Does intraperitoneal chemotherapy benefit optimally debulked epithelial ovarian cancer patients after neoadjuvant chemotherapy?

Objective

To compare survival of ovarian cancer patients treated with neoadjuvant chemotherapy followed by intraperitoneal (IP) versus intravenous (IV) chemotherapy after optimal interval debulking.

Methods

Optimally debulked patients after neoadjuvant IV platinum paclitaxel based chemotherapy followed by postoperative IP chemotherapy were reviewed. A similar cohort of patients treated postoperatively with IV platinum paclitaxel based chemotherapy was chosen as control. Patient and disease-related demographics were abstracted from electronic hospital medical records. Associations between categorical variables were determined using Chi square test. Cox regression and Kaplan-Meier method estimated progression-free and overall survival.

Results

Fifty-four IV and 17 IP treated patients after interval debulking were studied. The majority of patients had serous histology and grade 3 tumours. There was no significant difference between the two groups with respect to age and proportion of microscopic residual disease. Patients with macroscopic residual disease had a significantly worse prognosis (HR = 2.17, 95% CI = 1.23-3.85, p = 0.008). Clinical complete response after primary treatment was 67% and 88% in the IV and IP group, respectively (p = 0.36). Estimated mean progression-free survival was 18 months in the IV group and 14.1 months in the IP group (p = 0.42). IP chemotherapy was not predictive of progression-free survival in the Cox model adjusted for age and residual disease status (HR = 1.22, 95% CI = 0.62-2.4, p = 0.56). Estimated mean survival was 68.9 months in the IV group and 37.5 months in the IP group (p = 0.85).

Conclusions

Survival benefit associated with IP chemotherapy after optimal upfront surgery may not translate to the neoadjuvant setting.     

Passive,wireless transduction of electrochemical impedance across thin-film microfabricated coils using reflected impedance

A new method of wirelessly transducing electrochemical impedance without integrated circuits or discrete electrical components was developed and characterized. The resonant frequency and impedance magnitude at resonance of a planar inductive coil is affected by the load on a secondary coil terminating in sensing electrodes exposed to solution (reflected impedance), allowing the transduction of the high-frequency electrochemical impedance between the two electrodes. Biocompatible, flexible secondary coils with sensing electrodes made from gold and Parylene C were microfabricated and the reflected impedance in response to phosphate-buffered saline solutions of varying concentrations was characterized. Both the resonant frequency and impedance at resonance were highly sensitive to changes in solution conductivity at the secondary electrodes, and the effects of vertical separation, lateral misalignment, and temperature changes were also characterized. Two applications of reflected impedance in biomedical sensors for hydrocephalus shunts and glucose sensing are discussed.     

Special issue: Newborn screening research

This Special Issue provides a wide-ranging update from the front lines of newborn screening (NBS) research and is the result of conversations and collaborations facilitated by the Newborn Screening Translational Research Network (NBSTRN) across the NBS community and their extended networks. For 14 years NBSTRN has accelerated research efforts to advance NBS by creating a research infrastructure available to the NBS community to discover novel technologies to screen, diagnose, and treat newborns.Authors in this Special issues share their innovative and impactful efforts to advance NBS to include additional conditions, populations, genomics, and information sharing.     

Neutralizing Antibody Responses to SARS-CoV-2 in Korean Patients Who Have Recovered from COVID-19

PurposeNeutralizing antibodies (NAbs) have been considered effective in preventing and treating viral infections. However, until now, the duration and clinical implications of antibody-mediated nature immunity in Koreans have remained unknown. Therefore, we examined NAbs levels and clinical characteristics in recovered coronavirus disease 2019 (COVID-19) patients.Materials and MethodsBlood samples were collected from 143 adult patients who had been diagnosed with and had recovered from COVID-19 from February to March in 2020 at a tertiary-care university-affiliated hospital in Daegu, Korea. A plaque reduction neutralization test was conducted to analyze NAb titers. Individualized questionnaires were used to identify patient clinical information.ResultsThe median number of days from symptom onset to the blood collection date was 109.0 (104.0; 115.0). The NAb titers ranged from 10 to 2560. The median NAb titer value was 40. Of the 143 patients, 68 (47.6%) patients had NAb titers ≥80, and 31 (21.7%) patients had NAb titers ≥160. The higher the age or disease severity, the higher the NAb titer. In univariate logistic regression, statistically significant predictors of high NAb titers (≥80) were age, myalgia, nausea or vomiting, dyspnea, and disease severity (p<0.05). Multivariable logistic regression showed that age ≥50 years (p=0.013) and moderate or higher disease severity (p<0.001) were factors associated with high NAb titers (≥80). None of the patients had reinfection of COVID-19.ConclusionAll recovered patients were found to have NAbs regardless of the NAb titers maintained by natural immunity. Age and disease severity during COVID-19 infection were associated with high NAb titers.     

Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells

Historically, our understanding of molecular genetic aspects of human germ cell development has been limited, at least in part due to inaccessibility of early stages of human development to experimentation. However, the derivation of pluripotent stem cells may provide the necessary human genetic system to study germ cell development. In this study, we compared the potential of human induced pluripotent stem cells (iPSCs), derived from adult and fetal somatic cells to form primordial and meiotic germ cells, relative to human embryonic stem cells. We found that ～5% of human iPSCs differentiated to primordial germ cells (PGCs) following induction with bone morphogenetic proteins. Furthermore, we observed that PGCs expressed green fluorescent protein from a germ cell-specific reporter and were enriched for the expression of endogenous germ cell-specific proteins and mRNAs. In response to the overexpression of intrinsic regulators, we also observed that iPSCs formed meiotic cells with extensive synaptonemal complexes and post-meiotic haploid cells with a similar pattern of ACROSIN staining as observed in human spermatids. These results indicate that human iPSCs derived from reprogramming of adult somatic cells can form germline cells. This system may provide a useful model for molecular genetic studies of human germline formation and pathology and a novel platform for clinical studies and potential therapeutical applications.     

The helminth product ES-62 protects against septic shock via Toll-like receptor 4-dependent autophagosomal degradation of the adaptor MyD88

Sepsis is one of the most challenging health problems worldwide. Here we found that phagocytes from patients with sepsis had considerable upregulation of Toll-like receptor 4 (TLR4) and TLR2; however, shock-inducing inflammatory responses mediated by these TLRs were inhibited by ES-62, an immunomodulator secreted by the filarial nematode Acanthocheilonema viteae. ES-62 subverted TLR4 signaling to block TLR2- and TLR4-driven inflammatory responses via autophagosome-mediated downregulation of the TLR adaptor-transducer MyD88. In vivo, ES-62 protected mice against endotoxic and polymicrobial septic shock by TLR4-mediated induction of autophagy and was protective even when administered after the induction of sepsis. Given that the treatments for septic shock at present are inadequate, the autophagy-dependent mechanism of action by ES-62 might form the basis for urgently needed therapeutic intervention against this life-threatening condition.     

Characterisation of TNF block haplotypes affecting the production of TNF and LTA

Polymorphisms in the central major histocompatibility complex (MHC) (particularly TNF and adjacent genes) associate with several immunopathological diseases and with susceptibility to pneumonia. The MHC is characterised by strong linkage disequilibrium (LD), so identification of loci affecting disease must be based on haplotypes. We have defined 31 tumour necrosis factor (TNF) block haplotypes (denoted FV1-31) in Caucasians, Asians and Australian Aboriginals. This study correlates the carriage of TNF block haplotypes with TNF and lymphotoxin alpha (LTA) protein production by peripheral blood mononuclear cells from 205 healthy Caucasian subjects, following in vitro stimulation with Streptococcus pneumoniae (S. pneumoniae; gram-positive bacteria), Escherichia coli (E. coli; gram-negative bacteria) or TNF over 4, 8 and 24 h. Fifteen haplotypes were present at >1%, accounting for 94.5% of the cohort. The haplotypes were grouped into five families based on common alleles. Following stimulation, cells from carriers of the FV10 haplotype (family 2) produced less LTA compared with non-FV10 carriers. Carriers of the FV18 haplotype (family 4) produced more LTA than other donors. Induction of TNF by S. pneumoniae following 24 h stimulation was also greater in donors with FV18. The FV18 haplotype associated with the 44.1 MHC ancestral haplotype (HLA-A2, -C5, -B44, -DRB1*0401 and -DQB1*0301) that has few disease associations. FV16 occurred in the 8.1 MHC haplotype (HLA-A2, B8, DR3) that is associated with multiple immunopathological diseases. FV16 did not affect TNF or LTA levels. The findings suggest that many genetic variations critical in vivo are not effectively modelled by short-term cultures.     

Acute lung injury induces cardiovascular dysfunction: effects of IL-6 and budesonide/formoterol

Acute lung injury (ALI) is associated with systemic inflammation and cardiovascular dysfunction. IL-6 is a biomarker of this systemic response and a predictor of cardiovascular events, but its possible causal role is uncertain. Inhaled corticosteroids and long-acting β2 agonists (ICS/LABA) down-regulate the systemic expression of IL-6, but whether they can ameliorate the cardiovascular dysfunction related to ALI is uncertain. We sought to determine whether IL-6 contributes to the cardiovascular dysfunction related to ALI, and whether budesonide/formoterol ameliorates this process. Wild-type mice were pretreated for 3 hours with intratracheal budesonide, formoterol, or both, before LPS was sprayed into their tracheas. IL-6-deficient mice were similarly exposed to LPS. Four hours later, bronchoalveolar lavage fluid (BALF) and serum were collected, and endothelial and cardiac functions were measured, using wire myography of the aortic tissue and echocardiography, respectively. LPS significantly impaired vasodilatory responses to acetylcholine (P < 0.001) and cardiac output (P = 0.002) in wild-type but not IL-6-deficient mice. Intratracheal instillations of exogenous IL-6 into IL-6-deficient mice restored these impairments (vasodilatory responses to acetylcholine, P = 0.005; cardiac output, P = 0.025). Pretreatment with the combination of budesonide and formoterol, but not either alone, ameliorated the vasodilatory responses to acetylcholine (P = 0.018) and cardiac output (P < 0.001). These drugs also attenuated the rise in the systemic expression of IL-6 (P < 0.05) related to LPS. IL-6 contributes to the cardiovascular dysfunction related to LPS, and pretreatment with budesonide/formoterol reduces the systemic expression of IL-6 and improves cardiovascular dysfunction. ICS/LABA may reduce acute cardiovascular events related to ALI.     

The effect of school-based cervical cancer education on perceptions towards human papillomavirus vaccination among Hong Kong Chinese adolescent girls

Objective

To evaluate the effects of school-based cervical cancer education on Hong Kong Chinese adolescent girls.

Methods

Adolescent girls (n = 953) in local secondary schools attended a tailored educational program on cervical cancer prevention. Self-administered questionnaires were used before and after the program to measure its effects on participants’ knowledge, attitude and perceived social norms towards human papillomavirus (HPV) vaccination and their intention to be HPV vaccinated.

Results

Before the program, HPV vaccine acceptance was favorable but relevant knowledge was low. After the program, participants had greater knowledge and a more positive attitude (both p < 0.001), with more girls anticipating family (41.6% before vs. 58.9% after) and peer support (32.8% before vs. 56.9% after). There were 11.3% more girls who indicated an intention to accept the vaccine afterward. More knowledge, a more positive attitude and perceived support from significant others predicted a stronger intention to be HPV vaccinated.

Conclusion

The educational program had a positive impact on participants’ perceptions towards HPV vaccination and their intention to be vaccinated.

Practice implications

School-based cervical cancer education is a viable means to meet the substantial educational needs of adolescents. Promotion of HPV vaccination should also include educating and influencing perceptions of families and peers.