bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia
Authors: Kim Sung Wook , Oh Joo Suk , Park Jungtaek , Jeong Hyun Ho , Oh Young Min , Choi Semin , Choi Kyoung Ho
Published: June 2020

Background

Paricalcitol is known to attenuate ischemic-reperfusion injury of various organs. However, it is not known whether paricalcitol prevents neuronal injury after global cerebral ischemia. The purpose of this study is to investigate the neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia.

Methods

This is a prospective, randomized experimental study. Male Sprague-Dawley rats that survived 10 min of four-vessel occlusion were randomly assigned to two treatment groups: one group was treated with paricalcitol 1 μg/kg IP, and the other was given an equivalent volume of normal saline IP. Drugs were administered at 5 min, 1 day, 2 days, and 3 days after ischemia. Neurologic function was assessed at 2 h, 1 day, 2 days, 3 days, and 4 days after ischemia. We tested motor function 3 days after ischemia using the rotarod test. Also, we tested memory function 4 days after ischemia using the passive avoidance test. We assessed neuronal degeneration in the hippocampus of surviving rats 4 days after ischemia.

Results

Eight rats were allocated to each group. No significant differences were found between the groups in terms of survival rate, motor coordination, or memory function. The neurological function score 2-h post-ischemia was significantly higher in the paricalcitol group (p = 0.04). Neuronal degeneration was significantly less in the paricalcitol group compared with the control group (p = 0.01).

Conclusions

Paricalcitol significantly attenuated neuronal injury in the hippocampus. Although motor coordination, memory function, and survival rate were not significantly improved by paricalcitol treatment in this study, paricalcitol remains a potential neuroprotective drug after global cerebral ischemia.
The local hypothalamic–pituitary–adrenal axis in cultured human dermal papilla cells
Authors: Lee Eun Young , Nam You Jin , Kang Sangjin , Choi Eun Ju , Han Inbo , Kim Jinwan , Kim Dong Hyun , An Ji Hae , Lee Sunghou , Lee Min Ho , Chung Ji Hyung
Published: June 2020

Background

Stress is an important cause of skin disease, including hair loss. The hormonal response to stress is due to the HPA axis, which comprises hormones such as corticotropin releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cortisol. Many reports have shown that CRF, a crucial stress hormone, inhibits hair growth and induces hair loss. However, the underlying mechanisms are still unclear. The aim of this study was to examine the effect of CRF on human dermal papilla cells (DPCs) as well as hair follicles and to investigate whether the HPA axis was established in cultured human DPCs.

Results

CRF inhibited hair shaft elongation and induced early catagen transition in human hair follicles. Hair follicle cells, both human DPCs and human ORSCs, expressed CRF and its receptors and responded to CRF. CRF inhibited the proliferation of human DPCs through cell cycle arrest at G2/M phase and induced the accumulation of reactive oxygen species (ROS). Anagen-related cytokine levels were downregulated in CRF-treated human DPCs. Interestingly, increases in proopiomelanocortin (POMC), ACTH, and cortisol were induced by CRF in human DPCs, and antagonists for the CRF receptor blocked the effects of this hormone.

Conclusion

The results of this study showed that stress can cause hair loss by acting through stress hormones. Additionally, these results suggested that a fully functional HPA axis exists in human DPCs and that CRF directly affects human DPCs as well as human hair follicles under stress conditions.
Response to “understanding the behavioural determinants of opioid prescribing among family physicians: a qualitative study”
Authors: Busse Jason W. , Juurlink David , Buckley D. Norman , Guyatt Gordon H.
Published: June 2020

The 2017 Canadian opioid Guideline made both strong recommendations, indicating that all or almost all fully informed patients would choose the recommended course of action, and weak recommendations, in which different choices are appropriate for individual patients based on their values and preferences. The Guideline’s recommendation to taper legacy patients prescribed high-dose opioid therapy is weak, and mandatory tapering is expressly discouraged.
Genetic variants of VDR and CYP2R1 affect BMI independently of serum vitamin D concentrations
Authors: Bakos Bence , Szili Balázs , Szabó Boglárka , Horváth Péter , Kirschner Gyöngyi , Kósa János P. , Toldy Erzsébet , Lakatos Péter , Tabák Ádám G. , Takács István
Published: June 2020

Background

Vitamin D metabolism and obesity have been linked by several studies, however the reason for this association is unclear. Our objective was to investigate potential correlations between genetic variants in key enzymes of vitamin D metabolism and the body mass index on a representative and random sample of Hungarian adults.

Methods

Altogether 462 severely vitamin D deficient individuals were studied at the end of winter in order to decrease environmental and maximize any relevant genetic effect. Furthermore, participants with lifestyle factors known to affect vitamin D homeostasis were also excluded. We selected 23 target SNPs in five genes that encode key proteins of vitamin D metabolism (NADSYN1, GC, CYP24A1, CYP2R1, VDR).

Results

Variants in 2 genetic polymorphisms; rs2853564 (VDR) and rs11023374 (CYP2R1) showed a significant association with participants‘ BMI. These associations survived further adjustment for total-, free-, or bioactive-25(OH) vitamin D levels, although the variance explained by these 2 SNPS in BMI heterogeneity was only 3.2%.

Conclusion

Our results show two novel examples of the relationship between genetics of vitamin D and BMI, highlighting the potential role of vitamin D hormone in the physiology of obesity.
Factors influencing delivery of intersectoral actions to address infant stunting in Bogotá, Colombia – a mixed methods case study
Authors: Botero-Tovar Natalia , Arocha Zuluaga Gina Paola , Ramírez Varela Andrea
Published: June 2020

Background

Intersectoral actions (ISA) are a recognized relationship between the health sector and other sectors to improve health outcomes. Although a frequent topic in public health studies, evidence for systematic evaluation of implementation of ISA is scarce. An intersectoral health intervention for infants under one-year-old with, and at risk of, stunting (low height-for-age) was developed by a public-private partnership in Bogotá, Colombia, during 2018 and 2019. Here we report a case study conducted in parallel to the intervention designed to assess factors that influenced implementation of the ISA.

Methods

The case study was developed using a concurrent mixed-methods design, with the qualitative component giving context to the quantitative results. The qualitative component was obtained from four workshops, three focus groups, and 17 semi-structured interviews with actors involved in the intersectoral intervention. The quantitative component was obtained with two questionnaires that evaluated perceptions on improvement and partnership functioning of the ISA.

Results

This study collected information from 122 participants. The intervention demanded intersectoral collaboration. Political will, motivated human resources, and recognition that health improvement results from collaboration, were factors that facilitated intersectoral actions. Intersectoral actions were limited by difficulties in engaging the health sector, communication challenges related to local health service decentralization, and administrative barriers.

Conclusions

Intersectoral actions have recently been discussed in the literature due to challenges in implementation and doubts regarding economic outcomes. The implementation of intersectoral public health interventions can be jeopardized by a lack of coordination and management skills.
Open fenestration discectomy versus microscopic fenestration discectomy for lumbar disc herniation: a randomized controlled trial
Authors: Hamawandi Sherwan A. , Sulaiman Injam Ibrahim , Al-Humairi Ameer Kadhim
Published: June 2020

Background

Fenestration discectomy, for symptomatic lumbar disc herniation, is the most common surgical procedure in spine surgery. It can be done by open or microscopic procedures. This study compared the results of fenestration microdiscectomy with open fenestration discectomy in the treatment of symptomatic lumbar disc herniation as a relation to the functional outcome, leg pain, back pain, hospital stay, returns to daily activity, cost, recurrence, reoperation and type of surgery for recurrent disc herniation.

Methods

60 patients age (29 - 50 years), with L4-L5 disc herniation, are divided randomly into group A- 30 patients underwent an open fenestration discectomy- and group B- 30 patients underwent fenestration microdiscectomy. All patients are assessed at 1 week, 3 months, 6 months, 12 months after surgery for Oswestry disability index and Visual analogue scale for back pain and leg pain and followed up for 4 years.

Results

In both groups, all patients have minimal disability by Oswestry Disability Index after surgery.

There were significant differences between means of post-operative Visual Analogue Scale for back pain between these two groups after 1 week (3.7 in group A versus 2.2 in group B) (t = 13.28, P = < 0.001*) and after 3 months (1.73 in group A versus 0.43 in group B) (t = 10.54, P = < 0.001*).

There were no significant differences between two groups regarding post-operative VAS for leg pain, recurrence (5 patients in group A versus 4 patients in group B) and reoperation rate (2 patients in each group).

There were significant differences between means of length of hospital stay (2.10 in group A versus 1.06 in group B) (P < 0.001), time of returning to daily activities (7.33 in group A versus 4.03 in group B) (P < 0.001) and cost of surgery (1996.66 in group A versus 3003.3 in group B) (P < 0.001).

Conclusion

Use of microscope in fenestration discectomy for treatment of symptomatic lumbar disc herniation can achieve the same goals of open fenestration regarding nerve root decompression and relief of leg pain with advantage of less back pain, less hospital staying and early return to daily activities with disadvantage of more cost with the use of microscope. With 4 years follow up, there was no significant deference in rate of recurrence and reoperation with the use of microscope but we found that type of surgery for recurrent cases may be less invasive if microscope was used in primary surgery.

Trial registration

NCT, NCT04112485. Registered 30 September 2019 - Retrospectively registered, https://clinicaltrials.gov/NCT04112485
Endoscopic treatments prior to urethroplasty: trends in management of urethral stricture disease
Authors: Moynihan Matthew J. , Voelzke Bryan , Myers Jeremy , Breyer Benjamin N. , Erickson Bradley , Elliott Sean P. , Alsikafi Nejd , Buckley Jill , Zhao Lee , Smith Thomas , Vanni Alex J.
Published: June 2020

Background

To determine if the number of endoscopic treatments of urethral stricture disease (USD) prior to urethroplasty has changed in the context of new AUA guidelines on management of USD. In addition to an increase in practicing reconstructive urologists and published reconstructive literature, the AUA guidelines regarding the management of male USD were presented in May 2016, advocating consideration of urethroplasty in patients with 1 prior failed endoscopic treatment.

Methods

A retrospective review of a prospectively maintained, multi-institutional urethral stricture database of high volume, geographically diverse institutions was performed from 2006 to 2017. We performed a review of relevant literature and evaluated pre-urethroplasty endoscopic treatment patterns prior to and after the AUA male stricture guideline.

Results

2964 urethroplasties were reviewed in 10 institutions. There was both a decrease in the number of endoscopic treatments prior to urethroplasty in the pre-May 2016 compared to post-May 2016 cohorts both for overall urethroplasties (2.3 vs 1.6, P = 0.0012) and a gradual decrease in the number of pre-urethroplasty endoscopic treatments over the entire study period.

Conclusion

There was a decrease in the number of endoscopic treatments of USD prior to urethroplasty in the observed period of interest. Declining endoscopic USD management is not likely to be a reflection of a solely unique influence of the guidelines as endoscopic treatment decreased over the entire study period. Further research is needed to determine if there will be a continued trend in the declining use of endoscopic treatment and elucidate the barriers to earlier urethroplasty in patients with USD.
Study rationale and design of the EANITIATE study (EmpAgliflozin compared to NPH Insulin for sTeroId diAbeTEs) - a randomized, controlled, multicenter trial of safety and efficacy of treatment with empagliflozin compared with NPH-insulin in patients with newly onset diabetes following initiation of glucocorticoid treatment
Authors: Klarskov Carina Kirstine , Holm Schultz Helga , Persson Frederik , Møller Christensen Tomas , Almdal Thomas Peter , Snorgaard Ole , Bagge Hansen Katrine , Pedersen-Bjergaard Ulrik , Lommer Kristensen Peter
Published: June 2020

Background

A well-known metabolic side effect from treatment with glucocorticoids is glucocorticoid-induced diabetes mellitus (GIDM). Guidelines on the management of GIDM in hospitalized patients (in the non-critical care setting), recommend initiation of insulin therapy. The scientific basis and evidence for superiority of insulin therapy over other glucose lowering therapies is however poor and associated with episodes of both hypo- and hyperglycaemia. There is an unmet need for an easier, safe and convenient therapy for glucocorticoid-induced diabetes.

Methods

EANITIATE is a Danish, open, prospective, multicenter, randomized (1:1), parallel group study in patients with new-onset diabetes following treatment with glucocorticoids (> 20 mg equivalent prednisolone dose/day) with blinded endpoint evaluation (PROBE design). Included patients are randomized to either a Sodium-Glucose-Cotransporter 2 (SGLT2) inhibitor or neutral protamin Hagedorn (NPH) insulin and followed for 30 days. Blinded continuous glucose monitoring (CGM) will provide data for the primary endpoint (mean daily blood glucose) and on glucose fluctuations in the two treatment arms. Secondary endpoints are patient related outcomes, hypoglycaemia, means and measures of variation for all values and for time specific glucose values. This is a non-inferiority study with the intent to demonstrate that treatment with empagliflozin is not inferior to treatment with NPH insulin when it comes to glycemic control and side effects.

Discussion

This novel approach to management of glucocorticoid-induced hyperglycemia has not been tested before and if SGLT2 inhibition with empaglifozin compared to NPH-insulin is a safe, effective and resource sparing treatment for GIDM, it has the potential to improve the situation for affected patients and have health economic benefits.

Trial registration

www.clinicaltrialsregister.euno.:2018–002640-82. Prospectively registered November 20th. 2018.

Date of first patient enrolled:June 4th. 2019.

This protocol article is based on the EANITATE protocol version 1.3, dated 29. January 2018.
An unusual case of infected uterus masculinus in a dog
Authors: Kyllar Michal , Čížek Petr
Published: June 2020

Background

Paraprostatic cysts are large structures that develop between the prostate gland and urinary bladder, usually in older, intact dogs. Their incidence is reported to be 1.1–5.3% in dogs with prostatic disease. The aetiology of paraprostatic cysts is not fully understood, but they are believed to develop from the uterus masculinus. Whereas the uterus masculinus has been reported to communicate with the urethra in men and horses, no communication between the uterus masculinus and urethra has been identified in dogs.

Case presentation

An entire male dog was presented with a bloody discharge from its penis and tenesmus of 5 days’ duration. A diagnosis of cystic uterus masculinus was made on the basis of the findings of abdominal ultrasonography and histopathology of tissues obtained during an exploratory laparotomy. In addition, a Sertoli cell tumour affecting both testes was diagnosed following scrotal castration. The cystic uterus masculinus was completely resected, after which the tenesmus and bloody discharge resolved. Thus, cystic uterus masculinus should be considered as a differential diagnosis for a paraprostatic cyst when such a lesion develops as part of the feminising effect of a Sertoli cell tumour.

Conclusions

Cystic uterus masculinus should be considered as a differential diagnosis for tenesmus and penile discharge, and for structures resembling paraprostatic cysts. This case report confirms that a uterus masculinus can communicate with the urethra in dogs, as in other species, and demonstrates endocrine responsiveness, manifesting as epithelial and glandular metaplasia and mucus production, with the potential for subsequent infection.
Hospitalization for heart failure incidence according to the transition in metabolic health and obesity status: a nationwide population-based study
Authors: Lee You-Bin , Kim Da Hye , Kim Seon Mee , Kim Nan Hee , Choi Kyung Mook , Baik Sei Hyun , Park Yong Gyu , Han Kyungdo , Yoo Hye Jin
Published: June 2020

Background

We aimed to investigate the hazard of hospitalization for heart failure (hHF) according to the transitions in metabolic health and obesity status.

Methods

The Korean National Health Insurance Service datasets from 2002 to 2017 were used for this nationwide, longitudinal, population-based study. The hazard of hHF was analyzed according to the eight groups stratified by stability in metabolic health and transition in obesity status among initially metabolically healthy adults who underwent two cycles of health examinations in 2009–2010 and 2013–2014 (N = 7,148,763).

Results

During two examinations, 48.43% of the initially metabolically healthy obese (MHO) individuals and 20.94% of the initially metabolically healthy non-obese (MHNO) individuals showed changes in their metabolic health and obesity status. During a mean follow-up of 3.70 years, 3151 individuals were hospitalized for HF. When stable MHNO individuals were set as the reference, transition to metabolically unhealthy phenotype was associated with an increased hazard of hHF; the hazard ratio (HR) and 95% confidence interval (CI) in the individuals who transformed from MHO to metabolically unhealthy non-obese was 2.033 (1.579–2.616). The constant MHO group had a 17.3% increased hazard of hHF compared with the stable MHNO group [HR (95% CI) 1.173 (1.039–1.325)]. Individuals who shifted from MHO to MHNO showed a 34.3% lower hazard of hHF compared with those who maintained the MHO category [HR (95% CI) 0.657 (0.508–0.849)].

Conclusion

Dynamic changes in metabolic health and obesity status were observed during a relatively short interval of 3–5 years. Loss of metabolic health was significantly associated with an increased hazard of hHF. Even if metabolic health was maintained, persistent obesity remained as a risk factor for hHF, and transition from MHO to MHNO had a protective effect against hHF. Therefore, the prevention and control of obesity while maintaining metabolic health would be crucial in preventing hHF.
Peripheral arterial endothelial dysfunction predicts future cardiovascular events in diabetic patients with albuminuria: a prospective cohort study
Authors: Koo Bo Kyung , Chung Woo-Young , Moon Min Kyong
Published: June 2020

Background

Reactive hyperemia-peripheral arterial tonometry (RH-PAT) is a noninvasive and simple test for evaluating the endothelial function. There has been sparse evidence on the usefulness of the RH-PAT index (RHI) in predicting future cardiovascular diseases among diabetic patients.

Methods

Asymptomatic diabetic patients with albuminuria were selected; their medical history and laboratory findings were evaluated every 3 to 4 months, respectively. The primary outcome was a composite of three-point major adverse cardiovascular events (3-point MACE): death from cardiovascular causes, acute coronary events, or nonfatal stroke. On the contrary, secondary outcomes included a composite of 3-point MACE, hospitalization for heart failure, or chronic kidney disease (CKD) progression. RHI was measured using the Endo-PAT2000 at the baseline. RHI < 1.67 was considered to indicate peripheral endothelial dysfunction (PED).

Results

In total, 149 subjects were included (mean age, 61.8 ± 9.2 years; duration of diabetes was 12 years). During the follow-up period (median, 49.7 months), of the 149 subjects, primary outcomes were detected in 12 (1 [2.3%] and 11 [10.5%] of those without and with PED, respectively). The presence of PED in baseline measurements significantly increased both primary and secondary outcomes, following adjustment for age, sex, hypertension, glycated hemoglobin, low-density lipoprotein cholesterol, triglyceride, systolic blood pressure, baseline estimated glomerular filtration rate, overt proteinuria, duration of diabetes, premedical history of ischemic events, anti-platelet agents, and smoking history (hazard ratio [HR]: 10.95; 95% confidence interval CI 1.00–119.91 for the primary outcome; HR, 4.12; 95% CI 1.37–12.41 for secondary outcome). In addition, PED could predict secondary outcomes independent of the risk score according to the American College of Cardiology/American Heart Association (HR: 3.24; 95% CI 1.14–9.17).

Conclusions

PED can independently predict future cardiovascular events among diabetic patients with albuminuria.
Impact of diabetes mellitus on left ventricular longitudinal function of patients with non-ischemic dilated cardiomyopathy
Authors: Tanaka Hidekazu , Tatsumi Kazuhiro , Matsuzoe Hiroki , Matsumoto Kensuke , Hirata Ken-ichi
Published: June 2020

Background

Left ventricular (LV) longitudinal dysfunction has been identified in type 2 diabetes mellitus (T2DM) patients with preserved LV ejection fraction (LVEF). However, the impact of T2DM on LV longitudinal function or the association of LV longitudinal function with outcome for dilated cardiomyopathy (DCM) remains unclear.

Methods

We retrospectively studied 206 patients with non-ischemic DCM, mean age of 59 ± 17 years and LVEF of 31 ± 8% (all < 45%). All patients underwent a standard echocardiographic examination, and LV longitudinal function was assessed in terms of global longitudinal strain (GLS). Long-term outcomes were assessed, with a median follow-up period of 6.2 years, as primary endpoints of death from or hospitalization for deteriorating heart failure.

Results

GLS of DCM patients with T2DM (n = 55) was significantly lower than that in DCM patients without T2DM (n = 151) in spite of similar conventional LV function (7.0 ± 2.0% vs. 7.8 ± 2.2%, p = 0.03). Kaplan–Meier curves indicated that long-term outcomes for DCM patients without T2DM were better than for those with T2DM (log-rank p = 0.001). Subdividing the two groups into four with by using the median value of GLS (7.9%) showed long-term outcome was worst for DCM patients with T2DM and low GLS. Cox proportional hazards analyses demonstrated an independent association of T2DM, GLS and left atrial volume index with long-term outcome. Moreover, multiple regression analysis for the association of GLS showed that T2DM was the independent determinant parameter for GLS as well as for LVEF and left atrial volume index.

Conclusion

Management of DCM patients with T2DM may be improved by using GLS guidance.
ε2 allele and ε2-involved genotypes (ε2/ε2, ε2/ε3, and ε2/ε4) may confer the association of APOE genetic polymorphism with risks of nephropathy in type 2 diabetes: a meta-analysis
Authors: Shi Jikang , Cheng Zhaorui , Qiu Shuang , Cui Heran , Gu Yulu , Zhao Qian , Ren Yaxuan , Zhang He , Sun Helin , Liu Yunkai , Li Yong , Qiao Yichun , Hu Yueyang , Liu Yawen , Cheng Yi
Published: June 2020

Background

Diabetic nephropathy (DN) contributes to end-stage renal failure. Microvascular injury resulted from reactive oxygen species is implicated in the pathogenesis of DN. Genetic polymorphism of Apolipoprotein E (APOE) influences the antioxidative properties of the protein. The relationship of APOE polymorphism with the risks of nephropathy in type 2 diabetes (T2DN) remains elusive.

Methods

An up-to-date meta-analysis was conducted on the basis of studies selected from PubMed, WanFang database, Embase, Vip database, Web of Science, Scopus, and CNKI database.

Results

A total of 33 studies conferring 3266 cases and 3259 controls were selected on the basis of criteria of inclusion and exclusion in this meta-analysis. For APOE alleles, the pooled odds ratio (OR) of ε2 vs. ε3 was 1.89 (95% confidence intervals [95% CI]: 1.49–2.38, P < 0.0001). With regard to APOE genotypes, ε2/ε2, ε2/ε3, and ε2/ε4 increased the risk of T2DN (ε2/ε2 vs. ε3/ε3: OR = 2.32, 95% CI: 1.52–3.56, P = 0.0001; ε2/ε3 vs. ε3/ε3: OR = 1.97, 95% CI: 1.50–2.59, P<0.0001; ε2/ε4 vs. ε3/ε3: OR = 1.69, 95% CI: 1.18–2.44, P = 0.0046).

Conclusions

This meta-analysis found that the APOE ε2 allele and the ε2-involved genotypes (ε2/ε2, ε2/ε3, and ε2/ε4) are the risk factors of T2DN.
Correction to: Safety of long-term electrical peripheral nerve stimulation: review of the state of the art
Authors: Günter Clara , Delbeke Jean , Ortiz-Catalan Max
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Impact of HIV infection on consolidative radiotherapy for non-Hodgkin diffuse large B-cell lymphoma
Authors: Medici Carolina Trindade Mello , Mauro Geovanne Pedro , Casimiro Lucas Coelho , Weltman Eduardo
Published: June 2020

Objectives

Even though frequent, it is not known how HIV infection and treatment impact in the consolidation by radiotherapy of non-Hodgkin diffuse large B-cell lymphomas (DBCL). This article aim to assess that difference that HIV makes on radiation treatment.

Patients and methods

A retrospective cohort of all DBCL patients treated with chemotherapy and consolidative radiotherapy at a single institution between 2010 and 2018 was assessed. All patients had biopsy-proven lymphoma and were included if radiation was part of the treatment and had at least 6 months of follow-up or were followed until death.

Results

Three-hundred fifty-nine (359) patients were selected, with a median age at diagnosis of 57.7 years (13–90 years). Twenty-eight patients (7.8%) were HIV positive. Median follow-up was 48.0 months. Female patients were 51.3% and most had a good performance in the ECOG scale (78.8% are ECOG 0–1). Median overall survival was not reached, but mean OS was 50.1 months with 86 deaths. Median progression-free survival was 48.7 months. HIV infection had no impact on OS (p = 0.580) or PFS (p = 0.347) among patients treated with RT. HIV positive patients were more frequently staged only with CT (p > 0.05) with no impact on PFS (p = 0.191). No HIV positive patient received rituximab due to local policy restrictions and HIV positive patients were more prone to receive CHOP-like chemotherapy (p < 0.05), specially ones with etoposide (CHOEP). CHOP was associated with better survival (p = 0.015) in the overall population and in the HIV negative population (p = 0.002), but not in the HIV positive population (p = 0.982). RT toxicities were not overall more frequent in the HIV positive population (p = 0.567), except for fatigue (p < 0.05) and hematological toxicities (p = 0.022).

Conclusion

HIV status did not influence on survival when patients were treated with consolidative radiotherapy. HIV infection was a bias on our sample for staging methods and chemotherapy regimens choices. For HIV positive patients there was an increase in fatigue and hematological toxicities of any grade with radiation.
Improving the surgical consenting process for patients with acute hip fractures: a pilot quality improvement project
Authors: Singh Kirit , Assaf Ali , Bayley Morgan , Gillespie Gordon
Published: June 2020

Background

Consenting patients for trauma procedures following hip fracture is a key stage in the treatment pathway from admission to the operating theatre. Errors in this process can result in delayed procedures which may negatively impact patient recovery. The aim of this project was to identify and reduce errors in our consenting process for patients with capacity.

Methods

Consent forms for all adult patients with capacity admitted for surgical repair of traumatic hip fracture were reviewed over a 4-week period. The baseline measurement (n = 24), identified errors in three key process measures: clarity of documentation, failure to record procedure-specific risks and not offering a copy of the consent form to the patient. Pre-printed stickers and targeted teaching were then introduced as quality improvement measures. Their impact was evaluated over subsequent 4-week review of the same patient demographic, with further refinement of these interventions being carried out and re-evaluated for a final cycle.

Results

Cycle 1 (n = 26) following targeted teaching demonstrated a reduction in abbreviations from 38 to 20%, while doubling the documentation of discussion of procedure-specific risks from 31 to 72%. More patients were offered a copy of their consent form, rising from 12 to 48%. Cycle 2 (n = 24) saw the introduction of pre-printed “risk of procedure” stickers. Although clarity measures continued to improve, quality of pre-procedure risk documentation remained static while the number of forms being offered to patients fell to 8%.

Conclusions

Our project would suggest that while pre-printed stickers can be useful memory aids, specific teaching on consenting produces the greatest benefit. The usage of such tools should therefore be limited, as adjuncts only to specific training.
Serological evaluation of selected vector-borne pathogens in owned dogs from northern Spain based on a multicenter study using a commercial test
Authors: Díaz-Regañón David , Roura Xavier , Suárez María L. , León Marta , Sainz Ángel
Published: June 2020

Background

Environmental conditions in northern Spain allow the development of different arthropods involved in the transmission of significant canine vector-borne pathogens. The aim of the study was to systematically assess seroprevalence rates for Leishmania infantum, Ehrlichia canis, Anaplasma spp., Dirofilaria immitis and Borrelia burgdorferi, and risk factors in dogs from all regions of the north of Spain.

Methods

A total of 556 dogs were included in this study between January 2017 and December 2018, belonging to 30 practices covering all regions in northern Spain (Galicia, Asturias, Cantabria, Basque Country, Navarra, Aragon and Catalonia). All practices were located in the north of every region. Blood samples were analyzed using the 4DX SNAP® test (IDEXX Laboratories, Westbrook, Maine, USA) for the detection of D. immitis antigen and E. canis, B. burgdorferi and Anaplasma spp. antibodies. Leishmania SNAP® test (IDEXX Laboratories) was used for detection of L. infantum antibodies. Associations between prevalence of canine vector-borne pathogens, epidemiological and clinical signs data were statistically analyzed.

Results

The overall prevalence rates were 8.99% for L. infantum, 1.26% for Anaplasma spp., 0.9% for E. canis, 0.72% for B. burgdorferi, and 0.18% for D. immitis. Globally, 11.33% of the dogs included in the study were positive to any tested vector-borne pathogen. Leishmania infantum seroprevalence was the highest and the only one detected in all the regions. Leishmania infantum seropositivity was associated with age > 10 years-old, outdoor access, anemia, fever, dermatological signs, lympadenomegaly, muscular atrophy, ocular signs and renal disease. Ehrlichia canis seropositivity was associated with the summer season and living in urban areas. Apathy, weakness, anorexia, weight loss, anemia, fever and gastrointestinal clinical signs were also associated with E. canis antibody detection. Living in a rural area was also a risk factor for Anaplasma spp. and B. burgdorferi seropositivity.

Conclusions

To our knowledge, this is the first multicenter survey performed in northern Spain assessing different canine vector-borne diseases from all regions. Results show the presence of autochthonous cases of these diseases. The vector-borne pathogens found in this study should be included in the differential diagnosis in dogs from some areas previously considered non-endemic for these pathogens.
Blood parasites in vectors reveal a united blackfly community in the upper canopy
Authors: Chakarov Nayden , Kampen Helge , Wiegmann Anja , Werner Doreen , Bensch Staffan
Published: June 2020

Background

The behaviour of blood-sucking arthropods is a crucial determinant of blood protozoan distribution and hence of host-parasite coevolution, but it is very challenging to study in the wild. The molecular identification of parasite lineages in vectors can be a useful key to understand the behaviour and transmission patterns realised by these vectors.

Methods

In this study, we collected blackflies around nests of three raptor species in the upper forest canopy in central Europe and examined the presence of vertebrate DNA and haemosporidian parasites in them. We molecularly analysed 156 blackfly individuals, their vertebrate blood meals, and the haemosporidian parasite lineages they carried.

Results

We identified nine species of Simulium blackflies, largely belonging to the subgenera Nevermannia and Eusimulium. Only 1% of the collected specimens was visibly engorged, and only 4% contained remains of host DNA. However, in 29% of the blackflies Leucocytozoon lineages were identified, which is evidence of a previous blood meal on an avian host. Based on the known vertebrate hosts of the recorded Leucocytozoon lineages, we can infer that large and/or abundant birds, such as thrushes, crows, pigeons, birds of prey, owls and tits are the main targets of ornithophilic blackflies in the canopy. Blackfly species contained similar proportions of host group-specific parasite lineages and thus do not appear to be associated with particular host groups.

Conclusions

The Leucocytozoon clade infecting thrushes, crows, and pigeons present in most represented blackfly species suggests a lack of association between hosts and blackflies, which can increase the probability of host switches of blood parasites. However, the composition of the simuliid species differed between nests of common buzzards, goshawks and red kites. This segregation can be explained by coinciding habitat preferences between host and vector, and may lead to the fast speciation of Leucocytozoon parasites. Thus, subtle ecological preferences and lack of host preference of vectors in the canopy may enable both parasite diversification and host switches, and enforce a habitat-dependent evolution of avian malaria parasites and related haemosporidia.
Influence of age on the occurrence of adverse events in rheumatic patients at the onset of biological treatment: data from the BIOBADASER III register
Authors: Vela Paloma , Sanchez-Piedra Carlos , Perez-Garcia Carolina , Castro-Villegas María C. , Freire Mercedes , Mateo Lourdes , Díaz-Torné Cesar , Bohorquez Cristina , Blanco-Madrigal Juan M. , Ros-Vilamajo Inmaculada , Gómez Silvia , Caño Rocio , Sánchez-Alonso Fernando , Díaz-González Federico , Gómez-Reino Juan J.
Published: June 2020

Objectives

To assess whether age, at the beginning of biologic treatment, is associated with the time a first adverse event (AE) appears in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA).

Methods

All patients in the BIOBADASER registry diagnosed with RA, AS, and PsA, and classified as young (< 25 years old), adult (25–64 years old), elderly (65–75 years old) or very elderly (> 75 years old) at start of biological treatment were included. Factors associated with the appearance of a first AE using adjusted incidence rate ratios (IRR) (Poisson regression) were analyzed. Survival to first AE was studied by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression.

Results

2483 patients were included: 1126 RA, 680 PsA, and 677 AS. Age group stratification was as follows: 63 young, 2127 adults, 237 elderly, and 56 very elderly. Regression model revealed an increased probability of suffering a first AE at age 65 years or older [IRR elderly: 1.42 (CI95% 1.13–1.77)]. Other characteristics associated with AE were female gender, the use of DMARDs, including methotrexate, the presence of comorbidities, and the time of disease duration. Factors that had the greatest impact on survival over a first AE were age > 75 years [HR 1.50 (1.01–2.24)] and female gender [HR 1.42 (1.22–1.64)].

Conclusion

Age at the start of treatment and female gender are key factors associated with the appearance of a first AE with biologics. Other factors related to patient status and treatment were also associated with a first AE in rheumatic patients treated with biologics.
The role of O-polysaccharide chain and complement resistance of Escherichia coli in mammary virulence
Authors: Salamon Hagit , Nissim-Eliraz Einat , Ardronai Oded , Nissan Israel , Shpigel Nahum Y.
Published: June 2020

Mastitis, inflammation of the mammary gland, is a common disease of dairy animals. The disease is caused by bacterial infection ascending through the teat canal and mammary pathogenic Escherichia coli (MPEC) are common etiology. In the first phase of infection, virulence mechanisms, designated as niche factors, enable MPEC bacteria to resist innate antimicrobial mechanisms, replicate in milk, and to colonize the mammary gland. Next, massive replication of colonizing bacteria culminates in a large biomass of microbe-associated molecular patterns (MAMPs) recognized by pattern recognition receptors (PRRs) such as toll-like receptors (TLRs) mediating inflammatory signaling in mammary alveolar epithelial cells (MAEs) and macrophages. Bacterial lipopolysaccharides (LPSs), the prototypical class of MAMPs are sufficient to elicit mammary inflammation mediated by TLR4 signaling and activation of nuclear factor kB (NF-kB), the master regulator of inflammation. Using in vivo mastitis model, in low and high complements mice, and in vitro NF-kB luminescence reporter system in MAEs, we have found that the smooth configuration of LPS O-polysaccharides in MPEC enables the colonizing organisms to evade the host immune response by reducing inflammatory response and conferring resistance to complement. Screening a collection of MPEC field strains, we also found that all strains were complement resistant and 94% (45/48) were smooth. These results indicate that the structure of LPS O-polysaccharides chain is important for the pathogenesis of MPEC mastitis and provides protection against complement-mediated killing. Furthermore, we demonstrate a role for complement, a key component of innate immunity, in host-microbe interactions of the mammary gland.
High-dose methotrexate in ICU patients: a retrospective study
Authors: Valade Sandrine , Mariotte Eric , Azoulay Elie , Darmon Michael
Published: June 2020

Background

High-dose methotrexate (HD-MTX) is commonly used in the treatment of solid tumors and hematological malignancies. Severe toxicities are frequent, leading to organ dysfunction and death. Risk–benefit ratio of using HD-MTX in critically ill patients is unknown. This study aims to describe MTX-induced toxicities and to assess outcome in ICU patients. We conducted a retrospective single-center study conducted in a university hospital ICU between January 2002 and December 2018. Consecutive patients treated by HD-MTX were included.

Results

33 patients (24 men and 9 women) aged 48 years [34–63], were included. B cell lymphoma had been diagnosed in 31 patients (Burkitt, n = 14; diffuse large B-cell lymphoma with CNS (central nervous system) involvement, n = 9; primary CNS lymphoma, n = 5) and T-cell lymphoma in two patients. Patients were mainly admitted for coma (n = 14; 42%) or acute kidney injury (n = 8; 24%). MTX was administered at a median dose of 6.1 g [5–14]. Fourteen patients had concomitant medication interacting with MTX. Median MTX clearance was 4 days [4–5]. Frequent MTX-related complication were mucositis (n = 21, 64%), diarrhea (n = 14, 44%) or hepatic failure (n = 15, 45%). During ICU stay, 11 patients experienced acute kidney injury (KDIGO stage 3 [2–3]). Two patients received carboxypeptidase and three underwent dialysis. Overall, 19 patients (57%) required mechanical ventilation, 10 (30%) vasopressors. Hospital mortality was 30% (n = 10). Cox model identified MTX concentration 24 h after administration higher than 4.6 µmol/L as associated with hospital mortality (HR 6.7; 95% CI 1.6–27.3).

Conclusions

To our knowledge, this is the first study assessing characteristics and outcome of critically ill patients receiving HD-MTX. MTX concentration at H24 was associated with hospital mortality. Despite underlying malignancy, ICU support of these patients was associated with a meaningful survival.
Fredholm type integral equation in extended $M_{b}$-metric spaces
Authors: Mlaiki Nabil , Hajji Mohamed , Abdeljawad Thabet
Published: June 2020

In this manuscript, we prove some new fixed point results for a self-mapping on extended $M_{b}$Mb-metric spaces, under some new types of contractions, which generalizes many results in the literature. Also, we present some interesting examples to illustrate our work.
Diabetes mellitus in dogs attending UK primary-care practices: frequency, risk factors and survival
Authors: Heeley Angela M. , O’Neill Dan G. , Davison Lucy J. , Church David B. , Corless Ellie K. , Brodbelt Dave C.
Published: June 2020

Background

Diabetes mellitus (DM) is an important endocrine disorder of dogs. The objectives of this study were to estimate prevalence and incidence of DM in dogs, and to explore risk factors for DM and the survival of DM cases in primary-care clinics in the UK.

Results

A case-control study nested in the cohort of dogs (n = 480,469) aged ≥3 years presenting at 430 VetCompass clinics was used to identify risk factors for DM, using multivariable logistic regression. Overall 409 new and 863 pre-existing DM cases (total 1272) were identified in 2016, giving an apparent annual prevalence of 0.26% (95% confidence interval (CI): 0.25–0.28%), and an annual incidence risk of 0.09% (95%CI: 0.08–0.09%) in dogs aged ≥3 years. Factors associated with increased odds for DM diagnosis were all age categories > 8 years, female entire dogs (odds ratio (OR): 3.03, 95% CI 1.69–5.44,p < 0.001) and male neutered dogs (OR: 1.99, 95% CI 1.18–3.34,p = 0.010) compared to male entire dogs, Border Terriers (OR: 3.37, 95% CI 1.04–10.98,p = 0.043) and West Highland White Terriers (WHWT) (OR: 2.88, 95% CI 1.49–5.56,p = 0.002) compared to crossbreeds. Dogs that had received previous glucocorticoid treatment (OR: 2.19, 95% CI 1.02–4.70,p = 0.044) and those with concurrent conditions (documented obese, pancreatitis, hyperadrenocorticism) also had increased odds for DM diagnosis.

Cox regression modelling was used to evaluate factors associated with survival in the 409 incident DM cases in 2016. Increased hazard of death following diagnosis of DM was shown in dogs that were ≥ 10 years age, Cocker Spaniels (HR: 2.06, 95% CI 1.06–4.01,p = 0.034) compared to crossbreeds, had a blood glucose (BG) level at diagnosis > 40 mmol/L (HR: 2.73, 95% CI 1.35–5.55,p = 0.005) compared to < 20 mmol/L at diagnosis, or had received previous glucocorticoid treatment (HR: 1.86, 95% CI 1.21–2.86,p = 0.005). Dogs at reduced hazard of death included neutered dogs (HR: 0.58, 95% CI 0.42–0.79,p = 0.001), Border Collies (HR: 0.39, 95% CI 0.17–0.87,p = 0.022) and those starting insulin treatment (HR: 0.08 95% CI 0.05–0.12,p < 0.001).

Conclusions

Certain breeds and concurrent health conditions are associated with an increased risk of DM. In addition to certain signalment factors, a high BG level at diagnosis and prior glucocorticoid treatment were adversely associated with survival of dogs with DM.
Individualized body bioelectrical impedance parameters in newly diagnosed cancer children
Authors: Luna Taira Teresa Batista , González Maraelys Morales , Jarque Manuel Verdecia , González Tamara Rubio , Brooks Soraida Candida Acosta , Castañeda Antonio Rafael Selva , Regüeiferos Justa Carmen Columbié , González Victoriano Gustavo Sierra , Cabrales Luis Enrique Bergues
Published: June 2020

Background

The bioelectric impedance analysis permits to estimate electrical parameters and body composition of subjects who are either apparently healthy or sick with different pathologies. The aim of this study is to individualize the analysis of body bioelectrical impedance parameters in newly diagnosed cancer children, by means of the bioelectrical impedance analysis for each age group, gender and cancer histological variety.

Methods

This retrospective cross-sectional study consisted of 43 pediatric patients with different histological varieties of cancer, ages from 2 to 17. The body electrical resistance and body capacitive electrical reactance were measured with the Bodystat 1500-MDD analyzer. From these two electrical parameters the body electrical impedance modulus and the body phase angle were calculated.

Results

The results showed that 93.02% of cancer children were outside reference rectangles according to age groups and gender were showed. The values of body capacitive electrical reactance (72.5%) and body phase angle (90.70%) of these patients were below the lower limits of their respective rectangles. These findings were noticeable for patients who had solid tumors.

Conclusions

The BIA is feasible to individualize body bioelectrical parameters and body bioelectric state in newly diagnosed cancer children and how differ from those in apparently healthy subjects, for the same age group and gender. Additionally, the tumor electrical properties may have a noticeable role in changes of body bioelectric-physiological parameters of these newly diagnosed cancer children.
Educational innovation projects in Dutch higher education: bottom-up contextual coping to deal with organizational challenges
Authors: Schophuizen Martine , Kalz Marco
Published: June 2020

Understanding the process of initiation, design, implementation and embedding of educational innovations in higher education is necessary to develop better strategies for sustainable, large-scale educational innovation. Often early initiated educational innovation projects are not evaluated well enough, making it hard to identify lessons learned. The aim of this study is to investigate how project leaders of innovation projects in Dutch higher education institutions are coping with organizational challenges. To address this we analysed qualitative focus group data with innovators that run projects at Dutch higher education institutions through the lens of contextual coping theory. Results show that the innovators identified challenges (primary appraisal), proposed possible solutions (secondary appraisal) and also were able to take concrete steps (coping efforts) to overcome challenges to design and implement open online educational innovations. From these findings it can be concluded that bottom-up initiatives can create awareness and are capable of finding local resources to establish support for embedding innovations locally, yet, appropriate, synchronized and timely top-down action is needed in order to create a sustainable and institution wide support system for experimentation and embedding of educational innovations. These findings will contribute towards developing better strategies to develop innovative educational practices and quality education.