Adult chondrogenesis and spontaneous cartilage repair in the skate, Leucoraja erinacea

Mammalian articular cartilage is an avascular tissue with poor capacity for spontaneous repair. Here, we show that embryonic development of cartilage in the skate (Leucoraja erinacea) mirrors that of mammals, with developing chondrocytes co-expressing genes encoding the transcription factors Sox5, Sox6 and Sox9. However, in skate, transcriptional features of developing cartilage persist into adulthood, both in peripheral chondrocytes and in cells of the fibrous perichondrium that ensheaths the skeleton. Using pulse-chase label retention experiments and multiplexed in situ hybridization, we identify a population of cycling Sox5/6/9+ perichondral progenitor cells that generate new cartilage during adult growth, and we show that persistence of chondrogenesis in adult skates correlates with ability to spontaneously repair cartilage injuries. Skates therefore offer a unique model for adult chondrogenesis and cartilage repair and may serve as inspiration for novel cell-based therapies for skeletal pathologies, such as osteoarthritis

Adult chondrogenesis and spontaneous cartilage repair in the skate, Leucoraja erinacea

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Marconi, A., Hancock-Ronemus, A., & Gillis, J. A. Adult chondrogenesis and spontaneous cartilage repair in the skate, Leucoraja erinacea. Elife, 9, (2020): e53414, doi:10.7554/elife.53414.Mammalian articular cartilage is an avascular tissue with poor capacity for spontaneous repair. Here, we show that embryonic development of cartilage in the skate (Leucoraja erinacea) mirrors that of mammals, with developing chondrocytes co-expressing genes encoding the transcription factors Sox5, Sox6 and Sox9. However, in skate, transcriptional features of developing cartilage persist into adulthood, both in peripheral chondrocytes and in cells of the fibrous perichondrium that ensheaths the skeleton. Using pulse-chase label retention experiments and multiplexed in situ hybridization, we identify a population of cycling Sox5/6/9+ perichondral progenitor cells that generate new cartilage during adult growth, and we show that persistence of chondrogenesis in adult skates correlates with ability to spontaneously repair cartilage injuries. Skates therefore offer a unique model for adult chondrogenesis and cartilage repair and may serve as inspiration for novel cell-based therapies for skeletal pathologies, such as osteoarthritis.The authors acknowledge Dr. Kate Rawlinson, Prof. Brian Hall, Dr. Kate Criswell, Dr. Victoria Sleight, Christine Hirschberger and Jenaid Rees for a collective many years of helpful discussion around the topic of cartilage development and repair, Janice Simmons, Dan Calzarette, Scott Bennett, David Remsen and the staff of the Marine Biological Laboratory Marine Resources Center for expert assistance with animal maintenance and care, and Helen Skelton (Dept. of Pathology, University of Cambridge) and Debbie Sabin (Dept. of Veterinary Medicine, University of Cambridge) for assistance with adult skate tissue processing. This work was funded by the Wellcome Trust (PhD studentship 102175/Z/13/Z to AM), the Royal Society (University Research Fellowships UF130182 and URF/R/191007 and Research Fellows Enhancement Award RGF\EA\180087 to JAG), the Isaac Newton Trust (award 14.23z to JAG) and by a research grant from the Fisheries Society of the British Isles (to JAG)

Treating Substance Use Disorders: Enhancing Attendance at the Weekly Inpatient Medication Assisted Treatment Group

At a large academic tertiary medical center, an Integrated Medication Assisted Treatment (IMAT) program has been established for those medically stable inpatients with an addiction diagnosis. Over a four month period, this program had experienced a decline in attendance and a quality improvement project was initiated is to better understand the barriers to attendance and institute a process that would reverse the decline. A goal was established to improve attendance by medically stable patients that have consented to participate to a minimum of 50%. A root cause analysis outlined numerous causes for low attendance and several countermeasures were established to address these. Among them were the initiation of a KPI to collect patient attendance data and the creation of an IMAT order in EPIC. Since the IMAT order went “live” in EPIC and other countermeasures were started, the goal of 50% has been surpassed. Next steps include ongoing nurse, physician and care management education, and work with nursing informatics to develop an appointment feature for the IMAT order in EPIC

Is current preoperative frailty assessment adequate?

Preoperative frailty predicts adverse postoperative outcomes. Recommendations for preoperative assessment of elderly patients include performing a frailty assessment. Despite the advantages of incorporating frailty assessment into surgical settings, there is limited research on surgical health care professionals’ perception and use of frailty assessment for perioperative care. We surveyed local health care employees to assess their attitudes toward and practices for frail patients. Nurses and allied health professionals were more likely than surgeons to agree frailty should play a role in planning a patient’s care. Lack of knowledge about frailty issues was a prominent barrier to the use of frailty assessments in practice, despite clinicians understanding that frailty affects their patients’ outcomes. Results of this survey suggest further training in frailty issues and the use of frailty assessment instruments is necessary and could improve the uptake of such tools for perioperative care planning

Is current preoperative frailty assessment adequate?

Preoperative frailty predicts adverse postoperative outcomes. Recommendations for preoperative assessment of elderly patients include performing a frailty assessment. Despite the advantages of incorporating frailty assessment into surgical settings, there is limited research on surgical health care professionals’ perception and use of frailty assessment for perioperative care. We surveyed local health care employees to assess their attitudes toward and practices for frail patients. Nurses and allied health professionals were more likely than surgeons to agree frailty should play a role in planning a patient’s care. Lack of knowledge about frailty issues was a prominent barrier to the use of frailty assessments in practice, despite clinicians understanding that frailty affects their patients’ outcomes. Results of this survey suggest further training in frailty issues and the use of frailty assessment instruments is necessary and could improve the uptake of such tools for perioperative care planning

Patients over 65 years with Acute Complicated Calculous Biliary Disease are Treated Differently - Results and Insights from the ESTES Snapshot Audit

Background: Accrued comorbidities are perceived to increase operative risk. Surgeons may offer operative treatments less often to their older patients with acute complicated calculous biliary disease (ACCBD). We set out to capture ACCBD incidence in older patients across Europe and the currently used treatment algorithms. Methods: The European Society of Trauma and Emergency Surgery (ESTES) undertook a snapshot audit of patients undergoing emergency hospital admission for ACCBD between October 1 and 31 2018, comparing patients under and C 65 years. Mortality, postoperative complications, time to operative intervention, post-acute disposition, and length of hospital stay (LOS) were compared between groups. Within the C 65 cohort, comorbidity burden,mortality, LOS, and disposition outcomes were further compared between patients undergoing operative and non-operative management. Results: The median age of the 338 admitted patients was 67 years; 185 patients (54.7%) of these were the age of 65 or over. Significantly fewer patients C 65 underwent surgical treatment (37.8% vs. 64.7%, p\0.001). Surgical complications were more frequent in the C 65 cohort than younger patients, and the mean postoperative LOS was significantly longer. Postoperative mortality was seen in 2.2% of patients C 65 (vs. 0.7%, p = 0.253). However, operated elderly patients did not differ from non-operated in terms of comorbidity burden, mortality, LOS, or postdischarge rehabilitation need. Conclusions: Few elderly patients receive surgical treatment for ACCBD. Expectedly, postoperative morbidity, LOS, and the requirement for post-discharge rehabilitation are higher in the elderly than younger patients but do not differ from elderly patients managed non-operatively. With multidisciplinary perioperative optimization, elderly patients may be safely offered optimal treatment. Trial Registration ClinicalTrials.gov (Trial # NCT03610308)

Nicotine Replacement Therapies to Decrease Withdrawal Symptoms and Improve Patient Experience

Smoking is one the leading causes of preventable death in the United States. Patient centered care revolves around encouraging patients to reduce their chances of preventable disease and death. To that end, nicotine replacement therapy (NRT) prescribed within 24 hours of hospital admission increases the chance of quitting and decreases the chance of nicotine withdrawal. A pilot performance improvement project was initiated on two cardiac units at an academic tertiary medical center. The goal the project was to have NRT ordered within 24 hours of admission 100% of the time. Baseline metrics demonstrated admission NRT orders were below acceptable levels and subsequent root cause analyses showed barriers to reaching the established goal. Several countermeasures were initiated to include several KPIs. Post rollout, a significant increase in NRT orders was demonstrated. Next steps include educating staff on all hospital units as well as adding tobacco assessment to the yearly competency policy

Robot Assisted Surgical Ward Rounds: Virtually Always There

Background:  While an explosion in technological sophistication has revolutionized surgery within the operating theatre, delivery of surgical ward-based care has seen little innovation.  Use of telepresence allowing off-site clinicians communicate with patients has been largely restricted to outpatient settings or use of complex, expensive, static devices.  We designed a prospective study to ascertain feasibility and face validity of a remotely controlled mobile audiovisual drone (LUCY) to access inpatients.  This device is, uniquely, lightweight, freely mobile and emulates ‘human’ interaction by swiveling and adjusting height to patients’ eye-level.   Methods: Robot-assisted ward rounds(RASWR) were conducted over 3 months. A remotely located consultant surgeon communicated with patients/bedside teams via encrypted audiovisual telepresence robot (DoubleRoboticstm, California USA).  Likert-scale satisfaction questionnaires, incorporating free-text sections for mixed-methods data collection, were disseminated to patient and staff volunteers following RASWRs.  The same cohort completed a linked questionnaire following conventional (gold-standard) rounds, acting as control group. Data were paired, and non-parametric analysis performed.  Results: RASWRs are feasible (>90% completed without technical difficulty). The RASWR(n=52 observations) demonstrated face validity with strong correlations (r>0.7; Spearman, p-value <0.05) between robotic and conventional ward rounds among patients and staff on core themes, including dignity/confidentiality/communication/satisfaction with management plan. Patients (96.08%, n=25) agreed RASWR were a satisfactory alternative when consultant physical presence was not possible. There was acceptance of nursing/NCHD cohort (100% (n=11) willing to regularly partake in RASWR).  Conclusion: RASWRs receive high levels of patient and staff acceptance, and offer a valid alternative to conventional ward rounds when a consultant cannot be physically present

The effects of the HEALTHY study intervention on middle school student dietary intakes

<p>Abstract</p> <p>Background</p> <p>The HEALTHY study was designed to respond to the alarming trends in increasing rates of overweight, obesity, and type 2 diabetes mellitus in youth. The objective of this analysis was to examine the effects of the HEALTHY study on student self-reported dietary intakes (energy, macronutrients and grams consumed of selected food groups).</p> <p>Methods</p> <p>HEALTHY was a cluster-randomized study in 42 public middle schools. Students, n = 3908, self-reported dietary intake using the Block Kids Questionnaire. General linear mixed models were used to analyze differences in dietary intake at the end of the study between intervention and control schools.</p> <p>Results</p> <p>The reported average daily fruit consumption was 10% higher at the end of the study in the intervention schools than in the control schools (138 g or approximately 2 servings versus 122 g, respectively, p = 0.0016). The reported water intake was approximately 2 fluid ounces higher in the intervention schools than in the control (483 g versus 429 g respectively; p = 0.008). There were no significant differences between intervention and control for mean intakes of energy, macronutrients, fiber, grains, vegetables, legumes, sweets, sweetened beverages, and higher- or lower-fat milk consumption.</p> <p>Conclusion</p> <p>The HEALTHY study, a five-semester middle school-based intervention program that integrated multiple components in nutrition, physical education, behavior change, and social marketing-based communications, resulted in significant changes to student's reported fruit and water intake. Subsequent interventions need to go beyond the school environment to change diet behaviors that may affect weight status of children.</p> <p>Clinical Trials Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00458029">NCT00458029</a></p

Evaluation of an emergency safe supply drugs and managed alcohol program in COVID-19 isolation hotel shelters for people experiencing homelessness

BACKGROUND: During a COVID-19 outbreak in the congregate shelter system in Halifax, Nova Scotia, Canada, a multidisciplinary health care team provided an emergency “safe supply” of pharmaceutical-grade medications and beverage-grade alcohol to facilitate isolation in COVID-19 hotel shelters for residents who are dependent on these substances. We aimed to evaluate (a) substances and dosages provided, and (b) effectiveness and safety of the program. METHODS: We retrospectively reviewed medical records of all COVID-19 isolation hotel shelter residents during May 2021. We extracted data on medication and alcohol dosages provided each day. The primary outcome was residents prematurely leaving isolation against public health orders. Adverse events included (a) overdose; (b) intoxication; and (c) diversion, selling, or sharing of medications or alcohol. RESULTS: Over 25 days, 77 isolation hotel residents were assessed (mean age 42 ± 14 years; 24% women). Sixty-two (81%) residents were provided medications, alcohol, or cigarettes. Seventeen residents (22%) received opioid agonist treatment medications (methadone, buprenorphine, or slow-release oral morphine) and 27 (35%) received hydromorphone tablets. Thirty-one (40%) residents received stimulant tablets with methylphenidate (27; 35%), dextroamphetamine (8; 10%), or lisdexamfetamine (2; 3%). Six residents (8%) received benzodiazepines. Forty-two (55%) residents received alcohol, including 41 (53%) with strong beer, three (3%) with wine, and one (1%) with hard liquor. Over 14 days in isolation, mean daily dosages increased of hydromorphone (45 ± 32 to 57 ± 42mg), methylphenidate (51 ± 28 to 77 ± 37mg), dextroamphetamine (33 ± 16 to 46 ± 13mg), and alcohol (12.3 ± 7.6 to 13.0 ± 6.9 standard drinks). Six residents (8%) left isolation prematurely, but four of those residents returned. Over 1,059 person-days in isolation, there were zero overdoses. Documented concerns regarding intoxication occurred six times (0.005 events/person-day) and medication diversion or sharing three times (0.003 events/person-day). CONCLUSIONS: An emergency safe supply and managed alcohol program, paired with housing, was associated with low rates of adverse events and high rates of successful completion of the 14-day isolation period in COVID-19 isolation hotel shelters. This supports the effectiveness and safety of emergency safe supply prescribing and managed alcohol in this setting