bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 in a patient with SISTEMIC sclerosis: The role of ruxolitinib
Authors: Ucciferri Claudio , Auricchio Antonio , Marinari Stefano , Vecchiet Jacopo , Falasca Katia
Published: September 2021

We describe the case of a 78-year-old Italian woman with COVID-19 affected by Systemic Sclerosis with pulmonary fibrosis treated with Ruxolitinib (Ruxolitinib was provided free of charge by Novartis International AG). We chose Ruxolitinib, as a second-line treatment, after administering a standard therapy with hydroxychloroquine and lopinavir/ritonavir, due to a rapid deterioration in the patient’s lung function. Ruxolitinib is a janus kinase inibithor with selectivity for subtypes JAK1 and JAK2. A rapid improvement in the patient’s respiratory function, objectified with an increase in PO2/FiO2 value, has been observed in the 10 days after the introduction of Ruxolitinib. Surprisingly we noticed a reduction in pulmonary fibrosis by comparing the chest- CT made before and after the COVID-19 diagnosis. JAK/STAT signalling is involved both in pathogenesis of the second part of COVID-19 and in the modulation of fibrosis in patients with SSc. The use of ruxolitinib should be a new therapeutic option in patients with COVID-19 and lung fibrosis.
Clinical outcome and risk factors of patients with suspected pneumonia in Southwest district of Ethiopia, 2020: A retrospective study
Authors: Sebsibe Mengistu A , Kebede Molla A , Kazintet Yosef H , Gosaye Bizuayehu T , Teferi Addisalem M , Toru Milkiyas
Published: September 2021

Acute respiratory infections (ARIs), especially pneumonia, remain the leading cause of childhood mortality and the most common reason for adult hospitalization in low- and middle-income countries, despite advances in preventative and management strategies. This study was conducted to assess factors associated with poor clinical outcome of suspected pneumonia cases among hospitalized patients at the three public health hospitals in Southwest district of Ethiopia. A cross-sectional study was conducted from May to July, 2020. Those patients admitted with suspected pneumonia were followed up during their hospital stay, and data on outcomes were captured by study nurses. Socio-demographics, clinical features, and follow-up data were gathered, and analyzed using SPSS versions 20.0. The differences in patients’ outcome in relation to their clinical features and epidemiologically linked exposures were described and compared using chi-square tests at 95% confident intervals. In this study, 742 patients with suspected pneumonia were analyzed. Of these, 473 (62.8%) of them were male, and 264 (35.6%) were of age 1–4 years. About 533 (71.8%) patients with suspected pneumonia were presented with irregular respiratory signs/symptoms (more than one symptoms) and 132 (17.9%) had underline illnesses. About 633 (85.4%) of patients were improved after treatment, and 109 (14.7%) of them ended with poor clinical outcome after completion of their treatment. Age of the patients and presence of comorbid conditions such as HIV/AIDS infections and bronchial asthma were identified as the risk factors for poor outcome of patients with suspected pneumonia. The clinical outcome of patients with suspected pneumonia at the three hospitals in Southwest district of Ethiopia was not satisfactory. Our findings highlight that in order to reduce poor clinical outcome related to suspected pneumonia, the efforts should be focused on some factors like management and prevention of chronic comorbidities. Increasing clinicians’ awareness on early management of suspected pneumonia cases is also essential in reducing the burden of the disease .
Developing a Simpler Prognosticating Tool: Comparing the Combined Assessment of Risk Encountered in Surgery Score with Deyo-Charlson Comorbidity Index and The American Society of Anesthesiologists Physical Status Score in Predicting 2 years Mortality after Hip Fracture Surgery
Authors: Cher Eric Wei Liang , Carson John Allen , Sim Eileen Yilin , Abdullah Hairil Rizal , Howe Tet Sen , Koh Suang Bee Joyce,
Published: September 2021

Background: The use of risk stratification tools in identifying high-risk hip fracture patients plays an important role during treatment. The aim of this study was to compare our locally derived Combined Assessment of Risk Encountered in Surgery (CARES) score with the the American Society of Anesthesiologists physical status (ASA-PS) score and the Deyo–Charlson Comorbidity Index (D-CCI) in predicting 2-year mortality after hip fracture surgery. Methods and Material: A retrospective study was conducted on surgically treated hip fracture patients in a large tertiary hospital from Jan 2013 through Dec 2015. Age, gender, time to surgery, ASA-PS score, D-CCI, and CARES score were obtained. Univariate and multivariable logistic regression analyses were used to assess statistical significance of scores and risk factors, and area under the receiver operating characteristic (ROC) curve (AUC) was used to compare ASA-PS, D-CCI, and CARES as predictors of mortality at 2 years. Results: 763 surgically treated hip fracture patients were included in this study. The 2-year mortality rate was 13.1% (n = 100), and the mean ± SD CARES score of surviving and demised patients was 21.2 ± 5.98 and 25.9 ± 5.59, respectively. Using AUC, CARES was shown to be a better predictor of 2-year mortality than ASA-PS, but we found no statistical difference between CARES and D-CCI. A CARES score of 23, attributable primarily to pre-surgical morbidities and poor health of the patient, was identified as the statistical threshold for “high” risk of 2-year mortality. Conclusion: The CARES score is a viable risk predictor for 2-year mortality following hip fracture surgery and is comparable to the D-CCI in predictive capability. Our results support the use of a simpler yet clinically relevant CARES in prognosticating mortality following hip fracture surgery, particularly when information on the pre-existing comorbidities of the patient is not immediately available.
MutiLoc Nail Versus Philos Plate in Treating Proximal Humeral Fractures: A Retrospective Study Among the Alderly
Authors: Bu Guoyun , Sun Weitang , Li Jian’an , Yang Tao , Li Mingxin , Wei Wanfu
Published: September 2021

Background

Proximal humeral fractures (PHFs) account for 4–5% of all fractures in the elderly. There is still a controversy among the treatments in the displaced PHFs. Our aim was to explore the clinical outcome of PHFs with the treatment of MultiLoc nail or Philos plate in the elderly patients.

Methods

A total of 82 sustained elderly patients with PHFs were finally recruited between Dec 2016 and Dec 2017. 34 patients were treated with MultiLoc nail and 48 patients were treated with Philos plate. The demographics, fracture types, blood loss, operation time, union time, postoperative complications, visual analog scores (VASs), Constant scores, American Shoulder and Elbow Scores (ASESs), and neck-shaft-angle (NSA) between the two groups were compared.

Results

No differences were observed in the demographics, fracture types, VAS, Constant scores, and ASES scores between the two groups at final follow-up. Compared with the plate group, the blood loss, operation time, and union time were significantly lower in the nail group (all P < .05). The rate of general complications was 54.17% in the plate group, which was higher than that in the nail group (26.47%, P = .01). Three patients experienced reoperation in the plate group (3/48; 6.25%), but none in the nail group. Although there were no significant differences in intraoperative NSA between the two groups, the NSA at final follow-up in the nail group was much higher than the plate group (137.55 ± 5.53°vs 134.47 ± 5.92°, P = .02).

Conclusions

Multiloc intramedullary nail showed the similar effectiveness of final VAS, final Constant scores, and ASES scores in PHFs treatment with Philos plate. However, MultiLoc nail is superior to Philos plate in blood loss, operation time, complications, reoperation rate, and the change of NSA.
Translation Policy, Social System, and Ideology: A Study on the English Translation of Modern Chinese Fiction for America During the CWRAJ
Authors: Li Ping , Tian Chuanmao
Published: September 2021

This article explores translation policy on the English translations of modern Chinese fiction to American readers during China’s War of Resistance against Japan (1931–1945). The research findings show that translation policy may not be explicitly stated, but implicitly embodied in some political, diplomatic, and cultural policies made by the American and Chinese governments. Translation policy making as a social system is influenced by the political environment during the war. Different policy makers’ motives and policies change over time in reaction to each other with the course of the war, and the changing socio-political climate in China and the US had great effects on the English translations of Chinese fiction before the entry of the US into the war and after the US government became actively involved in translation projects. Moreover, the ideological preferences and political interests of the various actors shape actual translation practice—the selection of texts and actual choices in wording. This course of events affects the reception of these translations by the US public. In other words, the readership of these books grew after the Chinese government became allies in the war with the American government.
Measuring Entrepreneurial Orientation in Developing Economies: Scale Development and Validation
Authors: Ali Asif , Aima Ashok , Bhasin Jaya , Hisrich Robert D.
Published: September 2021

Entrepreneurial orientation (EO) refers to entrepreneurial activities of established and existing firms. It is different from individual entrepreneurial orientation (Popov et al., 2019, Education + Training, vol. 61, pp. 65–78). EO refers to the processes, practices, and decision-making activities that lead to new venture creation (Walter et al., 2006, Journal of Business Venturing, vol. 21, pp. 541–567). The EO scale by Lumpkin and Dess (1996, Academy of Management Review, vol. 21, pp. 135–172) consists of innovativeness, proactiveness, risk-taking, competitive aggressiveness, and autonomy. This scale is widely used in literature with major drawback of it being developed and evaluated in a developed economy (the USA) on large corporations. Very little literature is available with reference to validation of EO scales in developing economies, particularly India where firms are generally small. New Comprehensive Entrepreneurial Orientation Scale (CENTORES) has been developed and validated by adding additional dimension of strategic flexibility, which is the novelty of the present study. Data were collected using a survey instrument comprising of 19 items. The scientific scale development procedure as suggested by Schwab, (1980) was followed, first an exploratory factor analysis (EFA) was done to explore factors and later confirmatory factor analysis (CFA) was done to confirm factors (using SPSS and Amos). Six stable factors emerged from EFA which were subsequently confirmed through CFA. The measurement model confirmed the factors with good model fit indices as suggested by Hair et al. (2014). The model has CMIN/df = 2.237, CFI = 0.917, GFI = 0.928, NFI = 0.882, and RMSEA = 0.052.
Comparing Nonoperative Treatment, MPFL Repair, and MPFL Reconstruction for Patients With Patellar Dislocation: A Systematic Review and Network Meta-analysis
Authors: Liu Zhongcheng , Yi Qiong , He Liangzhi , Yao Changjiang , Zhang Lanfang , Lu Fan , Zhang Xiaohui , Wu Meng , Geng Bin , Xia Yayi , Jiang Jin
Published: September 2021

Background:

Medial patellofemoral ligament (MPFL) reconstruction, MPFL repair, and nonoperative treatment are important treatments for patients with patellar dislocation. However, it is unclear which treatment leads to better outcomes.

Purpose:

To determine the efficacy and safety of the 3 treatments in the treatment of patellar dislocation and compare the effect of MPFL reconstruction with MPFL repair, MPFL reconstruction with nonoperative treatment, and MPFL repair with nonoperative treatment.

Study Design:

Systematic review; Level of evidence, 3.

Methods:

The PubMed, Web of Science, Cochrane Library, Embase, CNKI (China National Knowledge Infrastructure), and Wanfang databases were searched from inception to December 2020. Included were clinical studies that described the efficacy and safety of 2 of the 3 treatments, studies directly comparing the clinical effects of the 2 operative techniques, or studies comparing the effects of reconstruction or repair with nonoperative treatment. Two reviewers independently extracted data and assessed the quality of the included studies with the Cochrane risk-of-bias tools. The outcomes evaluated were postoperative redislocation rate, revision rate, complications, and Kujala score. We used traditional direct pairwise meta-analysis as well as network meta-analysis for comprehensive efficacy of all 3 treatment measures.

Results:

Twelve studies were included: 5 compared MPFL reconstruction with MPFL repair, 2 compared MPFL reconstruction with nonoperative treatment, and 5 compared MPFL repair with nonoperative treatment. The risk of bias was serious in 4, moderate in 4 and low in 4 articles. MPFL reconstruction led to significantly reduced redislocation and improved Kujala scores compared with MPFL repair and nonoperative treatment. MPFL repair led to reduced redislocation rates compared with nonoperative treatment but did not show an obvious benefit in primary dislocations. There was no significant difference among the 3 treatments in terms of revision rate and incidence of complications, although we found that treatment-related complications were least likely to occur in nonoperative treatment.

Conclusion:

The results of this review indicate that MPFL reconstruction decreases recurrent dislocation compared with MPFL repair or nonoperative treatment, but it has a higher possibility of complications. MPFL repair resulted in less postoperative redislocation than nonoperative treatment but did not show an obvious benefit in primary dislocation.
University Teachers’ Decisions on Post-retirement Employment: Do Demographic Variables Count?
Authors: Salifu Inusah , Odame Ebenezer D. , Abubakar Jibreel U.
Published: September 2021

This research aimed to determine whether demographic characteristics of retiring university teachers were significantly associated with their post-retirement employment decisions, using three psychosocial theories–role theory, continuity theory and life course theory. The research used the cross-sectional survey design and relied on the simple random sampling technique to sample 235 participants who were left with 5 years or less to reach Ghana’s compulsory retirement age of 60 years. The participants were selected across 20 public universities in Ghana to complete a questionnaire. Based on a binary logistic regression analysis, the research found that, apart from the rank and health status of the participants, other variables such as gender, kind of university, family size, marital status and levels of involvement in university activities significantly determined the participants’ decisions regarding a working life after retirement. Against this backdrop, the research concluded that within the academic milieu, certain demographic factors were key determinants of post-retirement employment decisions.
Predictors of Biological Age: The Implications for Wellness and Aging Research
Authors: Lohman Trevor , Bains Gurinder , Berk Lee , Lohman Everett
Published: September 2021

As healthspan and lifespan research breakthroughs have become more commonplace, the need for valid, practical markers of biological age is becoming increasingly paramount. The accessibility and affordability of biological age predictors that can reveal information about mortality and morbidity risk, as well as remaining years of life, has profound clinical and research implications. In this review, we examine 5 groups of aging biomarkers capable of providing accurate biological age estimations. The unique capabilities of these biomarkers have far reaching implications for the testing of both pharmaceutical and non-pharmaceutical interventions designed to slow or reverse biological aging. Additionally, the enhanced validity and availability of these tools may have increasingly relevant clinical value. The authors of this review explore those implications, with an emphasis on lifestyle modification research, and provide an overview of the current evidence regarding 5 biological age predictor categories: Telomere length, composite biomarkers, DNA methylation “epigenetic clocks,” transcriptional predictors of biological age, and functional age predictors.
Addressing the ‘hypoxia paradox’ in severe COVID-19: literature review and report of four cases treated with erythropoietin analogues
Authors: Begemann Martin , Gross Oliver , Wincewicz Dominik , Hardeland Rüdiger , Daguano Gastaldi Vinicius , Vieta Eduard , Weissenborn Karin , Miskowiak Kamilla W. , Moerer Onnen , Ehrenreich Hannelore
Published: September 2021

Background

Since fall 2019, SARS-CoV-2 spread world-wide, causing a major pandemic with estimated ~ 220 million subjects affected as of September 2021. Severe COVID-19 is associated with multiple organ failure, particularly of lung and kidney, but also grave neuropsychiatric manifestations. Overall mortality reaches > 2%. Vaccine development has thrived in thus far unreached dimensions and will be one prerequisite to terminate the pandemic. Despite intensive research, however, few treatment options for modifying COVID-19 course/outcome have emerged since the pandemic outbreak. Additionally, the substantial threat of serious downstream sequelae, called ‘long COVID’ and ‘neuroCOVID’, becomes increasingly evident.

Main body of the abstract

Among candidates that were suggested but did not yet receive appropriate funding for clinical trials is recombinant human erythropoietin. Based on accumulating experimental and clinical evidence, erythropoietin is expected to (1) improve respiration/organ function, (2) counteract overshooting inflammation, (3) act sustainably neuroprotective/neuroregenerative. Recent counterintuitive findings of decreased serum erythropoietin levels in severe COVID-19 not only support a relative deficiency of erythropoietin in this condition, which can be therapeutically addressed, but also made us coin the term ‘hypoxia paradox’. As we review here, this paradox is likely due to uncoupling of physiological hypoxia signaling circuits, mediated by detrimental gene products of SARS-CoV-2 or unfavorable host responses, including microRNAs or dysfunctional mitochondria. Substitution of erythropoietin might overcome this ‘hypoxia paradox’ caused by deranged signaling and improve survival/functional status of COVID-19 patients and their long-term outcome. As supporting hints, embedded in this review, we present 4 male patients with severe COVID-19 and unfavorable prognosis, including predicted high lethality, who all profoundly improved upon treatment which included erythropoietin analogues.

Short conclusion

Substitution of EPO may—among other beneficial EPO effects in severe COVID-19—circumvent downstream consequences of the ‘hypoxia paradox’. A double-blind, placebo-controlled, randomized clinical trial for proof-of-concept is warranted.
Testicular mass: a rare presentation of Richter's syndrome
Authors: Desouky Elsayed , Al-Salti Wassim , Khan Muhammad
Published: September 2021

Background

Richter’s syndrome is the transformation of indolent lymphoma into an aggressive form, most commonly diffuse large B cell lymphoma. Most patients are known to have chronic lymphocytic leukemia. Richter’s syndrome arises in the lymph nodes or bone marrow and rarely presents with extra nodal involvement.

Case presentation

Our patient presented with Richter’s syndrome at an extremely uncommon site, i.e., testis. This is the fourth case reported in literature. Moreover, our case represents the longest follow-up reported so far with recurrence-free survival of more than 2 years now.

Conclusion

Testicular mass in a patient with a history of chronic lymphocytic leukemia should raise the clinical suspicion of Richter’s syndrome and accordingly the patient should be thoroughly investigated and treated. Treatment needs multidisciplinary team approach: urologist, pathologist and hematologist.
Primary bladder neck obstruction is one of the rare causes for renal failure in young adult males
Authors: Coguplugil Adem Emrah , Topuz Bahadir , Ebiloglu Turgay , Zor Murat , Gurdal Mesut
Published: September 2021

Background

Primary bladder neck obstruction (PBNO) is one of the causes of bladder outlet obstruction (BOO) and rarely results in renal failure. We are presenting the clinical characteristics of young male patients with PBNO and renal failure.

Methods

Medical records of patients between 18 and 40 years old with PBNO and renal failure were retrospectively reviewed (2014–2020). Patients with anatomical cause of BOO, and any urological or systemic disease or previous history of any surgical procedure associated with renal failure and/or lower urinary tract dysfunction were excluded. Serum creatinine measurement, ultrasonography, uroflowmetry, cystoscopy, and videourodynamics were performed.

Results

Seven male patients were identified, and the mean age of the patients was 28.8 years. Symptom duration was > 5 years in all patients. Two patients presented with difficult voiding, and five patients presented with both storage and voiding lower urinary tract symptoms (LUTS). Three patients were previously misdiagnosed as overactive bladder. At presentation, serum creatinine levels were between 1.7 and 2.4 mg/dl. One patient was under hemodialysis treatment and waiting for renal transplantation. Mean detrusor pressure at maximum measured flow rate, mean maximum flow rate (Qmax), and mean average flow rate (Qave) was 67.6 cm H2O, 9.5 ml/s, and 5.5 ml/s, respectively. With α-blocker treatment, serum creatinine levels were stable or decreased after 12 months follow-up and mean Qmax and Qave were increased to 14.8 ml/s and 10.1 ml/s, respectively.

Conclusions

PBNO is a common disease in young men presenting with a long history of LUTS. Videourodynamics is mandatory for accurate diagnosis, but having a high clinical suspicion for PBNO is key to ensure the diagnosis. Clinicians should pay more attention to PBNO in young male patients with a long history of LUTS to prevent misdiagnosis, incorrect treatment, and possible decrease in renal function by years.
Bias, dispersion, and accuracy of genomic predictions for feedlot and carcase traits in Australian Angus steers
Authors: Alexandre Pâmela A. , Li Yutao , Hine Brad C. , Duff Christian J. , Ingham Aaron B. , Porto-Neto Laercio R. , Reverter Antonio
Published: September 2021

Background

Improving feedlot performance, carcase weight and quality is a primary goal of the beef industry worldwide. Here, we used data from 3408 Australian Angus steers from seven years of birth (YOB) cohorts (2011–2017) with a minimal level of sire linkage and that were genotyped for 45,152 SNPs. Phenotypic records included two feedlot and five carcase traits, namely average daily gain (ADG), average daily dry matter intake (DMI), carcase weight (CWT), carcase eye muscle area (EMA), carcase Meat Standard Australia marbling score (MBL), carcase ossification score (OSS) and carcase subcutaneous rib fat depth (RIB). Using a 7-way cross-validation based on YOB cohorts, we tested the quality of genomic predictions using the linear regression (LR) method compared to the traditional method (Pearson’s correlation between the genomic estimated breeding value (GEBV) and its associated adjusted phenotype divided by the square root of heritability); explored the factors, such as heritability, validation cohort, and phenotype that affect estimates of accuracy, bias, and dispersion calculated with the LR method; and suggested a novel interpretation for translating differences in accuracy into phenotypic differences, based on GEBV quartiles (Q1Q4).

Results

Heritability (h2) estimates were generally moderate to high (from 0.29 for ADG to 0.53 for CWT). We found a strong correlation (0.73, P-value < 0.001) between accuracies using the traditional method and those using the LR method, although the LR method was less affected by random variation within and across years and showed a better ability to discriminate between extreme GEBV quartiles. We confirmed that bias of GEBV was not significantly affected by h2, validation cohort or trait. Similarly, validation cohort was not a significant source of variation for any of the GEBV quality metrics. Finally, we observed that the phenotypic differences were larger for higher accuracies.

Conclusions

Our estimates of h2 and GEBV quality metrics suggest a potential for accurate genomic selection of Australian Angus for feedlot performance and carcase traits. In addition, the Q1Q4 measure presented here easily translates into possible gains of genomic selection in terms of phenotypic differences and thus provides a more tangible output for commercial beef cattle producers.
Odorant-binding proteins in canine anal sac glands indicate an evolutionarily conserved role in mammalian chemical communication
Authors: Janssenswillen Sunita , Roelants Kim , Carpentier Sebastien , de Rooster Hilde , Metzemaekers Mieke , Vanschoenwinkel Bram , Proost Paul , Bossuyt Franky
Published: September 2021

Background

Chemical communication is an important aspect of the behavioural ecology of a wide range of mammals. In dogs and other carnivores, anal sac glands are thought to convey information to conspecifics by secreting a pallet of small volatile molecules produced by symbiotic bacteria. Because these glands are unique to carnivores, it is unclear how their secretions relate to those of other placental mammals that make use of different tissues and secretions for chemical communication. Here we analyse the anal sac glands of domestic dogs to verify the secretion of proteins and infer their evolutionary relationship to those involved in the chemical communication of non-carnivoran mammals.

Results

Proteomic analysis of anal sac gland secretions of 17 dogs revealed the consistently abundant presence of three related proteins. Homology searches against online databases indicate that these proteins are evolutionary related to ‘odorant binding proteins’ (OBPs) found in a wide range of mammalian secretions and known to contribute to chemical communication. Screening of the dog’s genome sequence show that the newly discovered OBPs are encoded by a single cluster of three genes in the pseudoautosomal region of the X-chromosome. Comparative genomic screening indicates that the same locus is shared by a wide range of placental mammals and that it originated at least before the radiation of extant placental orders. Phylogenetic analyses suggest a dynamic evolution of gene duplication and loss, resulting in large gene clusters in some placental taxa and recurrent loss of this locus in others. The homology of OBPs in canid anal sac glands and those found in other mammalian secretions implies that these proteins maintained a function in chemical communication throughout mammalian evolutionary history by multiple shifts in expression between secretory tissues involved in signal release and nasal mucosa involved in signal reception.

Conclusions

Our study elucidates a poorly understood part of the biology of a species that lives in close association with humans. In addition, it shows that the protein repertoire underlying chemical communication in mammals is more evolutionarily stable than the variation of involved glands and tissues would suggest.
The taxonomic distribution of histamine-secreting bacteria in the human gut microbiome
Authors: Mou Zhongyu , Yang Yiyan , Hall A. Brantley , Jiang Xiaofang
Published: September 2021

Background

Biogenic histamine plays an important role in immune response, neurotransmission, and allergic response. Although endogenous histamine production has been extensively studied, the contributions of histamine produced by the human gut microbiota have not been explored due to the absence of a systematic annotation of histamine-secreting bacteria.

Results

To identify the histamine-secreting bacteria from in the human gut microbiome, we conducted a systematic search for putative histamine-secreting bacteria in 36,554 genomes from the Genome Taxonomy Database and Unified Human Gastrointestinal Genome catalog. Using bioinformatic approaches, we identified 117 putative histamine-secreting bacteria species. A new three-component decarboxylation system including two colocalized decarboxylases and one transporter was observed in histamine-secreting bacteria among three different phyla. We found significant enrichment of histamine-secreting bacteria in patients with inflammatory bowel disease but not in patients with colorectal cancer suggesting a possible association between histamine-secreting bacteria and inflammatory bowel disease.

Conclusions

The findings of this study expand our knowledge of the taxonomic distribution of putative histamine-secreting bacteria in the human gut.
Accelerated hematopoietic mitotic aging measured by DNA methylation, blood cell lineage, and Parkinson’s disease
Authors: Paul Kimberly C , Binder Alexandra M , Horvath Steve , Kusters Cynthia , Yan Qi , Rosario Irish Del , Yu Yu , Bronstein Jeff , Ritz Beate
Published: September 2021

Background

Aging and inflammation are important components of Parkinson’s disease (PD) pathogenesis and both are associated with changes in hematopoiesis and blood cell composition. DNA methylation (DNAm) presents a mechanism to investigate inflammation, aging, and hematopoiesis in PD, using epigenetic mitotic aging and aging clocks. Here, we aimed to define the influence of blood cell lineage on epigenetic mitotic age and then investigate mitotic age acceleration with PD, while considering epigenetic age acceleration biomarkers.

Results

We estimated epigenetic mitotic age using the “epiTOC” epigenetic mitotic clock in 10 different blood cell populations and in a population-based study of PD with whole-blood. Within subject analysis of the flow-sorted purified blood cell types DNAm showed a clear separation of epigenetic mitotic age by cell lineage, with the mitotic age significantly lower in myeloid versus lymphoid cells (p = 2.1e-11). PD status was strongly associated with accelerated epigenetic mitotic aging (AccelEpiTOC) after controlling for cell composition (OR = 2.11, 95 % CI = 1.56, 2.86, p = 1.6e-6). AccelEpiTOC was also positively correlated with extrinsic epigenetic age acceleration, a DNAm aging biomarker related to immune system aging (with cell composition adjustment: R = 0.27, p = 6.5e-14), and both were independently associated with PD. Among PD patients, AccelEpiTOC measured at baseline was also associated with longitudinal motor and cognitive symptom decline.

Conclusions

The current study presents a first look at epigenetic mitotic aging in PD and our findings suggest accelerated hematopoietic cell mitosis, possibly reflecting immune pathway imbalances, in early PD that may also be related to motor and cognitive progression.
Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and other hematological parameters in psoriasis patients
Authors: Wang Wen-Ming , Wu Chao , Gao Yi-Meng , Li Feng , Yu Xiao-Ling , Jin Hong-Zhong
Published: September 2021

Background

Psoriasis is a chronic immune‐mediated skin disorder. Systemic inflammation plays an important role in the pathogenesis of psoriasis.

Methods

A total of 477 patients with psoriasis vulgaris (PsV, n = 347), generalized pustular psoriasis (GPP, n = 37), erythrodermic psoriasis (PsE, n = 45), arthritic psoriasis (PsA, n = 25) and mixed psoriasis (n = 23), and 954 healthy control subjects were included in the study. Demographic, clinical, and laboratory information were collected and compared between subgroups.

Results

Compared with the healthy control group, patients with psoriasis had higher total white blood cell (WBC), neutrophil, platelet counts, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR), but lower hemoglobin (Hb) levels, lymphocyte and red blood cell (RBC) counts. NLR values in the PsV group were significantly lower than those in the GPP, PsE, and PsA groups, with GPP group being the highest. PLR values in the PsV group were significantly lower than those in the GPP, PsE, and PsA groups. There was no significant correlation between the psoriasis area severity index (PASI) score and either the NLR or PLR in the PsV group.

Conclusions

Elevated NLR and PLR were associated with psoriasis and differed between subtypes, suggesting that they could be used as markers of systemic inflammation in psoriasis patients.
The effect of preventative cardiovascular therapies on coronary artery disease in people with and without type 2 diabetes: a propensity-matched score study
Authors: Kiburg Katerina V. , MacIsaac Andrew I. , McCluskey Georgia E. , Sundararajan Vijaya , MacIsaac Richard J.
Published: September 2021

Background

Although it is known that patients with Type 2 Diabetes Mellitus (T2DM) are at an increased risk of coronary artery disease (CAD), the actual coronary artery burden of atherosclerotic disease in patients with and without T2DM in a real-world setting and its possible modification by preventative therapies has not been extensively documented.

Methods

Merged coronary angiography and hospital discharge data between 2013 and 2019 were obtained for analysis and a random sub-sample of patient charts were reviewed for medication use. Propensity scores were estimated using logistic regression models and used to match patients, looking at the effect of severity of CAD over time in years in an ordinal logistic regression model. A separate propensity score was estimated and used to inverse probability weight the ordinal logistic regression looking at the effect of medication use on CAD severity in patients with and without T2DM.

Results

From 3,016 patients in the coronary angiography database, 1421 with T2DM and 1421 without T2DM were matched on propensity score. T2DM patients had more extensive CAD in 2018 compared to 2013 ((adjusted odds ratio) adjOR: 2.06 95% C.I. 1.38, 2.07), but this risk appeared to be attenuated in 2019. In contrast, there was no effect of time on CAD burden in patients without diabetes. In the sub-sample of 760 patients who underwent a chart review of their medication use, there were 367 (48%) with T2DM. For patients with T2DM 69.8% reported taking statins, 64.0% RAS inhibitors and 64.0% anti-platelet drugs. This was significantly higher than patients without diabetes of whom 46.6% reported taking statins, 49.0% RAS inhibitors and 49.9% anti-platelet drugs. As in the full matched sample, patients with diabetes had more extensive CAD (adjOR: 1.32 95% CI: 1.01, 1.74). However, after adjustment for the use of RAS inhibitors, statins and anticoagulants there was no difference in extent of CAD between patients with and without diabetes (adjOR: 1.14 95% CI: 0.85, 1.53).

Conclusions

Although patients with diabetes have a greater extent of CAD in comparison to those without T2DM, preventative medication use decreases this CAD burden significantly.
Myocardial dissection complicating left sinus of Valsalva aneurysm in silent takayasu arteritis
Authors: Astuti Astri , Kartamihardja Achmad Hafiedz Azis , Ilhamy Muhammad Adniel , Fahlavi Muhammad Dinnar , Kusumawardhani Nuraini Yasmin , Hasan Melawati , Hamijoyo Laniyati
Published: September 2021

Background

Myocardial dissection (MD) in a left sinus of Valsalva aneurysm (LSVA) is a rare condition that may lead to a fatal complication. Determining the MD etiology is challenging because of various possibilities ranging from congenital to acquired diseases. Here, we discuss an approach for determining the etiology of MD complicating LSVA in Takayasu arteritis (TA) and its treatment.

Case presentation

A 41-year-old man presented with dyspnea on heavy activities and a history of consciousness loss at the age of 24 years. He was diagnosed with dilated cardiomyopathy and MD complicating LSVA in TA based on combined clinical and pathognomonic diagnostic criteria of TA evaluated using vascular Doppler and computed tomography angiography of the aorta. The patient refused to undergo surgery and received an optimal dose of chronic heart failure therapy, a high-dose steroid, and azathioprine. The patient experienced some improvements in clinical condition, functional outcome, and inflammatory markers at 1-year follow-up.

Conclusions

Clinical criteria and various imaging modalities may be used to determine the etiology of MD complicating LSVA in silent TA. As an alternative to surgery, the optimal medical treatment might result in a satisfactory outcome.
Simultaneous acute limb ischemia related to acute Leriche syndrome and pulmonary embolism without existing patent foramen ovale: a case report
Authors: Li Ying-Sheng , Li Ying-Ching
Published: September 2021

Background

Aortoiliac occlusion disease, also called Leriche syndrome, is characterized by atherothrombotic obliteration of the aortic bifurcation and bilateral common iliac arteries; typically, it has a chronic presentation. Pulmonary embolism is more related to venous thromboembolism rather than arterial thromboembolic events. Therefore, cases of simultaneous acute Leriche syndrome and pulmonary embolism are rare. Existing intracardiac right-to-left shunt were detected in most previous cases. Herein, we present the first likely documented case wherein acute Leriche syndrome and pulmonary embolism occurred simultaneously without a patent foramen ovale.

Case presentation

A 58-year-old man with hyperlipidemia and coronary artery disease presented with a 4-h history of bilateral lower limb numbness. He was a heavy smoker with a history of stroke. Computed tomography angiography revealed pulmonary embolism and aortoiliac artery occlusion. Although a massive thrombus straddled the bilateral pulmonary arteries, orthopnea was his only presentation, without right ventricle failure. Cyanosis of the affected limbs was noted, and muscle strength in both limbs had regressed to grade 1. Owing to acute limb ischemia, he underwent an emergency operation to salvage the limbs. On postoperative day 5, the general condition of both the legs improved; the muscle strength improved to grade 4. He was then transferred to the general ward and enoxaparin was continued. Computed tomography angiography was repeated to evaluate the pulmonary embolism on postoperative day 8; the thrombus remained lodged in the bilateral main pulmonary arteries. Owing to persistent orthopnea and chest tightness with intermittent tachycardia, he underwent a staged operation for the pulmonary embolism on postoperative day 13. During the surgery, intraoperative transesophageal echocardiography showed no patent foramen ovale or an existing right-to-left shunt. Postoperatively, he was closely monitored in the intensive care unit for 3 days and then transferred to the general ward for 10 days. A final computed tomography angiography performed on postoperative day 18 revealed thrombus resolution. He was then discharged on postoperative day 30 without any in-hospital complications.

Conclusion

We present a case that might be the first documented report of acute Leriche syndrome co-occurring with pulmonary embolism without an existing patent foramen ovale.
Telehealth challenges during COVID-19 as reported by primary healthcare physicians in Quebec and Massachusetts
Authors: Breton Mylaine , Sullivan Erin E. , Deville-Stoetzel Nadia , McKinstry Danielle , DePuccio Matthew , Sriharan Abi , Deslauriers Véronique , Dong Anson , McAlearney Ann Scheck
Published: September 2021

Background

The COVID-19 pandemic has driven primary healthcare (PHC) providers to use telehealth as an alternative to traditional face-to-face consultations. Providing telehealth that meets the needs of patients in a pandemic has presented many challenges for PHC providers. The aim of this study was to describe the positive and negative implications of using telehealth in one Canadian (Quebec) and one American (Massachusetts) PHC setting during the COVID-19 pandemic as reported by physicians.

Methods

We conducted 42 individual semi-structured video interviews with physicians in Quebec (N = 20) and Massachusetts (N = 22) in 2020. Topics covered included their practice history, changes brought by the COVID-19 pandemic, and the advantages and challenges of telehealth. An inductive and deductive thematic analysis was carried out to identify implications of delivering care via telehealth.

Results

Four key themes were identified, each with positive and negative implications: 1) access for patients; 2) efficiency of care delivery; 3) professional impacts; and 4) relational dimensions of care. For patients’ access, positive implications referred to increased availability of services; negative implications involved barriers due to difficulties with access to and use of technologies. Positive implications for efficiency were related to improved follow-up care; negative implications involved difficulties in diagnosing in the absence of direct physical examination and non-verbal cues. For professional impacts, positive implications were related to flexibility (teleworking, more availability for patients) and reimbursement, while negative implications were related to technological limitations experienced by both patients and practitioners. For relational dimensions, positive implications included improved communication, as patients were more at ease at home, and the possibility of gathering information from what could be seen of the patient’s environment; negative implications were related to concerns around maintaining the therapeutic relationship and changes in patients’ engagement and expectations.

Conclusion

Ensuring that health services provision meets patients’ needs at all times calls for flexibility in care delivery modalities, role shifting to adapt to virtual care, sustained relationships with patients, and interprofessional collaboration. To succeed, these efforts require guidelines and training, as well as careful attention to technological barriers and interpersonal relationship needs.
Temporal trends in pre-ART patient characteristics and outcomes before the test and treat era in Central Kenya
Authors: Wekesa P. , McLigeyo A. , Owuor K. , Mwangi J. , Isavwa L. , Katana A.
Published: September 2021

Background

Retention of patients who did not initiate antiretroviral therapy (ART) has been persistently low compared to those who initiated ART. Understanding the temporal trends in clinical outcomes prior to ART initiation may inform interventions targeting patients who do not initiate ART immediately after diagnosis.

Methods

A retrospective cohort analysis of known HIV-infected patients who did not initiate ART from healthcare facilities in Central Kenya was done to investigate temporal trends in characteristics, retention, and mortality outcomes. The data were sourced from the Comprehensive Care Clinic Patient Application Database (CPAD) and IQ care electronic patient-level databases for those enrolled between 2004 and 2014.

Results

A total of 13,779 HIV-infected patients were assessed, of whom 30.7% were men.There were statisitically significant differences in temporal trends relating to marital status, WHO clinical stage, and tuberculosis (TB) status from 2004 to 2014. The proportion of widowed patients decreased from 9.1 to 6.0%. By WHO clinical stage at enrollment in program, those in WHO stage I increased over time from 8.7 to 43.1%, while those in WHO stage III and IV reduced from 28.5 to 10.8% and 4.0 to 1.1% respectively. Those on TB treatment during their last known visit reduced from 8.3 to 3.9% while those with no TB signs increased from 58.5 to 86.8%. Trends in 6 and 12 month retention in the program, loss to follow-up (LTFU) and mortality were statistically significant. At 6 months, program retention ranged between 36.0% in 2004 to a high of 54.1% in 2013. LTFU at 6 months remained around 50.0% for most of the cohorts, while mortality at 6 months was 7.5% in 2004 but reduced to 3.8% in 2014. At 12 months, LTFU was above 50.0% across all the cohorts while mortality rate reached 3.9% in 2014.

Conclusion

Trends in pre ART enrollment suggested higher enrollment among patients who were women and at earlier WHO clinical stages. Retention and mortality outcomes at 6 and 12 months generally improved over the 11 year follow-up period, though dipped as enrollment in asymptomatic disease stage increased.
Imaging features of skeletal muscle lymphoma: a case report and literature review
Authors: Gao Shuxi , Shu Hong , Yang Hua
Published: September 2021

Background

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), occurring predominantly in older people. Skeletal muscle lymphoma is a rare form of DLBCL, most frequently affecting the thigh, upper extremities, calf, and pelvis.

Case presentation

We report a case of skeletal muscle DLBCL that was diagnosed using ultrasound (US)-guided biopsy. A 70-year-old man presented with progressive swelling and pain in the left lower extremity and an elevated erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP), ferritin, and CA125 levels. US, magnetic resonance imaging (MRI), and computed tomography (CT) showed diffuse lesions in several muscles of the left lower extremity. Positron emission tomography/CT (PET/CT) showed FDG-uptake in the affected muscles. The patient was treated with chemotherapy and achieved a good response. A systematic review of the literature published between 1992 and 2019 was conducted to investigate the role of imaging, including imaging-guided biopsy, in the diagnosis of skeletal muscle lymphoma.

Conclusions

Skeletal muscle lymphoma is rare. US and MRI features include enlargement of muscular structures, with preservation of the architecture of the tissue and surrounding anatomical structures. Definitive diagnosis relies on histological and immunohistological analysis of a sample obtained through imaging-guided biopsy.
LAMA2 and LOXL4 are candidate FSGS genes
Authors: Vijayan Poornima , Hack Saidah , Yao Tony , Qureshi Mohammad Azfar , Paterson Andrew D. , John Rohan , Davenport Bernard , Lennon Rachel , Pei York , Barua Moumita
Published: September 2021

Background

Focal and segmental glomerulosclerosis (FSGS) is a histologic pattern of injury that characterizes a wide spectrum of diseases. Many genetic causes have been identified in FSGS but even in families with comprehensive testing, a significant proportion remain unexplained.

Methods

In a family with adult-onset autosomal dominant FSGS, linkage analysis was performed in 11 family members followed by whole exome sequencing (WES) in 3 affected relatives to identify candidate genes.

Results

Pathogenic variants in known nephropathy genes were excluded. Subsequently, linkage analysis was performed and narrowed the disease gene(s) to within 3% of the genome. WES identified 5 heterozygous rare variants, which were sequenced in 11 relatives where DNA was available. Two of these variants, in LAMA2 and LOXL4, remained as candidates after segregation analysis and encode extracellular matrix proteins of the glomerulus. Renal biopsies showed classic segmental sclerosis/hyalinosis lesion on a background of mild mesangial hypercellularity. Examination of basement membranes with electron microscopy showed regions of dense mesangial matrix in one individual and wider glomerular basement membrane (GBM) thickness in two individuals compared to historic control averages.

Conclusions

Based on our findings, we postulate that the additive effect of digenic inheritance of heterozygous variants in LAMA2 and LOXL4 leads to adult-onset FSGS. Limitations to our study includes the absence of functional characterization to support pathogenicity. Alternatively, identification of additional FSGS cases with suspected deleterious variants in LAMA2 and LOXL4 will provide more evidence for disease causality. Thus, our report will be of benefit to the renal community as sequencing in renal disease becomes more widespread.