Global assessment of effective population sizes: Consistent taxonomic differences in meeting the 50/500 rule.

Effective population size (Ne) is a particularly useful metric for conservation as it affects genetic drift, inbreeding and adaptive potential within populations. Current guidelines recommend a minimum Ne of 50 and 500 to avoid short-term inbreeding and to preserve long-term adaptive potential respectively. However, the extent to which wild populations reach these thresholds globally has not been investigated, nor has the relationship between Ne and human activities. Through a quantitative review, we generated a dataset with 4610 georeferenced Ne estimates from 3829 populations, extracted from 723 articles. These data show that certain taxonomic groups are less likely to meet 50/500 thresholds and are disproportionately impacted by human activities; plant, mammal and amphibian populations had a <54% probability of reaching N ̂ e = 50 and a <9% probability of reaching N ̂ e = 500. Populations listed as being of conservation concern according to the IUCN Red List had a smaller median N ̂ e than unlisted populations, and this was consistent across all taxonomic groups. N ̂ e was reduced in areas with a greater Global Human Footprint, especially for amphibians, birds and mammals, however relationships varied between taxa. We also highlight several considerations for future works, including the role that gene flow and subpopulation structure plays in the estimation of N ̂ e in wild populations, and the need for finer-scale taxonomic analyses. Our findings provide guidance for more specific thresholds based on Ne and help prioritise assessment of populations from taxa most at risk of failing to meet conservation thresholds.

Microgeographic variation in demography and thermal regimes stabilize regional abundance of a widespread freshwater fish.

Predicting the persistence of species under climate change is an increasingly important objective in ecological research and management. However, biotic and abiotic heterogeneity can drive asynchrony in population responses at small spatial scales, complicating species-level assessments. For widely distributed species consisting of many fragmented populations, such as brook trout (Salvelinus fontinalis), understanding the drivers of asynchrony in population dynamics can improve the predictions of range-wide climate impacts. We analyzed the demographic time series from mark-recapture surveys of 11 natural brook trout populations in eastern Canada over 13 years to examine the extent, drivers, and consequences of fine-scale population variation. The focal populations were genetically differentiated, occupied a small area (~25 km2 ) with few human impacts, and experienced similar climate conditions. Recruitment was highly asynchronous, weakly related to climate variables and showed population-specific relationships with other demographic processes, generating diverse population dynamics. In contrast, individual growth was mostly synchronized among populations and driven by a shared positive relationship with stream temperature. Outputs from population-specific models were unrelated to four of the five hypothesized drivers (recruitment, growth, reproductive success, phylogenetic distance), but variation in groundwater inputs strongly influenced stream temperature regimes and stock-recruitment relationships. Finally, population asynchrony generated a portfolio effect that stabilized regional species abundance. Our results demonstrated that population demographics and habitat diversity at microgeographic scales can play a significant role in moderating species responses to climate change. Moreover, we suggest that the absence of human activities within study streams preserved natural habitat variation and contributed to asynchrony in brook trout abundance, while the small study area eased monitoring and increased the likelihood of detecting asynchrony. Therefore, anthropogenic habitat degradation, landscape context, and spatial scale must be considered when developing management strategies to monitor and maintain populations that are diverse, stable, and resilient to climate change.

Effects of climate on salmonid productivity: A global meta-analysis across freshwater ecosystems.

Salmonids are of immense socio-economic importance in much of the world, but are threatened by climate change. This has generated a substantial literature documenting the effects of climate variation on salmonid productivity in freshwater ecosystems, but there has been no global quantitative synthesis across studies. We conducted a systematic review and meta-analysis to gain quantitative insight into key factors shaping the effects of climate on salmonid productivity, ultimately collecting 1321 correlations from 156 studies, representing 23 species across 24 countries. Fisher's Z was used as the standardized effect size, and a series of weighted mixed-effects models were compared to identify covariates that best explained variation in effects. Patterns in climate effects were complex and were driven by spatial (latitude, elevation), temporal (time-period, age-class), and biological (range, habitat type, anadromy) variation within and among study populations. These trends were often consistent with predictions based on salmonid thermal tolerances. Namely, warming and decreased precipitation tended to reduce productivity when high temperatures challenged upper thermal limits, while opposite patterns were common when cold temperatures limited productivity. Overall, variable climate impacts on salmonids suggest that future declines in some locations may be counterbalanced by gains in others. In particular, we suggest that future warming should (1) increase salmonid productivity at high latitudes and elevations (especially >60° and >1500 m), (2) reduce productivity in populations experiencing hotter and dryer growing season conditions, (3) favor non-native over native salmonids, and (4) impact lentic populations less negatively than lotic ones. These patterns should help conservation and management organizations identify populations most vulnerable to climate change, which can then be prioritized for protective measures. Our framework enables broad inferences about future productivity that can inform decision-making under climate change for salmonids and other taxa, but more widespread, standardized, and hypothesis-driven research is needed to expand current knowledge.

Accurate parameterization of the kinetic energy functional for calculations using exact-exchange.

Electronic structure calculations based on Kohn-Sham density functional theory (KSDFT) that incorporate exact-exchange or hybrid functionals are associated with a large computational expense, a consequence of the inherent cubic scaling bottleneck and large associated prefactor, which limits the length and time scales that can be accessed. Although orbital-free density functional theory (OFDFT) calculations scale linearly with system size and are associated with a significantly smaller prefactor, they are limited by the absence of accurate density-dependent kinetic energy functionals. Therefore, the development of accurate density-dependent kinetic energy functionals is important for OFDFT calculations of large realistic systems. To this end, we propose a method to train kinetic energy functional models at the exact-exchange level of theory by using a dictionary of physically relevant terms that have been proposed in the literature in conjunction with linear or nonlinear regression methods to obtain the fitting coefficients. For our dictionary, we use a gradient expansion of the kinetic energy nonlocal models proposed in the literature and their nonlinear combinations, such as a model that incorporates spatial correlations between higher order derivatives of electron density at two points. The predictive capabilities of these models are assessed by using a variety of model one-dimensional (1D) systems that exhibit diverse bonding characteristics, such as a chain of eight hydrogens, LiF, LiH, C4H2, C4N2, and C3O2. We show that by using the data from model 1D KSDFT calculations performed using the exact-exchange functional for only a few neutral structures, it is possible to generate models with high accuracy for charged systems and electron and kinetic energy densities during self-consistent field iterations. In addition, we show that it is possible to learn both the orbital dependent terms, i.e., the kinetic energy and the exact-exchange energy, and models that incorporate additional nonlinearities in spatial correlations, such as a quadratic model, are needed to capture subtle features of the kinetic energy density that are present in exact-exchange-based KSDFT calculations.

Accurate parameterization of the kinetic energy functional.

The absence of a reliable formulation of the kinetic energy density functional has hindered the development of orbital free density functional theory. Using the data-aided learning paradigm, we propose a simple prescription to accurately model the kinetic energy density of any system. Our method relies on a dictionary of functional forms for local and nonlocal contributions, which have been proposed in the literature, and the appropriate coefficients are calculated via a linear regression framework. To model the nonlocal contributions, we explore two new nonlocal functionals-a functional that captures fluctuations in electronic density and a functional that incorporates gradient information. Since the analytical functional forms of the kernels present in these nonlocal terms are not known from theory, we propose a basis function expansion to model these seemingly difficult nonlocal quantities. This allows us to easily reconstruct kernels for any system using only a few structures. The proposed method is able to learn kinetic energy densities and total kinetic energies of molecular and periodic systems, such as H2, LiH, LiF, and a one-dimensional chain of eight hydrogens using data from Kohn-Sham density functional theory calculations for only a few structures.

Nanomaterial Synthesis Insights from Machine Learning of Scientific Articles by Extracting, Structuring, and Visualizing Knowledge.

Nanomaterials of varying compositions and morphologies are of interest for many applications from catalysis to optics, but the synthesis of nanomaterials and their scale-up are most often time-consuming and Edisonian processes. Information gleaned from the scientific literature can help inform and accelerate nanomaterials development, but again, searching the literature and digesting the information are time-consuming manual processes for researchers. To help address these challenges, we developed scientific article-processing tools that extract and structure information from the text and figures of nanomaterials articles, thereby enabling the creation of a personalized knowledgebase for nanomaterials synthesis that can be mined to help inform further nanomaterials development. Starting with a corpus of ∼35k nanomaterials-related articles, we developed models to classify articles according to the nanomaterial composition and morphology, extract synthesis protocols from within the articles' text, and extract, normalize, and categorize chemical terms within synthesis protocols. We demonstrate the efficiency of the proposed pipeline on an expert-labeled set of nanomaterials synthesis articles, achieving 100% accuracy on composition prediction, 95% accuracy on morphology prediction, 0.99 AUC on protocol identification, and up to a 0.87 F1-score on chemical entity recognition. In addition to processing articles' text, microscopy images of nanomaterials within the articles are also automatically identified and analyzed to determine the nanomaterials' morphologies and size distributions. To enable users to easily explore the database, we developed a complementary browser-based visualization tool that provides flexibility in comparing across subsets of articles of interest. We use these tools and information to identify trends in nanomaterials synthesis, such as the correlation of certain reagents with various nanomaterial morphologies, which is useful in guiding hypotheses and reducing the potential parameter space during experimental design.

Opioid Prescriptions Among Women of Reproductive Age Enrolled in Medicaid - New York, 2008-2013.

Exposure to opioids during pregnancy can lead to adverse infant outcomes, including neonatal abstinence syndrome (1) and birth defects (2). Ascertaining opioid prescriptions for women who become pregnant or have no indication of contraceptive use is important to determine the number of women who are at potential risk for adverse fetal outcomes. The New York State (NYS) Department of Health (DOH) analyzed data for women aged 15-44 years (i.e., reproductive-aged women) enrolled in Medicaid to examine opioid drug prescriptions during 2008-2013. On the basis of Medicaid drug claims for any drug with an opioid ingredient, prescriptions were identified for the enrolled population of reproductive-aged women and for three subgroups: women whose diagnosis, procedure, and drug codes indicated contraceptive use or infertility; women who were not using contraceptives and not infertile; and women who had had a live birth during the reporting year. During 2008-2013, among all women of reproductive age, 20.0% received a prescription for a drug with an opioid component; the proportion was highest (27.3%) among women with an indication of contraceptive use or infertility, intermediate (17.3%) among women who had no indication of contraceptive use, and lowest (9.5%) among women who had had a live birth. Although New York's proportion of opioid prescriptions among female Medicaid recipients who had a live birth is lower than a recent U.S. estimate (3), these results suggest nearly one in 10 women in this group may have been exposed to opioids in the prenatal period.

3D-Printed Model in Preoperative Planning of Sciatic Nerve Decompression Because of Heterotopic Ossification: A Case Report.

CASE: A 31-year-old patient presented with an encapsulated sciatic nerve secondary to extensive hip heterotopic ossification (HO), which prevented visualization of a safe osteotomy site to avoid nerve damage. The 3D-printed model demonstrated an easily identifiable osseous reference point along the inferior aspect of the heterotopic mass, allowing for a vertical osteotomy to be safely performed. CONCLUSION: HO is associated with loss of normal anatomic topography. The current case report illustrates the use of a 3D-printed model to identify pertinent anatomic landmarks required for safe decompression of an encapsulated sciatic nerve within the anatomic region of the hip.

Mechanisms contributing to the dopamine induction of crawl-like bursting in leech motoneurons.

Dopamine (DA) activates fictive crawling behavior in the medicinal leech. To identify the cellular mechanisms underlying this activation at the level of crawl-specific motoneuronal bursting, we targeted potential cAMP-dependent events that are often activated through DA(1)-like receptor signaling pathways. We found that isolated ganglia produced crawl-like motoneuron bursting after bath application of phosphodiesterase inhibitors (PDIs) that upregulated cAMP. This bursting persisted in salines in which calcium ions were replaced with equimolar cobalt or nickel, but was blocked by riluzole, an inhibitor of a persistent sodium current. PDI-induced bursting contained a number of patterned elements that were statistically similar to those observed during DA-induced fictive crawling, except that one motoneuron (CV) exhibited bursting during the contraction rather than the elongation phase of crawling. Although DA and the PDIs produced similar bursting profiles, intracellular recordings from motoneurons revealed differences in altered membrane properties. For example, DA lowered motoneuron excitability whereas the PDIs increased resting discharge rates. We suggest that PDIs (and DA) activate a sodium-influx-dependent timing mechanism capable of setting the crawl rhythm and that multiple DA receptor subtypes are involved in shaping and modulating the phase relationships and membrane properties of cell-specific members of the crawl network to generate crawling.

Effect of Lateral Retinacular Release on Medial Patellofemoral Ligament Reconstruction.

BACKGROUND: When performing a medial patellofemoral ligament (MPFL) reconstruction, surgeons may place the MPFL graft under higher than anatomic tension to minimize the chance of recurrent instability. PURPOSE: To investigate whether a lateral retinacular release (LRR) significantly decreases patellofemoral contact pressures after an overtensioned (OT) MPFL reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: Mean and peak pressure across the patellofemoral joint at 30°, 45°, and 60° of flexion was assessed in 14 cadaveric knee specimens with intact MPFL, transected MPFL, reconstructed MPFL with graft OT, and OT MPFL with LRR. The Wilcoxon signed rank test was used to determine differences across states, with W and C values calculated when possible. RESULTS: Mean pressure decreased significantly after MPFL transection compared with intact at 30° (456.9 ± 116.8 vs 410.9 ± 109.4 N, P = .006, W < 7) and 45° (404.9 ± 91.7 vs 369.4 ± 85.3 N, P = .005, W < 5) and increased significantly from intact to OT graft at 30° (456.9 ± 116.8 vs 563.0 ± 11.2 N, P = .003, W < 7), 45° (404.9 ± 91.7 vs 481.4 ± 14.8 N, P = .005, W < 5), and 60° (272.9 ± 139.0 vs 367.0 ± 53.7 N, P = .007, W < 3). Peak pressure increased significantly between intact and OT graft at 30° (1364.0 ± 478.2 vs 2094.4 ± 619.8 N, P = .002, W < 9), 45° (1224.7 ± 491.5 vs 1676.7 ± 779.1 N, P = .005, W < 5), and 60° (1117.7 ± 566.8 vs 1604.2 ± 772.9 N, W < 3). In knees with significantly increased mean pressure after overtensioning, mean pressure increased by 23.3% (11/14 knees) at 30°, 18.3% (10/14 knees) at 45°, and 35.0% (10/14 knees) at 60°. Peak pressure increased significantly by 35.3% (30°), 25.2% (45°), and 29.3% (60°). A significant decrease in mean pressure, toward but not to baseline, was observed between the OT and LRR states at 30° (563.0 ± 11.2 vs 501.5 ± 9.3 N, W < 7) and 60° (367.0 ± 53.7 vs 302.0 ± 13.8 N, W < 5) and a decrease in peak pressure at 30° (2094.4 ± 619.8 vs 1886.5 ± 655.3 N; W < 9). CONCLUSION: LRR led to a statistically significant decrease in pressure across the patellofemoral joint in knees that demonstrated increased contact pressures after an OT MPFL graft. CLINICAL RELEVANCE: LRR after an MPFL reconstruction in which the MPFL graft has been OT may help reduce patellofemoral contact pressures at the time of surgery.

Surgically discovered xanthogranulomatous pyelonephritis invading inferior vena cava with coexisting renal cell carcinoma.

Xanthogranulomatous pyelonephritis (XGP) is a chronic inflammatory process that results in replacement of renal and/or perirenal tissue with a diffuse infiltrate of inflammatory cells referred to as xanthoma cells. We present a case of a 49-year-old man with an incidentally discovered renal mass with inferior vena cava (IVC) thrombus, who was found intraoperatively to have a significant inflammatory process involving the posterior wall of his IVC and right renal vein consistent with XGP surrounding a focus of clear cell renal cell carcinoma in the midportion of his right kidney.

Points to Consider: Best Practices to Identify Particle Entry Routes along the Manufacturing Process for Parenteral Formulations.

During the processes involved in pharmaceutical manufacturing, particulate matter may be introduced into a product from a variety of sources and at different points in the manufacturing process. Companies design quality at the beginning of the process to ensure against defects and strive to manufacture products that meet the pharmacopeial standard of being "practically/essentially free" of particles, which can be challenging, though necessary. As particulate matter recalls are predominantly associated with parenteral products, most companies employ a quality risk management program to identify critical parameters or conditions that could affect product quality or patient safety and incorporate systemic and procedural controls to mitigate or reduce the probability of their occurrence. Yet, determining where particulates are most likely to enter the process, what types of materials are most vulnerable, and how the size and number of particles might affect product quality can be very complex. Visual inspection and sampling of the manufactured drug product are designed to control the risk of particulate contamination; building prevention controls will ensure sustainability. This concept paper highlights the necessity of a more thorough understanding of the failure mechanisms that result in particle contamination across a range of products, such as elastomeric components and glass, and processes, such as the formulation and filling of injectables. The goal is to identify process steps within the end-to-end manufacturing process that are most critical to particle generation and entering of visible particles into the final drug product.LAY ABSTRACT: This concept paper highlights the necessity of a more thorough understanding of the failure mechanisms that result in particle contamination across a range of products, such as elastomeric components and glass, and processes, such as the formulation and filling of injectables. The goal is to identify process steps within the end-to-end manufacturing process that are most critical to particle generation and entering of visible particles into the final drug product.

Systemic and cell-specific immune response to laparoscopic and open nephrectomy in porcine model.

PURPOSE: To determine differences in the systemic and cell-specific immune response to open and laparoscopic nephrectomy in the porcine model. MATERIALS AND METHODS: Twenty male pigs (25-40 kg) were vaccinated with human adenovirus containing ovalbumin (Ova) and 3 weeks later underwent a sham procedure (N = 4), laparoscopic nephrectomy (LN)(N = 8), or open nephrectomy (ON) (N = 8). Blood was collected after anesthesia induction and immediately and 24 and 48 hours postoperatively and assayed for complete blood count (CBC), cortisol, and C-reactive protein (CRP). Natural killer (NK) cells were isolated and stimulated in vitro for 48 hours with polyinosinic:polycytidylic acid (Poly I:C) and interleukin (IL)-2 to determine cytotoxic activity. Peripheral blood mononuclear cells (PBMC) were isolated for flow cytometry staining with CD8, CD4, and CD25 markers. Additional PBMCs were stimulated in vitro with Ova and ConA for 48 hours to measure the production of IL-10 and interferon (IFN)-gamma and a thymidine-incorporation assay to determine T-cell proliferation. RESULTS: One animal in the ON group had signs of infection preoperatively and was removed from analysis. The LN took significantly longer than ON or sham nephrectomy (P = 0.002). Blood loss and animal weight were similar in the three groups. The CRP concentration increased more in the ON than the LN and sham-treatment groups in the first 48 hours (P = 0.01). No statistical differences were seen in the elevation of white blood cells or cortisol concentration. All groups demonstrated a decrease in the cytotoxic activity of NK cells postoperatively, with a significantly greater decrease in the sham-treated animals (P = 0.004). The LN group demonstrated greater T-cell activation than the ON and sham-treatment groups with both CD4(+) (P = 0.002) and CD8(+) (P = 0.028) cells increasing their expression of the activation marker CD25. The thymidine-incorporation assay demonstrated decreased T-cell proliferation in the ON group when stimulated with ConA (P = 0.014). Production of IL-10 decreased in the sham-treated and LN animals while increasing after ON. There was no difference in IFN-gamma among the groups. CONCLUSIONS: In a porcine model, ON produces higher CRP concentrations postoperatively, a larger decrease in T-cell proliferation ability, and more IL-10 activity than LN or sham treatment. Animals undergoing LN demonstrated greater T-cell activation postoperatively. White blood cell counts, serum cortisol concentration, and production of IFN-gamma were similar among the groups. These findings suggest ON causes greater immune suppression than LN in the porcine model.

Microtubule-stabilizing natural products as promising cancer therapeutics.

Paclitaxel and related taxanes exhibit their anticancer activity by promoting tubulin polymerization and stabilizing microtubules, which results in mitotic G2/M arrest and apoptosis. The clinical success of paclitaxel in treating a wide array of tumor types has led to numerous efforts to identify novel natural products with paclitaxel-like mechanisms of action, but which may overcome some of the liabilities of the taxanes. Although the list of natural products that share the paclitaxel-like mechanism is relatively small, it continues to expand and currently includes a number of structurally distinct classes. Despite the mechanistic similarities between these classes, differences exist which may translate into their differential efficacy in the clinic. The past several years have seen a considerable amount of pre-clinical and clinical progress in developing these novel microtubule-stabilizing natural products as cancer therapeutics. This review focuses primarily on recent advances published since 2002.

In vitro and in vivo anticancer activities of synthetic (-)-laulimalide, a marine natural product microtubule stabilizing agent.

Laulimalide is a cytotoxic natural product isolated from marine sponges. It is structurally distinct from taxanes. However, like paclitaxel, laulimalide binds to tubulin and enhances microtubule assembly and stabilization. It exhibits potent inhibition of cellular proliferation with IC50 values in the low nM range against numerous cancer cell lines. In contrast to paclitaxel, however, laulimalide is also very potent against multidrug-resistant (MDR) cancer cell lines which overexpress P-glycoprotein (PgP). It has unique structural and biological properties, and attempts at synthesis have attracted considerable effort in recent years, resulting in more than ten published total syntheses. Despite this extensive attention, there have been no reported in vivo evaluations of laulimalide to date, probably due to the structural complexity of laulimalide and the scarcity of natural material. In our studies to explore the therapeutic potential of laulimalide, a total synthesis capable of producing gram quantities of laulimalide was designed, which enabled both in vitro and in vivo evaluation. Our in vitro results with synthetic material confirmed the previous reports that laulimalide is a mitotic blocker that can inhibit the growth of a variety of both non-MDR and MDR human cancer cell lines. However, despite demonstrating promise in cell-based and pharmacokinetic studies, laulimalide exhibited only minimal tumor growth inhibition in vivo and was accompanied by severe toxicity and mortality. The unfavorable efficacy to toxicity ratio in vivo suggests that laulimalide may have limited value for development as a new anticancer therapeutic agent.

Oseltamivir for pandemic influenza preparation: Maximizing the use of an existing stockpile.

With the threat of significant morbidity and mortality following an influenza pandemic, stockpiling of antiviral agents such as oseltamivir is recommended. Shelf-life extension was explored to maximize use of an existing stockpile. This analysis demonstrated that oseltamivir retains potency defined by United States Pharmacopeia acceptance criteria beyond the labeled expiration date.

PKCα Attenuates Jagged-1-Mediated Notch Signaling in ErbB-2-Positive Breast Cancer to Reverse Trastuzumab Resistance.

PURPOSE: Breast cancer is the second leading cause of cancer mortality among women worldwide. The major problem with current treatments is tumor resistance, recurrence, and disease progression. ErbB-2-positive breast tumors are aggressive and frequently become resistant to trastuzumab or lapatinib. We showed previously that Notch-1 is required for trastuzumab resistance in ErbB-2-positive breast cancer. EXPERIMENTAL DESIGN: Here, we sought to elucidate mechanisms by which ErbB-2 attenuates Notch signaling and how this is reversed by trastuzumab or lapatinib. RESULTS: The current study elucidates a novel Notch inhibitory mechanism by which PKCα downstream of ErbB-2 (i) restricts the availability of Jagged-1 at the cell surface to transactivate Notch, (ii) restricts the critical interaction between Jagged-1 and Mindbomb-1, an E3 ligase that is required for Jagged-1 ubiquitinylation and subsequent Notch activation, (iii) reverses trastuzumab resistance in vivo, and (iv) predicts better outcome in women with ErbB-2-positive breast cancer. CONCLUSIONS: The clinical impact of these studies is PKCα is potentially a good prognostic marker for low Notch activity and increased trastuzumab sensitivity in ErbB-2-positive breast cancer. Moreover, women with ErbB-2-positive breast tumors expressing high Notch activation and low PKCα expression could be the best candidates for anti-Notch therapy.

The postoperative hemorrhage and hematoma patient safety indicator and its risk factors.

This study employed a retrospective cohort analysis using New York State's Statewide Planning and Research Cooperative System (SPARCS) to improve the Patient Safety Indicator (PSI) definition of postoperative hemorrhage/hematoma (POHH) and to identify patient risk factors associated with POHH. Study participants were nonobstetric, inpatient surgical admissions in SPARCS and readmissions within 30 days with a principal diagnosis of POHH. The main outcome measures were mortality rate, length of stay, and readmissions. The mortality rates of events identified by a secondary diagnosis only and by the PSI were not significantly different. The number of POHH events increased by 9.3% when readmissions were captured. The PSI definition of POHH may need modification to capture events with no secondary procedure. The PSI misses events identified on readmission, but the consequences of these events are not as severe as those currently captured. A variety of patient and hospital characteristics are predictive of a higher risk of POHH.

Early versus delayed rehabilitation following arthroscopic rotator cuff repair: A systematic review.

BACKGROUND: Early passive range of motion (ROM) following arthroscopic cuff repair is thought to decrease postoperative stiffness and improve functionality. However, early aggressive rehabilitation may compromise repair integrity. Our purpose was to perform a systematic review to determine if there are differences between early and delayed rehabilitation after arthroscopic rotator cuff repair in terms of clinical outcomes and healing. METHODS: We performed a literature search with the terms 'arthroscopic rotator cuff', 'immobilization', 'early', 'delayed', 'late', and 'rehabilitation' using PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Selection criteria included: level I/II evidence ≤ 6 months in duration, comparing early versus delayed rehabilitation following arthroscopic repair. Data regarding demographics, sample sizes, duration, cuff pathology, surgery, rehabilitation, functional outcomes, pain, ROM and anatomic assessment of healing were analyzed. PRIMSA criteria were followed. RESULTS: We identified six articles matching our criteria. Three reported significantly increased functional scores within the first 3-6 months with early rehabilitation compared to the delayed group, only one of which continued to observe a difference at a final follow-up of 15 months. Four articles showed improved ROM in the first 3-6 months post-operatively with early rehabilitation. One noted transient differences in pain scores. Only one study noted significant differences in ROM at final follow-up. No study reported any significant difference in rates of rotator cuff re-tear. However, two studies noted a trend towards increased re-tear with early rehabilitation that did not reach significance. This was more pronounced in studies including medium-large tears. CONCLUSIONS: Early rehabilitation after arthroscopic cuff repair is associated with some initial improvements in ROM and function. Ultimately, similar clinical and anatomical outcomes between groups existed at 1 year. While there was no significant difference between groups in anatomic failure of the repaired cuff, there may be a trend towards increased re-tear with larger tears.