bluuebunny/crossref_metadata_2025 huggingface dataset:
Basaloid Follicular Hamartoma: An Additional Criterion of Nevoid Basal Cell Carcinoma Syndrome
Authors: Chikeka Ijeuru , Chang Li-Wei , Collins Mary-Katherine , Pugliano Melissa , Ho Jonhan , House Nancy , Kazlouskaya Viktoryia
Published: June 2021

Basaloid follicular hamartoma (BFH) is a rare, benign follicular neoplasm which typically presents as brown to skin-colored papules on the face, scalp, and trunk. Histologically, BFH consists of cords and strands of basaloid cells forming cystic structures with scant stroma and should be distinguished from infundibulocystic basal cell carcinoma to avoid overly aggressive treatment. Although BFH has been found to be associated with distinct syndromes, including alopecia, myasthenia gravis, and cystic fibrosis, there is often clinical, histopathologic, and genetic overlap with nevoid basal cell carcinoma syndrome (NBCCS). In this article, we describe a case of a 13-year-old patient with NBCCS who presented with multiple BFHs and propose that it its inclusion into the diagnostic criteria for NBCCS be considered.
T-Cell–Driven Fibroinflammation Inducing Follicular Dedifferentiation in Alopecia Areata and IgG4-Modified Disease
Authors: Kossard Steven , Sheriff Tabrez , Murrell Dedee
Published: June 2021

The definition of IgG4-related diseases incorporates a broad range of systemic diseases particularly a subset dominated by fibroinflammation. CD4+cytotoxic T cells have emerged as the major driving force for the fibroinflammation, and the pathogenetic role of IgG4 still remains to be determined. Cutaneous involvement is uncommon and is not well defined as elevated tissue IgG4 plasma cells are not a specific marker and prominent cutaneous fibroinflammation is often absent in cutaneous disease. We report the case of a patient with longstanding alopecia universalis and severe atopic dermatitis who presented with diffuse induration and mottled dyspigmentation of his scalp. Multiple scalp biopsies revealed diffuse interfollicular fibroinflammation and IgG4 plasma cells with induction of distinctive dedifferentiated follicles not seen in alopecia areata. This complex case may provide insight into the role of specific subsets of T cells not only in respect to the fibroinflammation linked to IgG4-related diseases but also the capacity to modify disease, follicular stem cell activation, immune privilege, cytotoxicity in alopecia areata, and the presence of atopy that may have contributed to the pathogenesis of this case.
Atypical Fibroxanthoma Demonstrating HMB45+ Staining
Authors: Sahni Vikram N. , Sahni Dev R. , Cassarino David S.
Published: June 2021

Immunohistochemistry is useful and often necessary for the diagnosis of many histopathological entities, including atypical fibroxanthoma (AFX), which is typically considered a diagnosis of exclusion after ruling out spindle cell melanoma, sarcomatoid carcinoma, and other spindle cell tumors. AFX is a superficial fibrohistiocytic tumor previously believed to be related to pleomorphic sarcoma (formerly known as malignant fibrous histiocytoma), but is now considered a distinct clinicopathological entity. AFXs commonly express CD68, smooth muscle actin, and lysozyme and are usually negative for melanocytic markers such as HMB45 and S100. However, immunohistochemistry can sometimes be misleading, especially when used without other relevant markers in making a histopathologic diagnosis. HMB45 is a glycoprotein marker of premelanosomes and is often helpful in identifying melanoma because it stains melanosomes in the epidermis, dermis, and nevi glycocomplexes. We report a case of AFX which was strongly positive for HMB45, but negative for all other melanocytic markers. This case emphasizes the potential pitfall of relying on a single immunohistochemical marker to make the diagnosis, especially of melanoma, and also is one of the only rare reported cases of AFXs which are HMB45+.
Safety and Functional Pharmacokinetic Profile of APAC, a Novel Intravascular Antiplatelet and Anticoagulant
Authors: Craige Simon , Jouppila Annukka , Humphries Bob , Lassila Riitta
Published: June 2021

Vascular intervention–induced platelet and coagulation activation is often managed with a combination of antiplatelets and anticoagulants, with evident benefits, but with a risk of systemic bleeding. Antiplatelet and anticoagulant (APAC) is a dual antiplatelet and anticoagulant heparin bioconjugate, which targets vascular injury sites to act as a local antithrombotic. We assessed the nonclinical safety and exposure of intravenously infused APAC in rats and cynomolgus monkeys by using single-day and 14-day repeat dose toxicology and pharmacodynamic markers. Activated partial thromboplastin time (APTT) was used as a functional surrogate of anticoagulant exposure of APAC. Routine clinical in-life observations were followed by clinical pathology and necropsy. The no-observed-adverse-effect level (NOAEL) in rats for the single APAC dose was 20 mg/kg and for the repeated administration was 10 mg/kg/d. Monkeys tolerated a single APAC dose of 10 mg/kg, although the red blood cell count reduced 16%–19% correlating with tissue hemorrhage at vein puncture and affected muscle sites during handling of the animals. However, after 2-week recovery, all clinical signs were normal. The single dose NOAEL exceeded 3 mg/kg. The repeat administration of 3–6 mg/kg/d of APAC was tolerated, but some clinical signs were observed. The NOAEL for repeated dosing was 0.5 mg/kg/d. APAC prolonged APTT dose-dependently in both species, returning to baseline after 1.5 (<10 mg/kg) or essentially by 6 hours also under repetitive dosing. The toxicology profile supports the safety of an intravenous APAC dose of 0.5 mg/kg/d for possible clinical applications. APTT is an acceptable indicator of the immediate systemic anticoagulation effect of APAC.
Regulation of Mitochondrial Function by Noncoding RNAs in Heart Failure and Its Application in Diagnosis and Treatment
Authors: Yang Miaomiao , Wang Xinxing , Wang Tianhui
Published: June 2021

Heart failure (HF) is the terminal stage of multiple cardiovascular diseases. However, the pathogenesis of HF remains unclear and prompt; appropriate diagnosis and treatment of HF are crucial. Cardiomyocytes isolated from HF subjects frequently present mitochondrial impairment and dysfunction. Many studies have suggested that the regulation by noncoding RNAs (ncRNAs) of mitochondria can affect the occurrence and progression of HF. The regulation by ncRNAs of myocardial mitochondria during HF and the recent applications of ncRNAs in the diagnosis and treatment of HF are summarized in this review that is intended to gain keen insights into the mechanisms of HF and more effective treatments.
Vasculature-on-chip for Assessment of Bioresorbable Scaffolds and Endothelial Barrier Integrity
Authors: Tesfamariam Belay
Published: June 2021

Endothelial cells adhere to one another through junctional structures formed by intercellular adhesion molecules. These intercellular proteins regulate barrier function in response to the hemodynamic shear rate and enable the selective passage of solutes and fluids across the endothelium. After endovascular device implantation, the endothelial barrier is compromised and becomes discontinuous, which increases permeability, allowing transmigration of leukocytes and lipoproteins and leading to the accumulation of lipid-laden foamy macrophages in the subendothelial space. Drug-coated bioresorbable vascular scaffold implants have been associated with unexpected thrombotic complications, which were not predicted in animals because of dissimilarities in endothelial regeneration and realignment between animals and humans. The development of a microengineered, microfluidics-based system of patterned channels lined with human endothelial and smooth muscle cells perfused with blood allows for the evaluation of endothelial function and barrier integrity. This review highlights the translational potential of vasculature-on-chip, which recreates the microphysiological milieu to evaluate the impact of drug-eluting bioresorbable vascular scaffolds on endothelial barrier integrity and to characterize polymer biodegradation behavior and drug release kinetic profiles over time.
ChartSweep: A HIPAA-compliant Tool to Automate Chart Review for Plastic Surgery Research
Authors: Chartier Christian , Gfrerer Lisa , Austen William G.
Published: June 2021

Retrospective chart review (RCR) is the process of manual patient data review to answer research questions. Large and heterogeneous datasets make the RCR process time-consuming, with potential to introduce errors. The authors therefore designed and developed ChartSweep to expedite the RCR process while remaining faithful to its methodological rigor. ChartSweep is an open-source tool that can be customized for use with any electronic health record system. ChartSweep was developed by the authors to extract information from electronic health records using the Python coding language. As proof-of-concept, the tool was tested in three studies: RCR1—Identification of subjects who underwent radiofrequency ablation in a cohort of patients who had undergone headache surgery (n = 172); RCR2—Identification of patients with a diagnosis of thoracic outlet syndrome in patients who underwent peripheral neuroplasty (n = 806); RCR3—Identification of patients with a history of implant illness or breast implant-associated anaplastic large cell lymphoma in patients who had undergone implant-based breast augmentation or reconstruction (n = 1133). Inter-rater reliability was assessed. ChartSweep reduced the time required to conduct RCR1 by 1315 minutes (21.9 hours), RCR2 by 1664 minutes (27.7 hours), and RCR3 by 2215 minutes (36.9 hours). Inter-rater reliability was uncompromised (k = 1.00). Open-source Python libraries as leveraged by ChartSweep significantly accelerate the RCR process in plastic surgery research. Quality of data review is not compromised. Further analyses with larger, heterogeneous study populations are required to further validate ChartSweep as a research tool.
Traumatic Flap Complications After Femtosecond LASIK
Authors: Leccisotti Antonio , Fields Stefania V. , De Bartolo Giuseppe , Malandrini Alex
Published: June 2021

Purpose:

The purpose of this article was to evaluate the prognosis of traumatic flap dislocation or avulsion in a large series of laser-assisted in situ keratomileusis (LASIK) cases.

Methods:

Retrospective, consecutive, noncomparative case series analyzes the visual and anatomical results after flap dislocation or avulsion, caused by trauma occurred at least 1 month after LASIK.

Results:

A total of 37,315 eyes of 19,602 patients were reviewed. A traumatic flap complication was observed in 9 eyes of 9 patients, with a maximum interval of 37 months after surgery. Flap dislocation with central full-thickness folds was found in 5 cases; flap lifting and repositioning achieved a full recovery of uncorrected visual acuity. In another case, a partially detached flap was repositioned by a microsponge without lifting; self-limiting localized epithelial ingrowth followed. In 3 eyes, a complete flap avulsion occurred and, after epithelialization, a moderate refractive change was observed, comprised between −0.25 and −1 diopters (D) of spherical equivalent, with astigmatism <1 D; in 1 eye, the resulting myopia was corrected by repeat femtosecond LASIK.

Conclusions:

Traumatic flap complications after femtosecond LASIK are rare but can occur even in the long term; they have a favorable anatomic and visual prognosis.
Management of Keratoconus in Down Syndrome and Other Intellectual Disability
Authors: Stephenson Kirk A. J. , Power Barry , Malata Diana , Quill Barry , Murphy Conor C. , Power William J.
Published: June 2021

Purpose:

The purpose of this study was to assess an intellectual disability (ID) cohort with keratoconus (KC) regarding ophthalmic (visual acuity and corneal tomography) and systemic characteristics and to describe an appropriate clinical algorithm for investigation and management of KC in this setting.

Methods:

This was the retrospective cohort study of patients with ID (Down syndrome, autism, and other) in the cornea department of a tertiary referral ophthalmic hospital in Dublin, Ireland. Retrospective chart review was conducted on people with ID undergoing examination under anesthesia or crosslinking under general anesthetic. Key outcome data included corneal examination findings, corneal tomography, visual acuity, and examination findings (eg, type of ID, general anesthetic, and cardiac status).

Results:

Mean age of the 24 patients was 31.9 years (66.7% male). ID type was Down syndrome (66.7%), autism (25%), and other (8.3%). KC was diagnosed in 98% of eyes, with 45.8% having untreatable advanced disease (57.1% of these bilateral), 39.6% amenable to corneal collagen crosslinking (35.7% of these bilateral), and 6.3% having corneal transplantation. Congenital heart defects were present in 37.5% of the Down syndrome group. There were no serious ocular or systemic adverse events.

Conclusions:

KC is strikingly prevalent in the ID population. Ireland has the highest rate of Down syndrome in Europe (26.3:10,000 live births). This group is rarely suitable for corneal transplantation, and corneal collagen crosslinking is an effective intervention to prevent progression to advanced KC in this already socially restricted group. We propose an algorithm for investigation/treatment and also recommend uniform pediatric KC screening/treatment in ID populations.
Reliability of Several Glaucoma Tests in Patients With Boston Type 1 Keratoprosthesis
Authors: Akpek Esen K. , Karakus Sezen , Yohannan Jithin , Jabbour Samir , Sotimehin Ayodeji E. , Li Gavin , Ramulu Pradeep Y.
Published: June 2021

Purpose:

Managing glaucoma after Boston type 1 keratoprosthesis (KPro) surgery remains challenging. We herein assessed the fitness of commonly used clinical tests to evaluate glaucoma in KPro eyes versus eyes with penetrating keratoplasty (PK) as controls.

Methods:

Sixteen patients with KPro and 14 patients with PK tested in an identical manner. After the 10-2 visual field with size V stimulus, intraocular pressure (IOP) was estimated with palpation by the first observer. Then, retinal nerve fiber layer (RNFL) thickness analysis was performed twice using optical coherence tomography by an ophthalmic photographer, before and after a short break. After the second observer estimated the IOP, the visual field was repeated. Finally, color photographs of the optic disk were captured by an ophthalmic photographer. The cup-to-disk ratio was assessed by 2 masked observers, at 2 different time points, in a random manner. Agreements between and within observers and reliability of repeated measurements were evaluated using the intraclass correlation coefficient (ICC) and Bland–Altman plots.

Results:

Inter-rater agreement of palpation IOP estimate was moderate for eyes with KPro (ICC = 0.47) and fair for eyes with PK (ICC = 0.27). Visual field and RNFL thickness showed high test–retest reliability in both KPro and PK eyes (ICC > 0.80 for both). Inter-rater agreement of cup-to-disk ratio assessments was substantial in eyes with both KPro (ICC = 0.62) and PK (ICC = 0.70).

Conclusions:

The 10-2 visual field and RNFL thickness seem sufficiently repeatable and might allow the detection of glaucoma progression in KPro eyes. Such testing is important, given limited inter-rater agreement regarding the palpation IOP estimate.
Disseminated Aspergillosis Complicated With a Myocardial Abscess in an Immunodeficient Child
Authors: Werner Oscar , Gavotto Arthur , Théron Alexandre
Published: June 2021

Aspergillosis infection is a major complication of acquired immunosuppression, and is associated with poor prognosis in its invasive form. Cardiac dissemination of invasive aspergillosis is a rare and usually fatal consequence of systemic mycosis. We describe a pediatric case of myocardial aspergillosis abscess in a 12-year-old girl diagnosed with multimodality cardiac imaging approach. The patient underwent prolonged antimycotic treatment and bone marrow transplant, which improved her immunity, and, for the first time in the literature, resulted in a favorable outcome.
Hemophagocytic Lymphohistiocytosis in Langerhans Cell Histiocytosis: A Case Series and Literature Review
Authors: Tang Xue , Guo Xia , Gao Ju , Sun Jing-Jing , Wan Zhi
Published: June 2021

Langerhans cell histiocytosis (LCH) is characterized pathologically by langerin-positive (CD207+) dendritic cell proliferation and is considered by some as a myeloid neoplastic disorder. Hemophagocytic lymphohistiocytosis (HLH) is associated with immune dysregulation characterized by the accumulation of activated macrophages and hypercytokinemia. However, these 2 histiocytosis rarely coexist. Currently, the etiology, risk factors, optimal therapy, and outcomes of LCH-HLH remain unclear. We reviewed the medical records of 7 LCH-HLH patients from our hospital and analyzed 50 LCH-HLH patients reported in scientific literature. The median age of LCH onset of these 57 LCH-HLH patients was 1 year, and 91% (52/57) of patients diagnosed as LCH were less than 2 years old. Fifty-six LCH-HLH patients belonged to the multisystem LCH category and 84% (47/56) patients had risk-organ involvement. Twenty-three LCH-HLH patients were complicated with infection and 3 patients had a primary pathogenic mutation of HLH. Overall, 90% of LCH patients developed HLH at the diagnosis or during chemotherapy. Of the 57 LCH-HLH patients, 15 died. Multisystem LCH patients with risk-organ involvement under 2 years old were most likely to develop HLH when complicated with infection at diagnosis or during chemotherapy. Identifying LCH-HLH patients during early stages and treating them with prompt chemotherapy, hematopoietic stem cell transplantation, or supportive therapies are important for better survival.
Evaluation of Self-efficacy in Children and Adolescents With Thalassemia Major
Authors: Baghersalimi Adel , Darbandi Bahram , Kazemnezhad Leyli Ehsan , Kamran Mavardiani Zahra , Ahmad Sharbafi Monireh , Rezasefat Balesbaneh Azar
Published: June 2021

Background:

The survival of thalassemia patients has increased, but there are still challenges regarding the complications of cardiac or endocrine dysfunction and the psychological problems of these patients. Many patients with chronic disease, including thalassemia major (TM), have shown a reduction in communication skills and self-efficacy.

Objective:

The aim of this study was to investigate the self-efficacy among TM patients and determine the related factors among them.

Materials and Methods:

This research was a cross-sectional study and consisted of 40 TM patients 7 to 19 years of age. The control group was 80 nonthalassemia patients. Data were gathered using a 2-part questionnaire. The collected data was entered into the SPSS (version 21) and were analyzed using descriptive and analytical statistics (Mann-Whitney U, and multiple linear regression model).

Results:

According to the Mann-Whitney test, there was no significant difference between self-efficacy score among the affected and nonthalassemia groups (P=0.62). According to the regression model, only, the frequency of monthly blood transfusion was significantly correlated with self-efficacy score, so that by 1 U increase in frequency of monthly blood transfusion, we will have 11 U decrease in self-efficacy score (β=−11, P=0.011).

Conclusions:

The results of this study showed that the rate of self-efficacy in children with thalassemia was moderate (52.5%) to good (45%). The allocation of a specific ward, easy access to health care staff, and social support for patients may seem to justify the moderate to good self-efficacy in these patients.
A Rare Case of Diffuse-type Tenosynovial Giant Cell Tumor in a Teenager With Noonan Syndrome
Authors: Guiffre Danielle , Brien Earl , Shon Wonwoo , Geffner Mitchell E.
Published: June 2021

Noonan syndrome is a common autosomal dominant disorder associated with an increased risk of malignancy. We report a 16-year-old female with Noonan syndrome (KRAS gene variant, Q22R) and diffuse-type tenosynovial giant cell tumor, a proliferative disorder that has been rarely reported in this population. These tumors may represent a complication of the dysregulated RAS/MAPK signaling pathway that underlies Noonan syndrome. They lack typical clinical features, causing misdiagnosis and delays in management, which could lead to osseous invasion requiring more complicated surgical procedures. Increased awareness of this association will improve the clinical outcomes of patients with Noonan syndrome who develop diffuse-type tenosynovial giant cell tumors.
Features Associated With Weight Loss and Growth Stunting for Young Children During Cancer Therapy
Authors: Runco Daniel V. , Wasilewski-Masker Karen , Mazewski Claire M. , Patterson Briana C. , Mertens Ann C.
Published: June 2021

Features associated with malnutrition are poorly elucidated in pediatric cancer care. We aimed to better understand characteristics associated with weight-for-height (WHZ) and height-for-age (HAZ) changes for infants and young children during cancer treatment. This retrospective study included 434 patients diagnosed <3 years old from 2007 to 2015 at a large pediatric cancer center. Patients starting treatment outside our center, those with relapsed or secondary malignancies, or with inaccurate information were excluded. Abstracted weights and heights for a 24-month period after treatment initiation were converted to sex-specific and age-specific z scores. Although not statistically different at baseline, patients with hematologic malignancies gained weight over time, while other tumor types did not. Higher treatment intensity and younger age at diagnosis increased odds of clinically significant weight loss. Older children had higher HAZ at diagnosis and HAZ also significantly decreased over time for all examined risk factors, which is distinctly different from patterns in WHZ over time. In conclusion, WHZ and HAZ are affected differently by cancer treatment in infants and young children. We identify key risk factors for weight loss and growth stunting which will be necessary to develop prospective trials to examine anthropometric, biochemical, and patient recorded outcomes around nutrition.
Small Intestinal Adenocarcinomas Arising in Enteritis Cystica Profunda With Metaplasia: A Report of 2 Cases
Authors: Zhang Dongwei , Chen Irene , Liao Xiaoyan
Published: June 2021

Enteritis cystica profunda (ECP) is an uncommon benign condition arising after mucosal damage. We describe 2 cases of small intestinal adenocarcinomas associated with ECP at the distal ileum, one in a background of active Crohn ileitis (case 1), the other 22 years after pelvic radiation therapy (case 2). Both patients presented with small bowel obstruction and received ileocectomy. Macroscopic examination identified an indurated/strictured area in the distal ileum. Histologically, both cases showed a low-grade tubuloglandular adenocarcinoma arising in a background of chronic ischemic stricture and ECP lined by flat cuboidal cells with mild cytologic atypia resembling pancreatobiliary-type epithelium. There was no conventional dysplasia in the surface or adjacent mucosa. Immunohistochemically, both ECP with metaplasia and invasive carcinomas were diffusely positive for CK7 and CK19, while focally positive for CDX2 or CK20. Both cases showed normal wild-type p53 expression. Case 2 was also mismatch repair protein proficient, with membranous β-catenin staining, and retained nuclear SMAD4 expression. In summary, the 2 cases uniquely exhibits “enteritis-metaplasia-carcinoma” sequence, which has not been reported before. This process appears to bypass conventional dysplasia, be slow and indolent, independent of p53, APC/β-catenin, and SMAD4/TGFβ signaling pathways.
A New Concept of Narrowing Genioplasty: Home Plate–Shaped Sliding Osteotomy
Authors: Hirohi Toshitsugu
Published: June 2021

Background:

Narrowing genioplasty is commonly performed among East Asian populations, as a broad and/or square chin can be aesthetically unappealing. This study was aimed to introduce the home plate–shaped sliding osteotomy technique for narrowing genioplasty and to evaluate the results of this technique.

Methods:

A retrospective chart review of 117 patients who underwent home plate–shaped sliding osteotomy alone between 2011 and 2019 was performed. The angles of oblique osteotomy lines and measurements of caudal repositioning, which significantly affect the postoperative chin shape, were evaluated.

Results:

The home plate–shaped sliding osteotomy technique was successfully accomplished for narrowing genioplasty as an isolated procedure. The mean distance of caudal repositioning was 3.9 ± 0.8 mm, and the mean angles of oblique osteotomy lines were 23.3 ± 4.8 degrees on the right and 21.8 ± 3.5 degrees on the left. This produced an aesthetically pleasing rounded and proportionately narrow chin. The incidence of minor complications was 6.0 percent. There were no major complications. In particular, the risk of inferior alveolar nerve injury was obviated, as an additional mandibular border osteotomy was not typically used with this technique.

Conclusions:

This new surgical procedure for narrowing genioplasty provides improved aesthetic results by altering the chin shape, rather than reducing the transverse width of the chin. The versatility of this procedure allows the chin shape to be adjusted with respect to narrowing, vertical lengthening, anterior advancement, and asymmetric or cleft chin correction. The present study suggests that home plate–shaped sliding genioplasty may be an excellent alternative for correcting broad and/or square chins and more complex chin deformities.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Financial Analysis of Operating a Resident Aesthetic Clinic
Authors: Wagner Ryan D. , Raj Sarth , Davis Matthew J. , Bush Matthew , Perdanasari Aurelia Trisliana , Izaddoost Shayan A. , Reece Edward M. , Winocour Sebastian
Published: June 2021

Background:

Recent changes to the plastic surgery residency training requirements along with a general call for expanded education in cosmetic surgery have encouraged many institutions to incorporate resident aesthetic clinics into their curricula. Although the safety and satisfaction rates of resident aesthetic clinics have been well-studied, their financial viability has not. This study reviews the financial viability of the resident aesthetic clinic at the authors’ institution through a cost analysis.

Methods:

Billing data were analyzed for all patient visits to the resident aesthetic clinic of the authors’ institution during calendar year 2018. Data were extracted, including type and anatomical location of each procedure, charges collected, and supplies used. A financial analysis was performed based on fixed and variable costs and gross revenue.

Results:

A total of 100 unique patients were seen in the clinic over a 1-year period, resulting in 53 operations. This included 15 face, four breast, and 34 body contouring procedures. In addition, 160 cosmetic injections were performed. The gross revenue was $69,955 and the net revenue was $36,600.

Conclusions:

The resident aesthetic clinic at the authors’ institution proved to be financially viable. The authors encourage other institutions to more closely examine the financial state of their resident aesthetic clinics as well. Furthermore, the authors hope that this analysis demonstrates to other programs that, with certain practice models, cost should not be a barrier to initiating and maintaining this valuable training tool.
Clinical Effect of Systemic Steroids in Patients with Cirrhosis and Septic Shock
Authors: Piccolo Serafim Laura , Simonetto Douglas A. , Anderson Alexandra L. , Choi Dae Hee , Weister Timothy J. , Hanson Andrew C. , Kamath Patrick S. , Gajic Ognjen , Gallo de Moraes Alice
Published: June 2021

Purpose:

Evidence regarding the utility of systemic steroids in treating patients with cirrhosis and septic shock remains equivocal. This study aimed to evaluate and elucidate the association of steroid use with outcomes and adverse effects in a cohort of patients with cirrhosis and septic shock.

Patients and methods:

Retrospective cohort study of patients with cirrhosis and septic shock admitted to a tertiary hospital intensive care unit (ICU) from January 2007 to May 2017, using a validated ICU Datamart. Patients who received vasopressors within 6 h of ICU admission were included in the multivariate analysis. The effect of steroids on outcomes was evaluated using multivariable regression, adjusting for confounding variables.

Results:

Out of 179 admissions of patients with cirrhosis and septic shock, 56 received steroids during the ICU admission. Patients who received steroids received a higher total dose of vasopressors (91.2 mg vs. 39.1 mg, P = 0.04) and had a lower initial lactate level (1.8 mmol/L vs. 2.6 mmol/L, P = 0.007). The multivariate analysis included 117 patients and showed no significant differences in mortality, length of ICU admission, or length of hospital stay. Bleeding events, delirium, and renal-replacement therapy requirements were also not associated with the use of steroids.

Conclusion:

The use of systemic steroids was more prevalent in cirrhotic patients with higher vasopressor requirements. It was not associated with decreased mortality or increased ICU- and hospital-free days, or to adverse effects.
Duodenal-Jejunal Bypass Liner for the management of Type 2 Diabetes Mellitus and Obesity
Authors: Ruban Aruchuna , Miras Alexander D. , Glaysher Michael A. , Goldstone Anthony P. , Prechtl Christina G. , Johnson Nicholas , Chhina Navpreet , Al-Najim Werd , Aldhwayan Madhawi , Klimowska-Nassar Natalia , Smith Claire , Lord Joanne , Li Jia V. , Flores Lilliam , Al-Lababidi Moaz , Dimitriadis Georgios K. , Patel Mayank , Moore Michael , Chahal Harvinder , Ahmed Ahmed R. , Cousins Jonathan , Aldubaikhi Ghadah , Glover Ben , Falaschetti Emanuela , Ashrafian Hutan , Roux Carel W. le , Darzi Ara , Byrne James P. , Teare Julian P.
Published: June 2021

Objective:

The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation.

Summary Background Data:

This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery.

Methods:

In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months.

Results:

There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44–2.0;P= 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8–39;P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group.

Conclusions:

The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions.

Trial Registration:

ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.
Overall Volume Trends in Esophageal Cancer Surgery Results From the Dutch Upper Gastrointestinal Cancer Audit
Authors: Voeten Daan M. , Gisbertz Suzanne S. , Ruurda Jelle P. , Wilschut Janneke A. , Ferri Lorenzo E. , van Hillegersberg Richard , van Berge Henegouwen Mark I.
Published: June 2021

Objective:

In the pursuit of quality improvement, this study aimed to investigate volume-outcome trends in oncologic esophagectomy in the Netherlands.

Summary of Background Data:

Concentration of Dutch esophageal cancer care was dictated by introducing an institutional minimum of 20 resections/yr.

Methods:

This nationwide cohort study included all esophagectomy patients registered in the Dutch Upper Gastrointestinal Cancer Audit in 2016–2019 from hospitals currently still performing esophagectomies. Annual esophagectomy hospital volume was assigned to each patient and categorized into quartiles. Multivariable logistic regression investigated short-term surgical outcomes. Restricted cubic splines investigated if volume-outcome relationships eventually plateaued.

Results:

In 16 hospitals, 3135 esophagectomies were performed. First volume quartile hospitals performed 24–39 resections/yr; second, third, and fourth quartile hospitals performed 40–53, 54–69, and 70–101, respectively. Compared to quartile 1, in quartiles 2 to 4, overall/severe/technical complication, anastomotic leakage, and prolonged hospital/intensive care unit stay rates were significantly lower and textbook outcome and lymph node yield were higher. When raising the cut-off from the first to second quartile, higher-volume centers had less technical complications [Adjusted odds ratio (aOR): 0.82, 95% confidence interval (CI): 0.70–0.96], less anastomotic leakage (aOR: 0.80, 95% CI: 0.66–0.97), more textbook outcome (aOR: 1.25, 95% CI: 1.07–1.46), shorter intensive care unit stay (aOR: 0.80, 95% CI: 0.69–0.93), and higher lymph node yield (aOR: 3.56, 95% CI: 2.68–4.77). For most outcomes the volume-outcome trend plateaued at 50–60 annual resections, but lymph node yield and anastomotic leakage continued to improve.

Conclusion:

Although this study does not reflect on individual hospital quality, there appears to be a volume trend towards better outcomes in high-volume centers. Projects have been initiated to improve national quality of care by reducing hospital variation (irrespective of volume) in outcomes in The Netherlands.
Pre-transplant T-cell Clonality
Authors: Jones Stephen L. , Moore Linda W. , Li Xian C. , Mobley Constance M. , Fields Paul A. , Graviss Edward A. , Nguyen Duc T. , Nolte Fong Joy , Saharia Ashish , Hobeika Mark J. , McMillan Robert R. , Victor David W. , Minze Laurie J. , Gaber A. Osama , Ghobrial R. Mark
Published: June 2021

Objective:

This study investigated the ability of pre-transplant T-cell clonality to predict sepsis after liver transplant (LT).

Summary Background Data:

Sepsis is a leading cause of death in LT recipients. Currently, no biomarkers predict sepsis before clinical symptom manifestation.

Methods:

Between December 2013 and March 2018, our institution performed 478 LTs. After exclusions (eg, patients with marginal donor livers, autoimmune disorders, nonabdominal multi-organ, and liver retransplantations), 180 consecutive LT were enrolled. T-cell characterization was assessed within 48 hours before LT (immunoSEQ Assay, Adaptive Biotechnologies, Seattle, WA). Sepsis-2 and Sepsis-3 cases, defined by presence of acute infection plus ≥2 SIRS criteria, or clinical documentation of sepsis, were identified by chart review. Receiver-operating characteristic analyses determined optimal T-cell repertoire clonality for predicting post-LT sepsis. Kaplan-Meier and Cox proportional hazard modeling assessed outcome-associated prognostic variables.

Results:

Patients with baseline T-cell repertoire clonality ≥0.072 were 3.82 (1.25, 11.40; P = 0.02), and 2.40 (1.00, 5.75; P = 0.049) times more likely to develop sepsis 3 and 12 months post-LT, respectively, when compared to recipients with lower (<0.072) clonality. T-cell repertoire clonality was the only predictor of sepsis 3 months post-LT in multivariate analysis (C-Statistic, 0.75). Adequate treatment resulted in equivalent survival rates between both groups: (93.4% vs 96.2%, respectively, P = 0.41) at 12 months post-LT.

Conclusions:

T-cell repertoire clonality is a novel biomarker predictor of sepsis before development of clinical symptoms. Early sepsis monitoring and management may reduce post-LT mortality. These findings have implications for developing sepsis-prevention protocols in transplantation and potentially other populations.
A Randomized Controlled Trial Evaluating Electronic Outpatient Symptom Monitoring After Ambulatory Cancer Surgery
Authors: Pusic Andrea L. , Temple Larissa K. , Carter Jeanne , Stabile Cara M. , Assel Melissa J. , Vickers Andrew J. , Niehaus Kate , Ancker Jessica S. , McCready Taylor , Stetson Peter D. , Simon Brett A.
Published: June 2021

Objective:

We implemented routine daily electronic monitoring of patient-reported outcomes (PROs) for 10 days after discharge after ambulatory cancer surgery, with alerts to clinical staff for worrying symptoms. We sought to determine whether enhancing this monitoring by adding immediate automated normative feedback to patients regarding expected symptoms would further improve the patient experience.

Summary of Background Data:

PRO monitoring reduces symptom severity in cancer patients. In ambulatory cancer surgery, it reduces potentially avoidable urgent care center (UCC) visits, defined as those UCC visits without readmission.

Methods:

Patients undergoing ambulatory cancer surgery (n = 2624) were randomized to receive standard PRO monitoring or enhanced feedback. The primary study outcome was UCC visits without readmission within 30 days; secondary outcomes included patient anxiety and nursing utilization.

Results:

There was no significant difference in the risk of a potentially avoidable UCC visit [1.0% higher in enhanced feedback, 95% confidence interval (CI) -0.2–3.1%; P = 0.12]. There were similarly no significant differences in UCC visits with readmission or readmission overall (P = 0.4 for both). Patients randomized to enhanced feedback demonstrated a quicker reduction in anxiety (P < 0.001) and required 14% (95% CI 8–19%; P < 0.001) and 10% (95% CI 5–16%, P < 0.001) fewer nursing calls over 10 and 30 days postoperatively.

Conclusions:

Providing patients with feedback about symptom severity during recovery from ambulatory cancer surgery reduces anxiety and nursing workload without affecting UCC visits or readmissions. These results support wider incorporation of normative feedback in systems for routine PRO monitoring.
Altered intrinsic brain activity in mild Alzheimer’s disease patients with sleep disturbances
Authors: Wang Lei , Peng Dantao
Published: June 2021

Sleep disturbances are one of the preventive factors to delay the onset and progression of Alzheimer’s disease. Early identification of Alzheimer’s disease patients prone to develop sleep disturbances to offer early medical intervention is important. Resting-state functional MRI is a widely used method to investigate the neural mechanisms and find neuroimaging biomarkers in neuropsychiatric diseases. In this study, we applied percent amplitude of fluctuation (PerAF) and mPerAF (divided by global mean PerAF) to test the strength of intrinsic brain activity in 38 mild Alzheimer’s disease patients with sleep disturbances (ADSD) and 21 mild Alzheimer’s disease patients without sleep disturbances (ADNSD). Compared with ADNSD, we found decreased intrinsic brain activity in the calcarine gyrus, the lingual gyrus, the fusiform gyrus extending to the parahippocampal gyrus, the precentral gyrus, the postcentral gyrus (all in the left hemisphere) and the left brainstem. Conclusively, ADSD exhibited reduced neural activity in specific brain regions related to the sensorimotor network and the visual network, which indicated the contribution of sleep disturbances to the progression of Alzheimer’s disease. Especially, the ventral visual pathway to the hippocampus might serve for the memory impaired by sleep disturbances in Alzheimer’s disease, and the brainstem might be critical in the initiation of sleep disturbances in Alzheimer’s disease. These findings further elucidate the interactions between Alzheimer’s disease and sleep disturbances and could help with the early recognition of Alzheimer’s disease patients who tend to develop sleep disturbances.
CYP2C19 polymorphisms are associated with severity of depression at initial evaluation and after the treatment independently of the prescribed medications: 4 weeks prospective study
Authors: Strumila Robertas , Lengvenyte Aiste , Ambrozaityte Laima , Balkeliene Danute , Utkus Algirdas , Dlugauskas Edgaras
Published: June 2021

Background

The cytochrome P-450 2C19 (CYP2C19) enzyme is involved in the metabolism of numerous antidepressants. It also metabolises some endogenous substrates, which could also confer to vulnerability. We aimed to establish whether the severity of depression and treatment response are associated with the genetically predicted CYP2C19 phenotype.

Methods

We assessed the CYP2C19 genotype-predicted metabolic phenotypes (normal, intermediate or ultrarapid, there were no poor metabolisers) in patients with moderate or severe depression. We used the self-rated Beck Depression Inventory-II (BDI-II) scale and the clinician-rated Montgomery–Åsberg Depression Rating Scale (MADRS) at baseline, after 2 and 4 weeks of an empirical treatment trial. Patients and clinicians were blind to the genetic testing results.

Results

Seventy-six patients participated in the present study. At baseline, impaired CYP2C19 metabolisers, compared to normal metabolisers, had higher BDI-II (P = 0.046; ηp
2 = 0.08) but not MADRS score. Intermediate metabolisers more often had a diagnosis of severe depression than normal metabolisers (P = 0.003). After 4 weeks of empirical treatment, intermediate metabolisers had significantly higher MADRS and BDI-II scores than normal metabolisers (P = 0.006; ηp
2  = 0.131 and P = 0.030; ηp
2 = 0.091). These differences were independent of the use of CYP2C19-metabolised medications in the treatment trial, as well as the treatment discrepancy status.

Conclusions

Intermediate CYP2C19 polymorphism-predicted activity was associated with more severe depression after an empirical treatment trial. The lack of association between the prescription of CYP2C19-metabolised drugs and treatment response calls for a further look into the role of endogenous substrates of CYP2C19.
Correlated and geographically predictable Neanderthal and Denisovan legacies are difficult to reconcile with a simple model based on inter-breeding
Authors: Amos William
Published: June 2021

Although the presence of archaic hominin legacies in humans is taken for granted, little attention has been given as to how the data fit with how humans colonized the world. Here, I show that Neanderthal and Denisovan legacies are strongly correlated and that inferred legacy size, like heterozygosity, exhibits a strong correlation with distance from Africa. Simulations confirm that, once created, legacy size is extremely stable: it may reduce through admixture with lower legacy populations but cannot increase significantly through neutral drift. Consequently, populations carrying the highest legacies are likely to be those whose ancestors inter-bred most with archaics. However, the populations with the highest legacies are globally scattered and are unified, not by having origins within the known Neanderthal range, but instead by living in locations that lie furthest from Africa. Furthermore, the Simons Genome Diversity Project data reveal two distinct correlations between Neanderthal and Denisovan legacies, one that starts in North Africa and increases west to east across Eurasia and into some parts of Oceania, and a second, much steeper trend that starts in Africa, peaking with the San and Ju/’hoansi and which, if extrapolated, predicts the large inferred legacies of both archaics found in Oceania/Australia. Similar ‘double’ trends are observed for the introgression statistic
f
4
in a second large dataset published by Qin and Stoneking (Qin & Stoneking 2015
Mol. Biol. Evol.
32
, 2665–2674 (
doi:10.1093/molbev/msv141
)). These trends appear at odds with simple models of how introgression occurred though more complicated patterns of introgression could potentially generate better fits. Moreover, substituting archaic genomes with those of great apes yields similar but biologically impossible signals of introgression, suggesting that the signals these metrics capture arise within humans and are largely independent of the test group. Interestingly, the data do appear to fit a speculative model in which the loss of diversity that occurred when humans moved further from Africa created a gradient in heterozygosity that in turn progressively reduced mutation rate such that populations furthest from Africa have diverged less from our common ancestor and hence from the archaics. In this light, the two distinct trends could be interpreted in terms of two ‘out of Africa’ events, an early one ending in Oceania and Australia and a later one that colonized Eurasia and the Americas.
Local impacts of climate change on winter wheat in Great Britain
Authors: Putelat Thibaut , Whitmore Andrew P. , Senapati Nimai , Semenov Mikhail A.
Published: June 2021

Under future CMIP5 climate change scenarios for 2050, an increase in wheat yield of about 10% is predicted in Great Britain (GB) as a result of the combined effect of CO
2
fertilization and a shift in phenology. Compared to the present day, crops escape increases in the climate impacts of drought and heat stresses on grain yield by developing before these stresses can occur. In the future, yield losses from water stress over a growing season will remain about the same across Great Britain with losses reaching around 20% of potential yield, while losses from drought around flowering will decrease and account for about 9% of water limited yield. Yield losses from heat stress around flowering will remain negligible in the future. These conclusions are drawn from a modelling study based on the response of the Sirius wheat simulation model to local-scale 2050-climate scenarios derived from 19 Global Climate Models from the CMIP5 ensemble at 25 locations representing current or potential wheat-growing areas in GB. However, depending on susceptibility to water stress, substantial interannual yield variation between locations is predicted, in some cases suggesting low wheat yield stability. For this reason, local-scale studies should be performed to evaluate uncertainties in yield prediction related to future weather patterns.
Calibrating models of cancer invasion: parameter estimation using approximate Bayesian computation and gradient matching
Authors: Xiao Yunchen , Thomas Len , Chaplain Mark A. J.
Published: June 2021

We present two different methods to estimate parameters within a partial differential equation model of cancer invasion. The model describes the spatio-temporal evolution of three variables—tumour cell density, extracellular matrix density and matrix degrading enzyme concentration—in a one-dimensional tissue domain. The first method is a likelihood-free approach associated with approximate Bayesian computation; the second is a two-stage gradient matching method based on smoothing the data with a generalized additive model (GAM) and matching gradients from the GAM to those from the model. Both methods performed well on simulated data. To increase realism, additionally we tested the gradient matching scheme with simulated measurement error and found that the ability to estimate some model parameters deteriorated rapidly as measurement error increased.