The number of nasal endoscopies in the office and surgical procedures fell dramatically. Overall, 5 respondent rhinologists have been infected with COVID-19 and 27 have been furloughed. CONCLUSION: COVID-19 has drastically affected rhinologic practice. There is a dramatic reduction of in person care in the office setting and surgical management of sinonasal and skull base disease. Enhanced PPE is being used in only half of potentially aerosolizing procedures which represents an area of further education. Novel approaches such as use of virtual encounters and point of care testing should be considered as options to facilitate care.

MRI-Based Assessment of the Pharyngeal Constrictor Muscle as a Predictor of Surgical Margin after Transoral Robotic Surgery in HPV-Positive Tonsillar Cancer.

BACKGROUND AND PURPOSE: Transoral robotic surgery is an emerging strategy for treating human papillomavirus-positive cancers, but the role of MR imaging in predicting the surgical outcome has not been established. We aimed to identify preoperative MR imaging characteristics that predispose the outcome of transoral robotic surgery toward an insecure (positive or close) surgical margin in human papillomavirus-positive tonsillar squamous cell carcinoma. MATERIALS AND METHODS: Between December 2012 and May 2019, sixty-nine patients underwent transoral robotic surgery at our institution. Among these, 29 who were diagnosed with human papillomavirus-positive tonsillar squamous cell carcinoma, did not receive neoadjuvant treatment, underwent preoperative 3T MR imaging, and had postoperative pathologic reports and were included in this retrospective study. Two neuroradiologists evaluated the preoperative MR imaging scans to determine the tumor spread through the pharyngeal constrictor muscle using a 5-point scale: 1, normal constrictor; 2, bulging constrictor; 3, thinning constrictor; 4, obscured constrictor; and 5, tumor protrusion into the parapharyngeal fat. The risk of an insecure surgical margin (involved or <1 mm) according to the MR imaging scores was predicted using logistic regression with the Firth correction. RESULTS: The interobserver agreement for the MR imaging scores was excellent (κ = 0.955, P < .001). A score of ≥4 could predict an insecure margin with 87.5% sensitivity and 92.3% specificity (area under the curve = 0.899) and was the only significant factor associated with an insecure margin in the multivariable analysis (OR, 6.59; 95% CI, 3.11-22.28; P < .001). CONCLUSIONS: The pre-transoral robotic surgery MR imaging scoring system for the pharyngeal constrictor muscle is a promising predictor of the surgical margin in human papillomavirus-positive tonsillar squamous cell carcinoma.

A new aortoiliac calcification scoring system to predict grade C anastomotic leak following rectal cancer surgery.

BACKGROUND: Aortoiliac calcification may be a surrogate marker of decreased visceral perfusion causing anastomotic leak (AL). The aim of this study was to evaluate the predictive role of aortoiliac calcification for AL after rectal cancer surgery. METHODS: We enrolled patients with primary rectal cancer who had restorative resection at our institution between January 2013 and December 2015. An aortoiliac calcification score was calculated as the sum of calcification scores at the infrarenal aorta (0: no, 1: ≤ 3 cm, 2: > 3 cm) and the common iliac arteries (0: no, 1: unilateral, 2: bilateral). AL was classified into three grades: grade A, requiring no intervention; grade B, requiring therapeutic intervention without re-laparotomy; and grade C, requiring re-laparotomy. Clinicopathological characteristics were analyzed to identify risk factors for AL. RESULTS: There were 583 patients. Three-hundred forty-five (59.2%) had an aortoiliac calcification score ≥ 3, and 37 (6.3%) patients experienced AL, in 30 cases (5.1%) grade C AL. Patients with an aortoiliac calcification score ≥ 3 had a higher incidence of grade C AL (6.7% vs. 2.9%, p = 0.045). Multivariate logistic regression analysis revealed that an aortoiliac calcification score ≥ 3 was an independent risk factor for grade C AL (odds ratio = 2.669, 95% confidence interval 1.066-6.686, p = 0.036). CONCLUSIONS: Aortoiliac calcification may be considered a risk factor for grade C AL after rectal cancer surgery.

Atlantoaxial bands in small breed dogs: influence of external pressure by the endotracheal tube tie.

OBJECTIVES: To determine the prevalence of dorsal cervical spinal compression in a population of dogs susceptible to caudal occipital dysplasia. To determine whether endotracheal tube ties iatrogenically alter the dorsal compression ratio in the atlantoaxial region. MATERIALS AND METHODS: Prospective, randomised, controlled, cross-over, blinded cohort study of dogs weighing <15 kg and presenting for neurologic signs localised to the cervical region. In mid-sagittal T2-weighted MR images, dorsal cervical compression and cerebellar compression were evaluated. Dorsal cervical compression ratios were calculated and compared to determine the effect of the endotracheal tube tie on the atlantoaxial region depending on whether dogs were in extended or flexed neck position. RESULTS: Prevalence of dorsal cervical spinal compression consistent with an atlantoaxial band was 32/44 (73%) dogs without tie pressure and 37/44 (84%) dogs with tie pressure. Significantly higher compression ratios were found with tie placement over the craniocervical region. Dorsal compression ratios of dogs with cerebellar compression were significantly greater than those without it. CLINICAL SIGNIFICANCE: The location of the endotracheal tube tie can influence interpretation of MR images of the craniocervical region of small breed dogs. These breeds more often had greater dorsal cervical spinal compression with tie pressure, especially when they had cerebellar compression.

A FEASIBILITY TEST FOR QUICK RADON RISK ASSESSMENT BY MEASURING AN IN SITU RADIATION DOSE RATE.

Radon concentration was estimated using an accumulation chamber equipped with AlphaGUARD radon monitor. It varies from 12.6 ± 1.20 to 363 ± 19.3 Bq m-3 with a mean value of 180 ± 11.2 Bq m-3. A good correlation between radium content and radon concentrations was obtained of R = 0.754, which suggests that radium is the main reason of releasing radon to the atmosphere. Radon emanation coefficient and exhalation rate were also calculated. Furthermore, the radiation dose rate was measured with a high-pressure ionization chamber detector. The radiation dose rate was strongly correlated with the radon concentration and exhalation rate of R = 0.85 and 0.63. The obtained results support our idea that the radiation dose rate can be a good indicator to the radon level in the atmosphere. In addition, the dependence of radon concentration on the water content was discussed.

Prognosis of surgical hernia repair in cirrhotic patients with refractory ascites.

BACKGROUND: Abdominal wall hernias are common in patients with ascites. Elective surgical repair is recommended for the treatment of abdominal wall hernias. However, surgical hernia repair in cirrhotic patients with refractory ascites is controversial. In this study, we aimed to evaluate the outcomes of elective surgical hernia repair in patients with liver cirrhosis with and without refractory ascites. METHOD: From January 2005 to June 2018, we retrospectively reviewed the records of consecutive patients with liver cirrhosis who underwent a surgical hernia repair. RESULTS: This study included 107 patients; 31 patients (29.0%) had refractory ascites. Preoperatively, cirrhotic patients with refractory ascites had a higher median model for end-stage liver disease (MELD) score (13.0 vs 11.0, P = 0.001) than those without refractory ascites. The 30-day mortality rate (3.2% vs 0%, P = 0.64) and the risk of recurrence (hazard ratio 0.410; 95% CI 0.050-3.220; P = 0.39) did not differ significantly between cirrhotic patients with refractory ascites and cirrhotic patients without refractory ascites. Among cirrhotic patients with refractory ascites, albumin (P = 0.23), bilirubin (P = 0.37), creatinine (P = 0.97), and sodium levels (P = 0.35) did not change significantly after surgery. CONCLUSION: In advanced liver cirrhosis patients with refractory ascites, hernias can be safely treated with elective surgical repair. Mortality rate within 30 days did not differ by the presence or absence of refractory ascites. Elective hernia repair might be beneficial for treatment of abdominal wall hernia in cirrhotic patients with refractory ascites.

Functional characterisation of two phytochelatin synthases in rice (Oryza sativa cv. Milyang 117) that respond to cadmium stress.

Cadmium (Cd) is one of the most toxic heavy metals and a non-essential element to all organisms, including plants; however, the genes involved in Cd resistance in plants remain poorly characterised. To identify Cd resistance genes in rice, we screened a rice cDNA expression library treated with CdCl2 using a yeast (Saccharomyces cerevisiae) mutant ycf1 strain (DTY167) and isolated two rice phytochelatin synthases (OsPCS5 and OsPCS15). The genes were strongly induced by Cd treatment and conferred increased resistance to Cd when expressed in the ycf1 mutant strain. In addition, the Cd concentration was twofold higher in yeast expressing OsPCS5 and OsPCS15 than in vector-transformed yeast, and OsPCS5 and OsPCS15 localised in the cytoplasm. Arabidopsis thaliana plants overexpressing OsPCS5/-15 paradoxically exhibited increased sensitivity to Cd, suggesting that overexpression of OsPCS5/-15 resulted in toxicity due to excess phytochelatin production in A. thaliana. These data indicate that OsPCS5 and OsPCS15 are involved in Cd tolerance, which may be related to the relative abundances of phytochelatins synthesised by these phytochelatin synthases.

Acetabular morphology in slipped capital femoral epiphysis: comparison at treatment onset and skeletal maturity.

PURPOSE: To investigate changes in acetabular morphology during the follow-up of slipped capital femoral epiphysis (SCFE) and search for factors associated with acetabular dysplasia at skeletal maturity. METHODS: We evaluated 108 patients with unilateral SCFE (mean age at slip, 12.3 years sd 1.7) to skeletal maturity, with a minimum follow-up of two years (median 4.5 years; interquartile range 3.2 to 6.2). Acetabular parameters obtained from initial and most recent radiographs included the lateral centre-edge angle (LCEA), Tönnis angle (TA) and acetabular depth-width ratio (ADR). Acetabular dysplasia was considered for LCEA < 20° or TA > 10°. Femoral parameters consisted of the most recent head diameter, neck-shaft angle, neck length, articulotrochanteric distance and alpha angle. RESULTS: At SCFE onset, the affected hip showed a slightly lower LCEA (26.4° sd 6.1° versus 27.3° sd 5.7°; p = 0.01) and ADR (330 sd 30 versus 340 sd 30; p < 0.001) compared with the uninvolved hip. At final follow-up, the affected hip showed lower LCEA (24.5° sd 7.6° versus 28.8°sd 6.6°; p < 0.001) and ADR (330 sd 40 versus 350 sd 40; p < 0.001), and TA was larger (5.5° sd 5.4° versus 2.3° sd 4.2°; p < 0.001) compared with the uninvolved hip. Acetabular dysplasia was observed in 27 (25%) of 108 hips with SCFE. Femoral head overgrowth, age at slip and SCFE severity were independent factors associated with acetabular dysplasia (p < 0.05). CONCLUSION: Acetabular coverage and depth are not increased in SCFE, and the acetabular coverage tends to decrease up to skeletal maturity. A potential disturbance in the acetabular growth and remodelling exists mainly for young children with severe SCFE, and a potential for acetabular insufficiency may be observed at the diagnosis and follow-up of SCFE. LEVEL OF EVIDENCE: Prognostic Level IV.

Comparative study of precise measurements of natural radionuclides and radiation dose using in-situ and laboratory γ-ray spectroscopy techniques.

In this study, in-situ and laboratory γ-ray spectroscopy techniques were compared to evaluate the activity concentration of natural radionuclides in soil. The activity concentrations of 238U (226Ra), 232Th, and 40K in the soil in 11 sites were simultaneously measured with in-situ portable HPGe and the NaI(Tl) detectors. In parallel, 55 soil samples collected from these sites were analyzed with a laboratory γ-ray spectroscopy technique (HPGe). A strong correlation was observed between the in-situ and laboratory HPGe techniques with a linear correlation coefficient (R2) of 0.99 for 226Ra and 232Th and 0.975 for 40K, respectively. The in-situ HPGe technique shows a strong correlation with the NaI(Tl) detector. γ-Rays cps of 226Ra, 232Th, and 40K of the NaI (Tl) detector were then converted to specific activities (Bq kg-1 unit) in soil using the empirical formulas obtained in this study. The absorbed dose rate in air at 1 m height above ground due to these radionuclides was calculated using the Beck's formula and the results were compared with measured values obtained with an high pressure ionization chamber. The results of the calculated and measured dose rate show a strong correlation of R2 = 0.96. The reliability and precision of analytical spectroscopy techniques of radioactivity and radiation dose were confirmed in this work.

Depigmentation efficacy of galacturonic acid through tyrosinase regulation in B16 murine melanoma cells and a three-dimensional human skin equivalent.

Sugar is a well-known cosmetic ingredient for moisturizing skin with minimal side-effects. Several reports have demonstrated an antimelanogenic effect of sugar in melanocytes. We evaluated the whitening efficacy of galacturonic acid (GA), the main component of pectin, as an anti-melanogenic agent. GA significantly suppressed melanin synthesis and secretion in a concentration-dependent manner in α-melanocyte stimulating hormone-treated B16 melanoma cells, and inhibited tyrosinase activity and expression at a dose of 10 mmol/L. In a three-dimensional human skin equivalent (MelanoDerm), GA clearly brightened tissue colour. Haematoxylin and eosin and Fontana-Masson (F&M) staining of tissue sections revealed decreased melanin production without skin tissue collapse in the presence of GA. Interestingly, GA dramatically suppressed gene expression of the melanogenic proteins tyrosinase, tyrosinase-related protein (TYRP)-1 and microphthalmia-associated transcription factor, but not TYRP-2. The results support the utility of GA as an effective candidate antimelanogenic agent.

Comparison of overall survival between antiviral-induced viral suppression and inactive phase chronic hepatitis B patients.

Nucleot(s)ide analogues (NAs) reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. However, the risk of HCC is reportedly higher for NA-treated patients than for patients in the inactive CHB phase. This study aimed to compare the long-term outcomes of CHB patients with NA-induced viral suppression and those of patients with inactive CHB. This retrospective study involved 1118 consecutive CHB patients whose HBV DNA level was continuously <2000 IU/mL during follow-up with/without antiviral agents. The patients were classified into inactive CHB (n = 373) or NA groups (n = 745). The primary endpoint was overall survival. Secondary endpoints included development of HCC and other liver-related events. The median duration of follow-up was 41.0 (interquartile range = 26.5-55.0) months. The difference in overall survival between the NA group vs. the inactive CHB group was not significant (hazard ratio [HR] = 0.78; 95% confidence interval [CI] = 0.33-1.85; P = .57). The NA group showed a significantly higher risk of HCC (HR = 3.44; 95% CI = 1.82-6.52; P < .01), but comparable risk for non-HCC liver-related events (HR = 1.02; 95% CI = 0.66-1.59; P = .93), compared with the inactive CHB group. Among patients with cirrhosis, the NA group showed a significantly lower risk of death (HR = 0.31; 95% CI = 0.097-0.998; P = .05) and non-HCC liver-related events (HR = 0.51; 95% CI = 0.31-0.83; P < .01), but a slightly higher risk of HCC (HR = 2.39; 95% CI = 0.85-6.75; P = .09), compared to the inactive CHB group. The overall survival of untreated patients with inactive CHB and of CHB patients achieving viral suppression with NA was comparable. However, NA treatment of cirrhotic patients was significantly associated with longer overall survival and lower risk of liver-related events.

Intensity of surveillance for hepatocellular carcinoma determines survival in patients at risk in a hepatitis B-endemic area.

BACKGROUND: Data are insufficient regarding the survival benefit of surveillance for hepatocellular carcinoma (HCC). AIM: To investigate the effectiveness of HCC surveillance in a hepatitis B-endemic population. METHODS: This retrospective cohort study included 1402 consecutive patients who were newly diagnosed with HCC between 2005 and 2012 at a single tertiary hospital in Korea. The primary endpoint was overall survival. Lead-time and length-time biases were adjusted (sojourn time = 140 days) and sensitivity analyses were performed. RESULTS: The most common aetiology was hepatitis B (80.4%). Cirrhosis was present in 78.2%. HCC was diagnosed during regular surveillance (defined as mean interval of ultrasonography <8 months, n = 834), irregular surveillance (n = 104) or nonsurveillance (n = 464). Patients in the regular surveillance group were diagnosed at earlier stages ([very] early stage, 64.4%) than the irregular surveillance (40.4%) or nonsurveillance (26.9%) groups and had more chance for curative treatments (52.4%) than the irregular surveillance (39.4%) or nonsurveillance (23.3%) groups (all P < 0.001). Mortality risk was significantly lower in the regular surveillance group (adjusted hazard ratio [aHR], 0.69; 95% [CI], 0.57-0.83) but not in the irregular surveillance group (aHR, 0.94; 95% CI, 0.69-1.28) compared with the nonsurveillance group after adjusting for confounding factors and lead-time. When the subjects were restricted to cirrhotic patients or Child-Pugh class A/B patients, similar results were obtained for mortality risk reduction between groups. CONCLUSIONS: HCC surveillance was associated with longer survival owing to earlier diagnosis and curative treatment. Survival advantage was significant with regular surveillance but not with irregular surveillance.

Preliminary results of an anteverting triple periacetabular osteotomy for the treatment of hip instability in Down syndrome.

PURPOSE: To investigate the outcomes of an anteverting triple periacetabular osteotomy for the treatment of hip instability in skeletally immature patients with Down syndrome. METHODS: We evaluated 16 patients (21 hips) with Down syndrome and hip instability who underwent an anteverting triple periacetabular osteotomy between 2007 and 2016. There were nine females and seven males with an average age of 7.4 years SD 2.0. We assessed the level of hip pain, gait ability and clinical stability at a minimum of one year after surgery. Radiographic evaluation included pre- and postoperative lateral centre-edge angle (LCEA), Tönnis acetabular angle and extrusion index. RESULT: After an average follow-up of 4.1 years SD 2.6, 20 of 21 hips (95%) remained clinically stable. In all, 12 of 16 (75%) patients had a full gait without a major limp, but three patients (19%) had a persistent limp. Of the 21 procedures, one hip (5%) was considered a failure due to persistent instability. There was a mean increase of 18.3º SD 15.3º of the LCEA (p < 0.001); a mean decrease of 15.2º SD 11.6º (p < 0.001) for the Tönnis angle and the extrusion index had a mean decrease of 0.27 SD 0.20 (p < 0.001). The most common complications were minor and included nonunion of the pubis or ischium (24%) and stress fractures of the pubis and ischium (14%). Only one patient required unplanned surgery for the treatment of an infection; which was considered a major complication. CONCLUSION: The anteverting triple periacetabular osteotomy provided global deformity correction and achieved hip stability in 95% of the hips after a mean follow-up of 4.1 years. LEVEL OF EVIDENCE: Therapeutic level IV.