Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma.

The sub-ventricular zone (SVZ) is the most well-characterized neurogenic area in the mammalian brain. We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and emergence of recurrence. Here, we built a single-nucleus RNA-sequencing-based microenvironment landscape of the tumor mass (T_Mass) and the SVZ (T_SVZ) of 15 GBM patients and 2 histologically normal SVZ (N_SVZ) samples as controls. We identified a mesenchymal signature in the T_SVZ of GBM patients: tumor cells from the T_SVZ relied on the ZEB1 regulatory network, whereas tumor cells in the T_Mass relied on the TEAD1 regulatory network. Moreover, the T_SVZ microenvironment was predominantly characterized by tumor-supportive microglia, which spatially co-exist and establish heterotypic interactions with tumor cells. Lastly, differential gene expression analyses, predictions of ligand-receptor and incoming/outgoing interactions, and functional assays revealed that the IL-1ß/IL-1RAcP and Wnt-5a/Frizzled-3 pathways are therapeutic targets in the T_SVZ microenvironment. Our data provide insights into the biology of the SVZ in GBM patients and identify specific targets of this microenvironment.

Novel scores relevant to antimicrobial resistance and hospital-acquired infections developed with data from a multi-hospital consortium in the Parisian region of France.

PURPOSE: Indicators for comparing and understanding differences in antimicrobial resistance (AMR) and healthcare-associated infections (HAIs) for benchmarking are essential to identify priorities for hospitals. METHODS: This study measured the incidence of hospital-acquired or resistant Gram-negative bacilli bloodstream infections (GNB-BSIs) in a large public healthcare consortium in the Parisian region of France. RESULTS: Within each hospital, there was a strong positive correlation between the incidence of GNB-BSIs due to resistant GNB and the incidence of hospital-acquired GNB-BSIs. Two scores measuring AMR and HAI rates by combining different GNB-BSI incidence rates were developed as indicators. These scores were highly variable within the hospital consortium. On multi-variate analysis, AMR and HAI scores were significantly associated with the proportion of surgical beds, staff absenteeism and the consumption of alcohol-based hand rub, with the latter two characteristics being amenable to interventions. Carbapenem use was also linked to AMR, but this may be because carbapenems are the preferred drug for treating resistant infections. CONCLUSION: These results shed light on the incidence of HAIs and AMR in the study hospitals, and suggest possibilities for targeted interventions at healthcare facility level.

Biomechanical Performance of Biodegradable Screw Fixation in Mandibular Distraction Osteogenesis.

Internal distraction devices are commonly used in congenital micrognathia. The eventual need for device and screw removal can be challenging, requiring extensive dissection and disturbance of bone regenerate. Bioabsorbable poly-L-lactide (PLLA) screws, compared to traditional titanium screws, simplify device removal. Previous in vivo studies have found that the maximal compressive force generated by mandibular distraction is 69.4N. We hypothesized that PLLA screws could support these compressive/distraction forces. Ten mandibles were obtained from 5 canine cadavers. Paired mandibles from the same cadaver were each fixated to a mandibular distractor with eight screws (either titanium or PLLA). Devices were each set to 15 and 30 mm of distraction distance. Compression force of 80 N was then generated parallel to the axis of the distraction device. Distractor displacement was measured to detect any mechanical failure during this pre-set load. Finally, if no failure was observed at 80 N, a load-to-failure compression test was done in the PLLA group to determine the mechanical failure point. All distractors in both the titanium and PLLA screw groups withstood 80 N of compression without failure. When the load-to-failure test was performed in the PLLA group, the average device failure point was 172.8 N (range 148-196 N). Review of high-frame-rate video demonstrated that all failures occurred due to the PLLA screws breaking or falling out. Bioabsorbable PLLA screws can withstand compressive forces more than double that of the maximal in vivo forces needed during mandibular distraction. These screws may be an acceptable alternative for the fixation of internal mandibular distractors.

Annual pulses of copper-enriched sediment in a North American river downstream of a large lake following the catastrophic failure of a mine tailings storage facility.

Failures of mine tailings storage facilities (TSF) can have profound and long-lasting effects on the downstream receiving environment. Virtually all spills to date have been into river systems without large lakes that may buffer downstream impacts. In August 2014, the failure of the Mount Polley copper (Cu)-gold mine TSF in British Columbia, Canada, released ~25 × 106 m3 of water and solids; globally, this is the second largest TSF spill in history. Over 18 × 106 m3 was delivered to Quesnel Lake, which is ~9 km from the TSF and is the third deepest lake in North America, and a crucial habitat for Pacific salmon and trout populations. We determined the sediment-associated Cu concentrations and fluxes in Quesnel River, downstream of the lake, from August 2014 to February 2021 based on the analysis of >400 samples of sediment, mainly collected using a continuous-flow centrifuge. During each winter since the spill, Cu concentrations in the fluvial sediment in the upper reaches of the river (~35 km from the TSF) were elevated relative to regional background concentrations and samples collected before the spill. Maximum Cu concentrations were ~410 mg kg-1 which exceeds Canadian sediment quality guidelines for the protection of aquatic organisms (197 mg kg-1). Monitoring of Quesnel Lake since the spill shows that these annual pulses in the winter are due to resuspension of unconsolidated tailings and sediments at the bottom of Quesnel Lake, during autumnal lake turnover, which become mixed throughout the water column and subsequently flow into Quesnel River. Results show that while large lakes may buffer downstream aquatic systems from contaminated sediment, they may prolong the environmental impact. These findings are crucial in understanding how lake processes may modify the effects of TSF spills on downstream aquatic systems.

A randomized controlled trial evaluating a theory driven, complex intervention centered on task sharing and mobile health to improve selfcare and outcomes in heart failure - The PANACEA-HF RCT: Design and rationale.

Background: We developed a three-pronged complex intervention to improve selfcare and deliver whole person care for patients with heart failure, underpinned by the 'extant cycle' theory - a theory based on our formative work. Methods: This is a 3 centre, 2-arm, 1:1, open, adaptive stratified, randomized controlled trial. We included patients aged ≥ 18 years with heart failure, taking any of the key guideline directed medical treatments, with a history of or currently on a high ceiling diuretic. We excluded end stage renal disease, clinically diagnosed severe mental illness or cognitive dysfunction and having no caregivers. Interventions included, (i) trained hospital based lay health worker mediated assessment of patients' current selfcare behaviour, documenting barriers and facilitators and implementing a plan to 'transition' the patient toward optimal selfcare. (ii) m-health mediated remote monitoring and (iii) dose optimization through a 'physician supervisor'. Results: We recruited 301 patients between Jan 2021 and Jan 2022. Mean age was 59.8 (±11.7) years, with 195 (64.8 %) from rural or semi-urban areas and 67.1 % having intermediate to low health literacy. 190 (63.1 %) had an underlying ischemic cardiomyopathy. In the intervention arm, 142 (94.1 %) had a Selfcare in Heart Failure Index (SCHFI) score of ≤70, with significant barriers being 'lack of knowledge' 105 (34.5 %) and 'behavioural passivity' 23 (7.5 %). Conclusion: This is the first South Asian trial evaluating a complex intervention underpinned by behaviour change theory for whole person heart failure care. These learnings can be applied to heart failure patient care in other resource constrained health systems.

Reconstruction of Congenital Sternal Cleft: A Systematic Review of the Literature.

INTRODUCTION: Sternal cleft (SC) is a rare congenital deformity that results from failure of sternal bar fusion. Sternal cleft can be categorized as superior partial, inferior partial, or complete. Each form of SC can present as an isolated defect or in association with other congenital deformities, which presents a unique challenge for reconstructive surgeons. In our systematic review, we aim to summarize the published experience on repair of SCs and present a pragmatic approach to help guide reconstructive planning. METHODS: A systematic review was performed to identify all reported SC cases in literature that underwent sternal reconstruction. RESULTS: Seventy-one studies were identified from 1970 to 2019, which included a total of 115 patients. Superior partial SC was the most common SC variant, accounting for 65.2% (75/115) of all reported cases. There were 31 cases of complete SC (27.0%) and 9 cases (7.8%) of inferior partial SC; 49.6% of the patients (57/115) in our review had isolated SC without any other congenital deformities. Sixty-seven patients (60.3%) were treated with primary closure, with or without secondary maneuvers, such as chondrotomies, cartilage resection, or periosteal flaps. Alternative methods included interposition grafts, with autologous rib graft in 18 patients (15.8%), permanent mesh in 8 patients (7.0%), acellular dermal matrix in 5 patients (4.4%), sternal plate flap in 5 patients (4.4%), and nonthoracic autologous bone grafts in 4 patients (3.5%). CONCLUSIONS: Our review supports that primary closure should be attempted regardless of patient age. For wider sternal gap, reconstruction with an autologous local graft or flap should be considered. When the patient does not have sufficient autologous tissue for a successful sternal reconstruction, alloplastic or allograft interposition options are a reasonable choice.

Patient and caregiver reported facilitators of self-care among patients with chronic heart failure: report from a formative qualitative study.

Background: Adherence to a complex, yet effective medication regimen improves clinical outcomes in patients with chronic heart failure (CHF). However, patient adherence to an agreed upon plan for medication-taking is sub-optimal and continues to hover at 50% in developed countries. Studies to improve medication-taking have focused on interventions to improve adherence to guideline-directed medication therapy, yet few of these studies have integrated patients' perceptions of what constitutes effective strategies for improved medication-taking and self-care in everyday life. The purpose of this formative study was to explore patient perceived facilitators of selfcare and medication-taking. Methods: We conducted in-depth interviews of patients with long standing heart failure admitted to the cardiology and internal medicine wards of a South Indian tertiary care hospital. We purposively sampled using the following criteria: sex, socio-economic status, health literacy and patient reported medication adherence in the month prior to hospitalization. We employed inductive coding to identify facilitators. At the end of 15 interviews (eight patients and seven caregivers; seven patient-caregiver dyads), we arrived at theoretical saturation for facilitators. Results: Facilitators could be classified into intrinsic (patient traits - situational awareness, self-efficacy, gratitude, resilience, spiritual invocation and support seeking behavior) and extrinsic (shaped by the environment - financial security and caregiver support, company of children, ease of healthcare access, trust in provider/hospital, supportive environment and recognizing the importance of knowledge). Conclusions: We identified and classified a set of key patient and caregiver reported self-care facilitators among Indian CHF patients. The learnings from this study will be incorporated into an intervention package to improve patient engagement, overall self-care and patient-caregiver-provider dynamics.

Global Burden of Craniofacial Disorders: Where Should Volunteering Plastic Surgeons and Governments Focus Their Care?

PURPOSE: Approximately 11% of the global burden of disease is surgically treatable. When located within the head, face, and neck region, plastic surgeons are particularly trained to treat these conditions. The purpose of this study was to describe the etiology, disability, and barriers to receiving care for diseases of the head, face, mouth, and neck region across 4 low-and-middle-income countries. METHODS: The Surgeons OverSeas Assessment of Surgical Need (SOSAS) instrument is a cluster randomized, cross-sectional, national survey administered in Nepal, Rwanda, Sierra Leone, and Uganda from 2011 to 2014. The survey identifies demographic characteristics, etiology, disease timing, proportion seeking/receiving care, barriers to care, and disability. RESULTS: Across the 4 countries, 1413 diseases of head, face, mouth, and neck region were identified. Masses (22.13%) and trauma (32.8%) were the most common etiology. Nepal reported the largest proportion of masses (40.22%) and Rwanda reported the largest amount of trauma (52.65%) (P < 0.001). Rwanda had the highest proportion of individuals seeking (89.6%) and receiving care (83.63%) while Sierra Leone reported the fewest (60% versus 47.77%, P < 0.001). In our multi-variate analysis literacy and chronic conditions were predictors for receiving care while diseases causing the greatest disability predicted not receiving care (ORa .58 and .48 versus 1.31 P < 0.001). CONCLUSIONS: The global volunteering plastic surgeon should be prepared to treat chronic craniofacial conditions. Furthermore, governments should address structural barriers, such as health illiteracy and lack of access to local plastic surgery care by supporting local training efforts.

Nasal Dorsal Augmentation with Freeze-Dried Allograft Bone: 10-Year Comprehensive Review.

BACKGROUND: The aim of this study was to evaluate freeze-dried cortical allograft bone for nasal dorsal augmentation. The 42-month report on 18 patients was published in 2009 in Plastic and Reconstructive Surgery with 89 percent success at level II evidence, and this article is the 10-year comprehensive review of 62 patients. METHODS: All grafts met standards recommended by the American Association of Tissue Banks, the U.S. Food and Drug Administration, and the Centers for Disease Control and Prevention. Objective evaluation of the persistence of graft volume was obtained by cephalometric radiography, cone beam volumetric computed tomography, and computed tomography at up to 10 years. Vascularization and incorporation of new bone elements within the grafts were demonstrated by fluorine-18 sodium fluoride positron emission tomography at up to 10 years. Subjective estimation of graft volume persisting up to 10 years was obtained by patient response to a query conducted by an independent surveyor. RESULTS: The authors report objective proof of persistence of volume alone or combined with proof of neovascularization in 16 of 19 allografts. The authors report the patient's subjective opinion of volume persistence in 37 of 43 grafts. The dorsal augmentation was assessed overall to be successful in 85 percent of 62 patients evaluated between 1 and 10 years, with a mean of 4.7 years. CONCLUSIONS: Freeze-dried allograft bone is a safe and equal alternative for dorsal augmentation without donor-site morbidity. Further studies are needed to (1) confirm these findings for young patients needing long-term reconstruction, and (2) partially demineralize allograft bone to allow carving with a scalpel. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Athletic pubalgia: Return to play after targeted surgery.

BACKGROUND: Surgery for athletic pubalgia usually consists in abdominal wall repair combined with routine bilateral adductor tenotomy. We currently confine the surgical procedure to the injured structure(s) (abdominal wall only, adductor tendon only, or both) to limit morbidity and expedite recovery. Outcomes of this à la carte approach are unclear. The objectives of this retrospective study were to determine the return to play (RTP) time, evaluate the potential influence of injury location, and assess the frequency of recurrence or contralateral involvement. HYPOTHESIS: À la carte surgery for athletic pubalgia is associated with similar RTP times as the conventional procedure and is not followed by recurrence. MATERIAL AND METHODS: Consecutive adults younger than 40 years of age who underwent surgery for athletic pubalgia with injury to the abdominal wall and/or adductor attachment sites between 2009 and 2015 were included. Patients with intra-articular hip disorders, isolated pubic symphysis involvement, or herniation were not eligible. The diagnosis was established clinically then confirmed by at least one imaging technique (ultrasonography plus either a radiograph of the pelvis or magnetic resonance imaging of the pelvis). The criterion for performing surgery was failure of appropriate conservative therapy followed for at least 3 months. RESULTS: Of the 27 included patients, eight had abdominal wall involvement only, seven adductor tendon involvement only, and 12 both. Overall, 25 (92.6%) patients returned to play at their previous level, after a mean of 112±38 days (range, 53-223 days), and experienced no recurrence during the 1-year follow-up. Mean RTP time was significantly shorter in the group with abdominal wall injury only (91.1±21.0 days) compared to the groups with adductor tendon injury only (101.7±42.0 days) or combined injuries (132.5±39.0) (p=0.02). DISCUSSION: In patients with athletic pubalgia, à la carte surgery confined to the injured structure(s) produces excellent RTP outcomes. RTP time is shortest in patients with isolated lower abdominal wall injuries. LEVEL OF EVIDENCE: IV, retrospective study with no control group.

Role of cytochrome P450 2B sequence variation and gene copy number in facilitating dietary specialization in mammalian herbivores.

Theory postulates that dietary specialization in mammalian herbivores is enabled by a specialized set of liver enzymes that process the high concentrations of similar plant secondary metabolites (PSMs) in the diets of specialists. To investigate whether qualitative and quantitative differences in detoxification mechanisms distinguish dietary specialists from generalists, we compared the sequence diversity and gene copy number of detoxification enzymes in two woodrat species: a generalist, the white-throated woodrat (Neotoma albigula) and a juniper specialist, Stephens' woodrat (N. stephensi). We focused on enzymes in the cytochrome P450 subfamily 2B (CYP2B), because previous research suggests this subfamily plays a key role in the processing of PSMs. For both woodrat species, we obtained and sequenced CYP2B cDNA, generated CYP2B phylogenies, estimated CYP2B gene copy number and created a homology model of the active site. We found that the specialist possessed on average ~5 more CYP2B gene copies than the generalist, but the specialist's CYP2B sequences were less diverse. Phylogenetic analysis of putative CYP2B homologs resolved woodrat species as reciprocally monophyletic and suggested evolutionary convergence of distinct homologs on similar key amino acid residues in both species. Homology modelling of the CYP2B enzyme suggests that interspecific differences in substrate preference and function likely result from amino acid differences in the enzyme active site. The characteristics of CYP2B in the specialist, that is greater gene copy number coupled with less sequence variation, are consistent with specialization to a narrow range of dietary toxins.

Early strength recovery after anterior cruciate ligament reconstruction using the fascia lata.

INTRODUCTION: After undergoing anterior cruciate ligament (ACL) reconstruction, patients must recover at least 80% of their hamstring and quadriceps strength to be able to return to sports without risk to the graft. Harvesting of the patellar tendon leads to large deficits in quadriceps strength, while harvesting the hamstring tendons leads to large deficits in hamstring strength. However, there are no published studies on the strength deficit after ACL reconstruction with the fascia lata. The objective of this study was to evaluate the results of isokinetic testing in patients who underwent ACL reconstruction with a fascia lata graft and to analyze the individual factors affecting these results. The hypothesis was that preserving the quadriceps and hamstrings would lead to satisfactory isokinetic testing results by preserving the physiological balance between the flexor and extensor mechanisms in the leg. MATERIALS AND METHODS: In this retrospective, single-center study, 53 patients had their quadriceps and hamstring strength recovery evaluated 6 months and 1 year post-ACL reconstruction by concentric isometric testing at a slow (90°/s) and fast velocity (240°/s). These results were analyzed as a function of individual characteristics such as age, sex, preinjury level and type of sports activity, and IKDC and Lysholm scores. RESULTS: The quadriceps strength deficit at the slow and fast velocities was 27.5% and 22.5% at 6 months and 15.5% and 11% at 1 year, respectively. The hamstring strength deficit at the slow and fast velocities was 12.1% and 7% at 6 months and 8% and 6.4% at 1 year, respectively. The quadriceps to hamstring ratio at the slow and fast velocities was 66.7±16.5 and 71.3±15.5 at 6 months, and 61.1±14.9 and 67.6±12.5 at 1 year. Being less than 25 years of age, having a subjective IKDC grade or Lysholm score above 90, and being a professional athlete were significant predictors of better muscle strength recovery. DISCUSSION: Isokinetic testing at 6 months and 1 year after ACL reconstruction surgery using the fascia lata showed that the quadriceps to hamstring ratio is close to physiological standards. LEVEL OF EVIDENCE: IV retrospective study.

Return to sports and functional results after revision anterior cruciate ligament reconstruction by fascia lata autograft.

INTRODUCTION: The surgical revision rate following anterior cruciate ligament (ACL) surgery is 3% at 2 years and 4% at 5 years. Revision ACL surgery raises the question of the type of graft to be used. The present study assessed return to sports and functional results after revision ACL reconstruction by fascia lata graft. The hypothesis was that fascia lata provides a reliable graft in revision ACL surgery. MATERIAL AND METHODS: A single-center retrospective continuous study included 30 sports players with a mean age of 26.8±8 years undergoing surgical revision for iterative ACL tear between 2004 and 2013. Multi-ligament lesions were excluded. Type and level of sports activity were assessed preoperatively, after primary surgery and at end of follow-up. Clinical assessment used subjective IKDC, Lysholm and KOOS scores. RESULTS: At a mean 4.6±1.6 years' follow-up, all patients had resumed sport activity, but only 12 with the same sport at the same level. Median subjective IKDC score increased from 57 [54.3; 58.5] preoperatively to 82 [68.3; 90] at last follow-up, and Lysholm score from 46 [42.3; 51] to 90.5 [80.8; 96.8]; KOOS score at last follow-up was 94.7 [83; 100]. CONCLUSION: Functional results in revision ACL reconstruction by fascia lata graft were satisfactory, with similar return-to-sports rates as with other techniques. Fascia lata provides a reliable graft in revision ACL surgery. LEVEL OF EVIDENCE: IV, retrospective study.

Head and neck adenoid cystic carcinoma: A prospective multicenter REFCOR study of 95 cases.

OBJECTIVES: To describe the clinical, histological and therapeutic characteristics of a prospective multicenter series of 95 head and neck adenoid cystic carcinoma patients, and to determine any prognostic factors for disease-free survival. PATIENTS AND METHODS: Ninety-five patients with adenoid cystic carcinoma were included in the Réseau d'Expertise Français Des Cancers ORL Rares (REFCOR, French Rare Head and Neck Cancer Expert Network) database between 2009 and 2012. The primary site was the salivary glands in 39 cases, sinus cavities (including hard palate) in 36 cases, pharynx-larynx-trachea in 14 cases, and lips and oral cavity in 4 cases. The tumor was stage I in 15% of cases, stage II in 23%, stage III in 26% and stage IV in 36%. Nine patients had cervical lymph node involvement and 5 had metastases at diagnosis. Fifty-six percent of patients were managed by surgery with postoperative radiation therapy. During follow-up, 3 patients died, 9 developed metastases and 12 showed recurrence or local progression. RESULTS: Mean follow-up was 18 months. On univariate analysis, disease-free survival correlated with T stage (P=0.05), N stage (P=0.003), resection margins (P=0.04), lymph node involvement on histology (P=0.01), and absence of chemotherapy (P=0.03). On multivariate analysis, disease-free survival correlated with T stage (P=0.01), N stage (P=0.09) and surgery (P=0.005). CONCLUSION: The essential issue in adenoid cystic carcinoma is long-term control. The present results confirm that the reference attitude is radical surgical resection for optimal local control. Adjuvant radiation therapy did not emerge as a prognostic factor. This study also provides a starting-point for translational studies in pathology and genetics.