Is there a causal relationship between autoimmune diseases and oropharyngeal cancer?

BACKGROUND: Autoimmune diseases (AIDs) are linked to oropharyngeal cancer (OPC), but the exact nature of this association remains unclear. This study aims to examine the potential causal effect of AIDs on the risk of developing OPC. METHOD: Information regarding AIDs was collected from the UK Biobank dataset and the Finn Gen study. OPC data were sourced from the IEU Open GWAS project. All data were derived from European populations. Inverse variance weighted (IVW) to two-sample Mendelian randomization (MR) was complemented by weighted median and MR Egger validation analyses. RESULT: The development of asthma (AS), multiple sclerosis (MS), and rheumatoid arthritis (RA) influenced the risk of developing OPC. However, the reverse MR analysis did not provide evidence for the impact of OPC on AIDs. Sensitivity analysis using MR corroborated the IVW results. The IVW results indicate OR values of 1.004 for AS, 0.936 for MS, and 1.0002 for RA. CONCLUSION: This MR study supports a causal relationship between asthma and rheumatoid arthritis for OPC in a European population. Multiple sclerosis was protective against OPC.

Prehospital Time Following Traumatic Injury Is Independently Associated With the Need for In-Hospital Blood and Early Mortality for Specific Injury Types.

OBJECTIVE: Treating traumatic hemorrhage is time sensitive. Prehospital care and transport modes (eg, helicopter and ground) may influence in-hospital events. We hypothesized that prehospital time (on-scene time [OST] and total prehospital time [TPT]) and transport mode are associated with same-day transfusion and mortality. Furthermore, we sought to identify regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. METHODS: We obtained prehospital, in-hospital, and trauma registry data from an 8-center cohort of adult nonburn trauma patients from 2017 to 2022 directly transported from the scene to the hospital and having an Injury Severity Score (ISS) > 9 for the Task Order 1 project of the Linking Investigators in Trauma and Emergency Services research network. We excluded patients missing prehospital times, patients < 18 years of age, patients from interfacility transfers, and recipients of prehospital blood. Our same-day outcomes were in-hospital transfusions within 4 hours and 24-hour mortality. Each outcome was adjusted using multivariable logistic regression for covariates of prehospital phases (OST and TPT), mode of transport (helicopter and ground), age, sex, ISS, Glasgow Coma Scale motor subscale score < 6, and field hypotension (systolic blood pressure < 90 mm Hg). We evaluated the association of prehospital time on outcomes for scene missions by transport mode across severe injury patterns defined by Abbreviated Injury Scale > 2 body regions. RESULTS: Of 78,198 subjects, 34,504 were eligible for the study with a mean age of 47.6 ± 20.3 years, ISS of 18 ± 11, OST of 15.9 ± 9.5 minutes, and TPT of 48.7 ± 20.3 minutes. Adjusted for injury severity and demographic factors, transport type significantly modified the relationship between prehospital time and outcomes. The association of OST and TPT with the odds of 4-hour transfusion was absent for the ground emergency medical services (GEMS) cohort and present for the helicopter emergency medical services (HEMS) ambulance cohort, whereas these times were associated with decreased 24-hour mortality for both transport types. When stratifying by injury to most anatomic regions, OST and TPT were associated with a decreased need for 4-hour transfusions in the GEMS cohort. However, OST was associated with increased early transfusion only among patients with severe injuries of the thorax, and this association persisted after adjusting additionally for injury type (odds ratio [OR] = 1.03; 95% confidence interval [CI], 1.00-1.05; P = .02). The presence of polytrauma supported an association between prehospital time and decreased 24-hour mortality for the GEMS cohort (OST: OR = 0.97; 95% CI, 0.95-0.99; P < .01; TPT: OR = 0.99; 95% CI, 0.98-0.99; P = .02), whereas no injuries showed significant association of helicopter prehospital time on mortality after adjustment. CONCLUSION: We determined that transport type affects the relationship between prehospital time and hospital outcomes (4-hour transfusion: positive relationship for HEMS and negative for GEMS, 24-hour mortality: negative for both transport types). Furthermore, we identified regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. Of these regions, most notable were severe isolated injuries to the thorax that supported a positive relationship between HEMS OST and 4-hour transfusions and polytrauma that showed a negative relationship between GEMS OST or TPT and 24-hour mortality after adjustment.

Changes in serum hepatitis B surface and e antigen, interferon-inducible protein 10, and aminotransferase levels during combination therapy of immune-tolerant chronic hepatitis B.

BACKGROUND AND AIMS: Treatment of immune-tolerant (IT) children and adults with combined peginterferon alfa-2a and entecavir results in a decline in serum HBeAg and HBsAg concentrations but rarely results in loss of HBeAg or sustained off-treatment response. Factors associated with declines in these viral antigens during treatment remain unexplored. APPROACH AND RESULTS: We investigated the pattern of virologic and biochemical response in 86 participants (59 children, 27 adults) by serial quantitative measurement of HBsAg (qHBsAg), quantitative HBeAg (qHBeAg), HBV RNA, interferon-inducible protein (IP-10), IL-18, and alanine aminotransferase (ALT). Each individual had previously been treated with 8 weeks of entecavir followed by 40 weeks of combined peginteferon and entecavir. We defined the interrelationships between these parameters and virologic response measured as nadir declines from baseline for HBeAg and HBsAg. The patterns of HBsAg and HBeAg decline were similar in pediatric and adult participants. Higher levels of IP-10 were observed during treatment in participants with greater ALT elevations and greater reductions of qHBsAg and qHBeAg. Individuals with peak ALT values exceeding three times the upper limit of normal were significantly more likely to have >1 log10 decline in both viral antigens. HBV DNA became undetectable in 21 of 86 (24%) and HBV RNA in 4 of 77 (5%) during therapy, but both markers remained negative only in those who became HBsAg negative, all of whom also had ALT elevations. CONCLUSIONS: Induction of IP-10 during peginterferon treatment in adults and children in the IT phase of chronic HBV infection is associated with ALT elevations and decline in viral antigens, suggesting a degree of interferon-inducible viral control.

Symptoms of Liver Disease During Tenofovir Therapy With or Without Peginterferon: Results from the Hepatitis B Research Network Immune Active Trial.

AIMS: Evaluate patient-reported liver symptoms during treatment for chronic hepatitis B viral (HBV) infection and associations between changes in symptoms and levels of alanine aminotransferase (ALT) and viral markers. METHODS: Data from 200 participants in the Hepatitis B Research Network Immune Active Trial who completed symptom assessments were analyzed. Patients were treated with tenofovir, with or without peginterferon (TDF + PegIFN vs. TDF alone) for 192 weeks. Participants completed a Symptom Checklist at baseline and every 4-12 weeks. A total symptom score was created, ranging from 0 (none) to 40 (severe). The SF-36 was completed every 48 weeks. Associations of symptom scores with ALT and viral markers were evaluated at baseline and end of treatment. RESULTS: Participants were 65% male, 83% Asian, with a mean age of 42. Baseline symptoms were mild (median = 2, range 0-25) and associated with baseline ALT, HBV DNA levels and HBeAg + status. Patients on TDF alone experienced a more rapid and greater improvement in symptoms, but by week 192, symptom improvement was similar in both groups (54% vs 36%). Symptom improvements correlated with ALT and HBV DNA, most markedly among those with symptoms at baseline. Most patients (4 out of 6) who achieved HBsAg loss experienced symptom improvements. Overall, SF-36 scores did not change with treatment. CONCLUSIONS: Reduction in ALT and HBV DNA levels with therapy are associated with significant improvement in liver symptoms such as fatigue and pain over the liver, especially among those with higher ALT, HBV DNA, symptoms and HBeAg + status prior to treatment.

Chronic Hepatitis Is Common and Often Untreated Among Children with Hepatitis B Infection in the United States and Canada.

OBJECTIVE: To determine the outcomes of chronic hepatitis B virus (HBV) infection in a large, prospectively studied cohort of children in the US and Canada. STUDY DESIGN: This was a prospective, observational study of children with chronic HBV enrolled in 7 clinical centers and evaluated at baseline, weeks 24 and 48, and annually thereafter, with analysis of demographic, clinical, physical examination, and blood test data. RESULTS: Among 362 children followed for a median of 4.2 years, elevated alanine aminotransferase (ALT) levels (>1 upper limit of normal) were present in 72% at last evaluation, including in 60% of children with loss of hepatitis B e antigen during follow-up and 70% of those who were hepatitis B e antigen negative at baseline. Significant ALT flares (male patients ≥400 U/L, female patients ≥350 U/L) occurred in 13 children. Of 129 children who fulfilled the American Association for the Study of Liver Diseases treatment criteria during follow-up, anti-HBV treatment was initiated in only 25. One child died (unrelated to liver disease), 1 developed cirrhosis, but no episodes of cirrhotic decompensation or hepatocellular carcinoma were observed. Decline in platelet count was inversely associated with ALT elevations. CONCLUSIONS: In a cohort of children with chronic HBV infection in the US and Canada, many children remained at risk of progressive liver disease due to active hepatitis, but major clinical outcomes such as cirrhosis, cancer, and death were rare. Many children who met criteria for treatment remained untreated.

Combination of Entecavir/Peginterferon Alfa-2a in Children With Hepatitis B e Antigen-Positive Immune Tolerant Chronic Hepatitis B Virus Infection.

The optimal management strategy for children with immune-tolerant chronic hepatitis B virus (HBV) infection remains unknown. The purpose of this clinical trial was to determine the safety and efficacy of therapy with entecavir and peginterferon in a group of children in the immune-tolerant phase of HBV infection. Children with immune-tolerant features of chronic hepatitis B (CHB) received entecavir once-daily in a dose of 0.015 mg/kg (0.5 mg maximum) for 48 weeks; peginterferon alfa-2a (180 µg/1.73m2 subcutaneously) once-weekly was added at the end of week 8 and continued until week 48. The primary endpoint was lack of detectable hepatitis B e antigen (HBeAg) with HBV DNA levels ≤1,000 IU/mL 48 weeks after stopping therapy. Sixty children (75% female), median age 10.9 (range, 3.4-17.9) years, were enrolled. All were positive for hepatitis B surface antigen (HBsAg) and HBeAg and had high levels of HBV DNA with normal or minimally elevated levels of alanine aminotransferase (ALT). Fifty-five children completed the entire 48-week course of therapy. At 48 weeks after treatment ended (week 96), 2 children (3%) achieved the primary endpoint and were also HBsAg negative and anti-hepatitis B surface antigen antibody (anti-HBs) positive. One child was HBeAg positive but HBsAg negative at week 60; another was HBeAg negative but HBsAg positive at week 72, which were their last clinic visits. In the remaining children, serum ALT and HBV DNA levels at week 96 were similar to baseline. Thirty-seven children experienced adverse events (AEs), and 1 had a serious AE (SAE). Conclusion: The combination of entecavir and peginterferon for up to 48 weeks rarely led to loss of HBeAg with sustained suppression of HBV DNA levels in children in the immune-tolerant phase of HBV infection, and treatment was associated with frequent AEs.

Entecavir and Peginterferon Alfa-2a in Adults With Hepatitis B e Antigen-Positive Immune-Tolerant Chronic Hepatitis B Virus Infection.

Monotherapy with interferon or nucleoside analog is generally not recommended during the immune-tolerant (IT) phase of chronic hepatitis B virus (HBV) infection. Recognition that high HBV DNA levels are associated with hepatocellular carcinoma has increased interest in treating HBV in the IT phase. Small pediatric studies reported efficacy with combination nucleoside analog and interferon therapy. The aim of this study was to evaluate the safety and efficacy of the combination of entecavir and peginterferon in adults in the IT phase of chronic HBV infection. Hepatitis B e antigen (HBeAg)-positive adults with HBV DNA > 107 IU/mL and alanine aminotransferase (ALT) ≤ 1.5 times the upper limit of normal (ULN) (male: ≤ 45, female: ≤ 30 U/L) received entecavir 0.5 mg daily for 8 weeks followed by the addition of peginterferon alfa-2a 180 µg/week to entecavir for an additional 40 weeks. The primary endpoint was HBeAg loss and HBV DNA ≤ 1,000 IU/mL 48 weeks after end of treatment (EOT). Among 28 participants from 11 sites, the median age was 37.2 (range: 22-61) years, 54% were male, and 96% were Asian. Nearly all were infected with genotype C (64%) or B (32%). Median baseline HBV DNA was 8.2 log10 IU/mL, and ALT was 0.9 times the ULN. Although one (4%) participant cleared HBeAg, none met the primary endpoint of both HBeAg loss AND HBV DNA ≤ 1,000 IU/mL 48 weeks post-EOT. ALT elevations > 5 times the ULN occurred in eight (29%) participants, and none were associated with icterus. Forty-eight weeks posttreatment, HBV DNA rebounded to baseline levels in all participants, including the participant who lost HBeAg, and ALT values returned to near baseline levels in all but four participants. Conclusion: A lead-in strategy of 8 weeks of entecavir followed by combination peginterferon and entecavir therapy for 40 weeks had limited efficacy in adults in the IT phase of chronic HBV infection and cannot be recommended.

Café-au-lait macules overlying segmental macular hyperpigmentation in a pediatric patient: an early sign for mosaic neurofibromatosis type 1.

The presentation of multiple café-au-lait macules (CALMs) in children is a common reason for referral to a dermatologist. Segmental CALMs, a subtype of CALMs, is usually limited to a specific part of the body. Mosaic neurofibromatosis type 1 (NF1; OMIM 162200) is a common congenital disorder associated with segmental CALMs with an incidence of about 1 case/40000 patients, which is lower than the prevalence of patients with germline NF1 mutations1,2 .

Immunocyte density in parathyroid carcinoma is correlated with disease relapse.

PURPOSE: Parathyroid carcinoma (PC) is an endocrine malignancy with a poor prognosis. The tumour immune microenvironment is a critical factor influencing the outcomes of multiple cancer types. However, knowledge of the immune microenvironment in PC remains limited. METHODS: The intratumoural density of immunocytes and the Ki-67 index were evaluated immunohistochemically in 51 PC patient samples and were compared with clinicopathological features and parafibromin staining results. The Kaplan-Meier method and Cox proportional hazards analysis were used to estimate the effects of these variables on clinical outcomes. RESULTS: Intratumoural immunocyte density was not correlated with age, gender, urolithiasis, or palpation of a neck mass. The Ki-67 index was correlated with the intratumoural density of CD3+ cells (P = 0.022) and CD8+ cells (P = 0.021) and serum calcium levels (P = 0.022). In the intratumoural area of primary foci, Kaplan-Meier method showed that the risk factors associated with recurrence/metastasis were a low density of CD3+ (P = 0.017), CD8+ (P = 0.019) and CD45+ cells (P = 0.047), a high density of CD163+ cells (P = 0.003) and a high Ki-67 index (P = 0.004). Cox regression multivariate analysis revealed that CD163+ cell density (hazard ratio (HR) 16.19, 95% confidence interval (CI) 1.99-131.66; P = 0.009) and CD8+ cell density (HR 0.13, 95% CI 0.02-0.76, P = 0.024) were independent factors associated with PC relapse. CONCLUSION: The immune microenvironment is an important factor influencing the relapse of PC. The intratumoural density of CD3+, CD8+, CD45+, and CD163+ immunocytes was correlated with disease-free survival (DFS) in patients with PC. Immunotherapy based on T lymphocytes or tumour-associated macrophages may be a promising treatment strategy.

Maternal knowledge of the risk of vertical transmission and offspring acquisition of hepatitis B.

INTRODUCTION AND OBJECTIVES: Universal vaccination at birth and in infancy is key to the elimination of chronic hepatitis B infection. We aimed to assess hepatitis B immune-prophylaxis and perinatal transmission knowledge, in a large and ethnically diverse cohort of previously pregnant North American women, chronically infected with hepatitis B. MATERIALS AND METHODS: The Hepatitis B Research Network (HBRN) is comprised of 28 Clinical Centers in the United States and Canada. Female cohort participants were administered a questionnaire to assess: (1) their assertion of knowledge regarding HBV prophylaxis at birth, testing, and diagnosis of hepatitis B in their children, and (2) the percentage of affirmative to negative responses for each of the HBV-related interventions her child may have received. The relationship between asserted knowledge, actions taken and maternal demographics were assessed. RESULTS: A total of 351 mothers with 627 children born in or after 1992 were included. Median age at enrollment was 39.8 years. Mothers were mostly foreign-born with the largest percentage from Asia (73.4%) and Africa (11.7%). Of the 627 children, 94.5% had mothers who asserted that they knew whether their child had received HBIG or HBV vaccine at birth, for 88.8% of the children, their mothers indicated that they knew if their child was tested for HBV and for 84.5% of children, their mothers knew if the child was diagnosed with HBV infection. Among children whose mothers asserted knowledge of their HBV management, 95.3% were reported to have received HBIG or HBV vaccine, 83.4% of children were said to have been tested for HBV, and 4.8% of children were said to have been diagnosed with HBV. Younger maternal age was the only factor significantly associated with higher percentage of children for whom mothers reported knowledge of testing (p=0.02) or diagnosis of HBV (p=0.02). CONCLUSIONS: While high percentages of North American children had mothers asserting knowledge of HBV prophylaxis and testing, knowledge gaps remain, with mothers of 5.5-15.5% of children lacking knowledge of key components of the HBV prevention and diagnosis in the perinatal setting. Targeted education of HBsAg-positive mothers may aid in closing this gap and reducing vertical transmission.

[The clinicopathologic features and prognostic analysis of pancreatic metastasis from clear cell renal cell carcinoma].

Objective: To investigate the clinicopathologic features and prognosis of the patients who had clear cell renal cell carcinoma (CCRCC) with metastasis to the pancreas. Methods: From Jan, 2000 to Dec, 2018, 18 patients with clear cell renal cell carcinoma (CCRCC) and had pathologically diagnosed metastasis to the pancreas were enrolled at Peking Union Medical College Hospital. The clinical and pathological data were retrospectively analyzed. Results: 11 out of 18 patients were male, and the other 7 were female. The average age of onset of CCRCC was 51.4 years. 8 cases (44.4%) occurred in the left kidney, and the other 10 cases (55.6%) with right kidney tumor. Three patients had synchronous pancreatic metastasis, and the other 15 patients had metachronous pancreatic metastasis. The median time from CCRCC onset to pancreas metastasis was 156 months. The main complaints of pancreas metastasis were abdominal pain, jaundice, gastrointestinal bleeding, nausea, weakness, loss of weight and so on. Seven patients (38.9%) had single lesion of pancreas, while 11 patients (66.1%) had multiple lesions of pancreas. Nine patients (50%) had other organs metastasis besides pancreatic metastasis at the same time. Five patients underwent pancreatic metastasis resection, while 15 patients received oral tyrosine kinase inhibitor(TKI). The mean follow-up was 171.7 months(1~361.5 months) and 5 patients died. The median overall survival (mOS) was 122 months, and the 5 year-survival rate was 81.4%. In univariate analysis, synchronous metastasis to the pancreas, relapse after 10 years, Memorial Sloan Kettering Cancer Center prognostic index, International Metastatic Renal Cell Carcinoma Database Consortium index were all significant parameters for patients'survival. Conclusions: Metastasis to the pancreas from clear cell renal cell carcinoma were rare. These patients had better survival outcomes, especially those relapsing after ten years. Pancreatic metastasis resection had no significant benefit on patient's survival.

Systematic review of randomized controlled trials on antibiotic treatment for osteomyelitis in diabetes.

AIM: To evaluate the efficacy of antibiotic therapy in osteomyelitis treatment among people with diabetes. METHODS: A systematic search of PubMed, EMBASE, AMED, Web of Science, the WHO trial registry, Cochrane library databases, and ClinicalTrials.gov, in addition to hand-searching, was undertaken in July 2018. Two reviewers independently extracted data. The studies' methodological quality was assessed using the modified Jadad scale. Descriptive analysis was performed. RESULTS: Seven randomized controlled trials, with 393 participants in total, were included. The antibiotic regimens, treatments and follow-up durations varied among the trials. The total scores showed that the overall methodological quality of the seven studies was high, despite two studies showing some flaws in double-blinding and withdrawals/drop-outs. Of four studies comparing different antibiotic regimens, three implied a similar remission effect, while one implied that ertapenem ± vancomycin treatment showed a higher remission rate than tigecycline treatment; this conclusion was not robust because of low power and small sample size. In the other three studies, which included two different doses of ciprofloxacin, an antibiotics group and a conservative surgical group, and two durations of the same antibiotic strategy, no significant differences in remission were reported between the groups. No difference was observed in the analyses of microbiological outcomes, superinfections and relapse, except adverse events. CONCLUSIONS: There is no definitive evidence supporting the superiority of any particular antibiotic agent, dose, or administration duration in the treatment of osteomyelitis in diabetes. As the included studies had some flaws and limitations, further research is necessary.

iTRAQ-based proteomics analysis reveals the deregulated proteins related to liver toxicity induced by melamine with or without cyanuric acid in mice.

The administration of melamine alone or its combination with cyanuric acid was shown to have certain liver toxicity. However, the injury mechanism of melamine-related toxicity to liver remains poorly understood. In the present study, we investigated the deregulated proteins related to liver toxicity induced by melamine with or without cyanuric acid in mice using iTRAQ quantitative proteomics technique. A total of 166 proteins were significantly changed by the melamine treatment, of which, 36 proteins were up-regulated and 130 proteins were down-regulated. Whereas, 242 proteins were significantly changed by the combined treatment of melamine and cyanuric acid, of which 81 proteins were up-regulated and 161 proteins were down-regulated. The enriched analysis of GO terms and KEGG pathway on the altered proteins showed that both enriched main GO terms and KEGG pathways appear to be different between the two kinds of treatments: melamine and mixture of melamine and cyanuric acid. Based on western blotting technique, it was confirmed that the expression of three proteins: heat shock protein 70 (HSP70), protein disulphide isomerase 6 (PDIA6) and heat shock 70 kDa protein 4-like (HSPA4L) were agreement with the findings in iTRAQ-Based quantitative analysis. These identified proteins might participate in the regulation of a wide range of biological processes, such as immune and inflammatory function, unfolded proteins response in endoplasmic reticulum, DNA damage, and the apoptosis of liver cells. These results from this study provide a new way to gain insight into the mechanisms of melamine-related toxicity to liver in animals.

Child maltreatment as a social determinant of midlife health-related quality of life in women: do psychosocial factors explain this association?

PURPOSE: We examined if child maltreatment (CM) is associated with worse health-related quality of life (HRQoL) in midlife women and if the association is mediated by psychosocial factors. METHODS: A total of 443 women were enrolled in the Pittsburgh site of the longitudinal Study of Women's Health Across the Nation-Mental Health Study. The analytic sample included 338 women who completed the SF-36 and the Childhood Trauma Questionnaire. Generalized linear regression was used to assess the association between CM and two HRQoL component scores. Structural nested mean models were used to evaluate the contribution of each psychosocial mediator (lifetime psychiatric history, depressive symptoms, sleep problems, very upsetting life events, low social support) to the association. RESULTS: Thirty-eight percent of women reported CM. The mean mental (MCS) and physical (PCS) SF-36 component scores were 2.3 points (95% CI - 4.3, - 0.3) and 2.5 points (95% CI - 4.5, - 0.6) lower, respectively, in women with any CM than in those without. When number of CM types increased (0, 1, 2, 3+ types), group mean scores decreased in MCS (52, 51, 48, 47, respectively; p < .01) and PCS (52, 52, 49, 49, respectively; p = .03). In separate mediation analyses, depressive symptoms, very upsetting life events, or low social support, reduced these differences in MCS, but not PCS. CONCLUSIONS: CM is a social determinant of midlife HRQoL in women. The relationship between CM and MCS was partially explained by psychosocial mediators. It is important to increase awareness among health professionals that a woman's midlife well-being may be influenced by early-life adversity.

[Sequential parathyroidectomy under cervical plexus anesthesia for secondary hyperparathyroidism with renal function failure].

Objective: To summarize the strategy of sequential parathyroidectomy for secondary hyperparathyroidism. Methods: Between January 2009 and December 2017, 32 patients with secondary hyperparathyroidism underwent parathyroidectomy in Department of General Surgery, Peking Union Medical College Hospital. There were 11 male and 21 female patients with a mean age of 51.3 years. Eleven of them underwent bilateral neck exploration under general anesthesia, while the rest of them underwent sequential parathyroidectomy. For the patients with sequential parathyroidectomy, a unilateral neck exploration was performed in the initial operation under cervical plexus blocking anesthesia. Second operation for contralateral parathyroid lesions was performed if the serum intact parathyroid hormone (iPTH) was still higher than 1 000 ng/L or related symptoms were not relieved significantly 6 months later after initial surgery. Fisher exact test was used to compare the date between the 2 groups. Results: In the bilateral exploration group, the serum iPTH level gradually exceeded above 1 000 ng/L in 5 patients during follow-up, and reoperation were performed in 3 patients of them. In the group with sequential parathyroidectomy, the serum iPTH level after initial operation exceeded above 1 000 ng/L in 15 patients. Eleven of them underwent contralateral parathyroidectomy, which decreases the serum iPTH levels to less than 1 000 ng/L in 10 patients. Compared with the sequential parathyroidectomy group (1/11), more patients needed to be treated in the intensive care unit after operation in bilateral exploration group (6/11), although the difference was statistically insignificant (P=0.063). Conclusions: Sequential parathyroidectomy strategy is feasible for the secondary hyperparathyroidism with severe complications. Prospective controlled observation with large sample size is needed to confirm its effect.

HLA-B*57 and IFNL4-related polymorphisms are associated with protection against HIV-1 disease progression in controllers.

Background: HIV-1-controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1-controllers have evidence of immunologic progression with marked CD4+T-cell decline. We investigated host genetic factors associated with protection against CD4+T-cell loss in HIV-1-controllers. Methods: We analysed the association of interferon lambda 4 (IFNL4)-related polymorphisms and HLA-B haplotypes within Long Term Non-Progressor HIV-1-controllers ((LTNP-C), defined by maintaining CD4+T-cells counts >500 cells/mm3 for more than 7 years after HIV-1 diagnosis) versus non-LTNP-C, who developed CD4+T-cells counts <500 cells/mm3 Both a Spanish study cohort (n=140) and an international validation cohort (n=914) were examined. Additionally, in a subgroup of individuals HIV-1-specific T-cell responses and soluble cytokines were analysed RESULTS: HLA-B*57 was independently associated with the LTNP-C phenotype (OR=3.056 (1.029-9.069) p=0.044 and OR=1.924 (1.252-2.957) p=0.003) while IFNL4 genotypes represented independent factors for becoming non-LTNP-C (TT/TT, ss469415590, OR=0.401 (0.171-0.942) p=0.036 or A/A, rs12980275, OR=0.637 (0.434-0.934) p=0.021) in the Spanish and validation cohort, respectively, after adjusting for sex, age at HIV-1 diagnosis, IFNL4-related polymorphisms and different HLA-B haplotypes. LTNP-C showed lower plasma IP-10 (p=0.019) and higher IFN-γ (p=0.02) levels than the HIV-1-controllers with diminished CD4+T-cell numbers. Moreover, LTNP-C exhibited higher quantities of IL2+CD57- and IFN-γ+CD57- HIV-1-specific CD8+T-cells (p=0.002 and 0.041, respectively) than non-LTNP-C. Conclusions: We have defined genetic markers able to segregate stable HIV-1-controllers from those who experience CD4+T-cell decline. These findings allow for identification of HIV-1-controllers at risk for immunologic progression, and provide avenues for personalized therapeutic interventions and precision medicine for optimizing clinical care of these individuals.

Health-related Quality of Life in Pediatric Patients With Chronic Hepatitis B Living in the United States and Canada.

OBJECTIVES: The aim of the study was to determine whether selected sociodemographic and hepatitis B virus (HBV)-specific clinical factors are associated with health-related quality of life (HRQoL) among pediatric patients chronically infected with HBV. METHODS: Children with chronic HBV enrolled in the Hepatitis B Research Network completed the Child Health Questionnaire at study entry. Caregivers of children 5 to <10 years completed the parent-reported form (CHQ-Parent Report Form); youth 10 to <18 years completed the child-reported CHQ-Child Report Form. We examined univariable associations of the Child Health Questionnaire scores with selected independent variables: sex, adoption status, maternal education, alanine aminotransferase (U/L), aspartate aminotransferase-to-platelet ratio index, and HBV-specific symptom count. RESULTS: A total of 244 participants (83 young children 5-<10 years, 161 youth 10-<18 years) were included, all HBV treatment-naïve. Among young children, increased alanine aminotransferase level was negatively associated with CHQ-Parent Report Form psychosocial summary t score (r = -0.28, P = 0.01). No other subscale comparisons for young children were statistically significant. Among youth, adoption was associated with better physical functioning and general health (P < 0.01). Higher maternal education was associated with better role/functioning-physical and -emotional scores (P < 0.05). Maternal education and adoption status were linked with adoption associated with higher maternal education. Increased symptom count in youth was associated with worse HRQoL in subscales measuring bodily pain, behavior, mental health, and self-esteem (P < 0.01). CONCLUSIONS: Although overall HRQoL is preserved in children with chronic HBV, some sociodemographic and HBV-related clinical factors were associated with impaired HRQoL in our pediatric patients at baseline. Measurement of HRQoL can focus resources on education and psychosocial support in children and families most in need.

A Microfluidic Approach for Studying Piezo Channels.

Microfluidics is an interdisciplinary field intersecting many areas in engineering. Utilizing a combination of physics, chemistry, biology, and biotechnology, along with practical applications for designing devices that use low volumes of fluids to achieve high-throughput screening, is a major goal in microfluidics. Microfluidic approaches allow the study of cells growth and differentiation using a variety of conditions including control of fluid flow that generates shear stress. Recently, Piezo1 channels were shown to respond to fluid shear stress and are crucial for vascular development. This channel is ideal for studying fluid shear stress applied to cells using microfluidic devices. We have developed an approach that allows us to analyze the role of Piezo channels on any given cell and serves as a high-throughput screen for drug discovery. We show that this approach can provide detailed information about the inhibitors of Piezo channels.

Interleukin-33 in children with asthma: A systematic review and meta-analysis.

BACKGROUND: Previous studies have shown that serum interleukin 33 serving as an "alarmin" is increased in children with asthma. The objective of this study was to assess the validity of serum IL33 test for early diagnosis of childhood asthma. METHODS: A literature search was performed in June 2016 using PubMed, Embase, the Cochrane Library and other Chinese Medical Databases to identify studies. The search terms used were "cytokine", "interleukin-33", "asthma" and "children". The meta-analysis was performed using Review Manager 5.3 software. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). RESULTS: A total of eight studies were included into this meta-analysis, involving 330 asthmatic children and 248 healthy children. The meta-analysis results revealed that the serum IL33 level was higher in asthmatic children compared to that in healthy children (SMD=1.29, 95%CI=0.53-2.05, P=0.0009), with significant heterogeneity across studies (I2=94% and P<0.00001). CONCLUSIONS: The meta-analysis showed that serum IL33 is a helpful biomarker for early diagnosis of childhood asthma. However, owing to lack of enough data, the increased serum concentration of IL33 cannot be an indicator for the asthma severity.

Correlation between three glycometabolic-related hormones and muscle glycolysis, as well as meat quality, in three pig breeds.

BACKGROUND: The present study aimed to evaluate the correlations among muscle concentrations of three glycometabolic-related hormones (insulin, epinephrine and glucagon), muscle glycolysis and meat quality in representative muscles of either glycolytic or oxidative types. Moreover, the relative glycometabolic-related gene expression was measured. One Western crossbreed DLY (Duroc × (Landrace × Yorkshire)), one crossbreed with half-Chinese native-pig origin DL (Duroc × LiangShan) and one pure Chinese native pig TP (Tibetan pig) were used in the present study. RESULTS: Among the three breeds, DLY had the greatest glucagon and epinephrine (P < 0.01). Compared with DLY, TP and DL had lower lactic acid concentrations, showing lower glycolytic potentials (GP), greater ultimate pH values (P < 0.01) and lower relative expression levels of glycometabolic-related genes (GYS1, PRKAG3 and PKM2). Compared with the glycolytic muscle (musculus longissimus dorsi), oxidative muscle PM (musculus psoas major) had lower glucagon and epinephrine contents, lower GP and better meat quality. The concentration of glycometabolic-related hormones in the muscle had significant correlations with muscle glycolysis, meat pH and lightness. CONCLUSION: The results obtained in the present study imply that glucagon and epinephrine levels could be used to indicate early glycolytic metabolism during postmortem. These findings may be helpful in identifying pork with undesirable quality traits. 2016 Society of Chemical Industry.