bluuebunny/crossref_metadata_2025 huggingface dataset:
The clinical applicability of polygenic risk scores for LDL-cholesterol: considerations, current evidence and future perspectives
Authors: Cupido Arjen J. , Tromp Tycho R. , Hovingh G. Kees
Published: February 2021

Purpose of review

The current review describes the development, clinical relevance and potential caveats of polygenic risk scores (PRS) for LDL cholesterol (LDL-C).

Recent findings

In recent years, a large number of common variants have been shown to have a small effect on LDL-C levels. The aggregate effect of all of these variants on LDL-C levels can be captured in a PRS and an elevated number of LDL-C increasing common variants is considered to be a cause of high LDL-C levels in patients with familial hypercholesterolemia (FH) without a large effect, rare mutation. PRS do not only serve as a tool in diagnostics, but are also helpful in cardiovascular disease (CVD) risk prediction. Moreover, PRS modulate CVD risk even in patients without a monogenic FH. However, future larger scale PRS directly aimed at CVD risk may serve as more sensitive tools to identify individuals with severely increased CVD risk.

LDL-C PRS help explain part of hypercholesterolemia in a proportion of dyslipidemic patients that do not have monogenic FH. Nevertheless, the CVD risk conferred by current PRS does not appear to match that of monogenic FH. LDL-C PRS are currently not widely used in clinical care.
Long-term outcomes of intestinal transplantation
Authors: Hind Jonathan M.
Published: February 2021

Purpose of review

In this article, data from the intestinal transplant registry, recent publications and reviews in the field will be used to describe mortality, morbidity, complications, nutritional and psychosocial outcomes in intestinal transplant recipients with a focus on those furthest out from transplant.

Recent findings

Registry data show static long-term survival data (41% 10-year survival in the most recent analysis), but experienced centres report improvements with survival between 60 and 70% at 10 years. Chronic rejection remains a problem for long-term graft survival, but understanding of humoral immunity is increasing. Nutritional outcomes are good with most recipients achieving enteral autonomy with an unrestricted diet. Health-related quality of life data generally shows improvement in the years after transplant, educational attainment is good, but some patients have ongoing psychosocial problems.

Most patients do well in the long-term after transplant. Survival outcomes have improved in experienced centres, and nutrition and quality of life outcomes are good. Recognition of psychosocial outcomes is increasing. Nevertheless, challenges remain in areas such as infectious complications, renal function, chronic rejection, social support and mental health.
Pancreas transplant versus islet transplant versus insulin pump therapy: in which patients and when?
Authors: Tamburrini Riccardo , Odorico Jon S.
Published: February 2021

Purpose of review

The aim of the present review is to gather recent reports on the use of pancreas and islet transplantation and conventional insulin therapy for treating patients experiencing diabetes and its related complications. The present review directs attention to the current status, challenges and perspectives of these therapies and sheds light on potential future cellular therapies.

Recent findings

The risks and benefits of diabetes treatment modalities continue to evolve, altering the risk versus benefit calculation for patients. As continuous subcutaneous insulin infusion and monitoring technologies demonstrate increasing effectiveness in achieving better diabetes control and reducing hypoglycemia frequency, so are pancreas and islet transplantation improving and becoming more effective and safer. Both beta-cell replacement therapies, however, are limited by a dependence on immunosuppression and a shortage of cadaver donors, restricting more widespread and safer deployment. Based on the effectiveness of clinical beta-cell replacement for lengthening lifespan and improving quality of life, scientists are aggressively investigating alternative cell sources, transplant platforms, and means of preventing immunological damage of transplanted cells to overcome these principle limitations.

Essential goals of diabetes therapy are euglycemia, avoidance of hypoglycemia, and prevention or stabilization of end-organ damage. With these goals in mind, all therapeutic options should be considered.
Pseudomonas aeruginosa in the healthcare facility setting
Authors: Spagnolo Anna Maria , Sartini Marina , Cristina Maria Luisa
Published: February 2021

Pseudomonas aeruginosa is a Gram-negative pathogen that has become an important cause of infection in humans and can be associated with significant morbidity and mortality.

Severe infections usually affect immunocompromised patients or those with chronic debilitating diseases. Its significance as a pathogen is exacerbated by its resistance to antibiotics, virulence factors and its ability to adapt to a wide range of environments. P. aeruginosa can have multiple intrinsic or acquired mechanisms of resistance, frequently with high resistance rates to various antimicrobial classes. In recent years, the worldwide spread of the so-called ‘high-risk clones’ of multidrug-resistant or extensively drug-resistant P. aeruginosa has become a public health threat that needs to be studied and managed with urgency and determination.

Among Gram-negative infections, P. aeruginosa is one of the most common Gram-negative bacteria causing nosocomial and healthcare-associated infections in hospitalised patients. According to WHO guidelines, measures to prevent the transmission of multiresistant P. aeruginosa in healthcare facilities should include at least hand hygiene (with the appropriate use of alcohol-based solutions), contact precautions, patient isolation (single room or cohort), environmental cleanliness and surveillance.
Respiratory Distress Observation Scale Italian Version
Authors: Tinti Stefania , Destrebecq Anne , Terzoni Stefano , De Maria Beatrice , Falcone Graziella , Da Col Daria , Pairona Giulia , Longhi Carla , Giudici Elisa , Pidone Irene Maria , Alberti Annalisa , Sofia Michele , Ramponi Ida , Campbell Margaret L.
Published: February 2021

Dyspnea can be assessed using self-rating scales but, as death approaches, self-reporting becomes difficult. The validated Respiratory Distress Observation Scale measures dyspnea distress. The aim of this study was to develop the Italian version of the Respiratory Distress Observation Scale and to examine its psychometric properties. This was a cross-sectional study, analyzing cultural and linguistic validation, content validity, and psychometric properties. Eighty-nine palliative care subjects were enrolled to validate the Italian version of the Respiratory Distress Observation Scale. Patients had an average age of 74.5 (SD, 11.6) years, and 52% (n = 46) were female. Fourteen experts in palliative care evaluated the Italian Respiratory Distress Observation Scale in terms of the content validity ratio and the content validity index (CVI). The Italian Respiratory Distress Observation Scale was reported with an internal consistency (Cronbach α value) of .72 and an overall substantial interrater reliability (Cohen κ method). The Italian Respiratory Distress Observation Scale achieved a scale-level CVI of 93%, an items-level CVI of greater than 86%, and a minimum content validity ratio value of 0.71. A weak positive correlation was found between the Respiratory Distress Observation Scale and the Dyspnea Visual Analog Scale scores (0.374; P < .001). The Italian Respiratory Distress Observation Scale showed good reliability and validity for patients in palliative care. The Respiratory Distress Observation Scale measured respiratory distress in patients nearest to death.
Photography's Underappreciated Contributions to Neuropsychiatry
Authors: Schildkrout Barbara , Raj Shreya , MacGillivray Lindsey , Lauterbach Margo D.
Published: February 2021

Photographers and filmmakers have made important contributions to the international mental health community through documentation and social commentary, leveraging the power of visual imagery. To illustrate, this article uses the example of W. Eugene Smith who photographed the catastrophic effects of methylmercury poisoning from industrial pollution in the region around Minamata Bay, Japan. Although many art forms have been comfortably integrated into mainstream psychiatry and neuropsychiatry, photography has been underappreciated and underutilized.
A Survey of American Psychiatrists Concerning Medication Prior Authorization Requirements
Authors: Barnett Brian S. , Bodkin J. Alexander
Published: February 2021

This study examined opinions of American psychiatrists regarding prior authorization (PA) requirements for third-party payer coverage of medications and quantified perceived impact of these requirements on clinical practice. One thousand selected psychiatrist members of the American Psychiatric Association were invited to participate in a survey. Response rate was 33.1%. Respondents predominantly believed the obligation to obtain PA reduces job satisfaction and negatively impacts patient care. A total of 59.9% of respondents reported employing either diagnosis modification or falsification of previous medication trials at least occasionally in order to obtain PA. A total of 66.6% refrained at least occasionally from prescribing preferred medications due to PA requirement or expectation of one. On multivariate analysis, risk factors for refraining at higher frequency included seeing 300 or more patients in the previous 3 months, engaging more frequently in diagnosis modification, and reporting increased perception that obtaining PA reduces time for patient care.
Maximizing Opportunities in Your Career
Authors: Cartwright Cathy C.
Published: February 2021

This month’s Magnet® Perspectives column is authored by one of the winners of the 2015 Magnet Nurse of the Year award. Cathy Cartwright, a pediatric clinical nurse specialist in neurosurgery, reflects on lessons learned during her nursing career by taking advantage of opportunities and persevering to maximize her impact on patient care.
Medical Observation Units and Emergency Department Collaboration
Authors: Gabele Danielle , Bugais Charlene , Laguna Joanne
Published: February 2021

OBJECTIVE:

The aim of this study was to identify whether observation status patients placed in a dedicated unit would decompress the emergency department (ED) more than observation patients who were admitted to other available beds.

BACKGROUND:

An urban quaternary hospital has a high volume of patients with average daily census of 95% capacity. A medical observation unit (MOU) was created to improve patient throughput.

METHODS:

In phase 1, the MOU charge nurse reviewed the ED patients to be admitted and selected appropriate patients based on unit inclusion criteria. In phase 2, the MOU charge nurse did rounds with the ED charge nurse once per shift.

RESULTS:

MOU observation patients demonstrated a 53-minute (16%) reduction in average overall ED length of stay compared with observation patients admitted to other units.

CONCLUSION:

Inclusion criteria, a rounding checklist, and engagement of MOU and ED nurses helped the MOU and ED with patient throughput.
The Impact of an Integrated Electronic Health Record Adoption on Nursing Care Quality
Authors: Walker-Czyz AnneMarie
Published: February 2021

OBJECTIVES:

The purpose of this study was to measure the impact of an integrated electronic health record (EHR) innovation adoption on the quality of nursing care delivered, including hospital-acquired falls, hospital-acquired pressure ulcers, ventilator-associated pneumonia (VAP), central line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), and costs measured in nursing hours. The impact on quality, cost, and nurse satisfaction measured in turnover rates before, during, and after implementation of EHR tools was also investigated.

BACKGROUND:

Little is known about the adoption patterns of computerized documentation by nursing and the effects on the practice environment.

METHODS:

A quantitative, retrospective analysis using interrupted time series model of a large data set was conducted in a 431-bed urban hospital, with 10 medical surgical units and 2 critical care units. The research was constructed using the Diffusion of Innovations (DOI) theory.

RESULTS:

Incorporating electronic, evidenced-based practice (EBP) tools into bedside nurse's workflow promotes decision making at the point of care that may improve quality with no negative impact on direct cost. The data revealed that total falls, CAUTI, and CLABSI rates were positively impacted after the implementation of an integrated EHR. Hospital-acquired pressure ulcer and VAP rates were negatively impacted at the implementation period followed by a significant positive rate reduction that surpassed the preimplementation period. Cost indicators, measured in hours per patient day and overtime, were negatively impacted during the implementation period followed by a return to baseline. Nurse turnover had a significant increase from the preimplementation to postimplementation period and failed to return to baseline.

CONCLUSIONS:

This study confirms that nurses have the ability to positively impact the quality of patient care through successful innovation adoption related to the use of EBP computerized documentation tools at the bedside. This study further clarified the practice environment of nurses during DOI.
Survey of Managers Regarding Nurses’ Performance of Nonnursing Duties
Authors: Kearney Anne , Grainger Patricia , Chubbs Katherine , Downey Joan
Published: February 2021

BACKGROUND:

The performance of nonnursing duties by nursing staff contributes to an already busy workload while taking time away from patient care.

OBJECTIVE:

This article reports on a process implemented by a large regional health authority in Canada to measure and address nurses’ performance of nonnursing duties through a newly created tool.

METHODS:

Process improvement methodology was used to conduct this project. A measurement tool, the “Non-Nursing Duties Tracking Tool,” was designed for frontline nursing staff and patient care attendants to document the performance of tasks classified as clerical, housekeeping, food services, clinical support, and transportation. This article reports on a survey of managers regarding information collected from frontline nurses and patient care attendants regarding their performance of nonnursing duties and actions taken or planned to address this.

RESULTS:

Tasks were identified that could be delegated to housekeeping, transport, and clerical staff. Both frontline nurses and managers expressed the need for administrative support to realign nonnursing tasks to more appropriate personnel. Although most managers of nurses expressed concern about the support of managers in other departments to make these changes, little resistance was encountered when adequate resources were in place.

CONCLUSIONS:

The “Non-Nursing Duties Tracking Tool” is a valid instrument to support the assessment of nonnursing direct care duties.
Diffusion of a Nurse-led Healthcare Innovation
Authors: Bender Miriam , Williams Marjory , Su Wei
Published: February 2021

BACKGROUND:

The Clinical Nurse Leader™ (CNL) initiative is in its 2nd decade. Despite a growing theoretical and empirical body of CNL knowledge, little is known about CNLs themselves or where and how their competencies are being integrated into care delivery across the country.

OBJECTIVE:

The aim of this study was to describe certified CNL characteristics and roles as part of a larger study validating a model for CNL practice.

METHODS:

This study used a descriptive analysis of survey data from a national sample of certified CNLs.

RESULTS:

Survey response rate was 19%. Sixty percent have greater than 10 years of RN experience, and 75% have additional specialty certifications. Fifty-eight percent are practicing in a formal CNL role and report a high degree of accountability for all 9 CNL essential competencies.

CONCLUSIONS:

Findings help understand the extent of CNL adoption and spread across the country and the level to which the initial vision of CNL practice is being achieved.
Distal Tubular Hyperplasia
Authors: Williamson Sean R. , Al-Obaidy Khaleel I. , Cheng Liang , Smith Steven C. , Cox Roni Michelle , McKenney Jesse K. , Gokden Neriman , Phillips Carrie L. , Giannico Giovanna A. , Gallan Alexander J. , Przybycin Christopher G. , Grignon David J.
Published: February 2021

We identified an unusual pattern of renal tubular proliferation associated with chronic renal disease, found in 23 patients, diffusely (n=12), or focally (n=11). Incidence was 5% of end-stage renal disease kidneys from one institution (8/177) and 7/23 patients with acquired cystic kidney disease–associated renal cell carcinoma from another. Most (19 patients) had 1 or more neoplasms including papillary (n=9), acquired cystic kidney disease (n=8), clear cell (n=4), or clear cell papillary (n=3) renal cell carcinoma. All (20 men, 3 women) had end-stage renal disease. The predominant pattern (n=18) was the indentation of chronic inflammation into renal tubules forming small polypoid structures; however, 5 had predominantly hyperplastic epithelium with less conspicuous inflammation. In 14 patients both patterns were appreciable, whereas the remainder had only the inflammatory pattern. Immunohistochemistry was positive for cytokeratin 7, high–molecular-weight cytokeratin, PAX8, and GATA3. Staining for alpha-methylacyl-CoA racemase was negative or weak, dramatically less intense than papillary neoplasms or proximal tubules. CD3 and CD20 showed a mixture of B and T lymphocytes in the inflammatory areas. Fluorescence in situ hybridization showed no trisomy 7 or 17 or loss of Y (n=9). We describe a previously uncharacterized form of renal tubular proliferation that differs from papillary adenoma (with weak or negative alpha-methylacyl-CoA racemase, lack of trisomy 7 or 17, and sometimes diffuse distribution). On the basis of consistent staining for high–molecular-weight cytokeratin and GATA3, we propose the name distal tubular hyperplasia for this process. Future studies will be helpful to assess preneoplastic potential and etiology.
Primary Giant Cell Tumors of the Lung
Authors: Oramas Diana M. , Moran Cesar A.
Published: February 2021

Three cases of primary giant cell tumors of the lung akin to those described in the soft tissues are presented. The patients are 3 men between the ages of 43 and 54 years who presented with nonspecific symptoms of cough, chest pain, and shortness of breath. None of the patients had any prior history of malignancy anywhere else. Diagnostic imaging disclosed the presence of an intrapulmonary mass. All the patients underwent lobectomy. Grossly, the tumors were described as solid, slightly hemorrhagic, and measuring between 1.8 and 2.4 cm in greatest diameter. Histologically, the tumors were characterized by a dual population of multinucleated giant cells admixed with a mononuclear proliferation. Nuclear atypia was mild to moderate, and mitotic activity varied but was under 5 mitotic figures per 10 high power fields. Immunohistochemical stains showed positive staining for vimentin, CD68, and cathepsin K, whereas the tumors were negative for keratin, TTF-1, p40, S-100 protein, and SABT-2. Clinical follow-up was obtained in 2 patients who have remained alive and without evidence of recurrence or metastasis up to 12 months after surgery. One patient was lost to follow-up. The current neoplasms represent a tumor that to the best of our knowledge has not been reported as a primary neoplasm of the lung. The cases herein described represent an unusual occurrence and should be maintained in the differential diagnosis of primary pulmonary tumors rich in multinucleated giant cells.
Primary Ovarian Melanoma Arising From a Mature Teratoma With Melanoma In Situ Present in the Ciliated Columnar and Squamous Epithelium in a Patient With Synchronous Skin Basal Cell Carcinoma
Authors: Lai Jinping , Garvey Katherine Y. , Li Peng , Azevedo Robert A.
Published: February 2021

Primary ovarian melanoma arising from ovarian teratomas are rarely reported and difficult to accurately diagnose. Cases in the literature rely on a diagnosis of exclusion, and cases of primary ovarian melanoma with pathologic evidence of melanoma in situ are exceedingly rare. We report a case of a 66-yr-old female who presented to emergency department with abdominal pain and bloating. Computed tomography scan showed a 21 cm complex pelvic mass. An urgent laparoscopic bilateral salpingo-oophorectomy was performed. Pathologically the mass was identified as a mature teratoma. Within the cystic teratoma, there was an area showing a sheet arrangement of atypical cells. Those atypical cells were positive for Melan A, Sox10, HMB45, and c-KIT, and negative for PD-L1. Melanoma in situ was present in both the squamous and ciliated columnar epithelium. The melanoma was negative for PD-L1, and no BRAF (codon 600, exons 11, 14, and 15) or c-KIT (exons 2, 9, 10, 11, 13, 14, 15, 17, 18) mutations were identified, thus supporting the so-called triple negative malignant melanoma. A thorough dermatologic exam was conducted and only a 3 mm skin basal cell carcinoma was confirmed on biopsy. At 11 mo of follow-up, the patient is disease free and doing well and no metastatic melanoma has been identified. To the best of our knowledge, this is the first documented case of a primary ovarian melanoma arising in a mature teratoma with evidence of melanoma in situ present in both ciliated columnar and squamous epithelium in a patient with synchronous skin basal cell carcinoma. Our case is positive for c-KIT protein (CD117) by immunohistochemistry, but negative for KIT mutation. More case reports are needed to further characterize the disease.
Use of Autologous Adipose-Derived Stromal Vascular Fractions in Revision Rhinoplasty for Severe Contractures in Asian Patients
Authors: Ahn Tae Hwan , Lee Won , Kim Hyoung Moon , Cho Sung Bin , Yang Eun-Jung
Published: February 2021

Background:

Autologous adipose-derived stromal vascular fraction treatments have been shown to elicit antiinflammatory, antifibrotic, immunomodulatory, angiogenic, and regenerative effects. Injections of adipose-derived stromal vascular fraction have been used to treat severely scarred tissues.

Methods:

Revision septorhinoplasty was performed in 40 patients with severely contracted noses. Clinical outcomes and adverse events were compared between one group of patients treated with adjuvant adipose-derived stromal vascular fraction injections and a control group of patients treated with adjuvant 0.9% preservative-free saline injections.

Results:

In the adipose-derived stromal vascular fraction group, nasal lengths were estimated at 4.2 ± 0.2 cm at baseline to 5.1 ± 0.2 cm at 18 months after revision septorhinoplasty. The lengths of nasal tip projection improved from 2.2 ± 0.2 cm at baseline to 2.9 ± 0.1 cm 18 months after surgery. In addition, nasofrontal angles improved from 125.6 ± 5.1 degrees at baseline to 128.1 ± 4.8 degrees 18 months after surgery. Nasolabial angles in the adipose-derived stromal vascular fraction group were estimated at 105.8 ± 6.5 degrees at baseline and 94.9 ± 5.6 degrees 18 months after surgery. Of these, nasal length, nasal tip projection, and nasolabial angle, but not nasofrontal angle, values improved more in the adipose-derived stromal vascular fraction group than in the control group.

Conclusion:

Preoperative and postoperative adjuvant adipose-derived stromal vascular fraction treatment markedly improved the therapeutic outcomes of revision rhinoseptoplasty of severely contracted noses without major side effects.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Subbrow Blepharoplasty in Caucasians
Authors: Eid Laura , Tsirbas Angelo
Published: February 2021

Subbrow blepharoplasty is widely used in Asian patient populations to preserve the natural upper lid crease while addressing dermatochalasis with lateral hooding. The authors describe the first use of this technique in Caucasians with dermatochalasis and lateral hooding. This is a retrospective case series of Caucasian patients who underwent subbrow blepharoplasty for moderate to severe dermatochalasis with lateral hooding. Patients were included when the skin excess of the upper lid was noted predominantly as a lateral hooding over the lateral half of the upper lid. A modified subbrow blepharoplasty technique was used and will be described in detail. Fifty patients underwent the procedure from January of 2017 to June of 2018, 18 female and 32 male patients. The average age of the patients was 71.4 years (range, 59 to 84 years). Minimum patient follow-up was 3 months. An internal browpexy and a periosteal fixation were combined with subbrow blepharoplasty for 22 patients (14 men and eight women). Patient satisfaction with the result of the procedure and incision line were assessed. All 50 patients were satisfied with the surgical results. No patients noted any issues with the incision. No patients complained of incision problems, but the surgeon noted two patients with redness in the scar at 3 months that improved over a 12-month follow-up. Subbrow blepharoplasty may be an alternative to the classic upper lid blepharoplasty in older Caucasian patients, as it can address moderate to severe dermatochalasis with lateral hooding.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
MemoryGel Breast Implants: Final Safety and Efficacy Results after 10 Years of Follow-Up
Authors: Caplin David A. , Calobrace M. Bradley , Wixtrom Roger N. , Estes Megan M. , Canady John W.
Published: February 2021

Background:

Mentor MemoryGel Breast Implants were approved by the U.S. Food and Drug Administration in November of 2006. Patients in the Core clinical study supporting this approval were followed for 10 years.

Methods:

This prospective, multicenter, clinical study included primary augmentation, revision augmentation, primary reconstruction, and revision reconstruction patients implanted with smooth or Siltex Texture MemoryGel Implants. Incidence, severity, and method of resolution for all postoperative complications were assessed on per-patient and per-implant bases. The primary effectiveness endpoints were overall mean change in chest circumference and bra cup size following the implantation procedure.

Results:

Primary augmentation (n = 552), revision augmentation (n = 145), primary reconstruction (n = 251), and revision reconstruction (n = 60) patients were enrolled in the study. Kaplan-Meier estimated 10-year cumulative incidence rates for key complications at the subject level for Baker grade III/IV capsular contracture were as follows: primary augmentation, 12.1 percent; revision augmentation, 24.4 percent; primary reconstruction, 20.5 percent; and revision reconstruction, 36.9 percent. For infection, rates were as follows: primary augmentation, 1.6 percent; revision augmentation, 1.4 percent; primary reconstruction, 6.2 percent; and revision reconstruction, 0 percent. For explantation with or without replacement, rates were as follows: primary augmentation, 11.6 percent; revision augmentation, 24.1 percent; primary reconstruction, 33.4 percent; and revision reconstruction; 37.8 percent. For rupture, rates were as follows: primary augmentation, 24.2 percent; revision augmentation, 23.7 percent; primary reconstruction, 32.7 percent; and revision reconstruction, 38.7 percent. For any reoperation, rates were as follows: primary augmentation, 25.5 percent; revision augmentation, 43.6 percent; primary reconstruction, 49.0 percent; and revision reconstruction, 50.7 percent.

Conclusion:

The results of this study demonstrate that MemoryGel Implants are safe and effective for use in women undergoing breast augmentation or reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Subcutaneous Regeneration of Engineered Cartilage: A Comparison of Cell Sheets and Chondrocyte-Scaffold Constructs in a Porcine Model
Authors: Ding Jinping , Bao Shiwei , Qian Wenjiang , Zhao Hongyi
Published: February 2021

Background:

Stable cartilage regeneration in immunocompetent large animals remains a bottleneck problem that restricts clinical application. The inflammation elicited by degradation products of scaffolds has a decisive influence on cartilage formation. Although prolonged preculture in vitro could form mature engineered cartilage and allow sufficient degradation of scaffolds, the inflammatory reaction was still observed. This study explored the feasibility of using chondrocyte sheet technology to regenerate stable cartilage in the subcutaneous environment with a pig model.

Methods:

Passage 1 chondrocytes were used to form cell sheets by high-density culture. As a control, chondrocytes were seeded onto polyglycolic acid/polylactic acid scaffolds for 6 and 12 weeks’ in vitro preculture, respectively. Then, they were autologously implanted subcutaneously into pigs for 2, 8, and 24 weeks. Gross view, histologic staining, and biochemical and biomechanical characteristics were evaluated.

Results:

With prolonged culture in vitro, relatively homogeneous engineered cartilages were formed with less scaffold residue. However, the chondrocyte–polyglycolic acid/polylactic acid group still encountered severe inflammation and inferior cartilage formation at 2 and 8 weeks in vivo. The engineered cartilage with cell sheet technique exhibited a relatively more stable and mature tissue structure without obvious inflammatory response at 24 weeks in vivo, which was similar to the native auricular cartilage.

Conclusions:

The chondrocyte sheet technique could successfully regenerate mature and stable engineered cartilages in pig models. It is possibly an effective method of repairing cartilage defects in the clinic that uses regenerated substitutes derived from autologous cell sheets.
Hypoxia-Induced Cyr61/CCN1 Production in Infantile Hemangioma
Authors: Wu Pinru , Xu Hui , Li Ningli , Huo Rongfen , Shen Baihua , Lin Xiaoxi , Ma Gang
Published: February 2021

Background:

Hypoxia may play a role in the pathogenesis of infantile hemangioma. Cysteine-rich angiogenic inducer 61 (Cyr61), or CCN1, can be induced under hypoxic conditions in several types of cells. However, whether CCN1 has any impact on infantile hemangioma remains unknown. This study aims to explore the expression of CCN1 in infantile hemangioma and to investigate the effect of hypoxia on CCN1 and vascular endothelial growth factor-A (VEGF-A) production.

Methods:

Hemangioma-derived endothelial cells and hemangioma-derived stem cells were isolated from surgical specimens of proliferative infantile hemangioma. RNA extracted from infantile hemangioma tissue, hemangioma-derived endothelial cells, and hemangioma-derived stem cells was used to analyze gene expression by real-time polymerase chain reaction. The effects of CCN1 blockade were examined in hemangioma-derived stem cells. Immunostaining, immunoblotting, and enzyme-linked immunosorbent assays were used to assess protein expression.

Results:

By double-label immunofluorescence staining, the authors first identified that CCN1 was abundant in proliferative infantile hemangioma lesions and colocalized well with immature microvessels. The authors found that the mRNA level of CCN1 in proliferative infantile hemangioma was significantly higher than in healthy controls, as was involuting infantile hemangioma. Treatment with the hypoxia inducer cobalt chloride dramatically increased CCN1 production in hemangioma-derived endothelial cells in a time-dependent manner. Furthermore, blocking or knockdown of CCN1 expression reduced the expression of VEGF-A in hemangioma-derived stem cells. Lastly, the signaling pathway study showed that CCN1 up-regulation of VEGF-A synthesis in hemangioma-derived stem cells depends on nuclear factor-κB and JNK activation.

Conclusions:

These findings provide new evidence that CCN1 participates in the crosstalk between hemangioma-derived endothelial cells and hemangioma-derived stem cells through promoting VEGF-A expression in the hypoxic environment of infantile hemangioma angiogenesis and vasculogenesis. Targeting of CCN1 might be a novel therapeutic strategy for infantile hemangioma.
Variation in Payment per Work Relative Value Unit for Breast Reconstruction and Nonbreast Microsurgical Reconstruction: An All-Payer Claims Database Analysis
Authors: Shamsunder Meghana G. , Sheckter Clifford C. , Sheinin Avraham , Rubin David , Berlin Nicholas L. , Mehrara Babak , Matros Evan
Published: February 2021

Background:

Commercial payments for implant-based breast reconstruction have increased within the past decade, whereas reimbursements have stagnated for microsurgical techniques. The physician payment–to–work relative value unit ratio allows for standardization when comparing procedures of differing complexity. This study aimed to characterize payment per work relative value unit for common breast and nonbreast microsurgical procedures.

Methods:

The Massachusetts All-Payer Claims Database was queried from 2010 to 2014 for Current Procedural Terminology (CPT) codes related to microsurgical and breast reconstruction. International Classification of Diseases codes were further used to categorize procedures by anatomical region, including head and neck, breast, trunk, and extremities. Physician payments, both commercial and governmental, were aggregated by anatomical region and CPT code. Payment distributions were described with means and medians and compared using statistical tests.

Results:

Among 3435 commercial claims, distributions of physician payments per work relative value unit for microsurgical and common breast procedures differed only for breast free flaps billed through S codes (p < 0.001). Microsurgical breast procedures (CPT code 19364) had significantly greater median payments per work relative value unit compared to microsurgery of the head and neck, trunk, and upper extremities (p = 0.004). Payment per work relative value unit for common breast and nonbreast microsurgical procedures did not differ significantly among governmental claims (p = 0.103).

Conclusions:

Adjustment of physician payments by work relative value units did not show significant variability across common breast procedures, except for S codes, suggesting that payments are mostly driven by differences in work relative value units and individual contractual negotiations. Lower payments per work relative value unit for other regions compared to breast suggests an opportunity for negotiation with commercial payers.
Women in Leadership and Their Influence on the Gender Diversity of Academic Plastic Surgery Programs
Authors: Keane Alexandra M. , Larson Ellen L. , Santosa Katherine B. , Vannucci Bianca , Waljee Jennifer F. , Tenenbaum Marissa M. , Mackinnon Susan E. , Snyder-Warwick Alison K.
Published: February 2021

Background:

Women seldom reach the highest leadership positions in academic plastic surgery. Contributing factors include lack of female role models/mentors and lack of gender diversity. Studies show that female role models and mentors are critical for recruiting and retaining female surgeons and that gender diversity within organizations more strongly influences women’s career choices. The authors therefore sought to determine the current gender diversity of academic plastic surgery programs and investigate influences of gender and leadership on program gender composition.

Methods:

A cross-sectional study of U.S. plastic surgery residency programs was performed in December of 2018. Genders of the leadership were collected, including medical school dean, department of surgery chair, department/division of plastic surgery chair/chief, plastic surgery program director, plastic surgery faculty, and plastic surgery residents. Gender relationships among these groups were analyzed.

Results:

Ninety-nine residency programs were identified (79 integrated with or without independent and 20 independent). Women represented a smaller proportion of academic plastic surgeons in more senior positions (38 percent residents, 20 percent faculty, 13 percent program directors, and 8 percent chairs). Plastic surgery chair gender was significantly correlated with program director gender, and plastic surgery faculty gender was significantly associated with plastic surgery resident gender. Although not statistically significant, female plastic surgery chair gender was associated with a 45 percent relative increase in female plastic surgery residents.

Conclusions:

Women in leadership and gender diversity influence the composition of academic plastic surgery programs. Gender disparity exists at all levels, worsening up the academic ladder. Recruitment, retention, and promotion of women is critical, as such diversity is required for continued progress in innovation and problem-solving within plastic surgery.
A Comparison of Pulsatile Hypothermic and Normothermic Ex Vivo Machine Perfusion in a Porcine Kidney Model
Authors: Vallant Natalie , Wolfhagen Nienke , Sandhu Bynvant , Hamaoui Karim , Cook Terence , Pusey Charles , Papalois Vassilios
Published: February 2021

Background.

Hypothermic machine perfusion (HMP) is a well-established method for deceased donor kidney preservation. Normothermic machine perfusion (NMP) might offer similar or greater advantages. We compared the 2 methods in an ex vivo perfusion model using 34 porcine kidneys.

Methods.

Thirty kidneys were stored on ice for 24 h before undergoing 4 h of HMP (n = 15) or NMP (n = 15) followed by 2 h of normothermic ex vivo reperfusion with whole blood. Four kidneys underwent 28 h of cold static storage followed by 2 h of normothermic ex vivo reperfusion. During the 2 h of normothermic ex vivo reperfusion, perfusate flow rates, urinary output, and oxygen consumption rates were compared between all groups.

Results.

Porcine kidneys after HMP showed significantly higher urinary output (5.31 ± 2.06 versus 2.44 ± 1.19 mL/min; P = 0.002), oxygen consumption (22.71 ± 6.27 versus 11.83 ± 1.29 mL/min; P = 0.0016), and perfusate flow rates (46.24 ± 12.49 versus 26.16 ± 4.57 mL/min; P = 0.0051) than kidneys after NMP. TUNEL staining of tissue sections showed significantly higher rates of apoptosis in kidneys after NMP (P = 0.027).

Conclusions.

In our study, the direct comparison of HMP and NMP kidney perfusion in a translational model demonstrated superiority of HMP; however, further in vivo studies would be needed to validate those results.
What have we learned from cognition in the oldest-old
Authors: Kawas Claudia H. , Legdeur Nienke , Corrada María M.
Published: February 2021

Purpose of review

People over 90 are the fastest growing segment of the population with the highest rates of dementia. This review highlights recent findings that provide insight to our understanding of dementia and cognition at all ages.

Recent findings

Risk factors for Alzheimer's disease (AD) and dementia differ by age, with some factors, like the development of hypertension, actually becoming protective in the oldest-old. At least half of all dementia in this age group is due to non AD pathologies, including microinfarcts, hippocampal sclerosis and TDP-43. The number of pathologic changes found in the brain is related to both risk and severity of dementia, but many people in this age group appear to be ‘resilient’ to these pathologies. Resilience to Alzheimer pathology, in part, may be related to absence of other pathologies, and imaging and spinal fluid biomarkers for AD have limited utility in this age group.

Studies of dementia in the oldest-old are important for our understanding and eventual treatment or prevention of dementia at all ages.
Abnormal synaptic pruning during adolescence underlying the development of psychotic disorders
Authors: Germann Monique , Brederoo Sanne G. , Sommer Iris E.C.
Published: February 2021

Purpose of review

Excessive synaptic pruning has first been suggested by Irwin Feinberg (1982) as an important pillar in the pathophysiology in schizophrenia (SCZ). This article reviews recent developments highlighting factors implicated in aberrant synaptic pruning and its contribution to disease onset and emergence of cognitive symptoms in SCZ. Unraveling these factors provides new insights for potential prevention and treatment strategies for psychotic disorders.

Recent findings

Increased pruning in SCZ was recently confirmed by a positron emission tomography-study employing the novel tracer [11C]UCB-J, demonstrating the consequential loss of synaptic density. Recent evidence supports the contributing role of astrocytes and increased complement-mediated microglial pruning in disease onset and cognitive symptoms in SCZ. Increased microglial pruning is mediated specifically by C4. Furthermore, environmental factors (e.g., infections and stress) can lead to dysbiosis which was recently linked to microglial activation and pruning in SCZ.

Recent findings render the pruning machinery a potential target for early treatment and prevention in individuals at high risk for SCZ. Minocycline can improve cognition in SCZ, probably by reducing excessive pruning. Probiotics might also have beneficial effects on cognition, although recent findings are not encouraging. N-acetyl-cysteine recovers functional connectivity in SCZ both in vitro and in vivo, making it an interesting candidate.
Lack of latent tuberculosis screening in HIV patients and delay in Anti-Retroviral Therapy initiation in HIV-TB co-infection: A 11-year study in an intermediate TB-burden country
Authors: Teng Vannesa Yue May , Chua Yan Ting , Lai Eunice En Ni , Mukherjee Shilpa , Michaels Jessica , Wong Chen Seong , Leo Yee Sin , Young Barnaby , Archuleta Sophia , Ong Catherine W.M.
Published: February 2021

Objectives

Tuberculosis (TB) is a common infection in HIV patients. Our study aims to determine the prevalence and characteristics of HIV-TB co-infected patients in Singapore, a high-income, intermediate TB-burden country.

Methods

Retrospective data of 11-years was obtained from the National University Hospital (NUH), a quaternary care hospital and the National Centre for Infectious Diseases, the national HIV centre.

Results

From December 2005 to December 2016, 48 out of 819 HIV patients and 272 out of 3,196 HIV patients who were managed in NUH and TTSH respectively, were diagnosed with TB. 89.1% (n=285) were males and 2 (0.6%) were screened for latent TB on HIV diagnosis. The median age at TB diagnosis was 47.3 years old (Interquartile range, IQR 41-57). Mean CD4 count at TB diagnosis was 125.0 ± 153.9 cells/mm3. 124 (38.6%) patients had CD4 < 50 cells/mm3. 41.3% (n=132) of patients had HIV diagnosed at least 6 weeks before TB diagnosis, indicating an opportunity to initiate latent TB preventive therapy. 55.0% (n=176) had HIV and TB concomitantly diagnosed within 6 weeks whilst 2.25% (n=7) had TB diagnosed before HIV. Of those HIV-TB co-infected patients with CD4 ≤ 50 cells/mm3, 18 (14.2%) had anti-retroviral therapy (ART) started <2 weeks. TB-related mortality was 5.3% (n=17) and 3.75% (n=12) were lost to follow-up.

Conclusion

There is a lack of latent TB screening in HIV patients and a delay in initiation of ART in HIV-TB patients with low CD4 counts in our study. Clinical practices can be further improved for the benefit of outcomes in HIV-TB patients.
Persisting adaptive immunity to SARS-CoV-2 in Lower Austria
Authors: Ladage Dennis , Harzer Oliver , Engel Peter , Winkler Hannes , Braun Ralf J.
Published: February 2021

The prevalence and persistence of adaptive immunity responses following a SARS-CoV-2 infection provides insights into potential population immunity. Adaptive immune responses comprise of antibody-based responses as well as T cell responses mainly addressing viruses and virus-infected human cells, respectively. A comprehensive analysis of both types of adaptive immunity is essential to follow population-based SARS-CoV-2-specific immunity. In this study, we assessed SARS-CoV-2-specific immunoglobulin A (IgA) levels, SARS-CoV-2-specific immunoglobulin G (IgG) levels, and SARS-CoV-2-specific T cell activities in patients who recovered from a COVID-19 infection in spring and autumn 2020. Here we observed a robust and stable SARS-CoV-2-specific adaptive immune response in both groups with persisting IgA and IgG levels as well as stable T cell activity. Moreover, there was a positive correlation of a lasting immune response with the severity of disease. Our data give evidence for a persisting adaptive immune memory, which suggest a continuing immunity for more than six months post infection.
The effect of special educational assistance in early childhood education and care on psycho-social difficulties in elementary school children
Authors: Biele Guido , Lekhal Ratib , Overgaard Kristin R. , Wang Mari Vaage , Brandlistuen Ragnhild Eek , Friis Svein , Zeiner Paal
Published: February 2021

Three to seven percent of preschoolers have developmental problems or child psychiatric disorders. Randomized controlled trials (RCTs) indicate that interventions in early childhood education and care improve long-term outcomes of children from disadvantaged backgrounds. It is unknown if effects generalize beyond the well-structured context of RCTs and to children who may not have a disadvantaged background but have developmental problems or psychiatric disorders. We use data from the population-based Norwegian Mother, Father and Child Cohort Study, recruiting pregnant women from 1999 to 2008, with child follow-up from ages 6, 18, and 36 months to ages 5, 7, and 8 years. This sub-study included 2499 children with developmental problems or psychiatric disorders at age five. We investigate the effects of special educational assistance at age five on mother-reported internalizing, externalizing, and communication problems at age eight. We analyze bias due to treatment by indication with directed acyclic graphs, adjust for treatment predictors to reduce bias, and estimate effects in different patient groups and outcome domains with a hierarchical Bayesian model. In the adjusted analysis, preschoolers with special educational assistance had on average by 0.1 (0.03-0.16) standardized mean deviation weaker psycho-social difficulties in elementary school. Mean effect sizes varied between groups and outcomes. We estimate positive effects of educational assistance during the transition from preschool to the school years. It should therefore be considered as an intervention for preschoolers with developmental or behavior problems. More research with improved measurements of treatment and outcomes is needed to identify success factors for their implementation.
The utility of homologous recombination deficiency biomarkers across cancer types
Authors: Takamatsu Shiro , Brown J.B. , Yamaguchi Ken , Hamanishi Junzo , Yamanoi Koji , Takaya Hisamitsu , Kaneyasu Tomoko , Mori Seiichi , Mandai Masaki , Matsumura Noriomi
Published: February 2021

Background

Genomic alterations in BRCA1/2 and genomic scar signatures are associated with homologous recombination DNA repair deficiency (HRD) and serve as therapeutic biomarkers for platinum and PARP inhibitors in breast and ovarian cancers. However, the clinical significance of these biomarkers in other homologous recombination repair-related genes or other cancer types is not fully understood.

Results

We analyzed the datasets of all solid cancers from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia, and found that the association between biallelic alterations in the homologous recombination pathway genes and genomic scar signatures differed greatly depending on gender and the presence of somatic TP53 mutation. Additionally, HRD cases identified by a combination of these indicators showed higher sensitivity to DNA-damaging drugs than non-HRD cases both in clinical samples and cell lines.

Conclusion

Our work provides novel proof of the utility of HRD analysis for all cancer types and will improve the precision and efficacy of chemotherapy selection in clinical oncology.