bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating Prospective Patient-Reported Pain and Function Outcomes After Ankle and Hindfoot Arthrodesis
Authors: Mehta Manish P. , Mehta Mitesh P. , Sherman Alain E. , Mutawakkil Muhammad Y. , Bell Raheem , Patel Milap S. , Kadakia Anish R.
Published: October 2021

Background:

Hindfoot and ankle fusions are mechanically limiting procedures for patients. However, patient-reported outcomes of these procedures have not been well studied. This study assessed outcomes of hindfoot and ankle fusions by using Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) and Pain Interference (PI) Computer Adaptive Tests (CATs).

Methods:

Between 2014 and 2018, 102 patients were prospectively enrolled after presenting to a tertiary care facility for ankle and hindfoot fusions, including tibiotalar, tibiotalocalcaneal, subtalar, and triple arthrodeses. Study participants completed preoperative and 12-month postoperative PF and PI CATs. The differences between mean 12-month postoperative and preoperative PROMIS PF and PI T scores were analyzed with paired t tests. The relationship between the 12-month PF and PI differences for the overall sample and patient factors was examined using multiple regression modeling.

Results:

The sample had mean age of 57.69 years; 48% were male, and 55% were obese. Patients who underwent ankle and hindfoot arthrodesis had statistically significant improvements from preoperative to 12 months postoperative in mean PF (36.26±7.85 vs 39.38±6.46, P = .03) and PI (61.07±7.75 vs 56.62±9.81, P = .02). Triple arthrodesis saw the greatest increases in physical function (▵PF = 7.22±7.31, P = .01) and reductions in pain (▵PI = –9.17±8.31, P = .01), achieving minimal clinically important difference (MCID). Patients who underwent tibiotalar fusion had significant improvement in physical function (▵PF = 4.18±5.68, P = .04) and pain reduction that approached statistical significance (▵PI = –6.24±8.50, P = .09), achieving MCID. Older age (≥60 years ) was associated with greater improvements in PF ( β = 0.20, P = .07) and PI ( β = –0.29, P = .04). Preoperative PF and PI T scores were significantly associated with the 12-month change in PF and PI T scores, respectively ( β = –0.74, P < .01; β = –0.61, P < .01).

Conclusion:

Hindfoot and ankle fusions are procedures with favorable patient outcomes leading to increased physical function and decreased pain at 12 months postoperation relative to preoperation.

Level of Evidence:

Level II, prospective comparative study.
Six-Minute Walk Test in Individuals With Unilateral Lower Limb Amputations
Authors: Younesian Hananeh , Ouellet Raphaël , Legrand Thomas , Turcot Katia
Published: October 2021

Background:

The 6-minute walk test (6MWT) is one of the common clinical tests to assess rehabilitation progress and needs in individuals with lower-limb amputation (iLLAs). However, the analysis of this test is mostly limited to the distance parameter. The first aim was to investigate effort intensity and spatiotemporal parameters of 6MWT in iLLAs using inertial measurement units (IMUs) and heart rate (HR) monitor, and second, to assess physical, physiological, and pain-related aspects of fatigue over 6MWT.

Methods:

Eleven unilateral iLLAs (57.91±15.63 years old) participated in this study. To evaluate HR and spatiotemporal parameters over 6MWT, data were classified using 6 intervals of 1 minute each (I1-I6). The pain level of participants was estimated using the visual analog scale (VAS).

Results:

Our results showed that the means of normalized HR gradually increased over 6MWT (I1: 61.59±10.73 HRmax%, I6: 70.15±12.26 HRmax%, P = .003). Variability of HR during the first interval of 6MWT was higher than the others ( P < .05). The stance ratio of the gait cycle increased over 6MWT ( P < .05). Cadence and speed decreased over 6MWT ( P < .05). VAS score after 6MWT was significantly higher than before 6MWT ( P = .016).

Conclusion:

In this preliminary study, effort intensity over 6MWT gradually increased because of enhancement of HR. Deterioration of speed and cadence and enhancement of stance ratio over 6MWT imply potential physical aspects of fatigue and instability.

Level of Evidence:

Level III, retrospective comparative study.
Serial Intralesional Steroid Injection for Subglottic Stenosis: Systemic Side Effects and Impact on Surgery‐Free Interval
Authors: Neevel Andrew J. , Schuman Ari D. , Morrison Robert J. , Hogikyan Norman D. , Kupfer Robbi A.
Published: October 2021

Objectives

In‐office serial intralesional steroid injections (SILSIs) have become a commonly used treatment for subglottic stenosis. We characterized the impact of SILSIs on the time between operating room visits and incidence of glucocorticoid systemic side effects.

Study Design

Retrospective case series.

Setting

Academic tertiary care center.

Methods

All patients with subglottic stenosis receiving SILSIs at 1 institution from 2016 to 2020 were included. Surgery‐free interval was compared using paired t tests. Side effect incidence was calculated with Kaplan‐Meier methodology for visualization.

Results

Nineteen patients and 207 procedures were included. The majority of patients were White (95%) and female (95%) and had idiopathic subglottic stenosis (53%). Mean surgery‐free interval for all patients was 8.7 months (95% CI, 5.6‐11.8) before initiating SILSIs. Of 11 patients with calculable surgery‐free interval, 10 experienced improvement, with a mean surgery‐free interval increase of 4.6 months (95% CI, 2.4‐6.7). Seven patients have not required surgery since initiation of SILSIs, with a mean follow‐up time of 28 months (95% CI, 25‐31). Noncutaneous systemic side effects occurred at a mean 3.2 months (95% CI, 2.4‐4.0) from first injection and included Cushing’s syndrome, increased intraocular pressure, central serous chorioretinopathy, and new insulin requirement in the setting of diabetes.

Conclusions

Ninety‐one percent of patients who initiated SILSIs and had a subsequent return to the operating room experienced a mean 4.6‐month increase in surgery‐free interval. Systemic side effects of glucocorticoids occurred in 32% of patients after initiating SILSIs. This should be considered in preprocedure counseling and side effect monitoring during treatment.
Optimization Methods and Implementation Science: An Opportunity for Behavioral and Biobehavioral Interventions
Authors: Guastaferro Kate , Collins Linda M.
Published: October 2021

This editorial introduces the multiphase optimization strategy (MOST), a principled framework for the development, optimization and evaluation of multicomponent interventions, to the field of implementation science. We suggest that MOST may be integrated with implementation science to advance the field, moving closer towards the ultimate goal of disseminating effective interventions to those in need. We offer three potential ways MOST may advance implementation science: (1) development of an effective and immediately scalable intervention; (2) adaptation of interventions to local contexts; and (3) optimization of the implementation of an intervention itself. Our goal is to inspire the integration of MOST with implementation science across a number of public health contexts.
Successful allogeneic hematopoietic stem cell transplantation in patients with VEXAS syndrome: a 2-center experience
Authors: Diarra Ava , Duployez Nicolas , Fournier Elise , Preudhomme Claude , Coiteux Valérie , Magro Leonardo , Quesnel Bruno , Heiblig Maël , Sujobert Pierre , Barraco Fiorenza , Balsat Marie , Scanvion Quentin , Hachulla Eric , Launay David , Yakoub-Agha Ibrahim , Terriou, Louis
Published: October 2021

The recently described vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is caused by somatic mutations in UBA1. Patients with VEXAS syndrome display late-onset autoinflammatory symptoms, usually refractory to treatment, and hematologic abnormalities. The identification of an easily-accessible specific marker (UBA1 mutations) is of particular interest as it allows the convergence of various inflammatory and hematological symptoms in a unique clinico-biological entity and gives the opportunity to design specific treatment strategies. Here we retrospectively identified 6 patients with VEXAS syndrome who underwent allogeneic hematopoietic stem cell transplantation (ASCT). To date, no treatment guidelines have been validated. In 4 patients, ASCT was guided by life-threatening autoinflammatory symptoms that were refractory to multiple therapies. Three patients are in durable complete remission 32, 38, and 37 months after ASCT. Two others are in complete remission response after 3 and 5 months. One unfortunately died post-ASCT. This report suggests that ASCT could be a curative option in patients with VEXAS syndrome and severe manifestations. Considering the complications and side effects of the procedure as well as the existence of other potential treatment, clinical trials are needed to define the subgroup of patients who will benefit from this strategy and its place in the therapeutic arsenal against VEXAS syndrome.
Integrative genomic and transcriptomic analysis in plasmablastic lymphoma identifies disruption of key regulatory pathways
Authors: Witte Hanno M. , Künstner Axel , Hertel Nadine , Bernd Heinz-Wolfram , Bernard Veronica , Stölting Stephanie , Merz Hartmut , von Bubnoff Nikolas , Busch Hauke , Feller Alfred C. , Gebauer Niklas
Published: October 2021

Plasmablastic lymphoma (PBL) represents a clinically heterogeneous subtype of aggressive B-cell non-Hodgkin lymphoma. Targeted-sequencing studies and a single-center whole-exome sequencing (WES) study in HIV-positive patients recently revealed several genes associated with PBL pathogenesis; however, the global mutational landscape and transcriptional profile of PBL remain elusive. To inform on disease-associated mutational drivers, mutational patterns, and perturbed pathways in HIV-positive and HIV-negative PBL, we performed WES and transcriptome sequencing (RNA-sequencing) of 33 PBL tumors. Integrative analysis of somatic mutations and gene expression profiles was performed to acquire insights into the divergent genotype–phenotype correlation in Epstein-Barr virus–positive (EBV+) and EBV– PBL. We describe a significant accumulation of mutations in the JAK signal transducer and transcription activator (OSMR, STAT3, PIM1, and SOCS1), as well as receptor tyrosine-kinase RAS (ERBB3, NRAS, PDGFRB, and NTRK) pathways. We provide further evidence of frequent perturbances of NF-κB signaling (NFKB2 and BTK). Induced pathways, identified by RNA-sequencing, closely resemble the mutational profile regarding alterations accentuated in interleukin-6/JAK/STAT signaling, NF-κB activity, and MYC signaling. Moreover, class I major histocompatibility complex–mediated antigen processing and cell cycle regulation were significantly affected by EBV status. An almost exclusive upregulation of phosphatidylinositol 3-kinase/AKT/mTOR signaling in EBV+ PBL and a significantly induced expression of NTRK3 in concert with recurrent oncogenic mutations in EBV– PBL hint at a specific therapeutically targetable mechanism in PBL subgroups. Our characterization of a mutational and transcriptomic landscape in PBL, distinct from that of diffuse large B-cell lymphoma and multiple myeloma, substantiates the pathobiological independence of PBL in the spectrum of B-cell malignancies and thereby refines the taxonomy for aggressive lymphomas.
Modeling of radial variations of wood properties in naturally regenerated trees of Betula platyphylla grown in Selenge, Mongolia
Authors: Erdene-Ochir Togtokhbayar , Ishiguri Futoshi , Nezu Ikumi , Tumenjargal Bayasaa , Baasan Bayartsetseg , Chultem Ganbaatar , Ohshima Jyunichi , Yokota Shinso
Published: October 2021

Wood properties, such as annual ring width, wood fiber length, vessel element length, basic density, air-dry density, dynamic Young’s modulus, modulus of elasticity (MOE), modulus of rupture (MOR), absorbed energy in impact bending, compressive strength parallel to grain, and shearing strength, were investigated for wood from 10 naturally regenerated trees of Betula platyphylla Sukaczev in Mandal, Selenge, Mongolia. Mixed-effects models were used to evaluate the radial variations in the wood properties. The mean values of wood properties obtained in the present study were in almost the same range, with a few exceptions, as those reported by other researchers for other Betula species. The radial variations of wood properties in B. platyphylla were well-fitted to a nonlinear mixed-effects model (logarithmic formula); all examined wood properties increased from the pith and then became constant toward the bark side. The wood properties significantly differed between the core and outer wood. Basic density, air-dry density, and dynamic Young’s modulus were significantly correlated with MOE, MOR, and compressive strength. It is concluded that when the wood of B. platyphylla is utilized as raw materials for solid wood products, the differences between the core wood and outer wood should be considered. In addition, the selection of wood with higher strength properties can be achieved using the wood density and dynamic Young’s modulus as indicators.
Extracellular matrix alterations in the skin of patients affected by psoriasis
Authors: Wagner Mariana Fatima Muaccad Gama , Theodoro Thérèse Rachell , Filho Carlos D’. Apparecida Santos Machad , Oyafuso Luiza Keiko Matsuka , Pinhal Maria Aparecida Silva
Published: October 2021

Background

Psoriasis is a chronic inflammatory disease dependent upon a complex interaction between genetic predisposition and immunological factors. It is characterized by skin lesions throughout the body, causing great morbidity and affecting life quality. The present study aimed to evaluate the protein and mRNA expression of heparanase-1 (HPSE), heparanase-2 (HPSE2), syndecan-1 (SYND1), metalloproteinases (MMP2, MMP9), and tissue inhibitor metalloproteinases 2 (TIMP2) in skin samples.

Methods

From each psoriasis patient, two samples were collected, one sample from a psoriasis plaque (n = 23) and the other sample from non-affected skin (n = 23), as well as tissue collected by blepharoplasty from control individuals (n = 18). Protein expression was investigated by immunohistochemistry, followed by digital quantification. Quantitative RT-PCR obtained mRNA expression. Statistical analyses were done, and p values < 0.05 were considered significant.

Results

A significant increase in protein and mRNA expression was observed in both heparanases (HPSE and HPSE2), and higher protein levels of MMP9 and TIMP2 were observed in the psoriasis plaque compared to the non-affected skin. The data point to a probable activation of MMP2 by TIMP2. Moreover, there was a significant increase in HPSE2, SYND1, MMP9, and TIMP2 in non-affected skin samples from patients with psoriasis than in the control sample (tissue obtained by individuals who do not have psoriasis).

Conclusions

These results show a possible correlation between the characteristic inflammatory process and alterations in the expression of the extracellular matrix in psoriasis. The increased expression of HPSE2, SYND1, MMP9, and TIMP2, even in the absence of psoriatic plaque, indicates that these molecules may be involved with extracellular matrix changes in the initial alterations the psoriatic process and may be candidates for the development of target treatments.
Genome-wide association study uncovers major genetic loci associated with seed flooding tolerance in soybean
Authors: Sharmin Ripa Akter , Karikari Benjamin , Chang Fangguo , Al Amin G.M. , Bhuiyan Mashiur Rahman , Hina Aiman , Lv Wenhuan , Chunting Zhang , Begum Naheeda , Zhao Tuanjie
Published: October 2021

Background

Seed flooding stress is one of the threatening environmental stressors that adversely limits soybean at the germination stage across the globe. The knowledge on the genetic basis underlying seed-flooding tolerance is limited. Therefore, we performed a genome-wide association study (GWAS) using 34,718 single nucleotide polymorphism (SNPs) in a panel of 243 worldwide soybean collections to identify genetic loci linked to soybean seed flooding tolerance at the germination stage.

Results

In the present study, GWAS was performed with two contrasting models, Mixed Linear Model (MLM) and Multi-Locus Random-SNP-Effect Mixed Linear Model (mrMLM) to identify significant SNPs associated with electrical conductivity (EC), germination rate (GR), shoot length (ShL), and root length (RL) traits at germination stage in soybean. With MLM, a total of 20, 40, 4, and 9 SNPs associated with EC, GR, ShL and RL, respectively, whereas in the same order mrMLM detected 27, 17, 13, and 18 SNPs. Among these SNPs, two major SNPs, Gm_08_11971416, and Gm_08_46239716 were found to be consistently connected with seed-flooding tolerance related traits, namely EC and GR across two environments. We also detected two SNPs, Gm_05_1000479 and Gm_01_53535790 linked to ShL and RL, respectively. Based on Gene Ontology enrichment analysis, gene functional annotations, and protein-protein interaction network analysis, we predicted eight candidate genes and three hub genes within the regions of the four SNPs with Cis-elements in promoter regions which may be involved in seed-flooding tolerance in soybeans and these warrant further screening and functional validation.

Conclusions

Our findings demonstrate that GWAS based on high-density SNP markers is an efficient approach to dissect the genetic basis of complex traits and identify candidate genes in soybean. The trait associated SNPs could be used for genetic improvement in soybean breeding programs. The candidate genes could help researchers better understand the molecular mechanisms underlying seed-flooding stress tolerance in soybean.
Acute stroke treatment and outcome in the oldest old (90 years and older) at a tertiary care medical centre in Germany-a retrospective study showing safety and efficacy in this particular patient population
Authors: Kauffmann Jil , Grün Daniel , Yilmaz Umut , Wagenpfeil Gudrun , Faßbender Klaus , Fousse Mathias , Unger Marcus M.
Published: October 2021

Background

Stroke is among the most common causes of death and disability worldwide. Despite the relevance of stroke-related disease burden, which is constantly increasing due to the demographic change in industrialized countries with an ageing population and consecutively an increase in age-associated diseases, there is sparse evidence concerning acute stroke treatment and treatment-related outcome in the elderly patient group. This retrospective study aimed at analysing patient characteristics, therapy-related complications and functional outcome in stroke patients aged 90 years or older who underwent acute stroke treatment (i.e. intravenous thrombolysis, mechanical thrombectomy, or both).

Methods

We identified files of all inpatient stays at the Department of Neurology at Saarland University Medical Center (tertiary care level with a comprehensive stroke unit) between June 2011 and December 2018 and filtered for subjects aged 90 years or older at the time of admission. We reviewed patient files for demographic data, symptoms upon admission, (main) diagnoses, comorbidities, and administered therapies. For patients admitted due to acute stroke we reviewed files for therapy-related complications and functional outcome. We compared the modified Rankin scale (mRS) scores upon admission and at discharge for these patients.

Results

We identified 566 inpatient stays of subjects aged 90 years or older. Three hundred sixty-seven of the 566 patients (64.8%) were admitted and discharged due to symptoms indicative of stroke. Two hundred eleven patients received a diagnosis of ischaemic stroke. These 211 patients were analysed subsequently. Sixty-four patients qualified for acute stroke treatment (intravenous thrombolysis n = 22, mechanical thrombectomy n = 26, intravenous thrombolysis followed by mechanical thrombectomy n = 16) and showed a significant improvement in their functional status as measured by change in mRS score (admission vs. discharge, p 0.001) with 7 (10.9%) observed potentially therapy-related complications (relevant drop in haemoglobin n = 2, subarachnoidal haemorrhage n = 1, cerebral haemorrhage n = 3, extracranial bleeding n = 1). One intravenous thrombolysis was stopped because of an uncontrollable hypertensive crisis. Patients who did not qualify for these treatments (including those declining acute treatment) did not show a change of their functional status between admission and discharge (p 0.064).

Conclusion

Our data indicate that acute stroke treatment is effective and safe in the oldest old. Age alone is no criterion to withhold an acute intervention even in oldest old stroke patients.
Comparison of clinical manifestation of dengue fever in Bangladesh: an observation over a decade
Authors: Hasan Mohammad Jahid , Tabassum Tamanna , Sharif Mohiuddin , Khan Md. Abdullah Saeed , Bipasha Akhi Roy , Basher Ariful , Islam Mohammad Rafiqul , Amin Mohammad Robed
Published: October 2021

Background

The clinical presentation of dengue fever had been observed to change with time since its first outbreak in 2000 in Bangladesh. This report showed the clinical presentation of the 2019 outbreak in Bangladesh along with its comparison to previous outbreaks witnessed in this region.

Methods

This hospital-based cross-sectional study was conducted in one of the largest tertiary care hospitals in Dhaka city. A total of 553 laboratory-confirmed and 194 probable dengue cases were interviewed. The clinical manifestation of the confirmed cases of the current outbreak was compared with three of the outbreak reports retrieved from the databases. R version 3.6.3 was used for data analysis.

Results

Among the confirmed cases, two-thirds were male (63.2%) and the average age was 27(± 11) years. Positive tests for NS1 and IgM were present in 99.6% (n = 525/527) and 82.6% (n = 38/46) of the cases, respectively. Thrombocytopenia was present in 66.1% of cases. Fever (100%) was common for all. Gastrointestinal (GIT) features, including abdominal pain (86.5%), anorexia and/or vomiting (69.6%), and Diarrhea (> 3 motions/day) (26.2%) were more frequent than typical rash and other pain symptoms. Hypotension was present in approximately a quarter of patients (25%). GIT features (anorexia, nausea, and/or vomiting) and hypotension were more common among adult participants while bleeding manifestation (melena and vaginal bleeding, p = 0.009 & 0.032) was more frequent in pediatric patients. Compared to outbreaks of 2008, 2016, and 2018, increasing trends in GIT symptoms e.g. anorexia, abdominal pain, and diarrhea were observed. While a negative trend in hemorrhagic manifestations (skin rash, melena, and conjunctival hemorrhage/hemorrhagic sclera) and arthralgia/joint pain were found.

Conclusion

The present outbreak was noticeably characterized by GIT symptoms and hypotension in addition to the typical clinical features like rash and pain symptoms. An increasing trend in GIT features and decreasing trend in hemorrhagic manifestations was noted over the last decade of dengue outbreaks.
Preventive HIPEC in combination with perioperative FLOT versus FLOT alone for resectable diffuse type gastric and gastroesophageal junction type II/III adenocarcinoma – the phase III “PREVENT”- (FLOT9) trial of the AIO /CAOGI /ACO
Authors: Götze Thorsten O. , Piso Pompiliu , Lorenzen Sylvie , Bankstahl Ulli S. , Pauligk Claudia , Elshafei Moustafa , Amato Giuseppe , Reim Daniel , Bechstein Wolf O. , Königsrainer Alfred , Mönig Stefan P. , Rau Beate , Schwarzbach Matthias , Al-Batran Salah-Eddin
Published: October 2021

Background

The main reason for treatment failure after curative surgical resection of gastric cancer is intra-abdominal spread, with 40–50% peritoneal seeding as primary localization of recurrence. Peritoneal relapse is seen in 60–70% of tumors of diffuse type, compared to only 20–30% of intestinal type.

Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) is an increasingly used therapy method for patients with peritoneal metastases. The preventive use of HIPEC could represent an elegant approach for patients (pts) before macroscopic peritoneal seeding, since pts. with operable disease are fit and may have potential risk of microscopic involvement, thus having a theoretical chance of cure with HIPEC even without the need for cytoreduction.

No results from a PCRT from the Western hemisphere have yet been published.

Methods

This is a multicenter, randomized, controlled, open-label study including a total of 200 pts. with localized and locally advanced diffuse or mixed type (Laurens’s classification) adenocarcinoma of the stomach and Type II/III GEJ.

All enrolled pts. will have received 3–6 pre-operative cycles of biweekly FLOT (Docetaxel 50 mg/m2; Oxaliplatin 85 mg/m2; Leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2wk).

Pts will be randomized 1:1 to receive surgery only and postoperative FLOT (control arm) or surgery + intraoperative HIPEC (cisplatin 75 mg/m2 solution administered at a temperature of 42 °C for 90 min) and postoperative FLOT (experimental arm). Surgery is carried out as gastrectomy or transhiatal extended gastrectomy. Primary endpoint is PFS/DFS, major secondary endpoints are OS, rate of pts. with peritoneal relapse at 2 and 3 years, perioperative morbidity/mortality and quality of life.

The trial starts with a safety run-in phase. After 20 pts. had curatively intended resection in Arm B, an interim safety analysis is performed.

Recruitment has already started and first patient in was on January 18th, 2021.

Discussion

If the PREVENT concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, pts. with gastric cancer and no peritoneal involvement will not be treated with HIPEC during surgery.

Trial registration

The study is registered on June 25th, 2020 under ClinicalTrials.gov Identifier: NCT04447352; EudraCT: 2017-003832-35.
Survival improvement and prognosis for hepatocellular carcinoma: analysis of the SEER database
Authors: Ding Jingli , Wen Zhili
Published: October 2021

Background

Hepatocellular carcinoma (HCC) incidences have been increasing in the United States. This study aimed to examine temporal trend of HCC survival and determine prognostic factors influencing HCC survival within the U.S. population.

Methods

The Surveillance Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with primary HCC from 1988 to 2015. Overall survival (OS) and disease-specific survival (DSS) were calculated by the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for prognostic factors and comparing survival between patients diagnosed at different periods (per 5-year interval).

Results

A total of 80,347 patients were included. The proportions of both young patients (< 45 years) and old patients (≥75 years) decreased over time (P < 0.001) and the male-to-female ratio increased over time (P < 0.001). Significant decreasing temporal trends were observed for HCC severity at diagnosis, including SEER stage, tumor size, tumor extent, and lymph node involvement (P < 0.001 for all). OS and DSS of patients with HCC improved over time (P < 0.001). After adjusting for patient and tumor characteristics and treatment difference, period of diagnosis retained an independent factor for improved DSS and its prognostic significance was evident for localized and regional HCC (P < 0.001), but not for distant HCC. On multivariate analyses, young age, female gender, Hispanic ethnicity, and married status were predictors favoring DSS, whereas a worse DSS was observed for patients with tumor > 5 cm, with vascular invasion, and with lymph node involvement. Patients treated with liver-directed therapy (HR = 0.54, 95% CI: 0.35–0.56), hepatic resection (HR = 0.35, 95% CI: 0.33–0.37), and transplantation (HR = 0.14, 95% CI: 0.13–0.15) had significantly longer DSS compared with those who received no surgery. In stratified analyses, the beneficial effects of surgical approach, regardless therapy type, were significant across all stages.

Conclusions

Our results indicate a significant improvement in survival for HCC patients from 1988 to 2015, which may be attributable to advances in early diagnosis and therapeutic approaches.
Clinical spectrum and predictors of severity of dengue among children in 2019 outbreak: a multicenter hospital-based study in Bangladesh
Authors: Khan Md. Abdullah Saeed , Al Mosabbir Abdullah , Raheem Enayetur , Ahmed Ahsan , Rouf Rashawan Raziur , Hasan Mahmudul , Alam Fawzia Bente , Hannan Nahida , Yesmin Sabrina , Amin Robed , Ahsan Nazmul , Anwar Sayeeda , Afroza Syeda , Hossain Mohammad Sorowar
Published: October 2021

Background

The mosquito-borne arboviral disease dengue has become a global public health concern. However, very few studies have reported atypical clinical features of dengue among children. Because an understanding of various spectrums of presentation of dengue is necessary for timely diagnosis and management, we aimed to document the typical and atypical clinical features along with predictors of severity among children with dengue during the largest outbreak in Bangladesh in 2019.

Methods

We conducted a cross-sectional study between August 15 and September 30, 2019. in eight tertiary level hospitals in Dhaka city. Children (aged < 15 years) with serologically confirmed dengue were conveniently selected for data collection through a structured questionnaire. Descriptive, inferential statistics, and multivariable logistic regression were used to analyze data.

Results

Among the 190 children (mean age 8.8 years, and male-female ratio 1.22:1) included in the analysis, respectively 71.1 and 28.9% children had non-severe and severe dengue. All children had fever with an average temperature of 103.3 ± 1.2 F (SD). Gastrointestinal symptoms were the most common associated feature, including mostly vomiting (80.4%), decreased appetite (79.5%), constipation (72.7%), and abdominal pain (64.9%). Mouth sore, a less reported feature besides constipation, was present in 28.3% of children. Atypical clinical features were mostly neurological, with confusion (21.3%) being the predominant symptom. Frequent laboratory abnormalities were thrombocytopenia (87.2%), leucopenia (40.4%), and increased hematocrit (13.4%). Age (AOR 0.86, 95%CI 0.75–0.98,p = 0.023), mouth sore (AOR 2.69, 95%CI 1.06–6.96,p = 0.038) and a decreased platelet count (< 50,000/mm3) with increased hematocrit (> 20%) (AOR 4.94, 95%CI 1.48–17.31,p = 0.01) were significant predictors of severity.

Conclusions

Dengue in children was characterized by a high severity, predominance of gastrointestinal symptoms, and atypical neurological presentations. Younger age, mouth sores, and a decreased platelet with increased hematocrit were significant predictors of severity. Our findings would contribute to the clinical management of dengue in children.
Evolution of a refractory prolactin-secreting pituitary adenoma into a pituitary carcinoma: report of a challenging case and literature review
Authors: Dai Congxin , Sun Bowen , Guan Shusen , Wang Wei , Liu Honggang , Li Yong , Zhang Jialiang , Kang Jun
Published: October 2021

Background

Pituitary carcinomas (PCs), defined as distant metastases of pituitary neoplasms, are very rare malignancies. Because the clinical presentation of PCs is variable, early diagnosis and management remain challenging. PCs are always refractory to comprehensive treatments, and patients with PCs have extremely poor prognoses.

Case presentation

We describe one case of a prolactin-secreting pituitary adenoma (PA) refractory to conventional therapy that evolved into a PC with intraspinal metastasis. A 34-year-old female was diagnosed with an invasive prolactin-secreting PA in 2009 and was unresponsive to medical treatment with bromocriptine. The tumor was gross totally removed via transsphenoidal surgery (TSS). However, the patient experienced multiple tumor recurrences or regrowth despite comprehensive treatments, including medical therapy, two gamma knife radiosurgeries (GKSs), and four frontal craniotomies. In 2016, she was found to have an intradural extramedullary mass at the level of the fourth lumbar vertebra. The intraspinal lesion was completely resected and was confirmed as a metastatic PC based on histomorphology and immunohistochemical staining. The literature on the diagnosis, molecular pathogenesis, treatment, and prognosis of patients with prolactin-secreting PCs was reviewed.

Conclusion

PCs are very rare neoplasms with variable clinical features and poor prognosis. Most PCs usually arise from aggressive PAs refractory to conventional therapy. There is no reliable marker to identify aggressive PAs with a risk for progression to PCs; thus, it is difficult to diagnose these PCs early until the presence of metastatic lesions. It is still very challenging to manage patients with PCs due to a lack of standardized protocols for diagnosis and treatment. Establishing molecular biomarkers and the pathobiology of PCs could help in the early identification of aggressive PAs most likely to evolve into PCs.
A study of correlations between metabolic syndrome factors and osteosarcopenic adiposity
Authors: Su Yu-Hsiang , Chang Yu-Ming , Kung Chih-Ying , Sung Chiu-Kuei , Foo Wei-Shin , Wu Mei-Hua , Chiou Shang-Jyh
Published: October 2021

Background

Aging reduces the quality and strength of bones and muscles and increases body fat, which can lead to the simultaneous occurrence of sarcopenia, osteopenia, and adiposity, a condition referred to as OsteoSarcopenic Adiposity (OSA).

While previous studies have demonstrated that metabolic syndrome is associated with sarcopenia, osteopenia, and adiposity, the relationship between metabolic syndrome and OSA remains largely unknown.

Methods

We analyzed data for a sample of middle-aged individuals from a Health Management Center database, which was collected in 2016–2018. There are 2991 cases of people over 50 years from a physical examination center in a hospital in Taiwan during 2016–2018. In addition to descriptive statistics, chi-squared test, analysis of variance, and multinomial logistic regression analysis were conducted to examine OSA risk and associated factors.

Results

Based on multinomial logistic regression analysis, in different OSA severity level (1–3 more serious), those who are with metabolic syndrome has increased the 2.49–2.57 times risk of OSA (p < 0.001) in OSA = 2 and 3 groups while there is no significant difference in OSA =1 group.

Conclusion

The prevalence of OSA may impair the health and quality of life in the elderly group, especially those diagnosed with metabolic syndrome, increasing the risk of OSA. These results can help promote early diagnosis and treatment of OSA in clinical settings, particularly among aging individuals with abnormal physical function, the group with the highest OSA incidence.
Chemical profiles of the active fraction from Prinsepia utilis Royle leaves and its anti-benign prostatic hyperplasia evaluation in animal models
Authors: Peng Ying , Peng Chongsheng , Wu Yang , Sun Chongzhi , Li Xiaobo
Published: October 2021

Background

The Prinsepia utilis Royle leaves (P. utilis) is a folk herb used for benign prostatic hyperplasia (BPH) control by ethnic minorities for centuries in China with rich in resources. Our previous studies have confirmed the anti-BPH effect of its water extract (QCJ) and the active fraction (Fr. B) separated from the QCJ by animal test. The Fr. B from P. utilis should be a potential candidate for BPH control.

Methods

In this study, the chemical ingredients of Fr. B were identified by UPLC-QTOF-MS, and quantified by HPLC. Murine animal models were divided into 8 groups, Sham rats, BPH rats, BPH rats administered with finasteride (1 mg/kg), BPH rats administered with Pule’an (460 mg/kg), BPH rats administered with low, high dosage of QCJ (860 mg/kg, 2580 mg/kg respectively), BPH rats administered with low, high dosage of Fr. B (160 mg/kg, 480 mg/kg respectively). The expression of vascular endothelial growth factor (VEGF) in the prostate tissue of rats was tested, and serum levels of dihydrotestosterone (DHT), testosterone (T), estradiol (E2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA) in prostate homogenate were measured. One-way ANOVA followed by LSD was used for statistical analysis.

Results

The BPH rats treated by Fr. B exhibited significant reductions of VEGF and MDA levels, as well as significant increases of SOD, GSH-Px and CAT in the prostate tissue after 28 day administration (P < 0.05). Moreover, Fr. B significantly reduced DHT, DHT/E2 ratio, TNF-α, while increased T levels in serum of BPH rats (P < 0.05). UPLC-QTOF-MS analysis revealed 10 flavonoids as the key constituents of this fraction, which accounted for 54.96% of all substance of Fr. B. The relative contents of compound 1, 2 are 11.1%, 13% in Fr. B respectively.

Conclusions

These results indicated that the Fr. B obtained from P. utilis alleviated the symptoms of BPH rats through multiple mechanisms including reduction of DHT/E2 ratio, inhibition of growth factor, anti-inflammation and anti-oxidation, in which flavonoids might be the key constituents. It supported the hypothesis that the Fr. B should be further explored as a candidate for BPH patients.
Students with global experiences during medical school are more likely to work in settings that focus on the underserved: an observational study from a public U.S. institution
Authors: Slifko Shay E. , Vielot Nadja A. , Becker-Dreps Sylvia , Pathman Donald E. , Myers Justin G. , Carlough Martha
Published: October 2021

Background

Global health interest has grown among medical students over the past 20 years, and most medical schools offer global health opportunities. Studies suggest that completing global health electives during medical school may increase the likelihood of working with underserved populations in a clinical or research capacity. This study aimed to assess the association of global electives in medical school on subsequently working in global health and with underserved populations in the United States (U.S.), additionally considering students’ interests and experiences prior to medical school. We also examined whether respondents perceived benefits gained from global electives.

Methods

We surveyed medical school graduates (classes of 2011-2015) from a large public medical school in the U.S. to describe current practice settings and previous global health experience. We evaluated work, volunteer, and educational experiences preceding medical school, socioeconomic status, race and ethnicity using American Medical College Application Service (AMCAS) data. We assessed the association between students’ backgrounds, completing global health electives in medical school and current work in global health or with underserved populations in the U.S.

Results

In the 5 to 8 years post-graduation, 78% of 161 respondents reported work, research, or teaching with a focus on global or underserved U.S. populations. Completing a global health elective during medical school (p = 0.0002) or during residency (p = 0.06) were positively associated with currently working with underserved populations in the U.S. and pre-medical school experiences were marginally associated (p = 0.1). Adjusting for pre-medical school experiences, completing a global health elective during medical school was associated with a 22% greater prevalence of working with an underserved population. Perceived benefits from global electives included improved cultural awareness, language skills, public health and research skills, and ability to practice in technology-limited settings.

Conclusion

Medical school graduates who participated in global electives as students were more likely than their peers to pursue careers with underserved populations, independent of experiences prior to medical school. We hypothesize that by offering global health experiences, medical schools can enhance the interests and skills of graduates that will make them more likely and better prepared to work with underserved populations in the U.S. and abroad.
Neutrophil-mediated clinical nanodrug for treatment of residual tumor after focused ultrasound ablation
Authors: Shen Jian , Hao Junnian , Chen Yini , Liu Hairong , Wu Jianrong , Hu Bing , Wang Yan , Zheng Yuanyi , Cai Xiaojun
Published: October 2021

Background

The risk of local recurrence after high-intensity focused ultrasound (HIFU) is relatively high, resulting in poor prognosis of malignant tumors. The combination of HIFU with traditional chemotherapy continues to have an unsatisfactory outcome because of off-site drug uptake.

Results

Herein, we propose a strategy of inflammation-tendency neutrophil-mediated clinical nanodrug targeted therapy for residual tumors after HIFU ablation. We selected neutrophils as carriers and PEGylated liposome doxorubicin (PLD) as a model chemotherapeutic nanodrug to form an innovative cell therapy drug (PLD@NEs). The produced PLD@NEs had a loading capacity of approximately 5 µg of PLD per 106cells and maintained the natural characteristics of neutrophils. The targeting performance and therapeutic potential of PLD@NEs were evaluated using Hepa1-6 cells and a corresponding tumor-bearing mouse model. After HIFU ablation, PLD@NEs were recruited to the tumor site by inflammation (most in 4 h) and released PLD with inflammatory stimuli, leading to targeted and localized postoperative chemotherapy.

Conclusions

This effective integrated method fully leverages the advantages of HIFU, chemotherapy and neutrophils to attract more focus on the practice of improving existing clinical therapies.

Graphical Abstract
How could nanobiotechnology improve treatment outcomes of anti-TNF-α therapy in inflammatory bowel disease? Current knowledge, future directions
Authors: Eder Piotr , Zielińska Aleksandra , Karczewski Jacek , Dobrowolska Agnieszka , Słomski Ryszard , Souto Eliana B.
Published: October 2021

Despite significant advances in therapeutic possibilities for the treatment of inflammatory bowel disease (IBD) in recent years, there is still a big room for improvement. In particular, biological treatment can induce not only clinical remission but also mucosal healing of the gastrointestinal tract. Among these therapeutic molecules, anti-tumor necrosis factor-alpha (anti-TNF-α) antibodies were the first to revolutionize treatment algorithms in IBD. However, due to the parenteral route of administration and systemic mode of action, TNF-α blockers are characterised by high rates of immunogenicity-related loss of response and serious adverse events. Moreover, intravenous or subcutaneous therapy is not considered patient-friendly and requires occasional, direct contact with healthcare centres. To overcome these limitations, several attempts have been made to design oral pharmaceutical formulations of these molecules. It is hypothesized that oral anti-TNF-α antibodies therapy can directly provide a targeted and potent anti-inflammatory effect in the inflamed gastrointestinal tissues without significant systemic exposure, improving long-term treatment outcomes and safety. In this review, we discuss the current knowledge and future perspectives regarding different approaches made towards entering a new era of oral anti-TNF-α therapy, namely, the tailoring of biocompatible nanoparticles with anti-TNF-α antibodies for site-specific targeting to IBD. In particular, we discuss the latest concepts applying the achievements of nanotechnology-based drug design in this area.

Graphical Abstract
Platelet-derived sCD40L: specific inflammatory marker for early-stage severe acute respiratory syndrome coronavirus 2 infection
Authors: Hamzeh-Cognasse Hind , Mansour Alexandre , Reizine Florian , Mismetti Patrick , Gouin-Thibault Isabelle , Cognasse Fabrice
Published: October 2021

Background

The SARS-CoV-2 virus is the causing agent of the Coronavirus disease 2019 (COVID-19) characterized by a huge pro-inflammatory response and coagulation disorders that may lead to for its severe forms, in organ failure or even death. As major players of thrombo-inflammation, platelets release large amounts of immunomodulatory molecules and regulate leukocyte and endothelial activity, which are both altered in COVID-19. Altogether, this makes platelets a very likely actor of the thrombo-inflammatory complications of COVID-19. Thus, we propose to identify a platelet inflammatory signature of severe COVID-19 specifically modulated throughout the course of the disease.

Methods

Luminex technology and enzyme-linked immunosorbent assay were used to assess plasma levels of platelet inflammatory markers in patients with severe acute respiratory syndrome coronavirus 2 infection on admission and for 14 days afterwards.

Results

In accordance with the observations of other teams, we evidence that the plasma levels of the platelet soluble (s)CD40L is significantly elevated in the early stages of the disease. Interestingly we observe that the plasma level of sCD40L decreases overtime while that of sCD62P increases significantly.

Conclusions

Our data suggest that there is a platelet signature of inflammatory response to SARS-COv-2 infection which varies overtime and could serve as monitoring biomarkers of patient inflammatory state.

Clinical trial registration number: 2020-A01100-39; title: Human Ab Response & immunoMONItoring of COVID-19 Patients, registration date: 05/25/2020; URL of the registry:https://clinicaltrials.gov/ct2/history/NCT04373200?V_5=View.
Epidemiologic and clinical characteristics of human bocavirus infection in infants and young children suffering with community acquired pneumonia in Ningxia, China
Authors: Ji Kai , Sun Jinhan , Yan Yan , Han Lei , Guo Jianhui , Ma Anwen , Hao Xueqi , Li Fang , Sun Yuning
Published: October 2021

Background

Pneumonia has a high incidence rate and is a major cause of mortality in children, mostly community-acquired pneumonia (CAP). Human bocavirus (HBoV), since it first identified in 2005, has been repeatedly associated with respiratory tract infections. Nevertheless, the role and related information of HBoV as a pathogen of CAP has not been fulfilled. Here our study is to assess the epidemiological and clinical features in HBoV-positive children with CAP.

Methods

A total of 878 secretions of lower respiratory samples were obtained, multiplex PCR was used to detect HBoV and other respiratory viruses.

Results

Of all cases, HBoV was detected in 10.0%, with a peak incidence of infection among children < 2 year old, and predominantly noted in autumn and winter. Only 8 patients were HBoV single infection. Co-infection with other respiratory viruses was observed in 86.4%. Moreover, co-infection with bacteria occurred in 27.3% and with Mycoplasma pneumoniae (MP) in 33.0% of HBoV-positive patients. Among all HBoV-positive samples co-infected with bacteria, 87.5% are gram negative bacteria. Compared with HBoV-negative group, age (P = 0.048), wheezing (P = 0.015), tachypnea (P = 0.016), lactate dehydrogenase (P = 0.026) and severe pneumonia (P = 0.023) were statistically significant in HBoV-positive patients. Furthermore, HBoV-positive patients less than 1 year old were more likely to have co-infection with bacteria (P = 0.007).

Conclusions

HBoV can be detected alone in respiratory samples of children with CAP, maybe it is one of the causes of CAP in infants. The high incidence of severe pneumonia was found in HBoV-positive patients compared with HBoV-negative cases may indicate a relationship between severe pneumonia and HBoV.