bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced-Dose Ibrutinib Is Well Tolerated and Cost Effective for the Treatment of Chronic Lymphocytic Leukemia in Frail Older Adults
Authors: Chhina Arashpreet , Marin Monica Pernia , Thomas Shrina P , Vallejo Elizabeth G , Cappell Kathryn , Jain Maneesh
Published: November 2021

Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK) that is used for the treatment of multiple hematologic malignancies including chronic lymphocytic leukemia (CLL) with promising outcomes. Its use has been associated with significant side effects including diarrhea, fatigue, infections, arthralgias, hemorrhage, and atrial fibrillation among others. Ibrutinib-associated adverse events have led to its discontinuation in more than one-fifth of CLL patients treated. Specifically, in the real-world setting, 21% to 30% of patients have needed an Ibrutinib dose interruption or reduction. Moreover, the associated toxicity seems to be more prominent in the geriatric population given the poor functional reserve, impaired mobility, and preexisting comorbidities. In the elderly, moderate to severe treatment-related toxicity often times leads to a higher number of hospitalizations, which ultimately increases the risk of complications and health care costs. Some studies have reported that Ibrutinib dose reductions have not had a significant impact on the progression-free-survival or overall survival in the general population. Nevertheless, there is not sufficient data or consent about the use of a reduced dose of Ibrutinib for treatment of CLL in frail older adults. In addition, annual costs of treatment with complete-dose Ibrutinib for veterans exceed $100,000. As it is common to reach complete remission with Ibrutinib monotherapy, patients will remain on therapy long-term, compounding financial impact over their treatment lifetime. Reduced dose Ibrutinib can lower total cost by 50% or more and thereby increase patient adherence due to decreased economic burden. Therefore, we present a retrospective review of a series of 7 cases involving frail older adults with CLL treated with Ibrutinib at the Washington DC Veterans Affairs Medical Center. Six out of seven patients received a reduced Ibrutinib dose and had a complete response whereas one patient received the dose recommended by the manufacturer leading to a prolonged hospital stay due to the adverse effects. We report the disease control evidenced by a decrease in white blood cell count, alleviation of "B symptoms", and resolution of lymphadenopathy along with side effects with an Ibrutinib dose ranging from 140 to 280 mg per day. We also report the cost benefits obtained with the use of a reduced Ibrutinib dose. We hope that sharing our experience encourages clinical trials aiming to determine the minimal dose needed to effectively treat CLL while limiting toxicity, decreasing health care costs, and preserving quality of life in frail older adults.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
Clinical Characteristics and Survival of Non-Nasal Natural Killer/T-Cell Lymphoma from 2 Cancer Centers from Peru
Authors: Vasquez Jule F , Castro Melanie , Diaz Alonso , Barrionuevo Carlos , Samanez-Figari Cesar
Published: November 2021

Background

Natural killer/T-cell lymphoma (NKTCL) is an aggressive lymphoma with poor prognosis mainly seen in Asian and South American countries, most patients have nasal involvement. Non-nasal NKTCL have a dismal prognosis. However, data about this very specific population is mostly known in Asians but little known in Latin American (LATAM) population. Our aim is to describe the clinical characteristics and survival of newly diagnosed NKTCL patients in Peru

Methods: This is a retrospective study, including all patients with a pathological diagnosis of NKTCL patients >13 years at the Instituto Nacional de Enfermedades Neoplasicas (INEN) and Oncosalud between 2002 and 2019. The estimate of the survival curves was performed by the Kaplan-Meier method, and the difference was computed by the log-rank test.

Results: 60 patients were included for the analysis. The median age was 37 years (range 15-83). 62% were male, 51% had B-symptoms, 56% had stage III/IV disease, 54% had elevated serum LDH, 29% had nodal involvement. The most frequent non-nasal sites were oropharynx, soft tissue, cutaneous, gastrointestinal and orbit with 24%, 17%, 12%, 7% and 5%, respectively. 79% patients received systemic chemotherapy, 7% received radiotherapy alone and 14% did not received chemotherapy because poor performance status. Of patients who received chemotherapy only 20% received a L-asparaginase-based chemotherapy. The median follow-up time was 8 months (1-103). The median overall survival (OS) was 14 months (interquartile range [IQR] 4-29), 1y OS was 51% (95% CI 33-67), 3y OS 21% (95% CI 7-40), 5y OS 14% (95% CI 3-34), figure 1. The median overall survival according to LDH level was 10 months regardless of the levels (p=0.84), figure 2. The median OS for female and male were 8 and 10 months, respectively p=0.59)

Conclusions: Peruvian patients with non-nasal NKTCL are younger, with presence of B-symptoms, advance stage and elevated LDH levels compared to those reported in nasal NKTCL. The most frequent non nasal NKTCL is located on the oropharynx. OS of non-nasal NKTCL is extremely poor. Elevated LDH and sex are not prognostic factors for OS. A larger cohort and follow-up are needed to evaluate prognostic factors in this population.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
Leaf functional traits differentiation in relation to covering materials of urban tree pits
Authors: Zhu Jiyou , Cao Yujuan , He Weijun , Xu Qing , Xu Chengyang , Zhang Xinna
Published: November 2021

Background

Understanding the ecological strategies of urban trees to the urban environment is crucial to the selection and management of urban trees. However, it is still unclear whether urban tree pit cover will affect plant functional traits. Here, we study the response of urban trees to different tree pit covers, analyzed the effects of different cover types on soil properties and their trade-off strategies based on leaf functional traits.

Results

We found that there were obvious differences in the physical properties of the soil in different tree pit covers. Under the different tree pit cover types, soil bulk density and soil porosity reached the maximum under cement cover and turf cover, respectively. We found that tree pit cover significantly affected the leaf properties of urban trees. Leaf thickness, chlorophyll content index and stomatal density were mainly affected by soil bulk density and non-capillary porosity in a positive direction, and were affected by soil total porosity and capillary porosity in a negative direction. Leaf dry matter content and stomata area were mainly negatively affected by soil bulk density and non-capillary porosity, and positively affected by soil total porosity and capillary porosity. Covering materials of tree pits promoted the functional adjustment of plants and form the best combination of functions.

Conclusion

Under the influence of tree pit cover, plant have low specific leaf area, stomata density, high leaf thickness, chlorophyll content index, leaf dry matter content, leaf tissue density and stomata area, which belong to “quick investment-return” type in the leaf economics spectrum.
Association between enterocyte injury and fluid balance in patients with septic shock: a post hoc exploratory analysis of a prospective observational study
Authors: Yokoyama Haruka , Sekino Motohiro , Funaoka Hiroyuki , Sato Shuntaro , Araki Hiroshi , Egashira Takashi , Yano Rintaro , Matsumoto Sojiro , Ichinomiya Taiga , Higashijima Ushio , Hara Tetsuya
Published: November 2021

Background

The required fluid volume differs among patients with septic shock. Enterocyte injury caused by shock may increase the need for fluid by triggering a systematic inflammatory response or an ischemia-reperfusion injury in the presence of intestinal ischemia/necrosis. This study aimed to evaluate the association between enterocyte injury and positive fluid balance in patients with septic shock.

Methods

This study was a post hoc exploratory analysis of a prospective observational study that assessed the association between serum intestinal fatty acid-binding protein, a biomarker of enterocyte injury, and mortality in patients with septic shock. Intestinal fatty acid-binding protein levels were recorded on intensive care unit admission, and fluid balance was monitored from intensive care unit admission to Day 7. The association between intestinal fatty acid-binding protein levels at admission and the infusion balance during the early period after intensive care unit admission was evaluated. Multiple linear regression analysis, with adjustments for severity score and renal function, was performed.

Results

Overall, data of 57 patients were analyzed. Logarithmically transformed intestinal fatty acid-binding protein levels were significantly associated with cumulative fluid balance per body weight at 24 and 72 h post-intensive care unit admission both before (Pearson’s r = 0.490 [95% confidence interval: 0.263–0.666]; P < 0.001 and r = 0.479 [95% confidence interval: 0.240–0.664]; P < 0.001, respectively) and after (estimate, 14.4 [95% confidence interval: 4.1–24.7]; P = 0.007 and estimate, 26.9 [95% confidence interval: 11.0–42.7]; P = 0.001, respectively) adjusting for severity score and renal function.

Conclusions

Enterocyte injury was significantly associated with cumulative fluid balance at 24 and 72 h post-intensive care unit admission. Enterocyte injury in patients with septic shock may be related to excessive fluid accumulation during the early period after intensive care unit admission.
The effect of menopausal hormone therapy on gastrointestinal cancer risk and mortality in South Korea: a population-based cohort study
Authors: Nam Ji Hyung , Jang Sung-In , Park Hyun Soo , Kim Jae Hak , Lee Jun Kyu , Lim Yun Jeong , Koh Moon-Soo , Lee Jin Ho , Park Sohee , Nam Chung Mo , Park Eun-Cheol
Published: November 2021

Background

The effect of menopausal hormone therapy (MHT) on gastrointestinal (GI) cancers is controversial, and no research has been conducted in the East. This study investigates the association between MHT and GI cancer risks in South Korea.

Methods

A prescription-based cohort study was conducted using the NHIS Sample Cohort (2002–2013) of Korea. We used 1:5 propensity score matching, and 22,577 MHT users and 111,113 non-users were selected. Kaplan–Meier survival curves with log-rank tests were used. Cox proportional hazard models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Landmark analysis was used to determine dose–response relationship.

Results

The median follow-up was 79.6 of months. Kaplan–Meier survival curve showed less frequent GI cancer diagnoses in MHT users compared to non-users (0.13 vs. 0.16 per 100,000 person-years). Menopausal hormone therapy was associated with decreased incidence of GI cancer (HR = 0.809, 95%CI = 0.691–0.946) and colorectal cancer (CRC) (HR = 0.757, 95%CI = 0.577–0.995). Gastric cancer (GC) incidence showed marginal significance (HR = 0.787, 95%CI = 0.605–1.023). The mortality from GI cancer was lower in MHT users than in non-users (HR = 0.737, 95%CI = 0.547–0.993). The relationship between MHT and GI cancer was stronger with increasing MHT dose in terms of both incidence (Ptrend = 0.0002) and mortality (Ptrend = 0.0064).

Conclusions

The association between MHT use and reduced risks of GI cancers was attributed to CRC and GC and showed a dose–response relationship in a population-based cohort study.
Physical capacity, subjective health, and life satisfaction in older women: a 10-year follow-up study
Authors: Qazi Sarang Latif , Koivumaa-Honkanen Heli , Rikkonen Toni , Sund Reijo , Kröger Heikki , Isanejad Masoud , Sirola Joonas
Published: November 2021

Background

Physical capacity and subjective wellbeing are important for healthy aging. Our aim was to study how objective/subjective physical capacity and subjective health relate to life satisfaction, in a 10-year follow-up of aging women.

Methods

The participants (n = 1485, mean age 67.4 years) consisted of community-dwelling older women living in Kuopio, Finland. Grip strength and one-legged stance test time were used as objective, and self-rated mobility (SRM) as subjective physical capacity measures. Self-rated health (SRH) and SRM were assessed with one-item scales and life satisfaction with a 4-item scale. Correlation and linear regression were used to analyze these relationships and correlation network analysis to visualize them. Age and BMI were included in the analysis as adjusting factors.

Results

All the study variables were significantly correlated with baseline and follow-up life satisfaction, except BMI, which was only associated with life satisfaction at follow-up. On both occasions, SRH and SRM were the two strongest correlates of life satisfaction, but their mutual correlation was still higher. In linear regression analyses, SRH was positively associated with both baseline and follow-up life satisfaction, but physical capacity measures became non-significant after including SRH and SRM in the model. In the partial correlation network analyses, SRH and SRM were the most central nodes, connecting every other variable.

Conclusions

Self-reports on health, mobility, and life satisfaction are closely intertwined and provide easily accessible health information among aging women, but the impacts of objective physical capacity measures warrant further longitudinal studies in respect to subjective wellbeing among aging people.
The prognostic role of heart rate recovery after exercise and metabolic syndrome in IgA nephropathy
Authors: Sági Balázs , Késői István , Vas Tibor , Csiky Botond , Nagy Judit , Kovács Tibor
Published: November 2021

Background

Cardiovascular (CV) morbidity and mortality are higher in chronic kidney disease (CKD) than in the general population. Reduced heart rate recovery (HRR) is an independent risk factor for CV disease. The aim of the study was to determine the prognostic role of HRR in a homogenous group of CKD patients.

Methods

One hundred and twenty-five IgA nephropathy patients (82 male, 43 female, age 54.7 ± 13 years) with CKD stage 1–4 were investigated and followed for average 70 months. We performed a graded exercise treadmill stress test. HRR was derived from the difference of the peak heart rate and the heart rate at 1 min after exercise. Patients were divided into two groups by the mean HRR value (22.9 beats/min). The composite (CV and renal) endpoints included all-cause mortality and any CV event such as stroke, myocardial infarction, revascularisation (CV) and end-stage renal disease, renal replacement therapy (renal).

Results

Patients with reduced HRR (< 23 bpm) had significantly more end point events (22/62 patients vs. 9/53 patients, p = 0.013) compared to the higher HRR (≥23 bpm). Of the secondary the endpoints (CV or renal separately) rate of the renal endpoint was significantly higher in the lower HRR group (p = 0.029), while there was no significant difference in the CV endpoint between the two HRR groups (p = 0.285). Independent predictors of survival were eGFR and diabetes mellitus by using Cox regression analysis. Kaplan-Meier curves showed significant differences in metabolic syndrome and non-metabolic syndrome when examined at the combined endpoints (cardiovascular and renal) or at each endpoint separately. The primary endpoint rate was increased significantly with the increased number of metabolic syndrome component (Met.sy. comp. 0 vs. Met. sy. comp. 2+, primary endpoints, p = 0.012).

Conclusion

Our results showed that reduced HRR measured by treadmill exercise test has a predictive value for the prognosis of IgA nephropathy. The presence of metabolic syndrome may worsen the prognosis of IgA nephropathy.
Safety and efficacy of interleukin-6-receptor inhibitors in the treatment of neuromyelitis optica spectrum disorders: a meta-analysis
Authors: Kharel Sanjeev , Shrestha Suraj , Ojha Rajeev , Guragain Neha , Ghimire Rakesh
Published: November 2021

Background

Interleukin-6-receptor inhibitors like Tocilizumab and Satralizumab are showing promising results in the treatment of Neuromyelitis Optica spectrum disorder (NMOSD). We aimed to investigate the efficacy and safety of various Interleukin-6-receptor inhibitors in the management of NMO/NMOSD.

Methods

PubMed, Embase, and The Cochrane Library were systematically searched for suitable studies. Change in Annualized Relapse Ratio (ARR), Change in Extended Disability Status Scale (EDSS) s, the proportion of relapse-free patients and proportion of patients with adverse events, including serious adverse events and mortality were the parameters considered for the meta-analysis for Tocilizumab. Mean difference (MD) with 95% CI was used to quantify the change in ARR and change in EDSS before and after treatment. A forest plot was prepared to indicate the efficacy and adverse effects outcomes. The results were compared with those of Satralizumab included in two trials.

Results

A total of nine studies with 202 patients were included in our study. Tocilizumab found a good proportion (76.95% CI: 0.61–0.91; p < 0.001) of relapse free patients at follow up. It also significantly reduced mean ARR (mean difference: -2.6, 95% CI: − 2.71 to − 1.68; p < 0.001) and but did not show significant difference in change in EDSS score (mean difference = − 0.79, 95% CI: − 1.89 to − 0.31; p = 0.16). Also, the toxicity profile of Tocilizumab was acceptable considering the proportions of patients with adverse events 56% (95% C.I.;0.27–0.85, I2 = 88.95%, p < 0.001), proportions of patients with serious adverse events 11% (95% C.I.; 0.05 to 0.17, I2 = 0%, p < 0.001) and zero treatment related deaths. SAkura studies for Satralizumab showed similar relapse free patients (70% to 80%) and reduction of ARR and EDSS from baseline. Some studies of Tocilizumab have shown to reduce pain and fatigue while trials of Satralizumab had non-significant findings.

Conclusion

Interleukin-6-receptor inhibitors therapy showed a promising result with good efficacy and acceptable adverse events profile for treatment of NMOSD.
Immune checkpoint inhibitors plus neoadjuvant chemotherapy in early triple-negative breast cancer: a systematic review and meta-analysis
Authors: Xin Yuanfang , Shen Guoshuang , Zheng Yonghui , Guan Yumei , Huo Xingfa , Li Jinming , Ren Dengfeng , Zhao Fuxing , Liu Zhen , Li Zitao , Zhao Jiuda
Published: November 2021

Purpose

Some studies have shown that Immune checkpoint inhibitors (ICIs) have a favorable efficacy in advanced triple negative breast cancer (TNBC) patients, but the results are controversial in neoadjuvant chemotherapy (NACT) stage. The purpose of this study is to evaluate the efficacy and safety after NACT plus ICIs in early TNBC patients.

Methods

After searching PubMed, EMBASE, the Cochrane library and several mainly oncology conferences up to 30 January 2021 systematically, and define randomized controlled trials (RCTs) exploring the efficacy and safety of programmed death protein-1/programmed cell death-Ligand 1(PD-1/PD-L1) inhibitors plus neoadjuvant chemotherapy in TNBC patients. The primary endpoint was the pathological complete response (pCR) in intention-to-treat populations (ITT), and the secondary endpoints were event-free survival (EFS) and safety analysis in the ITT populations.

Results

Six RCTs (N = 2142) were included in our meta-analysis; NACT plus ICIs increased pCR rates compared with NACT in intention-to-treat (ITT) populations (OR: 1.91; 95% CI: 1.32–2.78, P < 0.001). The pCR rate also increased in both PD-L1 positive (OR: 1.65; 95% CI: 1.26–2.16, P < 0.001) and PD-L1 negative patients (OR: 1.56; 95% CI: 1.04–2.33, P = 0.03), especially in PD-L1 positive patients. The benefit was also observed in nodal-positive populations (OR: 2.52; 95% CI: 1.69–3.77, P < 0.001) and Eastern Cooperative Oncology Group performance-status score (ECOG PS) 0 subgroup (OR: 1.90; 95% CI: 1.42–2.53, P < 0.001). Three RCTs (N = 1615) reported EFS and the results showed that adding PD-1/PD-L1 inhibitors increased EFS (HR 0.65, 95% CI 0.50–0.83, P = 0.0007) in ITT populations with a short follow-up time. In the safety analysis of 2205 patients with early TNBC from five eligible studies, NACT plus ICIs had a higher risk of grade 3–4 diarrhea (OR: 2.54; 95% CI: 1.21–5.32; P = 0.01), any grade of adverse effects(AEs)including vomiting (OR: 1.37; 95% CI: 1.00–1.86; P = 0.05), hyperthyroidism (OR: 6.04; 95% CI: 2.39–15.29; P < 0.001), and hypothyroidism (OR: 5.04; 95% CI: 3.02–8.39; P < 0.001).

Conclusions

PD-1/PD-L1 inhibitors combined with chemotherapy can improve pCR rates and EFS, and with an increased incidence of some immune-related AEs compared with chemotherapy alone. NACT plus ICIs might be an option in patients with in PD-L1 positive and high-risk populations with positive nodal disease early TNBC.
Quadriceps muscle strength recovery with the use of high tone power therapy after anterior cruciate ligament reconstruction: a randomized controlled trial
Authors: Ogrodzka-Ciechanowicz Katarzyna , Głąb Grzegorz , Ślusarski Jakub , Gądek Artur
Published: November 2021

Background

There are no scientific reports clearly describing the effectiveness of the High Tone Power Therapy in patients after ACL reconstruction. This caused that in own research an attempt was made to present the possibilities of using the selected method of electrical stimulation in the treatment of an orthopaedic patient. The aim was to assess the effectiveness of electro stimulation of the quadriceps muscle in patients after ACL reconstruction, with the use of High Tone Power Therapy.

Methods

In randomized controlled trial took part thirty-five men, aged 21–50, after ACL reconstruction. The tests were carried prior to and 6 months following the ACL reconstruction. After the surgery, the patients were randomly divided into experimental group (17 patients) with the High Tone Power Therapy in rehabilitation and control group (18 patients) without the High Tone Power Therapy. Patients were subjected to 6-month rehabilitation. Research tools included the measurement of muscle strength torque, ROM, knee and thigh circumference measurements, the Lysholm and the VAS scale.

Results

After applying HiToP, the analysis showed a statistically significant improvement of muscle torque (p = 0.041, Es = 3.71), knee circumference (p = 0.039, Es = 1.65), thigh circumference (p = 0.049, Es = 1.26), knee extension (p < 0.001, Es = 2.20) in Experimental group compared to the control group. Only the results of the VAS scale did not differ statistically significantly both within a given group and between groups.

Conclusions

The results confirm the hypothesis that the use of HiToP in patients after ACLr have a beneficial effect on muscle strength, reduction of joint effusion, muscle mass gain and joint function. The assumption that HiToP significantly reduces pain levels is not supported - the results in both groups are statistically insignificant.

Trial registration

The research project was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR). Date of first registration 11.10.2016. Registration number: ACTRN12616001416482.
What are the effects of diagnostic imaging on clinical outcomes in patients with low back pain presenting for chiropractic care: a matched observational study
Authors: Jenkins Hazel J. , Kongsted Alice , French Simon D. , Jensen Tue Secher , Doktor Klaus , Hartvigsen Jan , Hancock Mark
Published: November 2021

Background

Evidence suggests that diagnostic imaging for low back pain does not improve care in the absence of suspicion of serious pathology. However, the effect of imaging use on clinical outcomes has not been investigated in patients presenting to chiropractors. The aim of this study was to determine if diagnostic imaging affects clinical outcomes in patients with low back pain presenting for chiropractic care.

Methods

A matched observational study using prospective longitudinal observational data with one year follow up was performed in primary care chiropractic clinics in Denmark. Data was collected from November 2016 to December 2019. Participants included low back pain patients presenting for chiropractic care, who were either referred or not referred for diagnostic imaging during their initial visit. Patients were excluded if they were less than 18 years old, had a diagnosis of underlying pathology, or had previous imaging relevant to their current clinical presentation. Coarsened exact matching was used to match participants referred for diagnostic imaging with participants not referred for diagnostic imaging on baseline variables including participant demographics, pain characteristics, and clinical history. Mixed linear and logistic regression models were used to assess the effect of imaging on back pain intensity and disability at two-weeks, three-months, and one-year, and on global perceived effect and satisfaction with care at two-weeks.

Results

2162 patients were included, with 24.1% referred for imaging. Near perfect balance between matched groups was achieved for baseline variables except age and leg pain. Participants referred for imaging had slightly higher back pain intensity at two-weeks (0.4, 95%CI: 0.1, 0.8) and one-year (0.4, 95%CI: 0.0, 0.7), and disability at two-weeks (5.7, 95%CI: 1.4, 10.0), but the changes are unlikely to be clinically meaningful. No difference between groups was found for the other outcome measures. Similar results were found when sensitivity analysis, adjusted for age and leg pain intensity, was performed.

Conclusions

Diagnostic imaging did not result in better clinical outcomes in patients with low back pain presenting for chiropractic care. These results support that current guideline recommendations against routine imaging apply equally to chiropractic practice.
Rare case of skeletal third class in a subject suffering from Solitary Median Maxillary Central Incisor syndrome (SMMCI) associated to panhypopituitarism
Authors: Nota Alessandro , Ehsani Shideh , Pittari Laura , Gastaldi Giorgio , Tecco Simona
Published: November 2021

Background

The median solitary maxillary central incisor syndrome (SMMCI) is a rare malformative syndrome consisting of multiple defects, mainly found on the body midline. It can be correlated to the etiopathological and phenotypic pattern of panhypopituitarism. This case-report describes the rare case of a patient suffering from SMMCI and panhypopituitarism, showing an unusual craniofacial morphology.

Case presentation

From the cephalometric analysis, a skeletal class III was identified (despite the other cases described in literature described as skeletal class II), derived from hypomaxillia and mandibular protrusion. A convex lip profile, with tendency to mandibular hyper-divergency, airway patency, anterior and posterior cross-bite were observed. At the clinical examination, a maxillary cant was evident on the frontal plane that appeared asymmetric, with the prevalence of the third lower part of the face. There were some dysmorphic signs such as: small nose, rectilinear eyelid line and reduced interocular distance.

Conclusions

The present clinical case shows how, despite the literature, SMMCI can be associated with a III skeletal class, with maxillary hypoplasia and mandibular protrusion. The interdisciplinary collaboration between dentist and pediatrician is therefore important for the early interception of the malocclusions associated with these syndromes.
Absence of menstruation in female athletes: why they do not seek help
Authors: Verhoef Saskia J. , Wielink Merel C. , Achterberg Edwin A. , Bongers Marlies Y. , Goossens Simone M. T. A.
Published: November 2021

Background

It is known that amenorrhea is highly prevalent among female athletes. However, a large percentage of them do not seek help if this complaint occurs. We performed this study to gain more insight into the reasons why female athletes do not seek help when experiencing amenorrhea and how care for these women could be improved.

Method

Qualitative focus group research. Female athletes were approached to take part in a focus group. They were asked about the main reasons for not reporting amenorrhea and how care for amenorrhea, in their opinion, would ideally be organised. The women were asked to make a list of their top five reasons for both subjects and discuss this among their peers.

Results

According to the participants, the five main reasons for not reporting the amenorrhea were: (1) normalizing of the subject, (2) the absence of menstruation is not perceived as a problem by the athletes themselves, (3) experienced shame and taboo, (4) prioritisation of sports performance, and (5) denial. Factors to improve care around menstrual cycle problems in female athletes were: (1) informing athletes, coaches, trainers and mentors, (2) informing doctors, (3) conducting more research on long-term consequences, (4) breaking the taboo on menstrual problems, and (5) having a multidisciplinary collaboration between different specialisms.

Conclusion

By informing athletes, coaches, trainers, and mentors about menstrual cycle problems in athletes, more awareness among those groups can be created. According to the athletes, more research is needed on the long-term consequences of amenorrhea in sports, to enable them to make a better assessment of their possible future health risks. Women experience a taboo on discussing menstrual problems; role models discussing the problem may help in decreasing the taboo. A multidisciplinary collaboration of health care providers may improve care around female athletes with menstrual problems.
Improving methods to measure comparable mortality by cause (IMMCMC): gold standard verbal autopsy dataset
Authors: Hazard Riley H. , Chowdhury Hafizur Rahman , Flaxman Abraham D. , Joseph Jonathan C. , Alam Nurul , Riley Ian Douglas , Streatfield Peter Kim , Gouda Hebe , Maraga Seri , Rarau Patricia , Sanvictores Diozele , Tallo Veronica , Lucero Marilla , Lopez Alan D.
Published: November 2021

Objectives

Gold standard cause of death data is critically important to improve verbal autopsy (VA) methods in diagnosing cause of death where civil and vital registration systems are inadequate or poor. As part of a three-country research study—Improving Methods to Measure Comparable Mortality by Cause (IMMCMC) study—data were collected on clinicopathological criteria-based gold standard cause of death from hospital record reviews with matched VAs. The purpose of this data note is to make accessible a de-identified format of these gold standard VAs for interested researchers to improve the diagnostic accuracy of VA methods.

Data description

The study was conducted between 2011 and 2014 in the Philippines, Bangladesh, and Papua New Guinea. Gold standard diagnoses of underlying causes of death for deaths occurring in hospital were matched to VAs conducted using a standardized VA questionnaire developed by the Population Health Metrics Consortium. 3512 deaths were collected in total, comprised of 2491 adults (12 years and older), 320 children (28 days to 12 years), and 702 neonates (0–27 days).
Atopy in Kashmir-validation from a case control study with respect to IgE and Interleukin genes
Authors: Qurashi Taha Ashraf , Shah Aaliya , Bhat Gulzar Ahmad , Khan Mosin Saleem , Rasool Roohi , Mudassar Syed
Published: November 2021

Objectives

Increased levels of serum Immunoglobulin-E (IgE) and different genetic variants of cytokines are common biochemical manifestation in Allergy. The current study was aimed to study the association of IgE and different variants of Interleukin-4 (IL-4), and Interleukin-13 (IL-13) genes with different kind of allergies.

Methods

A pre-tested questionnaire was used to collect all the dietary, life style and clinical details by a trained staff. A blood sample of 2 ml each was collected in coagulated and anti-coagulated vials. DNA and serum samples were extracted and stored until further use. Serum IgE were estimated by ELISA while as the genotypic analysis was done by PCR–RFLP methods.

Results

Statistically a significant difference of serum IgE levels were observed among cases and controls (P < 0.05). The observed significant difference of serum IgE levels were retained among subjects who also harboured variant genotypes of IL-4 and IL-13 genes (P < 0.05). Additionally, the above genetic variants significantly modified the risk of allergy when stratification was done based on various clinical characteristics.

Conclusion

Our study suggests that increased IgE levels and in association with variant forms of IL-4 and IL-13 genes are significantly associated with different types of allergies in study population.
What do patents tell us about microalgae in agriculture?
Authors: Murata Mayara Mari , Ito Morioka Luiz Rodrigo , Da Silva Marques Josemeyre Bonifacio , Bosso Alessandra , Suguimoto Hélio Hiroshi
Published: November 2021

Microalgae have been used widely as a biological source for several industries, such as biofuel, pharmaceutical and food. Recently, the agricultural industry has also began using microalgae as an alternative source for sustainable products to replace agrochemicals. Due to the lack of scientific articles in this research area, the objective of this study was to search for applications of microalgae and to characterize its use in agriculture using the patent documents available in three patent databases, World Intellectual Property Organization (WIPO), European Patent Office (EPO) and Brazilian Institute of Industrial Property (INPI). The search was carried out using the keyword “microalgae” and applying the filter for International Patent Classification (IPC) code “A01N” which corresponds to patents related to agriculture and cultivation of microalgae. Our patent database search returned 669 documents and 132 patents were selected for the study based on their abstracts. The first patent was registered in 1982 and described the use of microalgae Chlorella extract as a plant growth promoter. After that, no patent was registered for 15 years. From 2005 to 2014, only seven patents were found. However, the scenario changed from 2015 when the number of patents increased mainly in the United States, China and Europe. The patent analysis showed several applications for microalgae in the agricultural sector, such as plant growth promotion, biofertilization, plant disease control, weed management, and post-harvest quality. This review confirmed the increasing interest in microalgae-derived products in agriculture and the value of using patent documents to assess innovative areas.
TLR2 and TLR4 in Parkinson’s disease pathogenesis: the environment takes a toll on the gut
Authors: Gorecki Anastazja M. , Anyaegbu Chidozie C. , Anderton Ryan S.
Published: November 2021

Parkinson’s disease (PD) is an incurable, devastating disorder that is characterized by pathological protein aggregation and neurodegeneration in the substantia nigra. In recent years, growing evidence has implicated the gut environment and the gut-brain axis in the pathogenesis and progression of PD, especially in a subset of people who exhibit prodromal gastrointestinal dysfunction. Specifically, perturbations of gut homeostasis are hypothesized to contribute to α-synuclein aggregation in enteric neurons, which may spread to the brain over decades and eventually result in the characteristic central nervous system manifestations of PD, including neurodegeneration and motor impairments. However, the mechanisms linking gut disturbances and α-synuclein aggregation are still unclear. A plethora of research indicates that toll-like receptors (TLRs), especially TLR2 and TLR4, are critical mediators of gut homeostasis. Alongside their established role in innate immunity throughout the body, studies are increasingly demonstrating that TLR2 and TLR4 signalling shapes the development and function of the gut and the enteric nervous system. Notably, TLR2 and TLR4 are dysregulated in patients with PD, and may thus be central to early gut dysfunction in PD. To better understand the putative contribution of intestinal TLR2 and TLR4 dysfunction to early α-synuclein aggregation and PD, we critically discuss the role of TLR2 and TLR4 in normal gut function as well as evidence for altered TLR2 and TLR4 signalling in PD, by reviewing clinical, animal model and in vitro research. Growing evidence on the immunological aetiology of α-synuclein aggregation is also discussed, with a focus on the interactions of α-synuclein with TLR2 and TLR4. We propose a conceptual model of PD pathogenesis in which microbial dysbiosis alters the permeability of the intestinal barrier as well as TLR2 and TLR4 signalling, ultimately leading to a positive feedback loop of chronic gut dysfunction promoting α-synuclein aggregation in enteric and vagal neurons. In turn, α-synuclein aggregates may then migrate to the brain via peripheral nerves, such as the vagal nerve, to contribute to neuroinflammation and neurodegeneration typically associated with PD.
Developing a COVID-19 module for the European Social Survey
Authors: Hanson Tim , Helbling Marc , Maxwell Rahsaan , Traunmüller Richard , Gemenis Kostas , Littvay Levente
Published: November 2021

This short report describes the development of a COVID-19 module for Round 10 of the European Social Survey (ESS). The module is formed of 20 items, including 10 agreed with ESS National Coordinators and 10 developed by two academic teams following an external call for content. The majority of ESS participating countries will field the module for Round 10 fieldwork in 2020–2021. This report provides the rationale for the module, presents challenges of developing such a module for ESS, and gives an overview of the question development and testing process. The two external sub-modules—Government authority and legitimacy in the age of a pandemic and COVID-19 conspiracy beliefs and government rule compliance—are also introduced.
CT perfusion for response evaluation after interventional ablation of hepatocellular carcinoma: a prospective study
Authors: Osman Mohamed Fouad , Shawali Islam H. , Metwally Lamiaa I. A. , Kamel Ahmed Hosni , Ibrahim Mohamed El Sherbiny
Published: November 2021

Background

Computed tomography (CT) perfusion was found to be useful in assessing treatment response in a variety of cancers through the evaluation in the arterial perfusion changes. We investigated the performance of CT perfusion parameters for assessment of hepatocellular carcinoma (HCC) response to radiofrequency ablation (RFA) and trans-arterial chemoembolization (TACE). We conducted a prospective diagnostic test accuracy study that recruited 70 HCC patients who were scheduled to undergo TACE or RFA. For each dynamic CT scan acquisition, four single perfusion CT image maps were generated, including functional maps of blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface (PS).

Results

In TACE-treated lesions, the BV achieved a sensitivity and specific of 100% and 83.3%, at a cutoff level of ≤ 122 ml/min/100 gm, for responders. Likewise, at a cutoff level of > 10 s, transit time had a sensitivity of 90.5% and specificity of 100%. At a cutoff level of ≤ 14 ml/min/100 gm, the PS had a sensitivity of 100% and specificity of 83.33% for responders. In RFA-treated lesions, at a cutoff level of ≤ 170 ml/min/100 gm and ≤ 11 ml/100 gm, the BF and BV had a sensitivity of 100% and specificity 100%, respectively, for responders. At a cutoff level of ≤ 11 ml/min/100 gm, PS had a sensitivity 77.27% and specificity 80%.

Conclusions

The present study confirms the feasibility of CT perfusion for assessment of response to TACE and RFA among patients with HCC.
Awareness of the risk factors of stroke among non-teaching staff of the Nnamdi Azikiwe University, Nnewi Campus, Anambra State, Nigeria
Authors: Okonkwo Uchenna Prosper , Uzuh Favour Nnenna , Nwankwo Maduaburochukwu Joseph , Okoye Emmanuel Chiebuka , Ummuna Joseph Onuwa , Igwe Emeka Sylvester , Maduagwu Stanley Monday , Ani Kenneth Umezulike , Akobundu Uzoamaka Nwakaego , Nwanne Chiamaka Ann
Published: November 2021

Background

The prevalence of stroke is increasing in Nigeria due to a lack of awareness of their predisposing factors. There is therefore a need for good knowledge and awareness of stroke risk factors in the general populations. Thus, this study assessed the level of awareness of stroke risk factors among non-teaching staff in Nnamdi Azikiwe University, Nnewi Campus, Nigeria.

Results

Most of the participants were female, 89 (69%), and had a post-graduate degree, 84 (65.1%). A total of 129 participants participated in this survey, and 91 (70.5%) were familiar with the term “stroke.” The commonest risk factors were high blood pressure (86%), stress (74.4%), and lack of exercise (63.6%). The study showed that the awareness of stroke risk factors among the participants was poor (40.3%).

Conclusion

Stroke awareness was poor among the participants with the highest risk of stroke despite their high literacy level. Female participants, with a postgraduate level qualification and working as senior non-teaching staff, had a better awareness of stroke risk factors than their male colleagues. This shows a need to increase stroke awareness campaigns in the community.
Type II Abernethy malformation in an adult male patient—a rare and reversible cause of pulmonary hypertension: a case report with review of literature
Authors: Agarwal Arjun , Bhangale Durvesh , Sawardekar Vinayak M. , Puvvada Srikar
Published: November 2021

Background

Co-occurrence of Type II Abernethy malformation (AM) with Type 1 pulmonary hypertension (PH) is extremely rare. In these patients, management of AM leads to reversal of PH.

Case presentation

We report a case of 24-year-old male that presented with fever and dyspnea of insidious-onset. Initial X-ray chest revealed pulmonary edema, prominent pulmonary knuckle, and dilated right descending pulmonary artery. Two-dimensional echocardiography suggested raised pulmonary artery systolic pressure (145 mmHg) and pulmonary angiogram revealed findings suggestive of Type 1 PH. Treatment with Tab. Tadalafil-Bosentan (20/5 mg, thrice daily) was initiated, but no major relief was obtained. On day 10, dyspnea worsened. Routine ultrasound revealed splenomegaly. Further evaluation with Doppler of the portal vein was suggestive of portal hypertension, and arterial ammonia was found to be raised. Contrast-enhanced computed tomography of abdomen and pelvis demonstrated a single dilated (1.3 cm) and torturous venous shunt between right internal iliac vein and superior mesenteric vein. Thus, a definitive diagnosis of Type II AM was reached. The patient was stabilized and subjected to the shunt closure with ASD Cocoon stent graft and recovered well.

Conclusion

Our case demonstrates a rare but reversible cause of PH. Type II AM should be included in the differential diagnosis of a patient presenting with dyspnea and provisionally diagnosed as a case of PH.
Serum interleukin-17 and estradiol levels in postmenopausal women in relation to osteoporosis
Authors: El-Mallah Reem , Saab Azza A. , Nassar Nagwa
Published: November 2021

Background

In post-menopausal women, estrogen deficiency leads to instability between bone formation and resorption which is regulated by osteoclastogenic cytokines leading to resorption. Interleukin-17 (IL-17) a proinflammatory cytokine has been found as an important regulator of osteoclast-genesis induced by estrogen deficiency in favor of bone loss in animal studies.

The study aimed to evaluate levels of IL-17 and estrogen (E2) in relation to bone mineral density (BMD) and risk of fracture in postmenopausal women with and without osteoporosis.

Results

IL-17 levels were significantly higher and E2 levels were significantly lower in the osteoporotic group compared to the non-osteoporotic group (P value ≤ 0.01). There was a highly significant difference in DEXA score and FRAX index between two groups: with higher values of FRAX and lower values of DEXA score among osteoporotic group (P value ≤ 0.01). IL-17 was inversely correlated to estrogen level and highly significant negative correlation with DEXA as well as a highly significant positive one with FRAX index. IL-17 serum level was able to diagnose osteoporosis at a cutoff level of > 80 pg/mL with 100% sensitivity, 100% specificity, 100% positive predictive value (PPV), and 100% negative predictive value (NPV).

Conclusions

Serum IL-17 was significantly elevated in osteoporotic postmenopausal women when compared to healthy postmenopausal ones and was inversely correlated with estrogen level and DEXA.
Usefulness of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography combined with the platelet-lymphocyte ratio in predicting the prognosis of nasopharyngeal carcinoma
Authors: Xian Wei jun , Feng Yan lin , Wang Ying , Yang Ming , Lu Sheng nan
Published: November 2021

Objectives:

To investigate the value of 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) combined with the platelet-lymphocyte ratio (PLR) in predicting the prognosis of nasopharyngeal carcinoma (NPC).

Methods:

This was a retrospective analysis of the data of 73 patients with NPC who underwent 18F-FDG PET/CT before treatment from January 2010 to December 2014. The maximum standard uptake value (SUVmax) of NPC and the PLR within 1 week before treatment were both measured. The Mann-Whitney U-test was used to compare the differences between the SUVmax and PLR among the different clinical characteristics of patients with NPC and the 5-year progression-free survival (PFS) rate; according to the receiver operating characteristic (ROC) curve, the best cutoff values of the SUVmax and PLR were obtained and used to group patients. The Kaplan-Meier method and Log-rank test were used to conduct univariate analysis of 5-year PFS in patients with NPC, and Cox regression was used to conduct multivariate analysis; differences in the 5-year PFS of patients with different SUVmax values combined with the PLR were compared.

Results:

The SUVmax and PLR of patients with disease progression within 5 years were higher than those of patients without disease progression (p = 0.006 and p = 0.026). SUVmax = 9.7 and PLR = 132.98 had the best prognostic diagnostic efficiency for patients. Cox multivariate analysis showed that the SUVmax and PLR are independent factors affecting the prognosis of NPC. The 5-year PFS of patients with SUVmax <9.7 was significantly higher than that of patients with SUVmax ≥9.7 in the high PLR group (PLR ≥132.98) and in the low PLR group (PLR <132.98) (59.3% vs  29.4%, p = 0.033 and 90.9% vs 42.9%, p = 0.006, respectively). For patients with SUVmax <9.7, the 5-year PFS of the high PLR group was significantly lower than the low PLR group (59.3% vs  90.9%, p = 0.016); for patients with SUVmax ≥9.7, there was no significant difference in 5-year PFS between the high PLR group and the low PLR group (29.4% vs  42.9%, p = 0.406).

Conclusions:

Both the SUVmax of the primary tumor and the PLR before treatment have an important influence on the prognosis of NPC. Combining the SUVmax and the PLR can more accurately predict the prognosis of patients with NPC.

Advances in knowledge

In this study, we evaluated the prognostic value of combining pretreatment tumor 18F-FDG uptake on PET/CT imaging and PLR in NPC patients. We found that both SUVmax and PLR are independent factors for the PFS of NPC patients, and a low SUVmax (SUVmax <9.7) combined with a low PLR (PLR <132.98) revealed significant PFS benefit.