Abstract Therapies selectively targeting ischemic myocardium could be applied by intravenous injection. Here, we report an approach for ischemic tissue-selective targeting based on in vivo screening ...of random peptide sequences using phage display. We performed in vivo biopanning using a phage library in a rat model of ischemia–reperfusion and identified three peptide motifs, CSTSMLKAC, CKPGTSSYC, and CPDRSVNNC, that exhibited preferential binding to ischemic heart tissue compared to normal heart as well as other control organs. The CSTSMLKAC sequence was capable of mediating selective homing of phage to ischemic heart tissue. The CSTSMLKAC peptide was then made as a fusion protein with Sumo–mCherry and injected intravenously in a mouse model of myocardial ischemia–reperfusion injury; subsequently, bio-distribution of Sumo–mCherry–CSTSMLKAC was measured with quantitative ELISA. The targeting peptide led to a significant increase in homing to ischemic left ventricle compared to tissues from non-ischemic left ventricle, the right ventricle, lung, liver, spleen, skeletal muscle, and brain (all p < 0.001). These results indicate that the peptide sequence CSTSMLKAC represents a novel molecular tool that may be useful in targeting ischemic tissue and delivering bioengineered proteins into the injured myocardium by systemic intravenous administration.
Whole-brain radiation therapy (WBRT) is the standard of care after resection of a brain metastasis. However, concern regarding possible neurocognitive effects and the lack of survival benefit with ...this approach has led to the use of stereotactic radiosurgery (SRS) to the resection cavity in place of WBRT. We report our initial experience using an image-guided linear accelerator-based frameless stereotactic system and review the technical issues in applying this technique.
We retrospectively reviewed the setup accuracy, treatment outcome, and patterns of failure of the first 18 consecutive cases treated at Brigham and Women's Hospital. The target volume was the resection cavity without a margin excluding the surgical track.
The median number of brain metastases per patient was 1 (range, 1-3). The median planning target volume was 3.49 mL. The median prescribed dose was 18 Gy (range, 15-18 Gy) with normalization ranging from 68% to 85%. In all cases, 99% of the planning target volume was covered by the prescribed dose. The median conformity index was 1.6 (range, 1.41-1.92). The SRS was delivered with submillimeter accuracy. At a median follow-up of 12.7 months, local control was achieved in 16/18 cavities treated. True local recurrence occurred in 2 patients. No marginal failures occurred. Distant recurrence occurred in 6/17 patients. Median time to any failure was 7.4 months. No Grade 3 or higher toxicity was recorded. A long interval between initial cancer diagnosis and the development of brain metastasis was the only factor that trended toward a significant association with the absence of recurrence (local or distant) (log-rank p = 0.097).
Frameless stereotactic irradiation of the resection cavity after surgery for a brain metastasis is a safe and accurate technique that offers durable local control and defers the use of WBRT in select patients. This technique should be tested in larger prospective studies.
The optimal number of systematic biopsy cores in the era of multi-parametric MRI targeted biopsy remains unclear, especially on its impact of focal therapy planning. Our objective is to investigate ...the impact of reducing the number of systematic cores on prostate cancer detection in the era of MRI-US fusion targeted biopsy and as well as its relevance in template planning for focal therapy.
A retrospective analysis of 398 consecutive men who underwent both systematic saturation (~24 cores) and MRI-US fusion targeted biopsy was performed. Four reduced-core systematic biopsy strategies (two-thirds, half, one-third and one-quarter systematic cores) were modelled and the detection rates of clinically-significant prostate cancer (csPCa defined as grade group ≥2) were compared to that of a full systematic biopsy using McNemar's test. Focal therapy treatment plans were made based on positive cores on combined (targeted and systematic) biopsy and the various reduced-cores strategies to compare the proportion who had a change in treatment plan.
csPCa was detected in 42% (168/398) of this patient cohort. Non-targeted systematic saturation biopsy had a 21% (83/398) csPCa detection rate. Our four strategies reduced the mean number of non-targeted systematic cores from 21.8 to 14.5, 10.9, 7.3 and 5.4 cores and their csPCa detection rates were significantly decreased to 16%, 13%, 9% and 8% respectively (all p < 0.05). Compared to the reduced-core strategies, a full systematic saturation biopsy resulted in change to the focal therapy treatment plan in 12% (2/3 cores), 19% (1/2 cores), 24% (1/3 cores) and 29% (1/4 cores) of the time (p = 0.0434).
Reducing the number of systematic biopsies when performing an MRI-targeted biopsy leads to reduced detection of csPCa and alter the treatment plans for focal therapy, possibly limiting its oncological efficacy.
To review the safety and efficacy of linear accelerator-based stereotactic radiosurgery (SRS) for brainstem metastases. We reviewed all patients with brain metastases treated with SRS at DF/BWCC from ...2001 to 2009 to identify patients who had SRS to a single brainstem metastasis. Overall survival and freedom-from-local failure rates were calculated from the date of SRS using the Kaplan–Meier method. Prognostic factors were evaluated using the log-rank test and Cox proportional hazards model. A total of 24 consecutive patients with brainstem metastases had SRS. At the time of SRS, 21/24 had metastatic lesions elsewhere within the brain. 23/24 had undergone prior WBRT. Primary diagnoses included eight NSCLC, eight breast cancer, three melanoma, three renal cell carcinoma and two others. Median dose was 13 Gy (range, 8–16). One patient had fractionated SRS 5 Gy ×5. Median target volume was 0.2 cc (range, 0.02–2.39). The median age was 57 years (range, 42–92). Follow-up information was available in 22/24 cases. At the time of analysis, 18/22 patients (82%) had died. The median overall survival time was 5.3 months (range, 0.8–21.1 months). The only prognostic factor that trended toward statistical significance for overall survival was the absence of synchronous brain metastasis at the time of SRS; 1-year overall survival was 31% with versus 67% without synchronous brain metastasis (log rank
P
= 0.11). Non-significant factors included primary tumor histology and status of extracranial disease (progressing vs. stable/absent). Local failure occurred in 4/22 cases (18%). Actuarial freedom from local failure for all cases was 78.6% at 1 year. RTOG grade 3 toxicities were recorded in two patients (ataxia, confusion). Linac-based SRS for small volume brainstem metastases using a median dose of 13 Gy is associated with acceptable local control and low morbidity.
Multimessenger searches for binary neutron star (BNS) and neutron star-black hole (NSBH) mergers are currently one of the most exciting areas of astronomy. The search for joint electromagnetic and ...neutrino counterparts to gravitational wave (GW)s has resumed with ALIGO's, AdVirgo's and KAGRA's fourth observing run (O4). To support this effort, public semiautomated data products are sent in near real-time and include localization and source properties to guide complementary observations. In preparation for O4, we have conducted a study using a simulated population of compact binaries and a mock data challenge (MDC) in the form of a real-time replay to optimize and profile the software infrastructure and scientific deliverables. End-toend performance was tested, including data ingestion, running online search pipelines, performing annotations, and issuing alerts to the astrophysics community. We present an overview of the low-latency infrastructure and the performance of the data products that are now being released during O4 based on the MDC. We report the expected median latency for the preliminary alert of full bandwidth searches (29.5 s) and show consistency and accuracy of released data products using the MDC. We report the expected median latency for triggers from early warning searches (-3.1 s), which are new in O4 and target neutron star mergers during inspiral phase. This paper provides a performance overview for LIGO-Virgo-KAGRA (LVK) low-latency alert infrastructure and data products using theMDCand serves as a useful reference for the interpretation of O4 detections.
OBJECTIVE Minimally invasive anterior lumbar interbody fusion surgery (MIS ALIF) is a technique that restores disc height and lumbar lordosis through a smaller exposure and less soft-tissue trauma ...compared to open approaches. The mini-open and laparoscopic assistance techniques are two main forms of MIS ALIF. The authors conducted a systematic review that sought to critically summarize the literature on back pain following MIS ALIF. METHODS In March 2020, the authors searched the PubMed, Web of Science, and Cochrane Library databases for studies describing back pain visual analog scale (VAS) outcomes after MIS ALIF. The following exclusion criteria were applied to studies evaluated in full text: 1) the study included fewer than 20 patients, 2) the mean follow-up duration was shorter than 12 months, 3) the study did not report back pain VAS score as an outcome measure, and 4) MIS ALIF was not studied specifically. The methodology for the included studies were evaluated for potential biases and assigned a level of evidence. RESULTS There were a total of 552 patients included from 13 studies. The most common biases were selection and interviewer bias. The majority of studies were retrospective. The mean sample size was 42.3 patients. The mean follow-up duration was approximately 41.8 months. The mean postoperative VAS reduction was 5.1 points. The mean VAS reduction for standalone grafts was 5.9 points, and 5.0 points for those augmented with posterior fixation. The most common complications included bladder or urinary dysfunction, infection, and hardware-related complications. CONCLUSIONS This was a systematic review of back pain outcomes following MIS ALIF. Back pain VAS score was reduced postoperatively across all studies. The complication rates were low overall. MIS ALIF is safe and effective at reducing back pain in appropriate patient populations.
Complex hand dexterity is fundamental to our interactions with the physical, social, and cultural environment. Dexterity can be an expression of creativity and precision in a range of activities, ...including musical performance. Little is understood about complex hand dexterity or how virtuoso expertise is acquired, due to the versatility of movement combinations available to complete any given task. This has historically limited progress of the field because of difficulties in measuring movements of the hand. Recent developments in methods of motion capture and analysis mean it is now possible to explore the intricate movements of the hand and fingers. These methods allow us insights into the neurophysiological mechanisms underpinning complex hand dexterity and motor learning. They also allow investigation into the key factors that contribute to injury, recovery and functional compensation. The application of such analytical techniques within musical performance provides a multidisciplinary framework for purposeful investigation into the process of learning and skill acquisition in instrumental performance. These highly skilled manual and cognitive tasks present the ultimate achievement in complex hand dexterity. This paper will review methods of assessing instrumental performance in music, focusing specifically on biomechanical measurement and the associated technical challenges faced when measuring highly dexterous activities.
With the advent of minimally invasive techniques, minimally invasive spine surgery (MISS) has become a realistic option for many spine cases. This study aims to evaluate the operative and clinical ...outcomes of MISS for total versus subtotal tumor resection from current evidence.
A literature search was performed using the search term (Minimally invasive surgery OR MIS) AND (spine tumor OR spinal tumor). Studies including both minimally invasive total and subtotal resection cases with operative or clinical data were included.
Seven studies describing 159 spinal tumor cases were included. Compared with total resection, subtotal resection showed no significant differences in surgical time (mean difference (MD), 9.44 minutes; 95% confidence interval CI, –47.66 to 66.55 minutes; P = 0.37), surgical blood loss (MD, –84.72 mL; 95% CI, –342.82 to 173.39 mL; P = 0.34), length of stay (MD, 1.38 days; 95% CI, –0.95 to 3.71 days; P = 0.17), and complication rate (odds ratio, 9.47; 95% CI, 0.34–263.56; P = 0.12). Pooled analyses with the random-effects model showed that neurologic function improved in 89% of patients undergoing total resection, whereas neurologic function improved in 61% of patients undergoing subtotal resection.
Our analyses show that there is no significant difference in operative outcomes between total and subtotal resection. Patients undergoing total resection showed slightly better improvement in neurologic outcomes compared with patients undergoing subtotal resection. Overall, this study suggests that both total and subtotal resection may result in comparable outcomes for patients with spinal tumors. However, maximal safe resection remains the ideal treatment because it provides the greatest chance of long-term benefit.
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