bluuebunny/crossref_metadata_2025 huggingface dataset:
Subtalar Fusion for Correction of Forefoot Abduction in Stage II Adult-Acquired Flatfoot Deformity
Authors: Davies James P. , Ma Xiaoyue , Garfinkel Jonathan , Roberts Matthew , Drakos Mark , Deland Jonathan , Ellis Scott
Published: August 2020

Background

Correction of talonavicular uncoverage (TNU) in adult-acquired flatfoot deformities (AAFD) can be a challenge. Lateral column lengthening (LCL) traditionally is utilized to address this. The primary study objective is examining stage II AAFD patients and determining if correction can be achieved with subtalar fusion (STF) comparable to LCL.

Methods

Following institutional review board approval, retrospective chart review performed identifying patients meeting criteria for stage IIB AAFD who underwent either STF with concomitant flatfoot procedures (but not LCL) to correct TNU, or who underwent LCL as part of their flatfoot reconstruction. Patients indicated for STF had one or more of the following: higher body mass index (BMI), were older, had greater deformity, lateral impingement pain, intraoperative spring ligament hyperlaxity. Patients without 1-year follow-up or compete records were excluded. All other patients were included. A total of 27 isolated STFs identified, along with 143 who underwent LCL. Pre-/postoperative radiographic parameters obtained as well as PROMIS (Patient-Reported Outcomes Measurement Information System) and FAOS (Foot and Ankle Outcome Score) scores. Radiographic and patient reported outcomes both preoperatively and at 1-year follow-up evaluated for both groups.

Results

STF patients were older ( P < .05), with higher BMIs ( P < .004). STF had significantly worse TNU ( P < .001) than LCL patients, and average change in STF TNU was larger than LCL change postoperatively ( P = .006), after adjusting for age, BMI, gender. PROMIS STF improvement reached statistical significance in Physical Function (P 0.011), for FAOS Pain (P 0.025) and Function ( P = 0.04).

Conclusions

STF can be used in appropriately indicated patients to correct flatfoot deformity without compromising radiographic or clinical, correcting not only hindfoot valgus, but also talonavicular uncoverage (TNU) and corresponding medial arch collapse.

Levels of Evidence:

Level III: Retrospective chart review comparison study (case control)
Prevention of excessive scar formation using nanofibrous meshes made of biodegradable elastomer poly(3-hydroxybutyrate-co-3-hydroxyvalerate)
Authors: Kim Hye Sung , Chen Junyu , Wu Lin-Ping , Wu Jihua , Xiang Hua , Leong Kam W , Han Jing
Published: August 2020

To reduce excessive scarring in wound healing, electrospun nanofibrous meshes, composed of haloarchaea-produced biodegradable elastomer poly(3-hydroxybutyrate- co-3-hydroxyvalerate) (PHBV), are fabricated for use as a wound dressing. Three PHBV polymers with different 3HV content are used to prepare either solution-cast films or electrospun nanofibrous meshes. As 3HV content increases, the crystallinity decreases and the scaffolds become more elastic. The nanofibrous meshes exhibit greater elasticity and elongation at break than films. When used to culture human dermal fibroblasts in vitro, PHBV meshes give better cell attachment and proliferation, less differentiation to myofibroblasts, and less substrate contraction. In a full-thickness mouse wound model, treatment with films or meshes enables regeneration of pale thin tissues without scabs, dehydration, or tubercular scar formation. The epidermis of wounds treated with meshes develop small invaginations in the dermis within 2 weeks, indicating hair follicle and sweat gland regeneration. Consistent with the in vitro results, meshes reduce myofibroblast differentiation in vivo through downregulation of α-SMA and TGF-β1, and upregulation of TGF-β3. The regenerated wounds treated with meshes are softer and more elastic than those treated with films. These results demonstrate that electrospun nanofibrous PHBV meshes mitigate excessive scar formation by regulating myofibroblast formation, showing their promise for use as wound dressings.
The natural course of giant paraesophageal hernia and long‐term outcomes following conservative management
Authors: Oude Nijhuis Renske A B , van der Hoek Margot , Schuitenmaker Jeroen M , Schijven Marlies P , Draaisma Werner A , Smout Andreas J P M , Bredenoord Albert J
Published: August 2020

Background

Accurate information on the natural course of giant paraesophageal hernia is scarce, challenging therapeutic decisions whether or not to operate.

Objective

We aimed to investigate the long‐term outcomes, including hernia‐related deaths and complications (e.g. volvulus, gastrointestinal bleeding, strangulation) of patients with giant paraesophageal hernia that were conservatively managed, and to determine factors associated with clinical outcome.

Methods

We retrospectively analysed charts of patients diagnosed with giant paraesophageal hernia between January 1990 and August 2019, collected from a university hospital in The Netherlands. Included patients were subdivided into three groups based on primary therapeutic decision at diagnosis. Radiological, clinical and surgical characteristics, along with long‐term outcomes at most recent follow‐up, were collected.

Results

We included 293 patients (91 men, mean age 70.3 ± 12.4 years) with a mean duration of follow‐up of 64.0 ± 58.8 months. Of the 186 patients that were conservatively treated, a total hernia‐related mortality of 1.6% was observed. Hernia‐related complications, varying from uncomplicated volvulus to strangulation, occurred in 8.1% of patients. Only 1.1% of patients included in this study required emergency surgery. Logistic regression analysis revealed the presence of symptoms (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.8–20.6), in particular obstructive symptoms (vomiting, OR 15.7, 95% CI 4.6–53.6; epigastric pain, OR 4.4, 95% CI 1.2–15.8 and chest pain, OR 6.1, 95% CI 1.8–20.6) to be associated with the occurrence of hernia‐related complications.

Conclusions

Hernia‐related death and morbidity is low in conservatively managed patients. The presence of obstructive symptoms was found to be associated with the occurrence of complications during follow‐up. Conservative therapy is an appropriate therapeutic strategy for asymptomatic patients.
A comparison of risk profile for orthopaedic operations when utilizing individually wrapped screws (IWS) when compared with sterile screw caddies (screw racks)
Authors: Suchowersky Andrew M , Hua Martin , Lorentzos Peter , Ashton L Andrew
Published: August 2020

Introduction:

There has been a global trend towards individually packaged screws for orthopaedic operations. Traditional practice makes use of screw caddies that require re-sterilization. Individually wrapped screws (IWS) are purported to decrease infection rates and avoid the deleterious effects of repeated screw sterilizations, despite marginal evidence. This review aimed to evaluate the safety, effectiveness and economics of screw caddies with IWS.

Material and methods:

The literature was surveyed in a systematic fashion between 1998 and 2017 and all relevant health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, cohort studies, case-controlled studies and case series were sought. Any benefits or otherwise of IWS over screw caddies were then evaluated in the areas of safety, effectiveness and economics.

Results:

Two level III-3 papers suggested the use of caddies at least as safe as individual screws. Four level III-2 papers demonstrated that screws from caddies were as effective as individual alternatives, while a level III-3 paper reported that individual screws were significantly more expensive than screw caddies. Cost increases to our regional health service from ankle open reduction and internal fixations alone of at least $50,112 (AUD) per annum were calculated.

Conclusions:

From the results obtained, the authors recommend the continued use of screw caddies for orthopaedic procedures.
Pembrolizumab-Induced Diabetes Mellitus Presenting as Diabetic Ketoacidosis in a Patient With Metastatic Colonic Adenocarcinoma
Authors: Kichloo Asim , Albosta Michael S. , McMahon Shane , Movsesian Kimberly , Wani Farah , Jamal Shakeel M. , Aljadah Michael , Singh Jagmeet
Published: August 2020

Immunotherapy drugs are gaining popularity in the treatment of certain malignancies due to the success of these agents in recent clinical trials. Pembrolizumab is an immune checkpoint inhibitor that acts via binding to programmed cell death 1 (PD-1) receptors on T-cells, allowing for the constitutive activation of T-cells to fight malignant tumor cells. Immune checkpoint molecules such as PD-1 act to inhibit T-cell function, promoting tolerance to self-antigens. Inhibition of these molecules may lead to increased T-cell activation against cancer cells, but also against healthy tissue, leading to the side effects of these medications known as immune-related adverse events. In this article, we present the case of a 77-year-old female with a history of metastatic colonic adenocarcinoma presenting with new-onset diabetes mellitus and diabetic ketoacidosis in the setting of receiving pembrolizumab chemotherapy. Our patient was treated with hydration, insulin therapy, and management of her electrolytes, ultimately being discharged with the need for home insulin therapy to manage her new-onset diabetes. There are no current guidelines for the management or surveillance of patients receiving pembrolizumab chemotherapy, and further research should be done to determine which patients are at highest risk to developing this rare but potentially lethal side effect.
The big bang of neoliberal urbanism: The Gigantomachy of Santiago’s urban development
Authors: Vergara-Perucich Francisco , Boano Camillo
Published: August 2020

This study presents a spatial history of the origins of Santiago’s neoliberalisation, unveiling its urban history from the critical point of view of land at the centre of social classes’ dispute over city life. It situates the contestation and struggle over land in a genealogical progression from the origins of the disciplinary field of urbanism (1932) to the transformation of its regulatory framework, making it an exclusively profit-oriented practice complementary to processes of wealth creation through urban transformations (1979). As an allegory, we used the Gigantomachy to interpret these struggles. Special emphasis is given to the land struggles that occurred in Santiago as a part of this migratory process and how the contestation of private land became an alternative to the government’s incapacities to resolve the urban poor condition. This contestation would lead to the dominant class looking for alternative politics that ensure the defence of their property. This study presents neoliberalism as a response to such a call. Neoliberalism in Santiago was the way to transform the problem of housing scarcity in big business for the dominant class. The study historically outlines this process in what may be considered as the first neoliberal urban policy in the world, depicting the big bang of neoliberal urbanism.
LAITOR4HPC: A text mining pipeline based on HPC for building interaction networks
Authors: Piereck Bruna , Oliveira-Lima Marx , Benko-Iseppon Ana Maria , Diehl Sarah , Schneider Reinhard , Brasileiro-Vidal Ana Christina , Barbosa-Silva Adriano
Published: August 2020

Background

The amount of published full-text articles has increased dramatically. Text mining tools configure an essential approach to building biological networks, updating databases and providing annotation for new pathways. PESCADOR is an online web server based on LAITOR and NLProt text mining tools, which retrieves protein-protein co-occurrences in a tabular-based format, adding a network schema. Here we present an HPC-oriented version of PESCADOR’s native text mining tool, renamed to LAITOR4HPC, aiming to access an unlimited abstract amount in a short time to enrich available networks, build new ones and possibly highlight whether fields of research have been exhaustively studied.

Results

By taking advantage of parallel computing HPC infrastructure, the full collection of MEDLINE abstracts available until June 2017 was analyzed in a shorter period (6 days) when compared to the original online implementation (with an estimated 2 years to run the same data). Additionally, three case studies were presented to illustrate LAITOR4HPC usage possibilities. The first case study targeted soybean and was used to retrieve an overview of published co-occurrences in a single organism, retrieving 15,788 proteins in 7894 co-occurrences. In the second case study, a target gene family was searched in many organisms, by analyzing 15 species under biotic stress. Most co-occurrences regarded Arabidopsis thaliana and Zea mays. The third case study concerned the construction and enrichment of an available pathway. Choosing A. thaliana for further analysis, the defensin pathway was enriched, showing additional signaling and regulation molecules, and how they respond to each other in the modulation of this complex plant defense response.

Conclusions

LAITOR4HPC can be used for an efficient text mining based construction of biological networks derived from big data sources, such as MEDLINE abstracts. Time consumption and data input limitations will depend on the available resources at the HPC facility. LAITOR4HPC enables enough flexibility for different approaches and data amounts targeted to an organism, a subject, or a specific pathway. Additionally, it can deliver comprehensive results where interactions are classified into four types, according to their reliability.
Features of alternative splicing in stomach adenocarcinoma and their clinical implication: a research based on massive sequencing data
Authors: Zhang Yuanyuan , Ma Shengling , Niu Qian , Han Yun , Liu Xingyu , Jiang Jie , Chen Simiao , Lin Haolong
Published: August 2020

Background

Alternative splicing (AS) offers a main mechanism to form protein polymorphism. A growing body of evidence indicates the correlation between splicing disorders and carcinoma. Nevertheless, an overall analysis of AS signatures in stomach adenocarcinoma (STAD) is absent and urgently needed.

Results

2042 splicing events were confirmed as prognostic molecular events. Furthermore, the final prognostic signature constructed by 10 AS events gave good result with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.902 for 5 years, showing high potency in predicting patient outcome. We built the splicing regulatory network to show the internal regulation mechanism of splicing events in STAD. QKI may play a significant part in the prognosis induced by splicing events.

Conclusions

In our study, a high-efficiency prognostic prediction model was built for STAD patients, and the results showed that AS events could become potential prognostic biomarkers for STAD. Meanwhile, QKI may become an important target for drug design in the future.
Influence of biofilm growth age, media, antibiotic concentration and exposure time on Staphylococcus aureus and Pseudomonas aeruginosa biofilm removal in vitro
Authors: Chen Xiaofeng , Thomsen Trine Rolighed , Winkler Heinz , Xu Yijuan
Published: August 2020

Background

Biofilm is known to be tolerant towards antibiotics and difficult to eradicate. Numerous studies have reported minimum biofilm eradication concentration (MBEC) values of antibiotics for many known biofilm pathogens. However, the experimental parameters applied in these studies differ considerably, and often the rationale behind the experimental design are not well described. This makes it difficult to compare the findings. To demonstrate the importance of experimental parameters, we investigated the influence of biofilm growth age, antibiotic concentration and treatment duration, and growth media on biofilm eradication. Additionally, OSTEOmycin™, a clinically used antibiotic containing allograft bone product, was tested for antibiofilm efficacy.

Results

The commonly used Calgary biofilm device was used to grow 24 h and 72 h biofilms of Staphylococcus aureus and Pseudomonas aeruginosa, which were treated with time-dependent vancomycin (up to 3000 mg L− 1) and concentration-dependent tobramycin (up to 80 mg L− 1), respectively. Two common bacteriological growth media, tryptic soy broth (TSB) and cation-adjusted Mueller Hinton broth (CaMHB), were tested. We found for both species that biofilms were more difficult to kill in TSB than in CaMHB. Furthermore, young biofilms (24 h) were easier to eradicate than old biofilms (72 h). In agreement with vancomycin being time-dependent, extension of the vancomycin exposure increased killing of S. aureus biofilms. Tobramycin treatment of 24 h P. aeruginosa biofilms was found concentration-dependent and time-independent, however, increasing killing was indicated for 72 h P. aeruginosa biofilms. Treatment with tobramycin containing OSTEOmycin T™ removed 72 h and 168 h P. aeruginosa biofilms after 1 day treatment, while few 72 h S. aureus biofilms survived after 2 days treatment with vancomycin containing OSTEOmycin V™.

Conclusions

This study demonstrated biofilm removal efficacy was influenced by media, biofilm age and antibiotic concentration and treatment duration. It is therefore necessary to taking these parameters into consideration when designing experiments. The results of OSTEOmycin™ products indicated that simple in vitro biofilm test could be used for initial screening of antibiofilm products. For clinical application, a more clinically relevant biofilm model for the specific biofilm infection in question should be developed to guide the amount of antibiotics used for local antibiofilm treatment.
Implementation of the TaperGuard™ endotracheal tube in an unselected surgical population to reduce postoperative pneumonia
Authors: Martini Ross P. , Yanez N. David , Treggiari Miriam M. , Tekkali Praveen , Soelberg Cobin , Aziz Michael F.
Published: August 2020

Background

Endotracheal tube (ETT) designs to decrease the risk of ventilator associated pneumonia (VAP) include supraglottic suctioning, and/or modifications of the cuff shape. The TaperGuard™ ETT has a tapered, polyvinylchloride cuff designed to reduce microaspiration around channels that form with a standard barrel-shaped cuff. We compared risk of postoperative pneumonia using the TaperGuard™ ETT and the standard ETT in surgical patients requiring general anesthesia with endotracheal intubation.

Methods

We used an interrupted time-series design to compare endotracheal intubation using the TaperGuard™ ETT (intervention cohort), and a historic cohort using the standard ETT (baseline cohort), among surgical patients requiring hospital admission. We compared the incidence of postoperative pneumonia in the intervention and baseline cohorts. Data were collected from the electronic health record and linked to patient-level data from National Surgical Quality Improvement Project. Additionally, we performed secondary analyses in a subgroup of patients at high risk of postoperative pneumonia.

Results

15,388 subjects were included; 6351 in the intervention cohort and 9037 in the baseline cohort. There was no significant difference in the incidence of postoperative pneumonia between the intervention cohort (1.62%) and the baseline cohort (1.79%). The unadjusted odds ratio (OR) of postoperative pneumonia was 0.90 (95% CI: 0.70, 1.16; p = 0.423) and the OR adjusted for patient characteristics and potential confounders was 0.90 (95% CI: 0.69, 1.19; p = 0.469), comparing the intervention and baseline cohorts. There was no a priori selected subgroup of patients for whom the use of the TaperGuard™ ETT was associated with decreased odds of postoperative pneumonia relative to the standard ETT. Hospital mortality was higher in the intervention cohort (1.5%) compared with the baseline cohort (1.0%; OR 1.46, 95% CI: 1.09, 1.95; p = 0.010).

Conclusions

The broad implementation of the use of the TaperGuard™ ETT for intubation of surgical patients was not associated with a reduction in the risk of postoperative pneumonia. In the setting of a low underlying postoperative pneumonia risk and the use of recommended preventative VAP bundles, further risk reduction may not be achievable by simply modifying the ETT cuff design in unselected or high-risk populations undergoing inpatient surgery.

Trial registration

ClinicalTrials.gov, ID NCT02450929.
Determinants of persistent smoking after acute myocardial infarction: an observational study
Authors: Höpner Jens , Junge Udo , Schmidt-Pokrzywniak Andrea , Fischer Christian , Mikolajczyk Rafael
Published: August 2020

Background

Smoking cessation is one of the most effective secondary prevention measures after acute myocardial infarction (AMI). However, around 50% of smokers do not quit smoking after AMI. The aim of the present study is to estimate the proportion of patients quitting smoking and to identify determinants of persistent smoking after AMI in a region with increased cardiovascular mortality. We also assessed the time of smoking cessation after AMI.

Methods

We used follow-up data of patients registered with the Regional Myocardial Infarction Registry in Saxony-Anhalt (RHESA) in Germany. We assessed smoking status and determinants of persistent smoking six weeks after discharge from hospital after AMI. Information on smoking, sociodemographic characteristics, risk factors for AMI, experienced symptoms of AMI, and clinical care were gathered in a computer-assisted telephone interview and questionnaires filled out by study subjects and physicians or study nurses.

Results

Out of 372 smokers at the time of AMI, 191 (51.3%) reported that they quit smoking within six weeks after discharge from hospital after AMI. Strongest determinant of persistent smoking was a previous AMI before the current one (OR = 2.19, 95%CI 1.10–4.38) and strongest determinants of smoking cessation were experiencing complications in the hospital (0.37, 95%CI 0.12–1.12) and having a life partner (0.56, 95%CI 0.34–0.95). Most individuals who stopped smoking did so during the initial stay in the hospital, before the cardiac rehabilitation (CR).

Conclusions

Persistent smoking after AMI and its determinants were similar in our region to previous studies. CR cannot be viewed as determinant of smoking cessation – more likely the same teachable moment induces behavioural change with regard to smoking and participation in CR.
Impact of plasma potassium normalization on short-term mortality in patients with hypertension and hypokalemia or low normal potassium
Authors: Krogager Maria Lukács , Søgaard Peter , Torp-Pedersen Christian , Bøggild Henrik , Lee Christina Ji-Young , Bonde Anders , Thomassen Jesper Q. , Gislason Gunnar , Pareek Manan , Kragholm Kristian
Published: August 2020

Background

Hypokalemia is common in patients treated with antihypertensive drugs, but the impact of correcting hypokalemia is insufficiently studied. We examined the consequences of hypokalemia and borderline hypokalemia correction in patients with hypertension.

Methods

We identified 8976 patients with hypertension and plasma potassium concentrations ≤3.7 mmol/L within 100 days from combination antihypertensive therapy initiation. The first measurement between 6 and 100 days after the episode with potassium ≤3.7 mmol/L was retained. We investigated all-cause and cardiovascular mortality within 60-days from the second potassium measurement using Cox regression. Mortality was examined for seven predefined potassium intervals derived from the second measurement: 1.5–2.9 mmol/L (n = 271), 3.0–3.4 mmol/L (n = 1341), 3.5–3.7 (n = 1982) mmol/L, 3.8–4.0 mmol/L (n = 2398, reference), 4.1–4.6 mmol/L (n = 2498), 4.7–5.0 mmol/L (n = 352) and 5.1–7.1 mmol/L (n = 134).

Results

Multivariable analysis showed that potassium concentrations 1.5–2.9 mmol/L, 3.0–3.4 mmol/L, 4.7–5.0 mmol/L and 5.1–7.1 mmol/L were associated with increased all-cause mortality (HR 2.39, 95% CI 1.66–3.43; HR 1.36, 95% CI 1.04–1.78; HR 2.36, 95% CI 1.68–3.30 and HR 2.62, 95% CI 1.73–3.98, respectively). Potassium levels <3.0 and > 4.6 mmol/L were associated with increased cardiovascular mortality. The adjusted standardized 60-day mortality risks in the seven strata were: 11.7% (95% CI 8.3–15.0%), 7.1% (95% CI 5.8–8.5%), 6.4% (95% CI 5.3–7.5%), 5.4% (4.5–6.3%), 6.3% (5.4–7.2%), 11.6% (95% CI 8.7–14.6%) and 12.6% (95% CI 8.2–16.9%), respectively.

Conclusions

Persistent hypokalemia was frequent and associated with increased all-cause and cardiovascular mortality. Increase in potassium to levels > 4.6 mmol/L in patients with initial hypokalemia or low normal potassium was associated with increased all-cause and cardiovascular mortality.
A case of inflammatory pseudotumour of the gallbladder presenting as a big mass of uncertain behavior
Authors: Calvo Antonio , Salas Jesús , Muñoz Gloria , Díez Ana , de la Vega María Coral
Published: August 2020

Background

Inflammatory pseudotumour has been used to describe an inflammatory or fibrosing tumoral process of an undetermined cause that may involve a variety of organ systems, including the lungs, spleen, liver, lymph nodes, pancreas and extrahepatic bile duct with potential for recurrence and persistent local growth. In this article, we report a patient with a big mass of uncertain nature and behavior.

Case presentation

A 60-year-old woman presented with a 1-week history of abdominal pain, fever and jaundice. Six months before she had had right upper quadrant pain that was interpreted as biliary colic. A contrast-enhanced CT scan showed a big mass of soft tissue with diffuse infiltration of the gallbladder, displacement of the transverse colon, hepatic flexure and duodenum. For diagnostic distinction between a chronic inflammatory disease or a neoplasm, exploratory laparotomy was required. Intraoperative exploration disclosed a big mass of hard texture involving the gallbladder, with multiple concrements, hepatoduodenal ligament, right and transverse mesocolon, stomach and duodenum.

Cholecystectomy was performed, preserving adjacent organs with macroscopic desmoplastic reaction. Histopathologic examination of the gallbladder showed a spindle cell proliferation with diffuse chronic inflammatory infiltrate of lymphocytes, plasma cells and hyalinized fibrous stroma. No vascular invasion or cellular atypia were evident.

Conclusion

Inflammatory pseudotumour is a rare condition and diagnostic distinction from a chronic inflammatory disease or other neoplasm is only possible by histopathologic examination. There is a limited number of case reports in the literature indicating tumor location in the gallbladder.
A case report of pancreatic panniculitis due to acute pancreatitis with intraductal papillary mucinous neoplasm
Authors: Yamashita Yuki , Joshita Satoru , Ito Tetsuya , Maruyama Masafumi , Wada Shuichi , Umemura Takeji
Published: August 2020

Background

Pancreatic panniculitis is a rare skin manifestation in pancreatic disease patients that most frequently develops on the lower legs. We report the unique case of a 68-year-old man who suffered from pancreatic panniculitis on his trunk associated with acute pancreatitis due to an intraductal papillary mucinous neoplasm.

Case presentation

A 68-year-old man complained of a 2-day history of a tender subcutaneous nodule on his trunk. Laboratory tests and abdominal contrast computed tomography were consistent with acute pancreatitis due to an intraductal papillary mucinous neoplasm. A skin biopsy of the nodule histologically displayed lobular panniculitis with characteristic “ghost cells”, which indicated pancreatic panniculitis.

Conclusions

In order to avoid a missed or delayed diagnosis, clinicians should bear in mind that pancreatic panniculitis can be the first manifestation of pancreatic disease when encountering subcutaneous nodules on the trunk.
Mutant POLQ and POLZ/REV3L DNA polymerases may contribute to the favorable survival of patients with tumors with POLE mutations outside the exonuclease domain
Authors: Huang Fangjin , Tanaka Hisashi , Knudsen Beatrice S. , Rutgers Joanne K.
Published: August 2020

Background

Mutations in the exonuclease domain of POLE, a DNA polymerase associated with DNA replication and repair, lead to cancers with ultra-high mutation rates. Most studies focus on intestinal and uterine cancers with POLE mutations. These cancers exhibit a significant immune cell infiltrate and favorable prognosis. We questioned whether loss of function of other DNA polymerases can cooperate to POLE to generate the ultramutator phenotype.

Methods

We used cases and data from 15 cancer types in The Cancer Genome Atlas to investigate mutation frequencies of 14 different DNA polymerases. We tested whether tumor mutation burden, patient outcome (disease-free survival) and immune cell infiltration measured by ESTIMATE can be attributed to mutations in POLQ and POLZ/REV3L.

Results

Thirty six percent of colorectal, stomach and endometrial cancers with POLE mutations carried additional mutations in POLQ (E/Q), POLZ/REV3L (E/Z) or both DNA polymerases (E/Z/Q). The mutation burden in these tumors was significantly greater compared to POLE-only (E) mutant tumors (p < 0.001). In addition, E/Q, E/Z, and E/Q/Z mutant tumors possessed an increased frequency of mutations in the POLE exonuclease domain (p = 0.013). Colorectal, stomach and endometrial E/Q, E/Z, and E/Q/Z mutant tumors within TCGA demonstrated 100% disease-free survival, even if the POLE mutations occurred outside the exonuclease domain (p = 0.003). However, immune scores in these tumors were related to microsatellite instability (MSI) and not POLE mutation status. This suggests that the host immune response may not be the sole mechanism for prolonged disease-free survival of ultramutated tumors in this cohort.

Conclusion

Results in this study demonstrate that mutations in POLQ and REV3L in POLE mutant tumors should undergo further investigation to determine whether POLQ and REV3L mutations contribute to the ultramutator phenotype and favorable outcome of patients with POLE mutant tumors.
Delayed diagnoses of mitochondrial cytopathies in patients presenting with end stage kidney disease: two case reports
Authors: Roper Tayeba , Harber Mark , Jones Gareth , Pitceathly Robert D. S. , Salama Alan D.
Published: August 2020

Background

Up to one third of patients on renal replacement programmes have an unknown cause of kidney disease, and the diagnosis may only be established following renal transplantation when the disease recurs or if new extra-renal symptoms develop.

Case presentation

We present two patients who presented with progressive chronic kidney disease of unknown cause. Both patients underwent successful renal transplantation but subsequently developed multisystem abnormalities, and were ultimately diagnosed with mitochondrial cytopathy 10–15 years following transplantation.

Conclusions

Mitochondrial cytopathies are rare inborn errors of metabolism that should be considered in adults with renal impairment, especially in those with a family history of kidney or other multisystem disease. The widespread availability of genetic testing provides the potential for earlier diagnoses, thereby enhancing management decisions, anticipation of complications, avoidance of mitotoxic drugs, and informed prognosis prediction.
Men, trans/masculine, and non-binary people’s experiences of pregnancy loss: an international qualitative study
Authors: Riggs Damien W. , Pearce Ruth , Pfeffer Carla A. , Hines Sally , White Francis Ray , Ruspini Elisabetta
Published: August 2020

Background

Growing numbers of men, trans/masculine, and non-binary people are becoming gestational parents, yet very little is known about experiences of pregnancy loss among this diverse population.

Methods

The study employed a cross sectional design. Interviews were undertaken with a convenience sample of 51 trans/masculine and non-binary people who had undertaken at least one pregnancy, living in either Australia, the United States, Canada, or the European Union (including the United Kingdom). Participants were recruited by posts on Facebook and Twitter, via researcher networks, and by community members. 16 (31.2%) of the participants had experienced a pregnancy loss and are the focus of this paper. Thematic analysis was used to analyse interview responses given by these 16 participants to a specific question asking about becoming pregnant and a follow up probe question about pregnancy loss.

Results

Thematic analysis of interview responses given by the 16 participants led to the development of 10 themes: (1) pregnancy losses count as children, (2) minimizing pregnancy loss, (3) accounting for causes of pregnancy loss, (4) pregnancy loss as devastating, (5) pregnancy loss as having positive meaning, (6) fears arising from a pregnancy loss, (7) experiences of hospitals enacting inclusion, (8) lack of formal support offered, (9) lack of understanding from family, and (10) importance of friends.

Conclusions

The paper concludes by outlining specific recommendations for clinical practice. These include the importance of focusing on the emotions attached to pregnancy loss, the need for targeted support services for men, trans/masculine, and non-binary people who undertake a pregnancy (including for their partners), and the need for ongoing training for hospital staff so as to ensure the provision of trans-affirming medical care.
Nomogram model for predicting cause-specific mortality in patients with stage I small-cell lung cancer: a competing risk analysis
Authors: Li Jianjie , Zheng Qiwen , Zhao Xinghui , Zhao Jun , An Tongtong , Wu Meina , Wang Yuyan , Zhuo Minglei , Zhong Jia , Yang Xue , Jia Bo , Chen Hanxiao , Dong Zhi , Wang Jingjing , Chi Yujia , Zhai Xiaoyu , Wang Ziping
Published: August 2020

Background

The five-year cumulative incidence rate in patients diagnosed with stage I small-cell lung cancer (SCLC) who were instructed to undergo surgery was from 40 to 60%.The death competition influence the accuracy of the classical survival analyses. The aim of the study is to investigate the mortality of stage I small-cell lung cancer (SCLC) patients in the presence of competing risks according to a proportional hazards model, and to establish a competing risk nomogram to predict probabilities of both cause-specific death and death resulting from other causes.

Methods

The study subjects were patients diagnosed with stage I SCLC according to ICD-O-3. First, the cumulative incidence functions (CIFs) of cause-specific death, as well as of death resulting from other causes, were calculated. Then, a proportional hazards model for the sub-distribution of competing risks and a monogram were constructed to evaluate the probability of mortality in stage I SCLC patients.

Results

1811 patients were included in this study. The five-year probabilities of death due to specific causes and other causes were 61.5 and 13.6%, respectively. Tumor size, extent of tumor, surgery, and radiotherapy were identified as the predictors of death resulting from specific causes in stage I SCLC. The results showed that surgery could effectively reduce the cancer-specific death, and the one-year cumulative incidence dropped from 34.5 to 11.2%. Like surgery, chemotherapy and radiotherapy improved the one-year survival rate.

Conclusions

We constructed a predictive model for stage I SCLC using the data from the SEER database. The proportional sub-distribution models of competing risks revealed the predictors of death resulting from both specific causes and other causes. The competing risk nomogram that we built to predict the prognosis showed good reliability and could provide beneficial and individualized predictive information for stage I SCLC patients.
Molecular evidence of IGFBP-3 dependent and independent VD3 action and its nonlinear response on IGFBP-3 induction in prostate cancer cells
Authors: Igarashi Ko , Yui Yoshihiro , Watanabe Kenta , Kumai Jun , Nishizawa Yasuko , Miyaura Chisato , Inada Masaki , Sasagawa Satoru
Published: August 2020

Background

Clinical trials have been conducted to clarify the beneficial effects of VD3 (1α,25-dihydroxy vitamin D3, also known as calcitriol) treatment in prostate cancer. However, the molecular mechanisms underlying these effects are not fully understood. Recent studies on IGFBP-3 have indicated its intracellular functions in cell growth and apoptosis. The aim of this study was to confirm the benefits of low-dose VD3 treatment and clarify the molecular mechanisms underlying these beneficial effects in prostate cancer cells.

Methods

The molecular effects of simultaneous treatment of LNCaP cells and their genetically modified cell lines with low concentration of docetaxel and VD3 were biologically and biochemically analyzed. To further determine the effects of VD3 treatment on IGFBP-3 induction system, cells were temporarily treated with VD3 in combination with a transcriptional inhibitor or protein synthesis inhibitor. Bcl-2 protein and its mRNA behavior were also observed in Igfbp-3 expression-modified LNCaP cells to determine the involvement of IGFBP-3 in the suppression of Bcl-2 by VD3 treatment.

Results

Changes in IGFBP-3 expression levels in LNCaP cells indicated that it mediated the inhibition of cell growth induced by VD3 treatment. IGFBP-3 was also found to be a mediator of the enhanced cytotoxicity of prostate cancer cells to VD3 in combination with the anti-cancer drug. We further identified the distinct property of the IGFBP-3 induction system, wherein temporal VD3 stimulation-induced prolonged IGFBP-3 expression and VD3 treatment-induced increase in IGFBP-3 expression were optimized based on the protein concentration rather than the mRNA concentration. Meanwhile, Bcl-2 expression was down-regulated by VD3 treatment in an IGFBP-3-independent manner.

Conclusion

These findings indicate the molecular mechanisms of IGFBP-3 induction stimulated by VD3 and IGFBP-3 independent Bcl-2 suppression by VD3 treatment in prostate cancer cells. The results could prompt a re-evaluation of VD3 usage in therapy for patients with prostate cancer.
Protocol for expanded indications of endoscopic submucosal dissection for early gastric cancer in China: a multicenter, ambispective, observational, open-cohort study
Authors: Zheng Zhi , Yin Jie , Li Ziyu , Ye Yingjiang , Wei Bo , Wang Xin , Tian Yantao , Li Mengyi , Zhang Qian , Zeng Na , Xu Rui , Chen Guangyong , Zhang Jie , Li Peng , Cai Jun , Yao Hongwei , Zhang Jun , Zhang Zhongtao , Zhang Shutian
Published: August 2020

Background

The main treatment methods for early gastric cancer (EGC) include endoscopic submucosal dissection (ESD) and radical gastrectomy. However, appropriate treatment for patients who exceed the absolute indications for ESD remains unestablished. In China, evidence-based medicine for the expanding indications of ESD and accurate diagnostic staging for EGC patients are lacking. Thus, clinical studies involving Chinese patients with EGC are necessary to select appropriate treatment options and promote China’s expanded indications for ESD and diagnostic staging scheme.

Methods

This is a multicenter, ambispective, observational, open-cohort study that is expected to enroll 554 patients with EGC. The study was launched in May 2018 and is scheduled to end in March 2022. All enrolled patients should meet the inclusion criteria. Case report forms and electronic data capture systems are used to obtain clinical data, which includes demographic information, results of perioperative blood- and auxiliary examinations, surgical information, results of postoperative pathology, and the outcomes of postoperative recovery and follow-up. Patients are followed up every 6 months after surgery for a minimum of 5 years. The primary endpoint is the rate of lymph node metastasis (LNM), whereas the secondary endpoints include the following: consistency, sensitivity, and specificity of the results of preoperative examinations and postoperative pathology; cut-off values for LNM; logistic regression model of expanded indications for ESD; and incidence of postoperative complications within the 30-day and 5-year relapse-free survival rates.

Discussion

This study will explore and evaluate expanded indications for ESD that match the characteristics of the Chinese population in patients with EGC and will introduce a related staging procedure and examination scheme that is appropriate for China. Ethical approval was obtained from all participating centers. The findings are expected to be disseminated through publications or presentations and will facilitate clinical decision-making in EGC.

Trial registration

The name of the registry is ChiCTR. It was registered on May 9, 2018, with the registration number (ChiCTR1800016084). The clinical trial was launched in May 2018 and will end in March 2022, with enrollment to be completed by December 2021. Trial status: Ongoing.
Neutrophil-to-lymphocyte ratio and scoring system for predicting coronary artery lesions of Kawasaki disease
Authors: Chang Ling-Sai , Lin Yi-Ju , Yan Jia-Huei , Guo Mindy Ming-Huey , Lo Mao-Hung , Kuo Ho-Chang
Published: August 2020

Background

Kawasaki disease (KD) causes coronary artery lesions (CAL) and is the leading cause of acquired heart disease in children. The aim of this study is to evaluate the risk factors and set-up a scoring system for predicting CAL of KD.

Methods

We retrospectively reviewed a total of 478 patients diagnosed with KD. We compared age, gender, laboratory data, and treatment response in two groups and developed a scoring system for predicting CAL.

Results

During the study period, 365 of these patients had complete medical records of coronary surveys by echocardiography. Anemia, hypoalbuminemia, C reactive protein (CRP), alanine aminotransferase, neutrophil count, and neutrophil/lymphocyte ratio (NLR) showed significant differences with CAL formation. We determined the cut-off value using a receiver-operating-characteristic (ROC) curve, and following multivariate logistic regression analysis, four independent risk factors demonstrated a significant difference with CAL formation, including CRP > 103 mg/L, NLR > 3.5, male gender, and intravenous immunoglobulin (IVIG) resistance. We established a score system based on the above evaluation, for which a ROC curve was performed, and a total score of ≥ 2 points showed a sensitivity of 60.8% and a specificity of 70.6%, with an area under the ROC curve of 0.696.

Conclusions

Identifying children at risk is important in order to prevent CAL from developing. Four independent risk factors that can predict CAL formation were CRP > 103 mg/L, NLR > 3.5, male gender, and IVIG resistance. This first report incorporated NLR into score systems to predict CAL reinforces previously well-known risk factors for the CAL formation among KD patients.
The experience of loneliness among young people with depression: a qualitative meta-synthesis of the literature
Authors: Achterbergh Louis , Pitman Alexandra , Birken Mary , Pearce Eiluned , Sno Herman , Johnson Sonia
Published: August 2020

Background

Young people have a higher prevalence of loneliness than other age groups, and they are also at risk of depression. Quantitative studies describe a bidirectional association between loneliness and depression, but there is limited understanding of how these influence each other. Little is known about the experience of loneliness among young people with depression. Qualitative approaches may help understand the relationship between loneliness and depression among young people, and how to intervene to improve outcomes. We aimed to conduct a meta-synthesis to understand the complex inter-relationship between loneliness and depression among young depressed people by synthesising evidence from a systematic review of qualitative studies.

Methods

We conducted a meta-synthesis of qualitative studies capturing experiences of loneliness among young people with depression. We systematically searched six electronic databases for selected search terms, critically appraised eligible studies, and analysed the data from included studies using the approach of thematic synthesis. We used feedback from an inter-disciplinary research workshop to improve reflexivity.

Results

Our inclusion criteria identified fourteen studies. Our analysis identified four themes: (1) social withdrawal due to poor mental health, (2) non-disclosure of depression contributing to social distance, (3) the desire to connect, and (4) paradoxes of loneliness and depression. These themes illustrated a range of pathways between depression and loneliness, and a sense of how these might be mutually reinforcing. Our findings suggest that where depressed individuals engage in certain behaviours (withdrawing; not confiding) for a range of reasons, this can lead to feelings of loneliness, an awareness of which worsens their mood, thus perpetuating their depression.

Conclusions

Young people with depression experience loneliness as an insurmountable distance between themselves and others. Our findings identified non-disclosure of depression, and the debilitating nature of the depressive symptomatology, as factors perpetuating a vicious cycle of loneliness and depression. They suggest that approaches to tackling the problem might include helping young people communicate about their depression to trusted friends and educating their social networks in how to support them. The wider research literature suggests that cognitive interventions may have a role in shifting maladaptive cognitions about their social world.
Factors associated with resilience among non-local medical workers sent to Wuhan, China during the COVID-19 outbreak
Authors: Lin Jing , Ren Yun-Hong , Gan Hai-Jie , Chen Ying , Huang Ying-Fan , You Xue-Mei
Published: August 2020

Background

To investigate the resilience of non-local medical workers sent to support local medical workers in treating the outbreak of 2019 novel coronavirus disease (COVID-19).

Methods

In February 2020, non-local medical workers who had been sent to Wuhan as support staff to respond to the COVID-19 outbreak were asked to complete an online survey composed of the Connor Davidson Resilience Scale (CD-RISC), Hospital Anxiety Depression Scale (HADS) and Simplified Coping Style Questionnaire (SCSQ).

Results

Survey responses from 114 non-local medical workers were analyzed. CD-RISC scores were high (67.03 ± 13.22). The resilience level was highest for physicians (73.48 ± 11.49), followed by support staff, including health care assistants, technicians (67.78 ± 12.43) and nurses (64.86 ± 13.46). Respondents differed significantly in the levels of education, training/support provided by the respondent’s permanent hospital (where he or she normally works), and in their feelings of being adequately prepared and confident to complete tasks (P < 0.05). Resilience correlated negatively with anxiety (r = −.498, P < 0.01) and depression (r = −.471, P < 0.01) but positively with active coping styles (r = .733, P < 0.01). Multiple regression analysis showed that active coping (β = 1.314, p < 0.05), depression (β = −.806, p < 0.05), anxiety (β = − 1.091, p < 0.05), and training/support provided by the respondent’s permanent hospital (β = 3.510, p < 0.05) were significant associated with resilience.

Conclusion

Our data show that active coping, depression, anxiety, and training/support provided by the respondent’s permanent hospital are associated with resilience. Managers of medical staff should use these data to develop psychosocial interventions aimed at reinforcing the resilience of medical workers during highly stressful and prolonged medical emergencies, as seen during the COVID-19 outbreak.