Moving academic research forward during COVID-19 Wigginton, N S; Cunningham, R M; Katz, R H ...
Science (American Association for the Advancement of Science),
06/2020, Letnik:
368, Številka:
6496
Journal Article
Recenzirano
Odprti dostop
A gradual, stepwise approach to reopening, informed by public health expertise, will be essential
The coronavirus disease 2019 (COVID-19) pandemic has led to an unprecedented disruption of society. ...Institutions of higher education have been no exception. To preserve the safety of their communities and adhere to public health guidance, universities and colleges around the world have rapidly pivoted to fully online teaching and learning models, implemented remote work for the majority of employees, and shuttered countless public spaces and programs. Most “on-site” research activities—in laboratories, in clinics, or in the field—also ground to a halt. Many institutions are now planning or implementing a ramp-up of on-site research activities, which offers an opportunity to begin implementing policies and practices that will lay the groundwork for the eventual reopening of additional onsite academic programming, including teaching. To ramp up safely, institutions are working with stakeholder groups—such as public health experts, as well as faculty, staff, and students—to develop guiding principles that will help inform and drive decision-making over the coming months. We synthesized several risk and decision-making frameworks under development at our universities to develop a set of criteria informed by public health expertise that institutions should consider before and during the first stages of restoring research activities and less certain factors to consider for subsequent phases.
Background
In recent literature, the increasing number of medical litigations, both in terms of the number of cases being filed and the substantive costs associated with lawsuits, has been described. ...This study aims to provide an overview of the profile of litigation for orthopedic and trauma surgery to describe the differences and the development of the number of cases over time.
Patients and Materials
A retrospective review of all litigations between 2000 and 2017 was conducted using the institutional legal database. The causes of litigation were documented and classified into seven major categories. In addition to plaintiff characteristics, the litigation outcomes and the differences between emergency and elective surgery were analyzed.
Results
A total of 230 cases were evaluated. The mean age of the plaintiffs was 44.6 ± 20.1 years, and 56.8% were female. The main reasons for litigation were claimed inappropriate management (46.1%), misdiagnosis (22.6), and poor nursing care (8.3%). Significantly more litigations were filed against surgeons of the orthopedic subspecialty compared with trauma surgeons (78%;
p
≤ 0.0001). There were significantly fewer litigations per 1000 cases filed overall in 2009–2017 (65% less;
p
= 0.003) than in 2000–2008.
Conclusion
Our results could not confirm the often-stated trend of having more litigations against orthopedic and trauma surgeons. Although the absolute numbers increased, the number of litigations per 1000 patients treated declined. Patients who underwent elective surgery were more likely to file complaints than emergency patients.
In this work an efficient approach for a posteriori error estimation for POD-DEIM reduced nonlinear dynamical systems is introduced. The considered nonlinear systems may also include time- and ...parameter-affine linear terms as well as parametrically dependent inputs and outputs. The reduction process involves a Galerkin projection of the full system and approximation of the system's nonlinearity by the DEIM method S. Chaturantabut and D. C. Sorensen, SIAM J. Sci. Comput., 32 (2010), pp. 2737--2764. The proposed a posteriori error estimator can be efficiently decomposed in an offline/online fashion and is obtained by a one-dimensional auxiliary ODE during reduced simulations. Key elements for efficient online computation are partial similarity transformations and matrix-DEIM approximations of the nonlinearity Jacobians. The theoretical results are illustrated by application to an unsteady Burgers equation and a cell apoptosis model. PUBLICATION ABSTRACT
Two‐dimensional (2D) in vitro culture systems have for a number of years provided a controlled and versatile environment for the study of cell adhesion and migration, two interrelated cell functions ...critical to cancer metastasis. However, the organization and functions of focal adhesion proteins in cells embedded in physiologically more relevant 3D matrices is qualitatively and functionally different from their organization and functions on conventional 2D planar substrates. In a 3D, crosslinked, fibrillar collagen matrix, cell migration and protrusion activity are still regulated by focal adhesion proteins, such as pl30Cas, FAK, Zyxin, Vinculin, Talin, and VASP, but differently from the 2D case. This talk will describe the implications of the dependence of focal adhesion rotein‐based cellular functions on microenvironmental dimensionality in cancer. We will discuss the implications of this work in cancer metastasis.
MMSET/WHSC1 is a histone methyltransferase (HMT) overexpressed in t(4;14)+ multiple myeloma (MM) patients, believed to be the driving factor in the pathogenesis of this MM subtype. MMSET ...overexpression in MM leads to an increase in histone 3 lysine 36 dimethylation (H3K36me2), and a decrease in histone 3 lysine 27 trimethylation (H3K27me3), as well as changes in proliferation, gene expression and chromatin accessibility. Prior work linked methylation of histones to the ability of cells to undergo DNA damage repair. In addition, t(4;14)+ patients frequently relapse after regimens that include DNA damage-inducing agents, suggesting that MMSET may play a role in DNA damage repair and response. In U2OS cells, we found that MMSET is required for efficient non-homologous end joining as well as homologous recombination. Loss of MMSET led to loss of expression of several DNA repair proteins, as well as decreased recruitment of DNA repair proteins to sites of DNA double-strand breaks (DSBs). By using genetically matched MM cell lines that had either high (pathological) or low (physiological) expression of MMSET, we found that MMSET-high cells had increased damage at baseline. Upon addition of a DNA-damaging agent, MMSET-high cells repaired DNA damage at an enhanced rate and continued to proliferate, whereas MMSET-low cells accumulated DNA damage and entered cell cycle arrest. In a murine xenograft model using t(4;14)+ KMS11 MM cells harboring an inducible MMSET shRNA, depletion of MMSET enhanced the efficacy of chemotherapy, inhibiting tumor growth and extending survival. These findings help explain the poorer prognosis of t(4;14) MM and further validate MMSET as a potential therapeutic target in MM and other cancers.
Stabilization of metastatic acetabular defects with a bone cement-augmented revision support cup for remobilization of oncological patients in advanced cancer stages.
Metastatic acetabular defects ...(Metastatic Acetabular Classification, MAC 2-4) in patients with a prognostic medium or long-term survival.
Highly limited survival due to metastatic disease (< 6 weeks). Local bone or soft tissue infection. Primary bone tumor with curative treatment option. Advanced pelvic discontinuity. Recent wound compromising systemic therapy.
Standard hip approach. Curettage of the metastatic defect and careful reaming of the acetabulum before insertion of the cup. Predrilling of the dome und flange screws before application of the bone cement through the center hole of the implant and filling of the acetabular defect. Complete insertion of the screws for compound osteosynthesis. Implant of a modular inlay or dual mobility system.
Full weight bearing or mobilization with two crutches according to the level of pain. Adjuvant local radiation therapy after wound consolidation. Continuation of systemic therapy according to tumor board decision.
Between 2012 and 2019, we treated 14 patients with metastatic acetabular defects using the modular revision support cup "MRS-TITAN® Comfort", MRS-C, Peter Brehm GmbH, Weisendorf, Germany) at our institution. Mean Harris Hip Score improvement was 23.2 with a mean patient's survival of 9.7 months due to the reduced cancer-related prognosis; 13 of the 14 implants endured the patient's prognosis. One implant had to be removed due soft tissue defect-related periprosthetic joint infection.
Background. Physiotherapy prior to open-heart surgery lowers the rate of pneumonia and length of the hospital stay. Pneumonia is a major contributor to short-term mortality following transcatheter ...aortic valve replacement (TAVR). Hence, we hypothesized that pre- and intensified postprocedural physiotherapy in patients undergoing TAVR might impact the net functional and clinical outcome. Methods and Results. The 4P-TAVR study was a prospective, monocentric, randomized trial. The study was designed to compare the efficacy and safety of intensified periprocedural physiotherapy including inspiratory muscle training versus standard postprocedural physiotherapy. Patients were randomized in a 1 : 1 fashion. 108 patients were included and followed up for 90 days after TAVR. While patients in group A (control group: 50 patients, age: 81.7 ± 5.0 years, 52% male) did not receive physiotherapy prior to TAVR, group B (intervention group: 58 patients, age: 82.2 ± 5.82 years, 47% male) participated in intensive physiotherapy. Compared to the control group, patients in the interventional group showed a lower incidence of postinterventional pneumonia (10 20.0% vs. 3 5.1%, p=0.016) and had a 3-day shorter mean hospital stay (13.5 ± 6.1 days vs. 10.1 ± 4.7 days, p=0.02). The primary composite endpoint of mortality and rehospitalization was not different between the groups. Conclusion. Intensified physiotherapy is safe and has positive effects on clinical outcomes up to 90 days after TAVR but has no impact on the primary combined endpoint of mortality and rehospitalization. Longer follow-up, a multicenter design, and a higher number of subjects are needed to confirm these preliminary results. This trial is registered with DRKS00017239.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose and objective
Bone resection regarding adequate surgical margins is the treatment of choice for malignant bone tumors. In the case of metastasis-related complications, so-called ...skeletal-related events, it is highly important to achieve pain relief and a stable joint situation to re-mobilize the patients immediately following surgery. To bridge the often large osseous defect zones after tumor resection, both cemented and uncemented modular endoprosthetic systems are widely used. Patients undergoing tumor-related endoprosthetic orthopedic surgery are facing high risk for developing a periprosthetic joint infection (PJI). The immunocompromised condition due to anti-neoplastic treatment and long operation time with large exposure of tissue contributes to a high risk of infection.
Methods
The authors present a case series of 100 patients (31% primary bone tumor and 69% metastasis-related surgery) undergoing tumor-related lower limb salvage surgery with special regard to periprosthetic joint infection and the management of this “difficult to treat” situation. Furthermore, a review of the current literature regarding infection following bone tumor resection and endoprosthetic reconstruction is performed and discussed.
Results
The median follow-up was 24 months (range 12–108 months). Ten patients (10%) suffered from a periprosthetic joint infection. We recorded six acute infections (type I) <4 weeks after surgery, one infection >4 weeks after surgery (type II), and three late infections (type III). According to the definition of Laffer et al., three of our patients (30%) are probably free of infection, one patient died of PJI-associated sepsis, and five patients were free of infection, but without restoration of the affected joint.
Conclusion
In conclusion, our own results show that perimegaprosthetic joint infection among silver-coated implants, in patients undergoing tumor-related surgery of the lower limb, is lower compared to non-silver-coated implants. Due to heterogeneity of patients and potential treatment options, the treatment regime should be tailored for the patients’ individual situation.
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