bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial
Authors: Chávez-Iñiguez Jonathan S. , Ibarra-Estrada Miguel , Sánchez-Villaseca Sergio , Romero-González Gregorio , Font-Yañez Jorge J. , De la Torre-Quiroga Andrés , de Quevedo Andrés Aranda-G , Romero-Muñóz Alexia , Maggiani-Aguilera Pablo , Chávez-Alonso Gael , Gómez-Fregoso Juan , García-García Guillermo
Published: January 2022

Aim

The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF).

Methods

In a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion.

Results

From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53).

Conclusion

In patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered.
A case of vasculitis triggered by infective endocarditis in a patient undergoing maintenance hemodialysis: a case report
Authors: Park Hanui , Lee Miji , Jeong Jin Seon
Published: January 2022

Background

Immunoglobulin A vasculitis (IgA vasculitis) is one of the most common forms of vasculitis in children. It rarely occurs in adults. It is a systemic vasculitis with IgA deposition and is characterized by the classical tetrad of purpura, arthritis/arthralgia, gastrointestinal and renal involvement. Certain types of infections, and pharmacological agents have been reported to be associated with IgA vasculitis. Here, we describe a case of IgA vasculitis triggered by infective endocarditis in a patient undergoing maintenance hemodialysis.

Case presentation

A 70-year-old man undergoing hemodialysis was admitted because of skin purpura, abdominal pain, diarrhea, and lower back pain. We suspected him as IgA vasculitis based on the clinical features and skin biopsy findings. Transesophageal echocardiography revealed infective endocarditis, which predisposed him to IgA vasculitis. He was treated with antibiotics and low-dose corticosteroids, which led to resolution of vasculitis.

Conclusions

This is the first case of IgA vasculitis triggered by infective endocarditis in a patient undergoing hemodialysis. Patients undergoing hemodialysis are at a high risk of infection because of immune dysfunction and frequent venipuncture. The incidence of infective endocarditis associated with IgA vasculitis is very low, but it has been repeatedly reported. Therefore, it is necessary to consider infective endocarditis in patients with clinical features that indicate IgA vasculitis.
Assessment of bidirectional relationships between 98 genera of the human gut microbiota and amyotrophic lateral sclerosis: a 2-sample Mendelian randomization study
Authors: Zhang Linjing , Zhuang Zhenhuang , Zhang Gan , Huang Tao , Fan Dongsheng
Published: January 2022

Background

Growing evidence suggests a mutual interaction between gut microbiome alterations and ALS pathogenesis. However, previous studies were susceptible to potential confounding factors and reverse causation bias, likely leading to inconsistent and biased results.

Objectives

To decipher the potentially mutual relationship between gut microbiota and ALS, we used a bidirectional two-sample MR approach to examine the associations between the gut microbiome and ALS.

Results

Using the inverse variance-weighted method, OTU10032 unclassified Enterobacteriaceae species-level OTU and unclassified Acidaminococcaceae were associated with a higher risk of ALS (per relative abundance: OR, 1.04; 95% CI, 1.01–1.07; P = 0.011 and OR, 1.02; 95% CI, 1.01–1.04; P = 0.009, respectively). Importantly, Gamma-Glu-Phe was showed potential deleterious effects on the risk of ALS (genetically predicted per a 1-standard deviation increase in the level of Gamma-Glu-Phe: OR, 1.96; 95% CI, 1.50–2.55; P = 0.012). Sensitivity analysis of the two candidate genera and metabolites using the MR-Egger and weighted-median methods produced similar estimates, and no horizontal pleiotropy or outliers were observed. Intriguingly, genetically predicted ALS was associated with an increase in the relative abundance of OTU4607_Sutterella (per 1-unit higher log odds: β, 2.23; 95% CI, 1.27–3.18; P = 0.020) and Lactobacillales_ORDER (per 1-unit higher log odds: β, 0.51; 95% CI, 0.09–0.94; P = 0.019).

Conclusions

Our findings provide novel evidence supporting the bidirectional relationship between the gut microbiota and ALS. These results may contribute to designing microbiome- and microbiome-dependent metabolite interventions in future ALS clinical trials.
Impact of the Salud Mesoamerica Initiative on delivery care choices in Guatemala, Honduras, and Nicaragua
Authors: Hernandez Bernardo , Harris Katie Panhorst , Johanns Casey K. , Palmisano Erin B. , Cogen Rebecca , Thom Maximilian G. , Linebarger Emily , El Bcheraoui Charbel , Kamath Aruna M. , Camarda Joseph , Rios-Zertuche Diego , Zúñiga-Brenes María Paola , Bernal-Lara Pedro , Colombara Danny , Schaefer Alexandra , Salvatierra Benito , Mateus Julio César , Casas Isabel , Flores Giovanni , Iriarte Emma , Mokdad Ali H.
Published: January 2022

Background

The Salud Mesoamérica Initiative (SMI) is a public-private collaboration aimed to improve maternal and child health conditions in the poorest populations of Mesoamerica through a results-based aid mechanism. We assess the impact of SMI on the staffing and availability of equipment and supplies for delivery care, the proportion of institutional deliveries, and the proportion of women who choose a facility other than the one closest to their locality of residence for delivery.

Methods

We used a quasi-experimental design, including baseline and follow-up measurements between 2013 and 2018 in intervention and comparison areas of Guatemala, Nicaragua, and Honduras. We collected information on 8754 births linked to the health facility closest to the mother’s locality of residence and the facility where the delivery took place (if attended in a health facility). We fit difference-in-difference models, adjusting for women’s characteristics (age, parity, education), household characteristics, exposure to health promotion interventions, health facility level, and country.

Results

Equipment, inputs, and staffing of facilities improved after the Initiative in both intervention and comparison areas. After adjustment for covariates, institutional delivery increased between baseline and follow-up by 3.1 percentage points (β = 0.031, 95% CI -0.03, 0.09) more in intervention areas than in comparison areas. The proportion of women in intervention areas who chose a facility other than their closest one to attend the delivery decreased between baseline and follow-up by 13 percentage points (β = − 0.130, 95% CI -0.23, − 0.03) more than in the comparison group.

Conclusions

Results indicate that women in intervention areas of SMI are more likely to go to their closest facility to attend delivery after the Initiative has improved facilities’ capacity, suggesting that results-based aid initiatives targeting poor populations, like SMI, can increase the use of facilities closest to the place of residence for delivery care services. This should be considered in the design of interventions after the COVID-19 pandemic may have changed health and social conditions.
Factors associated with the level of physical activity in a multi-ethnic pregnant population – a cross-sectional study at the time of diagnosis with gestational diabetes
Authors: Garnweidner-Holme L , Henriksen L , Bjerkan K , Lium J , Lukasse M
Published: January 2022

Background

Regular physical activity during pregnancy can prevent several adverse health outcomes during this period of a woman’s life. Previous studies have shown that many women do not meet national recommendations for physical activity. This study aims to examine factors associated with sufficient leisure-time physical activity (LTPA) in a multicultural sample of pregnant women recently diagnosed with gestational diabetes mellitus (GDM).

Methods

We performed a cross-sectional study among 238 pregnant women. The women were recruited at diabetes outpatient clinics in the Oslo region of Norway from October 2015 to April 2017. The participants reported their activity levels using the Pregnancy Physical Activity Questionnaire (PPAQ). Pearson’s chi-square tests were used to assess differences in socio-demographic, health and pregnancy-related characteristics in relation to sufficient and insufficient LTPA, and logistic regression modelling was employed to predict the likelihood of insufficient LTPA.

Results

Less than half of the women in the sample (44.5%) had sufficient LTPA according to the minimum of ≥600 Met minutes per week. The majority of women were motivated to be physically active during pregnancy (84.9%). A low joint family income and being over 38 years of age increased the odds of not having sufficient LTPA. Women with sufficient LTPA had significantly higher scores of perceived health (p = 0.007).

Conclusions

The study indicates that pregnant women need to be better informed about the positive effects of physical activity on individually perceived health. To address the low levels of LTPA among pregnant women, communication strategies must be tailored towards women with low socio-economic backgrounds.

Trial registration:https://clinicaltrials.gov/ct2/show/NCT02588729
Obstetric and neonatal outcomes of gestational diabetes mellitus in twin pregnancies according to changes in its diagnostic criteria from National Diabetes Data Group criteria to Carpenter and Coustan criteria: a retrospective cohort study
Authors: Kim Yejin , Hong Sir-yeon , Kim Seo-yeon , Kim Yoo-min , Sung Ji-Hee , Choi Suk-Joo , Oh Soo-young , Roh Cheong-Rae
Published: January 2022

Background

To compare obstetric and neonatal outcomes in twin pregnancies with or without gestational diabetes mellitus (GDM) before and after changes in GDM diagnostic criteria.

Methods

This was a retrospective cohort study of 1,764 twin pregnancies including 130 women with GDM (GDM group) and 1,634 women without GDM (non-GDM group). Patients with pregestational diabetes, unknown GDM status, and fetal death at < 24 gestational weeks were excluded. Obstetric and neonatal outcomes were compared between the two groups by two periods: period 1 (1995–2005) and period 2 (2005–2018) when National Diabetes Data Group criteria and Carpenter and Coustan criteria were used for diagnosis of GDM, respectively.

Results

The incidence of GDM in twin pregnancies increased from 4.0% in period 1 to 9.3% in period 2. Composite obstetric complications rate was significantly higher in the GDM group than that in the non-GDM group during period 1 (72.0% vs. 45.5%,P = 0.009). However, it became comparable during period 2 (60.0% vs. 57.4%,P = 0.601). Interaction between GDM and period indicated a significant differential effect of GDM by period on the rate of composite obstetric complications. The rate of composite neonatal complications was similar between the two groups during both periods. The interaction between GDM and period was not significant.

Conclusion

After changes of GDM diagnostic criteria, the incidence of GDM increased more than twice, and the rate of composite obstetric complications decreased, but the rate of composite neonatal complications did not change significantly.
Microbiome composition indicate dysbiosis and lower richness in tumor breast tissues compared to healthy adjacent paired tissue, within the same women
Authors: Esposito Maria Valeria , Fosso Bruno , Nunziato Marcella , Casaburi Giorgio , D’Argenio Valeria , Calabrese Alessandra , D’Aiuto Massimiliano , Botti Gerardo , Pesole Graziano , Salvatore Francesco
Published: January 2022

Background

Breast cancer (BC) is the most common malignancy in women, in whom it reaches 20% of the total neoplasia incidence. Most BCs are considered sporadic and a number of factors, including familiarity, age, hormonal cycles and diet, have been reported to be BC risk factors. Also the gut microbiota plays a role in breast cancer development. In fact, its imbalance has been associated to various human diseases including cancer although a consequential cause-effect phenomenon has never been proven.

Methods

The aim of this work was to characterize the breast tissue microbiome in 34 women affected by BC using an NGS-based method, and analyzing the tumoral and the adjacent non-tumoral tissue of each patient.

Results

The healthy and tumor tissues differed in bacterial composition and richness: the number of Amplicon Sequence Variants (ASVs) was higher in healthy tissues than in tumor tissues (p = 0.001). Moreover, our analyses, able to investigate from phylum down to species taxa for each sample, revealed major differences in the two richest phyla, namely, Proteobacteria and Actinobacteria. Notably, the levels of Actinobacteria and Proteobacteria were, respectively, higher and lower in healthy with respect to tumor tissues.

Conclusions

Our study provides information about the breast tissue microbial composition, as compared with very closely adjacent healthy tissue (paired samples within the same woman); the differences found are such to have possible diagnostic and therapeutic implications; further studies are necessary to clarify if the differences found in the breast tissue microbiome are simply an association or a concausative pathogenetic effect in BC. A comparison of different results on similar studies seems not to assess a universal microbiome signature, but single ones depending on the environmental cohorts’ locations.
Landscape of homologous recombination deficiencies in solid tumours: analyses of two independent genomic datasets
Authors: Lai Zhongwu , Brosnan Matthew , Sokol Ethan S. , Xie Mingchao , Dry Jonathan R. , Harrington Elizabeth A. , Barrett J. Carl , Hodgson Darren
Published: January 2022

Background

DNA repair deficiencies are characteristic of cancer and homologous recombination deficiency (HRD) is the most common. HRD sensitizes tumour cells to PARP inhibitors so it is important to understand the landscape of HRD across different solid tumour types.

Methods

Germline and somatic BRCA mutations in breast and ovarian cancers were evaluated using sequencing data from The Cancer Genome Atlas (TCGA) database. Secondly, a larger independent genomic dataset was analysed to validate the TCGA results and determine the frequency of germline and somatic mutations across 15 different candidate homologous recombination repair (HRR) genes, and their relationship with the genetic events of bi-allelic loss, loss of heterozygosity (LOH) and tumour mutation burden (TMB).

Results

Approximately one-third of breast and ovarian cancer BRCA mutations were somatic. These showed a similar degree of bi-allelic loss and clinical outcomes to germline mutations, identifying potentially 50% more patients that may benefit from precision treatments. HRR mutations were present in sizable proportions in all tumour types analysed and were associated with high TMB and LOH scores. We also identified numerous BRCA reversion mutations across all tumour types.

Conclusions

Our results will facilitate future research into the efficacy of precision oncology treatments, including PARP and immune checkpoint inhibitors.
Metastatic gastroesophageal cancer in older patients – is this patient cohort represented in clinical trials?
Authors: Hennessy Maeve A. , Hamid Munzir , Keegan Niamh M. , Corrigan Lynda , Goggin Caitriona , Oo Nay Myo , Carrigan Marie , Mockler David , O’Donovan Anita , Horgan Anne M.
Published: January 2022

Background

Older patients are underrepresented in the clinical trials that determine the standards of care for oncological treatment. We conducted a review to identify whether there have been age-restrictive inclusion criteria in clinical trials over the last twenty five years, focusing on patients with metastatic gastroesophageal cancer.

Methods

A search strategy was developed encompassing Embase, PubMed and The Cochrane Library databases. Completed phase III randomised controlled trials evaluating systemic anti-cancer therapies in metastatic gastroesophageal malignancies from 1st January 1995 to 18th November 2020 were identified. These were screened for eligibility using reference management software (Covidence; Veritas Health Innovation Ltd). Data including age inclusion/exclusion criteria and median age of participants were recorded. The percentage of patients ≥ 65 enrolled was collected where available. The change over time in the proportion of studies using an upper age exclusion was estimated using a linear probability model.

Results

Three hundred sixty-three phase III studies were identified and screened, with 66 trials remaining for final analysis. The majority of trials were Asian (48%; n = 32) and predominantly evaluated gastric malignancies, (86%; n = 56).

The median age of participants was 62 (range 18–94). Thirty-two percent (n = 21) of studies specified an upper age limit for inclusion and over half of these were Asian studies. The median age of exclusion was 75 (range 65–80). All studies prior to 2003 used an upper age exclusion (n = 12); whereas only 9 that started in 2003 or later did (17%). Among later studies, there was a very modest downward yearly-trend in the proportion of studies using an upper age exclusion (-0.02 per year; 95%CI -0.05 to 0.01; p = 0.31). Fifty-two percent (n = 34) of studies specified the proportion of their study population who were ≥ 65 years. Older patients represented only 36% of the trial populations in these studies (range 7–60%).

Conclusions

Recent years have seen improvements in clinical trial protocols, with many no longer specifying restrictive age criteria. Reasons for poor representation of older patients are complex and ongoing efforts are needed to broaden eligibility criteria and prioritise the inclusion of older adults in clinical trials.
Optimal surgical treatment for paratesticular leiomyosarcoma: retrospective analysis of 217 reported cases
Authors: Kamitani Rei , Matsumoto Kazuhiro , Takeda Toshikazu , Mizuno Ryuichi , Oya Mototsugu
Published: January 2022

Background

Paratesticular leiomyosarcoma (LMS) is a rare tumor. Conventionally, tumor resection by high inguinal orchiectomy is performed as the preferred treatment approach for paratesticular sarcoma. On the other hand, testis-sparing surgery has recently attracted attention as a less-invasive treatment option for paratesticular sarcoma. However, the prognostic predictors and optimal treatment strategy for paratesticular LMS remain unclear because of its rarity. In this study, we systematically reviewed previously reported cases of paratesticular LMS to evaluate the prognostic factors and establish the optimal treatment strategy.

Methods

A systematic search of Medline, Web of Science, Embase, and Google was performed to find articles describing localized paratesticular LMS published between 1971 and 2020 in English. The final cohort included 217 patients in 167 articles. The starting point of this study was the time of definitive surgical treatment, and the end point was the time of local recurrence (LR), distant metastasis (DM), and disease-specific mortality.

Results

Patients with cutaneous LMS had a slightly better LR-free survival, DM-free survival, and disease-specific survival than those with subcutaneous LMS (p = 0.745, p = 0.033, and p = 0.126, respectively). Patients with higher grade tumors had a significantly higher risk of DM and disease-specific mortality (Grade 3 vs Grade 1 p < 0.001, and Grade 3 vs Grade 1 p < 0.001, respectively). In addition, those with a microscopic positive margin had a significantly higher risk of LR and DM than those with a negative margin (p < 0.001, and p = 0.018, respectively). Patients who underwent simple tumorectomy had a slightly higher risk of LR than those who underwent high inguinal orchiectomy (p = 0.067). Subgroup analysis of cutaneous LMS demonstrated that the difference in LR between simple tumorectomy and high inguinal orchiectomy was limited (p = 0.212). On the other hand, subgroup analysis of subcutaneous LMS revealed a significant difference in LR (p = 0.039).

Conclusions

Our study demonstrated that subcutaneous LMS and high-grade tumors are prognostic factors for paratesticular LMS. For subcutaneous LMS, tumorectomy with high inguinal orchiectomy should be the optimal treatment strategy to achieve a negative surgical margin.
Assessing frequency and clinical outcomes of BRCA mutated ovarian cancer in Saudi women
Authors: Agha Naela , Alshamsan Bader , Al-Farsi Sharifa , Ateya Heba Aly , Almugbel Fahad A. , Alotaibi Hazem Abdullah , Omar Ayman , Mohamed Amgad Shahin , Alharthy Hanan , Elhassan Tusneem , Salem Hany , Alhusaini Hamed
Published: January 2022

Purpose

BRCA gene mutations (BRCAm) have an impact on patients’ characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women.

Methods

This retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. Statistical analysis performed with SPSS (Version 27).

Result

Sixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The most common deleterious germline BRCA1 mutation was c.1140dupG (39%). Most women (72%) had no family history of cancers and 82% had advanced stage. Regardless of BRCA mutations, an optimal overall response rate (ORR) to first-line treatment has been achieved although most cases relapsed (84%) and the majority were platinum-sensitive relapse (85%). Higher ORR to subsequent lines and better survival were obtained in women with BRCA-mutation.

Conclusion

The prevalence of BRCAm of OC was higher in Saudi women compared to regional and most of the international figures. The better clinical outcomes of BRCAm women agreed with the reported evidence. Further studies on BRCA mutations of OC and genetic counseling are highly recommended.

Trial registration

Trial approved by the Institutional Review Board of King Faisal Specialist Hospital and Research Center (RAC # 2171137) and conducted at King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11,211, Saudi Arabia.
High score of LDH plus dNLR predicts poor survival in patients with HER2-positive advanced breast cancer treated with trastuzumab emtansine
Authors: Li Liru , Ai Lin , Jia Lin , Zhang Lei , Lei Boya , Zhang Qingyuan
Published: January 2022

Objective

To investigate the prognostic value of derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) in patients with advanced HER2 positive breast cancer treated with trastuzumab emtansine.

Methods

Fifty one patients with advanced HER2 positive breast cancer who received T-DM1 treatment in Harbin Medical University Cancer Hospital were selected. The clinical data and blood test indexes were collected, and the ROC curve determined the optimal cut-off value. Kaplan-Meier survival curve and Cox regression model was used to analyze the effect of different levels of dNLR,LDH,LNI (dNLR combined with LDH index) before and after T-DM1 treatment on the survival of patients.

Results

The median PFS and OS of the patients with advanced HER2 positive breast cancer who received T-DM1 treatment were 6.9 months and 22.2 months, respectively. The optimal cut-off value of LDH and dNLR before T-DM1 treatment was 244 U / L (P = 0.003) and 1.985 (P = 0.013), respectively. Higher LDH and dNLR were significantly correlated with shorter median PFS and OS (P < 0.05). The median PFS of patients with LNI (0), LNI (1) and LNI (2) were 8.1 months, 5.5 months and 2.3 months, respectively, P = 0.007. Univariate and multivariate analysis showed that LDH > 244 U / L, dNLR > 1.985, LNI > 0, ECOG ≥1 and HER-2 (IHC2 +, FISH+) before the T-DM1 treatment were the poor prognostic factors. LDH uptrend after the T-DM1 treatment also predicted poor prognosis.

Conclusion

Serum LDH > 244 U / L and dNLR > 1.985 before the T-DM1 treatment were prognostic risk factors for patients with advanced HER2 positive breast cancer receiving T-DM1 treatment. The higher LNI score was significantly associated with shorter PFS and OS. LDH uptrend after T-DM1 treatment was also related to the poor prognosis.
A phase IA dose-escalation study of PHI-101, a new checkpoint kinase 2 inhibitor, for platinum-resistant recurrent ovarian cancer
Authors: Park Soo Jin , Chang Suk-Joon , Suh Dong Hoon , Kong Tae Wook , Song Heekyoung , Kim Tae Hun , Kim Jae-Weon , Kim Hee Seung , Lee Sung-Jong
Published: January 2022

Background

PHI-101 is an orally available, selective checkpoint kinase 2 (Chk2) inhibitor. PHI-101 has shown anti-tumour activity in ovarian cancer cell lines and impaired DNA repair pathways in preclinical experiments. Furthermore, the in vivo study suggests the synergistic effect of PHI-101 through combination with PARP inhibitors for ovarian cancer treatment. The primary objective of this study is to evaluate the safety and tolerability of PHI-101 in platinum-resistant recurrent ovarian cancer.

Methods

Chk2 inhibitor for Recurrent EpitheliAl periToneal, fallopIan, or oVarian cancEr (CREATIVE) trial is a prospective, multi-centre, phase IA dose-escalation study. Six cohorts of dose levels are planned, and six to 36 patients are expected to be enrolled in this trial.

Major inclusion criteria include ≥ 19 years with histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer. Also, patients who showed disease progression during platinum-based chemotherapy or disease progression within 24 weeks from completion of platinum-based chemotherapy will be included, and prior chemotherapy lines of more than five will be excluded. The primary endpoint of this study is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of PHI-101.

Discussion

PHI-101 is the first orally available Chk2 inhibitor, expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial, DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a new combination regimen for the treatment of ovarian cancer.

Trial registration

ClinicalTrials.govIdentifier:NCT04678102.
Prognostic nomogram for patients with unresectable pancreatic cancer treated with gemcitabine plus nab–paclitaxel or FOLFIRINOX: A post–hoc analysis of a multicenter retrospective study in Japan (NAPOLEON study)
Authors: Shibuki Taro , Mizuta Toshihiko , Shimokawa Mototsugu , Koga Futa , Ueda Yujiro , Nakazawa Junichi , Komori Azusa , Otsu Satoshi , Arima Shiho , Fukahori Masaru , Makiyama Akitaka , Taguchi Hiroki , Honda Takuya , Mitsugi Kenji , Nio Kenta , Ide Yasushi , Ureshino Norio , Shirakawa Tsuyoshi , Otsuka Taiga
Published: January 2022

Background

No reliable nomogram has been developed until date for predicting the survival in patients with unresectable pancreatic cancer undergoing treatment with gemcitabine plus nab–paclitaxel (GnP) or FOLFIRINOX.

Methods

This analysis was conducted using clinical data of Japanese patients with unresectable pancreatic cancer undergoing GnP or FOLFIRINOX treatment obtained from a multicenter study (NAPOLEON study). A Cox proportional hazards model was used to identify the independent prognostic factors. A nomogram to predict 6–, 12–, and 18–month survival probabilities was generated, validated by using the concordance index (C–index), and calibrated by the bootstrapping method. And then, we attempted risk stratification for survival by classifying the patients according to the sum of the scores on the nomogram (total nomogram points).

Results

A total of 318 patients were enrolled. A prognostic nomogram was generated using data on the Eastern Cooperative Oncology Group performance status, liver metastasis, serum LDH, serum CRP, and serum CA19–9. The C–indexes of the nomogram were 0.77, 0.72 and 0.70 for 6–, 12–, and 18–month survival, respectively. The calibration plot showed optimal agreement at all points. Risk stratification based on tertiles of the total nomogram points yielded clear separations of the survival curves. The median survival times in the low–, moderate–, and high–risk groups were 15.8, 12.8 and 7.8 months (P<0.05), respectively.

Conclusions

Our nomogram might be a convenient and inexpensive tool to accurately predict survival in Japanese patients with unresectable pancreatic cancer undergoing treatment with GnP or FOLFIRINOX, and will help clinicians in selecting appropriate therapeutic strategies for individualized management.
Application of protection motivation theory (PMT) on skin cancer preventive behaviors amongst primary school students in rural areas of Fasa city-Iran
Authors: Khani Jeihooni Ali , Bashti Somayeh , Erfanian Bahareh , Ostovarfar Jeyran , Afzali Hasirini Pooyan
Published: January 2022

Background

Considering that exposure to sunlight in childhood and adolescence has an important role in skin cancer, so it seems that training protective behaviors in this period is more effective.

Objectives

To survey the application of protection motivation theory (PMT) on skin cancer preventive behaviors among students in rural areas of Fasa city, Iran.

Methods

This study was done in two stages: Phase I of this study, the descriptive-analytic and cross-sectional study was conducted in 2018 to investigate the predictive value of the protection motivation theory on skin cancer preventive behaviors. In the second stage, a quasi-experimental interventional study was conducted on 400 primary school students in 2019. The educational intervention was performed in the experimental group for 8 sessions. Data were collected using a demographic information questionnaire and protection motivation theory before and six months after the intervention.

Results

The constructs of protection motivation theory predicted 58.6% of skin cancer preventive behaviors. The results indicated that there was no significant difference between the two groups in terms of knowledge, perceived sensitivity, perceived severity, reward, fear, protection motivation, response efficacy, self-efficacy, response costs, and the skin cancer preventive behaviors in before the intervention (p > 0.05). However, six months after the intervention, the experimental group showed a significant increase in each of the mentioned constructs and skin cancer protective behaviors (p < 0.05).

Conclusion

This study showed the effectiveness of the intervention based on the PMT constructs in adoption of skin cancer preventive behaviors in 6 months’ post intervention in primary school students.
Role of intraretinal cysts in the prediction of postoperative closure and photoreceptor damages of the idiopathic full-thickness macular hole
Authors: Joo Jin-Ho , Nam Woo Ho , Joo Taesung , Moon Sang Woong
Published: January 2022

Background

To determine whether it would be effective in predicting the results of the postoperative full-thickness macular hole (FTMH) closure when intraretinal cyst (IRC) is present.

Methods

Case-control study. Patients with idiopathic FTMH who underwent pars plana vitrectomy with internal limiting membrane peeling were retrospectively reviewed. Preoperative spectral-domain optical coherence tomography was undertaken in all patients. The new parameter, macular hole closing factor (MHCF) was defined as the base diameter - (arm length + IRC height) by adding IRC to the existing parameter. After surgery, patients were classified and analyzed according to the type of hole closure and the damage of photoreceptor.

Results

Of the 35 patients, 28 (80.00%) had type 1 closure and seven (20.00%) had type 2 closure. There was a significant difference in postoperative BCVA (P < 0.01), base diameter (P = 0.037), arm length (P = 0.045), and IRC height (P = 0.011) between the two groups. In the type 1 closure, they were further divided into two subgroups according to photoreceptor damage, and it was confirmed that there were significant differences in postoperative BCVA (P = 0.045), hole height (P = 0.048), and IRC height (P = 0.046) in the two subgroups. As for the new parameters, a significant difference between the three groups was confirmed (P < 0.01).

Conclusion

IRC may help predict hole closure along with the known horizontal parameters. Therefore, the new parameter containing both two factors can help predict not only hole closure but also damage to photoreceptors that affects postoperative visual prognosis.
Analysis of the first tear film break-up point in Sjögren’s syndrome and non-Sjögren’s syndrome dry eye patients
Authors: Zhao Songjiao , Le Qihua
Published: January 2022

Background

Tear film instability plays an important role in the course of Sjögren’s Syndrome dry eye (SSDE) even though it is generally classified as aqueous-deficient dry eye. The measurement of the first tear film break-up point (FTBUP) helps to evaluate the most unstable position of the tear film on ocular surface. We aim to investigate FTBUP in Sjögren’s Syndrome dry eye (SSDE) and non-Sjögren’s Syndrome dry eye (NSSDE) patients, and explore its correlation with dry eye indices.

Methods

Twenty-two SSDE patients (44 eyes) and 22 NSSDE patients (44 eyes) were enrolled in the study. Oculus Keratograph K5M was used to measure FTBUP, the first and average non-invasive keratographic breakup time (f-NIKBUT and av-NIKBUT), the tear meniscus height, and meibomian gland dropout. Other tests of tear film were also performed including Ocular Surface Dryness Index (OSDI), Schirmer I test, fluorescein break-up time and corneal fluorescein staining. Dry eye indices and the locations of the FTBUP were compared between SSDE and NSSDE patients. Generalized estimating equation (GEE) was used to ajusted the correlations between right and left eyes. The correlations between the FTBUP and ocular symptoms and signs were investigated using Pearson’s correlation coefficient test.

Results

The FTBUP occurred at the supranasal quadrant in 12/88 eyes, supratemporal quadrant in 8/88 eyes, inferonasal quadrant in 34/88 eyes, and inferotemporal quadrant in 34/88 eyes. The percentage eyes with inferior FTBUP was significantly higher in the SSDE than in the NSSDE subjects (86.3% vs 68.1%, P = .049). Moreover, in SSDE subjects, temporal breakup point was seen more often in those who presented corneal fluorescein staining in any location, while nasal breakup point was more frequent in those who did not present any corneal fluorescein staining (P = .045).

Conclusion

The location of the FTBUP in SSDE patients had specific characteristics. However, the diagnostic potential of FTBUP in early recognition of SSDE needs further validation.
Topography and clinical features of iris melanoma
Authors: Krohn Jørgen , Sundal Kristoffer Våge , Frøystein Torbjørn
Published: January 2022

Background

To characterise the topographical and clinical features of primary iris melanoma and to visualise the patterns of tumour extent in the iris.

Methods

Clinical characteristics of iris melanomas were analysed, and data on their size, shape, and location were converted into a database of two-dimensional iris charts by means of computer-drawing software. The geometric centre of each tumour was entered into corresponding sectors of the chart. The extent of the melanomas was computationally visualised by merging the iris drawings and displaying the number of overlapping tumours on colour-coded iris maps.

Results

Twenty-nine patients (18 females and 11 males) with a mean age of 52 years met the inclusion criteria. The mean largest tumour diameter was 6.1 mm (range, 1.8–11.0 mm). Five tumours (17%) involved the pupillary margin, 10 (34%) involved the iris root, and 10 (34%) involved both sites. The hemispheric location of the tumour centroid was superior in 3 eyes (11%) and inferior in 25 (89%) (p < 0.0001), and the distribution between the temporal and nasal hemispheres was 17 (61%) and 11 (39%), respectively (p = 0.26). In females, the iris melanomas were located more temporally (p  =  0.02) and had more often originated from a pre-existing naevus (p = 0.03), than in males. There was also shift towards more temporally located melanomas in younger patients.

Conclusions

The lower temporal iris quadrant is the preferential area of melanoma occurrence and growth. Iris melanoma tends to be more temporally located in females, who compared with males also have a higher proportion of melanomas arising from a pre-existing naevus.
Predictive factors for the surgical treatment of necrotizing enterocolitis in preterm infants: a single-center retrospective study
Authors: Liu Yusheng , Qiao Lingyan , Wu Xiongwei , Jiang Zhong , Hao Xiwei
Published: January 2022

Background

Necrotizing enterocolitis (NEC) is a gastrointestinal disease that tends to occur in premature infants. Some features may be associated with an increased probability that preterm infants with NEC will require surgical treatment. This study aimed to identify the factors that increased the probability of surgical treatment in infants with NEC.

Methods

We retrospectively analyzed the data of premature infants with NEC who were hospitalized at The Affiliated Hospital of Qingdao University from April 2011 to April 2021. According to the treatments received, these patients were divided into medical NEC group and surgical NEC group. The perinatal characteristics, clinical manifestations, and laboratory values before the onset of NEC were subjected to univariate and multivariate analyses.

Results

A total of 623 preterm infants with NEC (> Bell’s stage I) were included in this study, including 350 (56%) who received surgical treatment and 273 (44%) who received conservative medical treatment. Multivariate analysis showed that lower gestational age (P = 0.001, odds ratio (OR) (95% CI) = 0.91[0.86–0.96]), early occurrence of NEC (P = 0.003, OR (95% CI) = 0.86 [0.77–0.95]), hemodynamically significant patent ductus arteriosus (P = 0.003, OR (95% CI) = 7.50 [2.03–28.47]), and low serum bicarbonate (P = 0.043, OR (95% CI) = 0.863 [0.749–0.995]) were associated with an increased probability of surgical treatment in preterm infants with NEC.

Conclusions

Our findings were applied to identify potential predictors for surgical treatment in preterm infants with NEC, which may facilitate early decisive management.
Determinants of life satisfaction and self-rated health in Iranian children and adolescents: a structure equation model
Authors: Angoorani Pooneh , Mahmoodi Zohreh , Ejtahed Hanieh-Sadat , Heshmat Ramin , Motlagh Mohammad Esmaeil , Qorbani Mostafa , Kelishadi Roya
Published: January 2022

Background

Life satisfaction (LS) and self-rated health (SRH) are related with health outcomes. It is expected that these items are also related to healthy behaviors. Therefore, this study was conducted in order to find out the main determinants of LS and SRH in nationwide representative sample of Iranian children and adolescents.

Methods

This study was performed on 13,834 students aged 7–18 years who were selected by multistage, stratified cluster sampling method from 30 provinces of Iran. Life satisfaction and SRH were assessed through a questionnaire based on World Health Organization-Global School-based Student Health Survey protocols. Path analysis was applied to evaluate the relationships among the study variables using the structural modeling.

Results

Life satisfaction was directly affected by age (− 0.037 in boys & -0.028 in girls); sedentary time (0.055 in boys & 0.048 in girls); school satisfaction (0.249 in boys & 0.250 in girls); and well-being (0.186 in boys & 0.176 in girls). Self-rated health was directly affected by LS (0.28 in boys & girls) and school satisfaction (0.21 in boys & 0.22 in girls); and indirectly affected by age (− 0.046 in boys & -0.017 in girls); sedentary time (− 1.99 in boys & -0.145 in girls); family size (− 0.005 in boys & -0.014 in girls); and socio-economic status (0.015 in boys & 0.058 in girls).

Conclusions

This study indicated that school satisfaction had the greatest positive direct effect on both LS and SRH.
Clinical and economic impact of molecular testing for BRAF fusion in pediatric low-grade Glioma
Authors: Rios Juan David , Velummailum Russanthy , Bennett Julie , Nobre Liana , Tsang Derek S. , Bouffet Eric , Hawkins Cynthia , Tabori Uri , Denburg Avram , Pechlivanoglou Petros
Published: January 2022

Background

Treatment personalization via tumor molecular testing holds promise for improving outcomes for patients with pediatric low-grade glioma (PLGG). We evaluate the health economic impact of employing tumor molecular testing to guide treatment for patients diagnosed with PLGG, particularly the avoidance of radiation therapy (RT) for patients with BRAF-fusion.

Methods

We performed a model-based cost-utility analysis comparing two strategies: molecular testing to determine BRAF fusion status at diagnosis against no molecular testing. We developed a microsimulation to model the lifetime health and cost outcomes (in quality-adjusted life years (QALYs) and 2018 CAD, respectively) for a simulated cohort of 100,000 patients newly diagnosed with PLGG after their initial surgery.

Results

The life expectancy after diagnosis for individuals who did not receive molecular testing was 39.01 (95% Confidence Intervals (CI): 32.94;44.38) years and 40.08 (95% CI: 33.19;45.76) years for those who received testing. Our findings indicate that patients who received molecular testing at diagnosis experienced a 0.38 (95% CI: 0.08;0.77) gain in QALYs and $1384 (95% CI: $-3486; $1204) reduction in costs over their lifetime. Cost and QALY benefits were driven primarily by the avoidance of long-term adverse events (stroke, secondary neoplasms) associated with unnecessary use of radiation.

Conclusions

We demonstrate the clinical benefit and cost-effectiveness of molecular testing in guiding the decision to provide RT in PLGG. While our results do not consider the impact of targeted therapies, this work is an example of the value of simulation modeling in assessing the long-term costs and benefits of precision oncology interventions for childhood cancer, which can aid decision-making about health system reimbursement.
Lumbar Puncture in the prone position for Low Birth Weight Neonates
Authors: Guo Wanxu , Ma Di , Qian Min , Zhao Xiaoqi , Zhang Jinpu , Liu Junjiao , Chi Di , Mao Fengmin , Zhang Yunfeng
Published: January 2022

Background

Lumbar puncture in the lateral decubitus position will make the neonates uncomfortable and is likely to cause position change and unstable vital signs, and the application of sedative drugs will cause adverse effects. This study explored a novel method for lumbar puncture in the prone position for low weight neonates.

Methods

The neonates were randomly assigned into the standard position group receiving lumbar puncture in the lateral decubitus position; and the improved position group receiving lumbar puncture in the prone position. The success rate of first time attempts and the overall success rate of lumbar puncture, incidence of adverse effects, NIAPAS scores were collected and compared between these two groups. The difference in success rate and adverse effects incidence rate was analysed through Chi-square. Student’s t-test was used for the test of NIAPAS rating.

Results

The improved position group had a higher success rate of first attempt and overall success rate, significantly lower incidence of adverse effect and lower NIAPAS scores than those of the standard position group (P<0.05).

Conclusion

This lumbar puncture in the prone position is safer, more effective, and more comfortable for preterm neonates and those with low birth weight. Thus, this method is worth of further promotion.

Trial registration

Registration number, ChiCTR2100049923; Date of Registration, August 11, 2021; Retrospectively registered.
Differential mRNA and long noncoding RNA expression profiles in pediatric B-cell acute lymphoblastic leukemia patients
Authors: Xia Jing , Wang Mengjie , Zhu Yi , Bu Chaozhi , Li Tianyu
Published: January 2022

Background

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides (nt) that are involved in the pathogenesis and development of various cancers including B cell acute lymphoblastic leukemia (B–ALL). To determine the potential roles of lncRNAs involved in pathogenesis of B-ALL, we analyzed the expression profile of lncRNAs and mRNAs in B-ALL, respectively, and constructed lncRNAs/mRNAs interaction network.

Methods

We performed RNA sequencing of 10 non-leukemic blood disease donors and 10 B-ALL patients for Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Interactions among mRNAs were predicted using the STRING database. Quantitative real time PCR (qRT-PCR) was performed to verify the RNA-seq data of lncRNAs and mRNAs. Potential functions of subtype-specific lncRNAs were determined by using coexpression-based analysis on distally (trans-pattern) located protein-coding genes.

Results

A total of 1813 differentially expressed transcripts (DETs) and 2203 lncRNAs were identified. Moreover, 10 dysregulated lncRNAs and 10 mRNAs were randomly selected, and further assessed by RT-qPCR in vitro. Go and KEGG analysis demonstrated that the differentially expressed mRNAs were most closely associated with myeloid leukocyte activation and in transcriptional misregulation in cancer, respectively. In addition, co-expression analysis demonstrated that these lncRNAs, including MSTRG.27994.3, MSTRG.21740.1, ENST00000456341, MSTRG.14224.1 and MSTRG.20153.1, may mediate the pathogenesis and development of B-ALL via lncRNA-mRNA network interactions.

Conclusions

These results showed that several mRNAs and lncRNAs are aberrantly expressed in the bone marrow of B-ALL patients and play potential roles in B-ALL development, and be useful for diagnostic and/or prognostic purposes in pediatric B–ALL.

Data availability

The datasets used during our study are available through HARVARD Dataverse Persistent ID doi:10.7910/DVN/LK9T4Z.