bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for anemia in patients with chronic kidney disease
Authors: Yin Ping , Wu Quan , Shou Lihong , Dong Xiaohui
Published: October 2021

Background:

Anemia in patients with chronic kidney disease (CKD) presents significant impacts on patients, the health-care system, and financial resources. Therefore, this study aimed to identify the risk factors of anemia among CKD patients.

Methods:

This meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement guidelines. Studies were identified through systematic searches in September 2021 with no restrictions on date and time, and publication status using the following bibliographic databases: Embase, Medline, PubMed, Web of Science, Science Direct, and the Cochrane Library. The search was conducted using the following terms and phrases: “anemia”, “risk factors”, “associated factors”, “chronic kidney injury”, “chronic kidney disease”, and “chronic renal insufficiency”. The quality of each included study was assessed according to the Newcastle-Ottawa scale. Meta-analysis was performed using STATATM version 14 statistical software for WindowsTM.

Results:

The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.

Conclusion:

This meta-analysis may help policymakers and program managers design evidence-based interventions on preventing the occurrence of anemia with CKD patient populations.
Efficacy of intravitreal dexamethasone implant in patients with Vogt–Koyanagi–Harada Disease and bilateral panuveitis
Authors: Chen Po-Lin , Chen San-Ni
Published: October 2021

Introduction:

Vogt–Koyanagi–Harada (VKH) disease is a multisystemic disorder characterized by intraocular inflammation associated with serous retinal detachment, optic disc edema, uveitis, and vitritis, and is often associated with neurologic and cutaneous manifestations. Diagnosis can be assisted by fluorescein angiography and optical coherence tomography that can help evaluate changes in the retina. Therapy relies mainly on the use of corticosteroids, administrated through oral or intravenous high-dose pulses, and immunosuppressants. The purpose of our study was to assess the outcome of VKH disease with bilateral panuveitis treated with dexamethasone intravitreal implant.

Patient concerns:

Two patients without underlying disease had severe vision deterioration, eye pain, following flu-like symptoms.

Diagnosis:

At initial diagnosis, macular edema and sub-retinal fluid lobulated accumulation were noted under SD-OCT exam. FAG revealed multiple pinpoint leakage around macula and pooling of dye within sub-retinal space.

Interventions:

All two patients received intravenous pulse methylprednisolone at the diagnosis, followed by oral prednisolone and cyclosporine. One patient received bilateral eye dexamethasone intravitreal implant two weeks after diagnosis, while the other received left eye dexamethasone intravitreal implant at the time of diagnosis.

Outcomes:

Vision and macular structure recovered more rapidly after receiving dexamethasone implants in the short-term follow-up. All macular structures recovered to normal, and vision recovered to 20/20 in both eyes. One patient, receiving bilateral dexamethasone implant, didn’t relapse during the 13-month follow-up; the other, receiving left eye dexamethasone implant, didn’t relapse during the 6-month follow-up. None of them required intravenous high-dose steroids again.

Conclusion:

VKH disease is a multisystemic disorder; intravenous pulse steroid therapy and oral prednisolone can control systemic inflammation. In addition to systemic prednisolone treatment of VKH disease in the acute phase, dexamethasone implants can enhance short-term and long-term control of intraocular anti-inflammation.
Efficacy of integrated traditional Chinese medicine and Western medicine in the treatment of poststroke insomnia
Authors: Li Wenwen , Liu Cuncheng , Wang Ruiqi , Liu Ruxue , Peng Min , Si Guomin
Published: October 2021

Background:

Western medicine has played an essential role in treating poststroke insomnia (PSI) in China, and traditional Chinese medicine therapy based on Chinese characteristics is also effective. Combined with China's national conditions, we plan to conduct this systematic review and meta-analysis to compare the efficacy of integrated traditional Chinese medicine and Western medicine (INTEGRATED TCM and WM) therapy and Western medicine alone for PSI.

Methods:

We will search the following 5 electronic databases: PubMed, Wanfang, Chinese biomedical literature database, the Chongqing VIP Chinese Science and Technology Periodical, and China national knowledge infrastructure. Randomized controlled trials that compared the efficacy of INTEGRATED TCM and WM with Western medicine alone in the treatment of PSI will be considered. Primary outcomes have Treatment effectiveness rate, and Pittsburgh sleep quality index. Secondary outcomes include traditional Chinese medicine syndrome score, Athens insomnia scale, the incidence of adverse reactions, and outcome follow-up. Based on the eligibility criteria, we will conduct literature screening and data extraction. The quality of the included literature will be evaluated using the Cochrane risk of bias tools. We will use Review Manager software (Version 5.3) for data synthesis and statistical analyses. If sources of heterogeneity exist, we will perform a subgroup analysis or sensitivity analysis. A funnel plot will be used to analyze publication bias.

Results:

This study will provide evidence-based medicine evidence for treatment of PSI with INTEGRATED TCM and WM in terms of its efficacy.

Conclusion:

This systematic review aims to provide new options for INTEGRATED TCM and WM treatment of PSI in terms of its efficacy.
Liquid combination of hyaluronan, glucosamine, and chondroitin as a dietary supplement for knee osteoarthritis patients with moderate knee pain
Authors: Wang Shyu-Jye , Wang Ya-Hui , Huang Liang-Chen
Published: October 2021

Background:

Hyaluronan (HA), glucosamine, and chondroitin sulfate are widely consumed as dietary supplements for the treatment of knee osteoarthritis (OA). This study aimed to explore the efficacy and safety of a dietary liquid supplement mixture containing HA, glucosamine, and chondroitin in patients with knee OA who had moderate knee pain (visual analogue scale of 4–6 points).

Methods:

This was a short-term, randomized, double-blind, placebo-controlled study. Subjects were allocated to administer either a bottle of 20 mL supplement mixture (50 mg HA plus 750 mg glucosamine plus 250 mg chondroitin, namely A + HA) or placebo once daily for 8 weeks. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, 36-item Short Form Survey (SF-36), Chinese version of Pittsburgh Sleep Quality Index, and incidence of adverse event were evaluated at the end of week 8. Efficacy analyses were conducted in the modified intent-to-treat population.

Results:

Of the 80 subjects in the modified intent-to-treat population, 39 received A + HA while 41 received placebo. After 8 weeks of treatment, the A + HA group failed to demonstrate a significant symptomatic efficacy and quality of life improvement in terms of Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, SF-36, and Chinese version of Pittsburgh Sleep Quality Index as compared to the placebo group. However, the mean changes in most of the SF-36 scale scores were numerically higher in the A + HA group than in the placebo group. No treatment-related adverse event was reported in both groups.

Conclusions:

This present study found that the combination of liquid low molecular weight HA, glucosamine, and chondroitin oral supplement did not effectively improve knee OA pain and symptoms after short-term use in knee OA patients with moderate knee pain. However, these results should be interpreted with caution due to the intrinsic limitation of the study design.
Derivation and external validation of a simple risk score to predict in-hospital mortality in patients hospitalized for COVID-19
Authors: Mann Charlotte Z. , Abshire Chelsea , Yost Monica , Kaatz Scott , Swaminathan Lakshmi , Flanders Scott A. , Prescott Hallie C. , Gagnon-Bartsch Johann A.
Published: October 2021

As severe acute respiratory syndrome coronavirus 2 continues to spread, easy-to-use risk models that predict hospital mortality can assist in clinical decision making and triage. We aimed to develop a risk score model for in-hospital mortality in patients hospitalized with 2019 novel coronavirus (COVID-19) that was robust across hospitals and used clinical factors that are readily available and measured standardly across hospitals.

In this retrospective observational study, we developed a risk score model using data collected by trained abstractors for patients in 20 diverse hospitals across the state of Michigan (Mi-COVID19) who were discharged between March 5, 2020 and August 14, 2020. Patients who tested positive for severe acute respiratory syndrome coronavirus 2 during hospitalization or were discharged with an ICD-10 code for COVID-19 (U07.1) were included. We employed an iterative forward selection approach to consider the inclusion of 145 potential risk factors available at hospital presentation. Model performance was externally validated with patients from 19 hospitals in the Mi-COVID19 registry not used in model development. We shared the model in an easy-to-use online application that allows the user to predict in-hospital mortality risk for a patient if they have any subset of the variables in the final model.

Two thousand one hundred and ninety-three patients in the Mi-COVID19 registry met our inclusion criteria. The derivation and validation sets ultimately included 1690 and 398 patients, respectively, with mortality rates of 19.6% and 18.6%, respectively. The average age of participants in the study after exclusions was 64 years old, and the participants were 48% female, 49% Black, and 87% non-Hispanic. Our final model includes the patient's age, first recorded respiratory rate, first recorded pulse oximetry, highest creatinine level on day of presentation, and hospital's COVID-19 mortality rate. No other factors showed sufficient incremental model improvement to warrant inclusion. The area under the receiver operating characteristics curve for the derivation and validation sets were .796 (95% confidence interval, .767–.826) and .829 (95% confidence interval, .782–.876) respectively.

We conclude that the risk of in-hospital mortality in COVID-19 patients can be reliably estimated using a few factors, which are standardly measured and available to physicians very early in a hospital encounter.
Prevalence, risk factors, and short-term outcomes of postparacentesis acute kidney injury using revised criteria of the international club of ascites
Authors: Shin Ye Ji , Heo Chan Mi , Kim Kwang Min , Shim Sang Goon , Sinn Dong Hyun
Published: October 2021

Acute kidney injury (AKI) can become complicated after paracentesis due to extrarenal fluid loss and inadequate blood flow to the kidneys. The objective of this study was to explore the incidence and clinical implications of postparacentesis AKI.

A retrospective cohort of 137 liver cirrhosis patients (mean age: 61.3 ± 11.8 years, male: 100 [73.0%], viral hepatitis: 93 [67.9%]) who underwent paracentesis was analyzed. The incidence of AKI as defined by the international club of ascites (ICA) criteria, the risk factors, and its impact on early mortality were all assessed.

Thirty two patients (23.4%) developed AKI after paracentesis. In multivariate analysis, the Model for end-stage liver disease (MELD)-Na score was an independent factor associated with AKI development (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.07–1.23) after paracentesis. The incidence of early mortality was significantly higher for those with AKI than without AKI (71.9% [23/32 patients] vs 11.4% [12/105 patients], P < .001). AKI (hazard ratio [HR], 7.56; 95% CI, 3.40–16.8) and MELD-Na score (HR, 1.08; 95% CI, 1.02–1.14) were independent factors associated with early mortality. In subgroup analysis, AKI after paracentesis was associated with significantly higher early mortality in both MELD-Na groups, that is, patients with a MELD-Na score >26 (87.5% vs 22.2%, P < .001) and those with a MELD-Na score ≤26 (56.3% vs 9.2%, P < .001).

Postparacentesis AKI occurred frequently in cirrhotic patients. Furthermore, it was associated with early mortality. Baseline MELD-Na score was associated with AKI, indicating that careful attention is required for those with a higher MELD-Na score who are being considered for therapeutic paracentesis.
Vitamin B6 as a novel risk biomarker of fractured ankles
Authors: Li Zhihao , Zhang Shaoan , Wan Lei , Song Xiaoyan , Yuan Dongtao , Zhang Shikui , Wu Dalong , Jiang Jiankui
Published: October 2021

Ankle fractures are the most common intra-articular fractures. Osteoporosis is a common and frequent disease among the elderly with a poor prognosis and high risk of fractured ankles. However, the relationship between vitamin B6 and the incidence of fractured ankles in patients with osteoporosis is unclear.

A total of 101 patients with osteoporosis were recruited. Clinical and followed-up information was recorded. And the vitamin B6, albumin, globulin, and hemoglobin in the blood were tested. Pearson's chi-squared and spearman test were performed to analyze the correlation between fractured ankles and relative parameters. Univariate and multivariate logistic regression, receiver operating characteristic curve analysis, univariate and multivariate Cox proportional hazards regression analysis, and Kaplan–Meier method were also performed.

There exist strong relation between the expression level of vitamin B6 and fractured ankle (P < .001). The expression of vitamin B6 [Odd ratio (OR) = 12.071, 95% confidence interval (CI): 4.69–31.143, P < .001] has a clear correlation with whether the patients have fractured ankles via the univariate logistic regression analysis. In terms of multivariate logistic regression level, vitamin B6 (OR = 15.384, 95% CI:5.195–45.556, P < .001) was significantly associated with fractured ankle. In addition, expression level of vitamin B6 [hazard ratio (HR) = 11.684, 95% CI: 6.419–21.267, P < .001] was significantly associated with Maintenance time from recovery to recurrence (MRTT) of patients with osteoporosis.

Enhanced vitamin B6 is significantly correlated with the poor prognosis of patients with osteoporosis and the increasing incidence of fractured ankles.
Dienogest-induced major depressive disorder with suicidal ideation
Authors: Lee Sang Min , Park Jin Kyung
Published: October 2021

Rationale:

Dienogest is a type of progestin used for the treatment of endometriosis (EM). However, a significant adverse effect of dienogest is depression; therefore, assessing for a history of mood disorders is recommended before prescribing the drug. Herein, we present the case of a patient with no history of psychiatric disorders who was diagnosed with dienogest-induced major depressive disorder. This case emphasizes the importance of close monitoring for negative mood changes in patients taking dienogest.

Patient concerns:

A 41-year-old woman underwent surgery for EM. Postoperatively, her gynecologist prescribed dienogest (2 mg/d) to control EM symptoms. Two months after the initiation of dienogest, she manifested insomnia almost daily, gradually became depressed, lost interest in all activities, had incessant cries, and repeatedly thought of death. She had no history of major physical or psychiatric disorders.

Diagnosis:

Major depressive disorder, single episode, severe.

Interventions:

A psychiatric consultation was recommended, an antidepressant was prescribed, and dienogest was discontinued.

Outcomes:

Two weeks later, there was significant improvement in the symptoms, and after 4 weeks, she remained in a stable mood with no suicidal thoughts. She was followed up for 13 months with a maintenance dose of escitalopram (5 −10mg/d), until the psychiatrist recommended treatment discontinuation, with a confirmed state of remission.

Lessons:

This was a case of dienogest-induced depression in a patient with no history of mood disorders. Clinicians should be aware of the possibility of the occurrence of severe depression in progestin users regardless of their previous history.
Outcomes of patients with Down syndrome and acute leukemia
Authors: Schmidt Madalina-Petronela , Colita Anca , Ivanov Anca-Viorica , Coriu Daniel , Miron Ingrith-Crenguta
Published: October 2021

Children with Down syndrome (DS) have a higher risk of developing acute leukemia than do those without DS. There are few studies in the literature about outcome, survival, and difficulties of treating patients with DS and acute leukemia in a developing country. This study aimed to analyze the outcome, response to treatment, survival, treatment complications, and causes of death in patients with DS and acute leukemia compared with those in patients with acute leukemia without DS diagnosed in the same period of time.

We conducted a retrospective observational analysis including a cohort of 21 patients with DS and acute leukemia diagnosed between 2009 and 2018 in 3 hemato-oncology centers (2 pediatric centers and 1 adult hematology center). A group of patients with DS-acute lymphoblastic leukemia (DS-ALL) was analyzed and compared with a group of 165 patients with acute lymphoblastic leukemia without DS, and a group of patients with DS-acute myeloid leukemia (DS-AML) was analyzed and compared with a group of 50 patients with acute myeloid leukemia without DS, which was diagnosed during the same period of time (2009–2018) and treated under similar conditions in terms of both treatment protocols and economic resources.

The overall survival rates in children with DS-ALL and DS-AML were 35.7% and 57.1%, respectively (P = .438). The overall survival rate was significantly worse in children with DS-ALL than in those with acute lymphoblastic leukemia without DS (35.71% vs 75.80%, P = .001). We noted that treatment-related mortality in the patients with DS-ALL was high (50%) (infections and toxicities related to chemotherapy); this result was significantly different from that for patients with leukemia without DS (P < .0001). The relapse rate was higher in patients with DS-ALL but not significantly higher than that in patients without DS (P = .13).

In contrast, the overall survival rate was better for patients with DS-AML than for those with acute myeloid leukemia without DS (57.1% vs 45.1%, P = .47).

Because of the particularities of the host, we suggest that DS-ALL and DS-AML should be considered as independent diseases and treated according to specific protocols with therapy optimization per the minimal residual disease.
Efficacy and safety of acupuncture combined with Chinese herbal medicine in the treatment of primary liver cancer
Authors: Dong Shen , Zhuang Xiong , Yangyang Liu , Yan Leng , Houbo Deng , Song Wang , Meng Xiangtong , Tiejun Liu
Published: October 2021

Background:

Primary liver cancer (PLC) is a common cancer, and its morbidity and mortality are ranked 6th and 3rd in the world for malignant tumors, respectively. And this number is still on the rise, seriously endangering people's health. In recent years, acupuncture combined with Chinese herbal medicine have been widely used in the treatment of PLC, and there are few restrictions. However, we have not found a meta-analysis of their synergistic effects. Therefore, this systematic review and meta-analysis will evaluate the efficacy and acupuncture combined with Chinese herbal medicine in the treatment of primary liver cancer.

Method:

We will search the following databases from inception up to August 20, 2021: PubMed, Web of Science, Embase, AMED, Cochrane Library, CNKI, VIP, CBM, and Wanfang. There will be no restrictions regarding publication date or language. We will apply a combination of medical keywords and words, including “acupuncture,” “Chinese herbal medicine” and “primary liver cancer”. Additionally, we will manually search all reference lists from relevant systematic reviews to find other eligible studies. We will use the random effects model in REVMAN v5.3 for meta-analysis. The study for acupuncture combined with Chinese herbal medicine in the treatment of PLC was a randomized controlled study. Two researchers will independently review the research selection, data extraction, and research quality assessments. Finally, we will observe the outcome measures.

Results:

This study will provide evidence-based medical evidence for the treatment of PLC with a combination of acupuncture and Chinese herbal medicine, and provide new ideas and methods for the treatment of PLC.

Registration number: INPLASY202180103
Integrative traditional Chinese medicine for lumbar disc herniation after surgery
Authors: Kim Hyungsuk , Kim Koh-Woon , Chung Won-Seok
Published: October 2021

Background:

Patients with lumbar disc herniation, who undergo spine surgery, occasionally complain of pain and functional disability. Fortunately, the concept of enhanced recovery after surgery has emerged recently. As a result, patients seek traditional Chinese medicine after spine surgery. This systematic review will thoroughly analyze and synthesize evidence on integrative traditional Chinese medicine therapy for lumbar disc herniation after surgery.

Methods:

The following databases will be utilized to search for pertinent studies: the Cochrane Central Register of Controlled Trials, MEDLINE/PubMed, EMBASE, Chinese National Knowledge Infrastructure, Japan Medical Abstracts Society, and 7 Korean databases (the Korean Studies Information Service System, Korean Association of Medical Journal Editors, National Digital Science Library, Database Periodical Information Academic Korean Traditional Knowledge Portal, Oriental Medicine Advanced Searching Integrated System, and Korean National Assembly Digital Library). The risk of bias of the selected studies will be assessed according to the Cochrane assessment tool for risk of bias. For articles that used the same measurements, a meta-analysis will be conducted to synthesize the results of each trial. Pain severity will be the primary outcome, while the results of functional questionnaires and range of motion, etc, will be the secondary outcomes.

Results and conclusion:

Since this protocol does not include any data from patients, ethics approval is not required. The results of this review will be disseminated through a peer-reviewed journal.

Registration number:

DOI 10.17605/OSF.IO/KP47A (https://osf.io/kp47a)
Recent Stressful Life Events and Suicidal Ideation in Schizophrenia
Authors: Wang Kevin Z. , Dai Nasia , Zai Clement C. , de Bartolomeis Andrea , Gerretsen Philip , Graff Ariel , De Luca Vincenzo
Published: October 2021

Half of patients with schizophrenia experience suicidal ideation. Only few studies have examined the effects of recent stress on both current and emergent suicidal ideation.

A cohort of 85 patients with schizophrenia spectrum disorders was assessed. The study was divided into a cross-sectional and longitudinal arms to test the effect of recent stress on suicidal ideation. Analysis was done using logistic regression models.

After correcting for covariates, recent stress had no significant effect on current suicidal ideation. However, increased total stress (odds ratio [OR] = 1.099 [1.032–1.170], p = 0.003) and health-related stress (OR = 1.331 [1.074–1.650], p = 0.009) at follow-up were predictive of emergent suicidal ideation.

With this sample size, we were unable to draw firm conclusions regarding the effect of specific life events on suicidal ideation. Further studies involving larger samples that investigate the interplay between several risk factors are needed.
Public Stigma of Prolonged Grief Disorder
Authors: Dennis Hayley , Eisma Maarten C. , Breen Lauren J.
Published: October 2021

Prolonged grief disorder's (PGD's) recent recognition as a psychiatric diagnosis has elicited concerns about stigmatization. Although prior research demonstrated that PGD elicits public stigma, moderators of this effect are unclear, and the effect requires replication in an English-speaking population. Therefore, we investigated the effects of PGD, sex of the bereaved, and death expectedness on public stigma toward bereaved persons. We randomly assigned 195 Australian adults (77% female; mean age, 35.7 years) to read one of eight vignettes describing a bereaved male or female subject, with or without PGD, after an expected or unexpected death. Participants reported their emotional reactions and negative attributions toward, and desired social distance from, the bereaved person. A person with PGD (vs. without) elicited stronger emotional reactions, negative attributions, and desired social distance. No robust moderator effects emerged. Results validate concerns that PGD causes stigma. Stigmatization may be targeted by information campaigns or psychological treatment.
Cervical Precancers Originate From Infected Proliferating Reserve Cells
Authors: Regauer Sigrid , Reich Olaf , Kashofer Karl
Published: October 2021

Human papillomavirus (HPV)-induced invasive cervical squamous cell cancer (SCC) develop via high-grade squamous intraepithelial lesion (HSIL). In contrast to classic thick HSIL, thin HSIL (≤9 cell layers) are poorly documented. This study compares histology, HPV genotypes, and aberrations in 50 cancer genes of 45 thin HSIL to 45 thick HSIL, 20 pT1a SCC, and 40 ≥pT1b SCC. Thin HSIL arose from proliferating reserve cells within endocervical epithelium or immature metaplasia throughout the transformation zone after infection with high-risk HPV genotypes (36/45; 80%), and 20% non–high-risk HPV genotypes compared with 2.5% thick HSIL, pT1a SCC, and ≥pT1b SCC. Thin HSIL were multifocal proliferations with varying epithelial thickness between 1 and 2 to 9 cell layers, with occasional transitions to thick HSIL or concomitant lesions of thick HSIL. Overall, 40% thin HSIL were located distant to and most thick HSIL occurred near or at the squamocolumnar junction. Only 20% thick HSIL showed koilocytosis. All HSIL lacked somatic gene mutations, compared with 30% pT1a and 55%≥pT1b SCC. Overrepresented rare germline variants in the MET, JAK3, and FGFR3 genes occurred in all patient groups. In summary, thin and thick HSIL arose independently of somatic gene mutations. The maturation level of the squamous epithelium at the time of transforming infection determines if a thick HSIL develops directly from HPV-infected proliferating reserve cells via thin HSIL or in stratified glycogenated squamous epithelium via low-grade squamous intraepithelial lesion. These observations raise doubts about the biological relevance of separation into thin and thick HSIL. The oncogenic potential of HPV genotypes but also germline variants may influence the natural history.
Coexpression of MCT1 and MCT4 in ALK-positive Anaplastic Large Cell Lymphoma
Authors: Choi Jung-Woo , Lee Youngseok , Kim Hyunchul , Cho Hyun Yee , Min Soo Kee , Kim Young-Sik
Published: October 2021

In solid tumors, glycolytic cancer or stromal cells export lactates through monocarboxylate transporter (MCT) 4, while oxidative cancer or stromal cells take up lactates as metabolic fuels or signaling molecules through MCT1. CD147 acts as a chaperone of MCT1 or MCT4. Unlike solid tumors, malignant lymphomas have a peculiar tumor microenvironment. To investigate the metabolic phenotype of malignant lymphoma associated with lactate transport, we analyzed immunohistochemical expressions of MCT1, MCT4, and CD147 in 247 cases of various malignant lymphomas. Surprisingly, both MCT1 and MCT4 were diffusely expressed on tumor cell membranes in all cases (11/11, 100%) of anaplastic lymphoma kinase (ALK) (+) anaplastic large cell lymphoma (ALCL). In contrast, only MCT1 was diffusely expressed in tumor cells of ALK(−) ALCL, as well as in B-cell, natural killer/T-cell, T-cell, and classic Hodgkin lymphomas. In these lymphomas, MCT4 expression was mostly localized to adjacent stromal cells. The pattern of diffuse membranous MCT1 and partial MCT4 expressions in tumor cells was observed in 1 case each of peripheral T-cell lymphoma (1/15, 6.7%) and multiple myeloma (1/34, 2.9%). CD147 was diffusely expressed in all types of lymphoma tumor and/or stromal cells. In conclusion, ALK(+) ALCL has a unique metabolism showing high coexpression of MCT1 and MCT4 in tumor cells. Because only ALK(+) ALCL overexpresses MCT4, immunostaining for MCT4 together with ALK is very useful for differential diagnosis from ALK(−) ALCL or peripheral T-cell lymphoma. Moreover, dual targeting against MCT1 and MCT4 would be an appropriate therapeutic approach for ALK(+) ALCL.
Imaging of Tumor Hypoxia With 18F-EF5 PET/MRI in Cervical Cancer
Authors: Narva Sara I. , Seppänen Marko P. , Raiko Juho R.H. , Forsback Sarita J. , Orte Katri J. , Virtanen Johanna M. , Hynninen Johanna , Hietanen Sakari
Published: October 2021

Purpose of the Report

The aim of this study was to evaluate the distribution of hypoxia using 18F-EF5 as a hypoxia tracer in cervical cancer patients with PET/MRI. We investigated the association between this 18F-EF5-PET tracer and the immunohistochemical expression of endogenous hypoxia markers: HIF1α, CAIX, and GLUT1.

Patients and Methods

Nine patients with biopsy-proven primary squamous cell cervix carcinoma (FIGO 2018 radiological stages IB1–IIIC2r) were imaged with dual tracers 18F-EF5 and 18F-FDG using PET/MRI (Int J Gynaecol Obstet. 2019;145:129–135). 18F-EF5 images were analyzed by calculating the tumor-to-muscle ratio to determine the hypoxic tissue (T/M ratio >1.5) and further hypoxic subvolume (HSV) and percentage hypoxic area. These 18F-EF5 hypoxic parameters were correlated with the size and localization of tumors in 18F-FDG PET/MRI and the results of hypoxia immunohistochemistry.

Results

All primary tumors were clearly 18F-FDG and 18F-EF5 PET positive and heterogeneously hypoxic with multiple 18F-EF5–avid areas in locally advanced cancer and single areas in clinically stage I tumors. The location of hypoxia was detected mainly in the periphery of tumor. Hypoxia parameters 18F-EF5 max T/M ratio and HSV in primary tumors correlated independently with the advanced stage (P = 0.036 and P = 0.040, respectively), and HSV correlated with the tumor size (P = 0.027). The location of hypoxia in 18F-EF5 imaging was confirmed with a higher hypoxic marker expression HIF1α and CAIX in tumor fresh biopsies.

Conclusions

The 18F-EF5 imaging has promising potential in detecting areas of tumor hypoxia in cervical cancer.
Solitary Hepatic Metastasis From Papillary Thyroid Carcinoma
Authors: Wen Xiaoxia , Yin Haixia , Zhao Deshan
Published: October 2021

Papillary thyroid carcinoma commonly metastasizes to regional lymph nodes. However, metastasis to liver alone is extremely rare. Here we present a 36-year-old woman who underwent total thyroidectomy and bilateral neck lymph nodes dissection for papillary thyroid carcinoma and received radioiodine (131I) ablation therapy for 2 times 1 month and 5 months after surgery, respectively. The images after the 131I therapy showed a solitary occult metastasis in the liver.
111In-Pentetreotide Uptake Due to COVID-19 Vaccination
Authors: Koyasu Sho , Nakamoto Yuji
Published: October 2021

A 72-year-old woman was referred for whole-body 111In-pentetreotide scintigraphy with SPECT/CT. There was increased uptake of lymphadenopathy in the left axilla and left deltoid muscle. The patient's history revealed that the patient received the first dose of the COVID-19 vaccine 3 days before the 111In-pentetreotide scintigraphy with SPECT/CT. This case demonstrates that the COVID-19 vaccine can cause 111In-pentetreotide uptake in the lymph nodes and the deltoid muscle.
Reconstruction of Extensive Oromandibular Defect With Simultaneous Dual Free Flap Transfer
Authors: Chung Jae-Ho , Kim Da-Som , Yoon Eul-Sik
Published: October 2021

Complex oromandibular defects are usually too extensive or complex to be reconstructed with a single free flap. In this situation, dual free flaps can provide an adequate amount of tissues and a three-dimensional structure for large composite defects.

In our institution, a total of 6 patients underwent immediate dual free-flap reconstruction between December 2013 and February 2020. In all patients, oromandibular defects were reconstructed with a combination of a fibula free flap and a vertical rectus abdominis myocutaneous, anterolateral thigh, or radial forearm free flap. All 6 patients showed tolerable flap status without any major complications, and could transit a diet from a dysphagia diet to a general diet on the final visit. Dual free flaps can be considered an optimal reconstructive option with favorable functional and aesthetic outcomes for complex oromandibular defects involving the bone, oral lining, external skin, or soft tissue.
State-of-the-Art Review: Sex Hormone Therapy in Trauma-Hemorrhage
Authors: Lang Eric , Abdou Hossam , Edwards Joseph , Patel Neerav , Morrison Jonathan J.
Published: October 2021

Trauma-hemorrhage is the leading cause of prehospital and early in-hospital deaths, while also significantly contributing to the later development of multisystem organ dysfunction/failure and sepsis. Common and advanced resuscitative methods would potentially demonstrate benefits in the prehospital setting; however, they face a variety of barriers to application and implementation. Thus, a dialogue around a novel adjunct has arisen, sex hormone therapy. Proposed candidates include estradiol and its derivatives, metoclopramide hydrochloride/prolactin, dehydroepiandrosterone, and flutamide; with each having demonstrated a range of salutary effects in several animal model studies. Several retrospective analyses have observed a gender-based dimorphism in mortality following trauma-hemorrhage, thus suggesting that estrogens contribute to this pattern. Trauma-hemorrhage animal models have shown estrogens offer protective effects to the cardiovascular, pulmonary, hepatic, gastrointestinal, and immune systems. Additionally, a series of survival studies utilizing 17α-ethinylestradiol-3-sulfate, a potent, water-soluble synthetic estrogen, have demonstrated a significant survival benefit and beneficial effects on cardiovascular function. This review presents the findings of retrospective clinical studies, preclinical animal studies, and discusses how and why 17α-ethinylestradiol-3-sulfate should be considered for investigation within a prospective clinical trial.
The emerging treatment landscape of advanced urothelial carcinoma
Authors: Cardenas Luisa , Dibajnia Pooya , Lalani Aly-Khan
Published: October 2021

Purpose of review

Urothelial carcinoma (UC) is one of the most common malignancies in the Western world. Historically, patients with advanced disease have had a poor prognosis and progress within months of completing upfront platinum-based chemotherapy. In the last two years, the treatment landscape for metastatic UC (mUC) has significantly shifted with the emergence of contemporary immunotherapy and targeted agents. The purpose of this review is to highlight the current and emerging systemic treatment options for mUC of the bladder.

Recent findings

PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have demonstrated activity in the postplatinum and platinum-ineligible settings. Additionally, they have become a standard maintenance treatment option after avelumab demonstrated increased overall survival in patients with stable disease or better after first line platinum-based chemotherapy. Novel targeted therapies and antibody-drug conjugates (ADCs) have been granted Food and Drug Administration approval for subsequent line therapy based on promising results in phase II and III trials.

There has been a considerable increase in the variety of effective therapies for mUC, including the utility of ICIs, novel targeted agents, and ADCs. Platinum-based chemotherapy remains an effective first-line option. As the role of novel therapies continues to shift toward earlier in the disease course, there remains an important need to develop feasible, globally accessible predictive biomarkers that can aid in patient selection and inform sequencing of therapeutic options.
Roseomonas ponticola sp. nov., a novel bacterium isolated from Pearl River estuary
Authors: Yin Ling-Zi , Li Jia-Ling , Fang Bao-Zhu , Liu Ze-Tao , Wang Pandeng , Dong Lei , Duan Li , Luo Xiao-Qing , Li Shan-Hui , Li Wen-Jun
Published: October 2021

A novel species of the genus

Roseomonas

, designated SYSU M41301T, was isolated from water sample of the Pearl River estuary in Guangdong, China. Polyphasic, taxonomic and phylogenomic analyses were used to determine the taxonomy position of the strain. Phylogenetic analysis using 16S rRNA gene sequence indicated that strain SYSU M41301T showed the highest sequence similarity to

Roseomonas stagni

KCTC 22213T (97.9 %) and

Roseomonas riguiloci

KCTC 23339T (96.4 %). The novel species could be differentiated from other species of the genus

Roseomonas

by its distinct phenotypic and genotypic characteristics. The isolate was Gram-staining-negative, aerobic, short rod-shape, oxidase-positive and non-motile. The predominant respiratory quinone was ubiquinone 8 (Q-8). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, and one unidentified polar lipid. The major fatty acids (>10 % of total) were 11-methyl C18 : 1
 ω7c, summed feature 3 (C16 : 1
 ω7c and/ or C16 : 1
 ω6c) and summed feature 8 (C18:  :1
 ω7c and/or C18 : 1
 ω6c). The G+C content of the novel isolate based on genomic DNA was 72.0 mol%. On the basis of phenotypic, genotypic and phylogenetic data, strain SYSU M41301T should be considered to represent a novel species in the genus Roseomonas, for which the name Roseomonas ponticola sp. nov. is proposed with the type strain SYSU M41301T (=KCTC 72726T=CGMCC 1.18613T).
Luteolibacter ambystomatis sp. nov., isolated from the skin of an Anderson’s salamander (Ambystoma andersoni)
Authors: Busse Hans-Jürgen , Kämpfer Peter , Szostak Michael Peter , Spergser Joachim
Published: October 2021

A bacterial strain designated 32AT was isolated from the skin of an Anderson’s salamander (Ambystoma andersoni) and subjected to a comprehensive taxonomic study. The strain was Gram-stain-negative, rod-shaped, non-motile, oxidase- and urease-negative, and catalase-positive. 16S rRNA gene sequence comparisons placed the strain in the genus

Luteolibacter

with highest sequence similarities to

Luteolibacter pohnpeiensis

A4T-83T (95.2%),

Luteolibacter gellanilyticus

CB-286403T (95.1%) and

Luteolibacter cuticulihirudinis

E100T (94.9%). Genomic sequence analysis revealed a size of 5.3 Mbp, a G+C-content of 62.2 mol% and highest ANI values with

Luteolibacter luteus

(71.2%),

Luteolibacter yonseiensis

(71.4%) and

L. pohnpeiensis

(69.5%). In the polyamine pattern, 1,3-diaminopropane and spermidine were predominant. The diagnostic diamino acid of the peptidoglycan was meso-diaminopimelic acid. The quinone system was composed of the major menaquinones MK-9 and MK-10. Major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, the unidentified aminolipid AL2, the unidentified phospholipid PL2 and the unidentified aminophospholipid APL1. The fatty acid profile contained major amounts of iso-C14:0, iso-C16:0, C16 : 0 and C16 : 1 ω9c. In addition, C14 : 0, C15:0, anteiso-C15 : 0, summed feature 2 (C14 : 0 3OH and/or iso-C16 : 0 I), and the hydroxylated fatty acids iso-C14 : 0 3OH, iso-C16 : 0 3OH and C16 : 0 3-OH were detected. Physiologically, strain 32AT is distinguishable from its next relatives. Based on phylogenetic, genomic, physiological and chemotaxonomic data, strain 32AT represents a novel species of the genus

Luteolibacter

for which we propose the name Luteolibacter ambystomatis sp. nov. The type strain is 32AT (=CCM 9141T=LMG 32214T).
Mapping the functional interactions at the tumor-immune checkpoint interface
Authors: Bozorgui Behnaz , Kong Elisabeth K. , Luna Augustin , Korkut Anil
Published: October 2021

It is challenging to identify the tumor-immune system interactions that modulate immune states and immunotherapy responses due to the prohibitively complex space of possible interactions. Our statistical analysis framework, ImogiMap quantifies tumor-immune interactions based on their synergistic co-associations with immune-associated phenotypes. ImogiMap-based analyses recapitulated known interactions modulating immunotherapy responses and nominated the CD86/CD70 axis as an immunotherapy target that overlaps with IFNG overexpression and patient survival in endometrial carcinoma.
Lysophosphatidylcholine acyltransferase 1 controls the mitochondrial reactive oxygen species generation and survival of the retinal photoreceptor cells
Authors: Nagata Katsuyuki , Hishikawa Daisuke , Sagara Hiroshi , Saito Masamichi , Watanabe Sumiko , Shimizu Takao , Shindou Hideo
Published: October 2021

Due to the high energy demands and characteristic morphology, retinal photoreceptor cells require a specialized lipid metabolism for survival and function. Accordingly, dysregulation of lipid metabolism leads to the photoreceptor cell death and retinal degeneration. Mice with a frameshift mutation of lysophosphatidylcholine acyltransferase 1 (Lpcat1), which produces saturated phosphatidylcholine (PC) composed of two saturated fatty acids, has been reported to cause spontaneous retinal degeneration (rd11 mice). In this study, we performed a detailed characterization of LPCAT1 in the retina and found that genetic deletion of Lpcat1 induces light-independent and photoreceptor-specific apoptosis in mice. Lipidomic analyses of the retina and isolated photoreceptor outer segment (OS) suggested that loss of Lpcat1 decreases saturated PC production and affects the proper cellular fatty acid flux, presumably by altering saturated fatty acyl-CoA availabilities. Furthermore, we demonstrated that Lpcat1 deletion increased mitochondrial reactive oxygen species (ROS) levels in photoreceptor cells, but not in other retinal cells without affecting the OS structure and trafficking of OS-localized proteins. These results suggest that the LPCAT1-dependent production of saturated PC is critical for metabolic adaptation during photoreceptor maturation. Our findings highlight the therapeutic potential of saturated fatty acid metabolism in photoreceptor cell degeneration-related retinal diseases.
Genomic and phenotypic characterization of Pseudomonas hygromyciniae, a novel bacterial species discovered from a commercially purchased antibiotic
Authors: Turner Timothy L. , Mitra Sumitra D. , Kochan Travis J. , Pincus Nathan B. , Lebrun-Corbin Marine , Cheung Bettina , Gatesy Samuel W. , Afzal Tania , Ozer Egon A. , Hauser Alan R.
Published: October 2021

A purchased lot of the antibiotic hygromycin B was found to be contaminated with a novel bacterial species, which we designate Pseudomonas hygromyciniae. Characteristics of P. hygromyciniae include its ability to use a variety of compounds as carbon sources, its pathogenicity towards lettuce and Galleria mellonella, and its ability to inhibit the growth of an E. coli strain. P. hygromyciniae is unlikely to be a human pathogen, as it did not survive at 37 °C and was not cytotoxic towards a mammalian cell line. The P. hygromyciniae strain harbors a novel 250 kb megaplasmid which confers resistance to hygromycin B and contains numerous other genes predicted to encode replication and conjugation machinery. These findings indicate that commercially manufactured antibiotics represent another extreme environment that may support the growth of novel bacterial species.

IMPORTANCE

Microbial ecologists have surveyed numerous natural and manmade environments in search of new microbial species. In some instances, these microbes are discovered in harsh conditions, such as deep-sea vents, and their discovery leads to better understanding of how microbes adapt to their environment. Here, we have discovered a new species of bacteria from an extreme manmade environment: a lyophilized, commercially available bottle of the antibiotic hygromycin B.
Bacterial invasion across the human skin barrier – mechanisms and ensuing tissue degradation
Authors: Lipsky Zachary W. , Patsy Marisa , Marques Cláudia N. H. , German Guy K.
Published: October 2021

Atopic Dermatitis (AD) is associated with a deficiency of skin lipids, increased populations ofStaphylococcus aureusin the microbiome, and structural defects in the stratum corneum (SC), the outermost layer of human skin. However, the pathogenesis of AD is ambiguous as it is unclear whether observed changes are the result of AD or contribute to the pathogenesis of the disease. Previous studies have shown thatS. aureusis capable of permeating across isolated human SC tissue when lipids are depleted to levels consistent with AD conditions. In this study, we expand upon this discovery to determine the mechanisms of bacterial penetration into the SC barrier. Specifically, we establish whether bacteria are permeating intercellularly, between corneocytes, or employing a combination pathway of both inter- and intra-cellular travel. The mechanical implications of bacterial invasion, lipid depletion, and media immersion are also evaluated using a newly developed, physiologically relevant, temperature-controlled drip chamber. Results reveal thatS. aureuscan be internalized by corneocytes, indicating transcellular movement through the tissue during permeation, consistent with previous theoretical models.S. aureusalso degrades the mechanical integrity of human SC, particularly when the tissue is partially depleted of lipids. These observed mechanical changes are likely the cause of broken or ruptured tissue seen as exudative lesions in AD flares. This work further highlights the necessity of lipids in skin microbial barrier function.

Importance

Millions of people suffer from the chronic inflammatory skin disease Atopic Dermatitis (AD), whose symptoms are associated with a deficiency of skin lipids that exhibit antimicrobial functions, and increased populations of the opportunistic pathogenStaphylococcus aureus. However, the pathogenesis of AD is ambiguous, and it remains unclear if these observed changes are merely the result of AD, or contribute to the pathogenesis of the disease. In this article, we demonstrate the necessity of skin lipids in preventingS. aureusfrom penetrating the outermost barrier of human skin thereby causing a degradation in tissue integrity. In terms of AD, this bacterial permeation into the viable epidermis could act as an inflammatory trigger of the disease and could also explain tissue fragility and lesion formation seen with AD patients. Moreover, bacterial induced degradation could lead to increased pathways and further allergen intervention creating chronic irritation.