Unravelling the Risk of Poisoning From Nicotine-Containing Tobacco Products in Children Less Than Five Years of Age.

For decades, young children in the United States have been accidentally poisoned by traditional tobacco products and the yearly incidence has slowly increased. More poisonings have accompanied the introduction of new products such as e-cigarettes and dissolvable tobacco, with renewed public attention. Using toxicological principles of human health risk assessment, published data from prior exposures, and information about the content and characteristics of specific products, I estimated the acute toxicological risk from exposure to various types and quantities of tobacco products for children <5 years old. Approximate reference levels for a non-lethal oral dose of nicotine were derived: A higher level potentially requiring medical care (0.2 mg per kg) and a lower level not potentially requiring medical care (0.04 mg per kg). A weight-based oral lowest lethal dose (LDLO) of 1-14 mg per kg in children <5 years old is estimated from the cited LDLOs in adults. I provide tables relating e-liquid concentration and volume to the oral LDLO in children <5 years old by weight and describing the amount of other tobacco products expected to result in lethality. Communications about safe storage practices should focus on the benefits of keeping any nicotine-containing product out of the reach of young children, and adults can be reminded to always reengage child-resistant closures on packages and call a poison center for accidental exposures. Healthcare providers, families, or any member of the public can also make reports about unexpected health or safety concerns related to tobacco products to the FDA using its online Safety Reporting Portal at https://www.fda.gov/TobaccoProducts/PublicHealthScienceResearch/ucm377563.htm. Tobacco products, particularly electronic nicotine delivery system (ENDS) liquids are highly toxic to children <5 years old in small amounts. Given that the concentration of nicotine in ENDS is 3 to 72 mg per mL, the lethal dose (LDLO) is expected to be 13-40 mL in a bottle containing a solution of 3 mg per mL liquid nicotine but may be as low as ½-2 mL in a bottle containing a highly concentrated solution of 72 mg per mL liquid nicotine. Features such as flow restrictors, child-resistant closures, and communication of safe storage practices to parents can help to lessen the morbidity and mortality from poisoning.

Medical device report analyses from MAUDE: Device and patient outcomes, adverse events, and sex-based differential effects.

Post-market medical device-associated failures and patient problems are reported in Medical Device Reports (MDRs) to the US Food and Drug Administration. Reports are accessible through Manufacturer and User Facility Device Experience (MAUDE), a database including both required and voluntary submissions. We present an overview of >10 million MDRs received from 2011 to 2021. Approximately 92% of reporting issues represent medical device physical or functional failures, categorized from 1704 codes related to medical device integrity or function. ∼8% were coded adverse events (AEs). Patient outcomes are reported via 998 patient codes in 19 medical specialties (cardiovascular, orthopedic, etc.). ∼40% of patient reports indicated "no health consequences"; however, a small number of devices had consistently high AE reports. While overall reports did not exhibit a sex-based dichotomy, ∼9% of the reported AEs occurred more frequently in females, many of which were related to immune effects. The analyses are subject to uncertainties and potential bias based on data available and data selected for analysis. However, such an overview of post-market MDR data, not previously published, fills a gap in understanding medical device issues and patient-based outcomes related to medical device use. Trends identified may be subjects of additional hypotheses, analysis, and research.

Reassessment of the cadmium toxicological reference value for use in human health assessments of foods.

The U.S. Food and Drug Administration (FDA) developed an oral toxicological reference value (TRV) for characterizing potential health concerns from dietary exposure to cadmium (Cd). The development of the TRV leveraged the FDA's previously published research including (1) a systematic review for adverse health effects associated with oral Cd exposure and (2) a human physiological based pharmacokinetic (PBPK) model adapted from Kjellstrom and Nordberg (1978) for use in reverse dosimetry applied to the U.S. population. Adverse effects of Cd on the bone and kidney are associated with similar points of departure (PODs) of approximately 0.50 µg Cd/g creatinine for females aged 50-60 based on available epidemiologic data. We also used the upper bound estimate of the renal cortical concentration (50 µg/g Cd) occurring in the U.S. population at 50 years of age as a POD. Based on the output from our reverse dosimetry PBPK Model, a range of 0.21-0.36 µg/kg bw/day was developed for the TRV. The animal data used for the animal TRV derivation (0.63-1.8 µg/kg bw/day) confirms biological plausibility for both the bone and kidney endpoints.

Short-term outcomes after primary reverse total shoulder arthroplasty in patients with cervical spine pathology or previous cervical spine surgery compared to those without.

BACKGROUND: Cervical spine (c-spine) and shoulder pathology have been known to cause similar symptoms and often co-exist, making an accurate diagnosis difficult, especially in an elderly population. Reverse total shoulder arthroplasty (rTSA) has been shown to decrease pain and improve quality of life when shoulder pathology is the source of pain and disability. The purpose of this study was to identify the prevalence of c-spine pathology in a cohort of patients who underwent rTSA and to compare postoperative outcome scores to a cohort without c-spine pathology. METHODS: A retrospective review was performed utilizing a single institution's operative records of primary rTSAs. Radiology reports, imaging, and operative reports were reviewed, and presence of any c-spine pathology or previous surgery were recorded. Additionally, postoperative outcome scores (American Shoulder and Elbow Surgeons [ASES], Constant Score, University of California, Los Angeles [UCLA], and Simple Shoulder Test [SST]) were evaluated at >2 years post-rTSA. RESULTS: A total of 438 primary rTSA cases were evaluated. Of these, 143 (32.6%) had documentation of prior c-spine pathology and/or history of previous c-spine surgery. After applying further exclusion criteria, a total of 50 patients with c-spine pathology and 108 patients without c-spine pathology were found to have complete medical records and postoperative outcome scores to allow comparison between groups. Patients without c-spine pathology were found to have statistically higher postoperative UCLA, ASES, and SST scores when compared to patients with c-spine pathology. Patients without c-spine pathology also demonstrated a significant improvement in the difference between their postoperative and preoperative UCLA and ASES scores. CONCLUSION: This study demonstrated a high prevalence of c-spine pathology (32.6%) in a cohort of patients who underwent primary rTSA. Additionally, short-term outcome scores of patients undergoing rTSA with concomitant c-spine pathology are significantly lower than those of patients without a history of c-spine pathology.

A systematic review of adverse health effects associated with oral cadmium exposure.

Scientific data characterizing the adverse health effects associated with dietary cadmium (Cd) exposure were identified in order to make informed decisions about the most appropriate toxicological reference value (TRV) for use in assessing dietary Cd exposure. Several TRVs are available for Cd and regulatory organizations have used epidemiologic studies to derive these reference values; however, risk of bias (RoB) evaluations were not included in the assessments. We performed a systematic review by conducting a thorough literature search (through January 4, 2020). There were 1714 references identified by the search strings and 328 studies identified in regulatory assessments. After applying the specific inclusion and exclusion criteria, 208 studies (Human: 105, Animal: 103) were considered eligible for further review and data extraction. For the epidemiologic and animal studies, the critical effects identified for oral Cd exposure from the eligible studies were a decrease in bone mineral density (BMD) and renal tubular degeneration. A RoB analysis was completed for 49 studies (30 epidemiological and 19 animal) investigating these endpoints. The studies identified through the SR that were considered high quality and low RoB (2 human and 5 animal) can be used to characterize dose-response relationships and inform the derivation of a Cd TRV.

Opioid requirements in primary versus revision reverse shoulder arthroplasty.

PURPOSE: The purpose of this study is to evaluate the inpatient pain medication use of patients who had a revision shoulder arthroplasty procedure performed and compare them to a cohort of patients who had a primary reverse total shoulder arthroplasty (rTSA) performed to determine whether revision shoulder arthroplasty requires more pain medication.. METHODS: A retrospective review was performed on patients undergoing revision arthroplasty (n = 75) and primary rTSA (n = 340). Inpatient medication records were reviewed to tabulate the visual analog pain (VAS) all narcotic medication use, and total morphine equivalent units (MEUs) were calculated for the duration of the inpatient stay. RESULTS: There was no significant difference between groups regarding age, sex, body mass index, Charlson Comorbidity Index, American Society of Anesthesiologists score, preoperative narcotic pain medication use, tobacco use, postoperative VAS scores or hospital length of stay. There were no predictors of total postoperative MEUs identified. Overall, patients in the revision arthroplasty group received significantly less total MEUs than those in the primary rTSA group, 134.96 MEUs vs. 69.79 MEUs, respectively (p < .0005). CONCLUSION: The perceived notion that revision shoulder arthroplasty is more painful may cause providers to be more inclined to increase narcotic use, or use more invasive pain control techniques. Based on these data, we found that revision shoulder arthroplasty did not require an increased opioid requirement, longer length of stay or increase VAS, suggesting that these patients can often be managed similarly to primary rTSA.

Routine postoperative laboratory tests are unnecessary after primary reverse shoulder arthroplasty.

BACKGROUND: Obtaining postoperative laboratory studies after primary reverse shoulder arthroplasty (RSA) is a common practice. However, justification of this practice remains unclear. This study assesses the utility of routine postoperative laboratory studies in RSA. METHODS: The electronic medical records of 369 patients who underwent RSA over 10 years were retrospectively reviewed. A total of 213 patients qualified for analysis. Primary outcomes were intervention related to abnormal laboratory values, length of stay, and 90-day emergency department visits/readmissions. Multivariate logistic regression analysis was performed to identify risk factors associated with abnormal laboratory values and postoperative visits/readmissions. RESULTS: Of 213 patients analyzed, 188 (88.7%) had abnormal postoperative laboratory values: 69% had an abnormal hemoglobin (Hgb) or hematocrit level, but only 12% underwent interventions. Lower preoperative Hgb was a significant predictor of receiving a transfusion. A significant association existed between abnormal postoperative electrolyte and creatinine levels with lower body mass index (BMI) and higher Charlson Comorbidity Index (CCI). Only 4 patients (1.8%) received non-transfusion related intervention. Emergency department visits were not statistically different between patients with positive or negative laboratory tests (P = .73). CONCLUSION: Because 87.3% of laboratory studies did not influence patient management, we recommend against routine testing for primary RSA. This study demonstrates that the practice of obtaining routine postoperative laboratory studies is not justified. We recommend selectively obtaining a postoperative basic metabolic profile in patients with increased American Society of Anesthesiologists classification and/or CCI with a lower BMI. We also recommend selectively ordering postoperative complete blood count in patients with a lower preoperative Hgb.

Scapula fracture incidence in reverse total shoulder arthroplasty using screws above or below metaglene central cage: clinical and biomechanical outcomes.

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) is a viable treatment option for rotator cuff tear arthropathy but carries a complication risk of scapular fracture. We hypothesized that using screws above the central glenoid axis for metaglene fixation creates a stress riser contributing to increased scapula fracture incidence. Clinical type III scapular fracture incidence was determined with screw placement correlation: superior screw vs. screws placed exclusively below the glenoid midpoint. Cadaveric RTSA biomechanical modeling was employed to analyze scapular fractures. METHODS: We reviewed 318 single-surgeon single-implant RTSAs with screw correlation to identify type III scapular fractures. Seventeen cadaveric scapula specimens were matched for bone mineral density, metaglenes implanted, and fixation with 2 screw configurations: inferior screws alone (group 1INF) vs. inferior screws with one additional superior screw (group 2SUP). Biomechanical load to failure was analyzed. RESULTS: Of 206 patients, 9 (4.4%) from the superior screw group experienced scapula fractures (type III); 0 fractures (0/112; 0%) were identified in the inferior screw group. Biomechanically, superior screw constructs (group 2SUP) demonstrated significantly (P < .05) lower load to failure (1077 N vs. 1970 N) compared with constructs with no superior screws (group 1INF). There was no significant age or bone mineral density discrepancy. CONCLUSION: Clinical scapular fracture incidence significantly decreased (P < .05) for patients with no screws placed above the central cage compared with patients with superior metaglene screws. Biomechanical modeling demonstrates significant construct compromise when screws are used above the central cage, fracturing at nearly half the ultimate load of the inferior screw constructs. We recommend use of inferior screws, all positioned below the central glenoid axis, unless necessary to stabilize the metaglene construct.

Core decompression and arthroplasty outcomes for atraumatic osteonecrosis of the humeral head.

BACKGROUND: Humeral head osteonecrosis treatment varies depending on the stage and symptoms. Successful outcomes for humeral head core decompression for stage I/II disease in chronic steroid-induced (CSI) osteonecrosis have been reported, but fewer data exist for sickle cell disease (SCD) etiology. Resurfacing and hemiarthroplasty or total shoulder arthroplasty (TSA) are common for advanced collapse, with mixed results. METHODS: We evaluate radiographic and functional outcomes after procedures for humeral head atraumatic avascular necrosis (HAAVN), decompression efficacy in CSI and SCD populations, and report outcomes of advanced disease requiring arthroplasty. Twenty-five shoulders were treated surgically for HAAVN. Post-traumatic AVN patients were excluded. Stage I/II disease received core decompression and ultrasound bone stimulation. Stage III received surface replacement or hemiarthroplasty, and arthroplasty was performed for stage IV/V. Radiographs and clinical scores were recorded preoperatively and postoperatively. RESULTS: Included were 25 HAAVN shoulders (13 SCD and 12 CSI). Eleven shoulders (stage I/II disease) underwent core decompression. Seven of 8 shoulders (88%) progressed to stage III/IV after decompression. All SCD patients progressed to collapse. The procedure in 19 shoulders was surface replacement, hemiarthroplasty, or TSA. Constant, American Shoulder and Elbow Surgeons, Simple Shoulder Test-12, and University of California Los Angeles Shoulder scores were significantly higher at 1- and 2-year follow-up with arthroplasty; 13 of 16 arthroplasty patients (81%) had satisfactory to excellent results. One surface replacement was revised to reverse TSA. CONCLUSIONS: Results suggest core decompression for AVN in SCD patients does not alter osteonecrosis progression and humeral head collapse. Resurfacing and hemiarthroplasty are viable treatment options for stage III, whereas shoulder replacement for stage IV/V disease appears to offer better functional results.

Proximal humeral fractures: pin, plate, or replace.

Proximal humeral fractures are becoming increasingly common in individuals older than 60 years, with only fractures of the hip and distal radius occurring with a higher frequency. Most proximal humeral fractures can be managed without surgery; however, if a fracture is displaced or angulated, surgical treatment may be required. There are four main options for the surgical management of proximal humeral fractures: minimally invasive percutaneous reduction and fixation, open reduction and periarticular plating, hemiarthroplasty, and reverse total shoulder arthroplasty.

Infection after primary anatomic versus primary reverse total shoulder arthroplasty.

BACKGROUND: Deep periprosthetic infection is a serious complication after total shoulder arthroplasty (TSA) and is associated with suboptimal clinical results. This retrospective study aimed to determine whether a difference in infection rate existed after primary anatomic TSA (aTSA) and primary reverse TSA (rTSA). METHODS: A TSA database was retrospectively reviewed to identify primary TSAs performed from 2004 to 2012 and isolate cases of confirmed deep periprosthetic infection. Data collected included age, sex, preoperative diagnosis, previous nonarthroplasty operative history, implant type, and infecting organism. RESULTS: From 814 primary TSAs performed, deep periprosthetic infections were confirmed in 16 shoulders. Infections occurred in 6 aTSAs and 10 rTSAs, with no significant difference among the prosthesis types. Pathogens included Staphylococcus spp, Propionibacterium acnes, and Escherichia coli. In the subgroup of shoulders with no previous operations, no significant difference in infection rate was found among the prosthesis types. Shoulders with previous nonarthroplasty operations undergoing primary TSA exhibited a significantly higher (P = .016) infection rate compared with shoulders with no operative history. Both aTSA and rTSA performed in previously operated-on shoulders demonstrated higher infection rates compared with shoulders with no prior operative intervention. The infection rate was significantly higher (P = .016) in the rTSA group. CONCLUSIONS: There is no difference in infection rate after primary aTSA and primary rTSA in shoulders that have not undergone previous operative interventions. Infection is more likely to develop in shoulders undergoing primary rTSA that have had one or more nonarthroplasty operative procedures.

Atmospheric particulate matter in proximity to mountaintop coal mines: sources and potential environmental and human health impacts.

Mountaintop removal mining (MTM) is a widely used approach to surface coal mining in the US Appalachian region whereby large volumes of coal overburden are excavated using explosives, removed, and transferred to nearby drainages below MTM operations. To investigate the air quality impact of MTM, the geochemical characteristics of atmospheric particulate matter (PM) from five surface mining sites in south central West Virginia, USA, and five in-state study control sites having only underground coal mining or no coal mining whatsoever were determined and compared. Epidemiologic studies show increased rates of cancer, respiratory disease, cardiovascular disease, and overall mortality in Appalachian surface mining areas compared to Appalachian non-mining areas. In the present study, 24-h coarse (>2.5 µm) and fine (≤2.5 µm) PM samples were collected from two surface mining sites in June 2011 showed pronounced enrichment in elements having a crustal affinity (Ga, Al, Ge, Rb, La, Ce) contributed by local sources, relative to controls. Follow-up sampling in August 2011 lacked this enrichment, suggesting that PM input from local sources is intermittent. Using passive samplers, dry deposition total PM elemental fluxes calculated for three surface mining sites over multi-day intervals between May and August 2012 were 5.8 ± 1.5 times higher for crustal elements than at controls. Scanning microscopy of 2,249 particles showed that primary aluminosilicate PM was prevalent at surface mining sites compared to secondary PM at controls. Additional testing is needed to establish any link between input of lithogenic PM and disease rates in the study area.

Cyclic stretch disrupts apical junctional complexes in Caco-2 cell monolayers by a JNK-2-, c-Src-, and MLCK-dependent mechanism.

The intestinal epithelium is subjected to various types of mechanical stress. In this study, we investigated the impact of cyclic stretch on tight junction and adherens junction integrity in Caco-2 cell monolayers. Stretch for 2 h resulted in a dramatic modulation of tight junction protein distribution from a linear organization into wavy structure. Continuation of cyclic stretch for 6 h led to redistribution of tight junction proteins from the intercellular junctions into the intracellular compartment. Disruption of tight junctions was associated with redistribution of adherens junction proteins, E-cadherin and ß-catenin, and dissociation of the actin cytoskeleton at the actomyosin belt. Stretch activates JNK2, c-Src, and myosin light-chain kinase (MLCK). Inhibition of JNK, Src kinase or MLCK activity and knockdown of JNK2 or c-Src attenuated stretch-induced disruption of tight junctions, adherens junctions, and actin cytoskeleton. Paracellular permeability measured by a novel method demonstrated that cyclic stretch increases paracellular permeability by a JNK, Src kinase, and MLCK-dependent mechanism. Stretch increased tyrosine phosphorylation of occludin, ZO-1, E-cadherin, and ß-catenin. Inhibition of JNK or Src kinase attenuated stretch-induced occludin phosphorylation. Immunofluorescence localization indicated that phospho-MLC colocalizes with the vesicle-like actin structure at the actomyosin belt in stretched cells. On the other hand, phospho-c-Src colocalizes with the actin at the apical region of cells. This study demonstrates that cyclic stretch disrupts tight junctions and adherens junctions by a JNK2, c-Src, and MLCK-dependent mechanism.

Trust your gut: Establishing confidence in gastrointestinal models - An overview of the state of the science and contexts of use.

The webinar series and workshop titled "Trust Your Gut: Establishing Confidence in Gastrointestinal Models ­ An Overview of the State of the Science and Contexts of Use" was co-organized by NICEATM, NIEHS, FDA, EPA, CPSC, DoD, and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT) and hosted at the National Institutes of Health in Bethesda, MD, USA on October 11-12, 2023. New approach methods (NAMs) for assessing issues of gastrointestinal tract (GIT)- related toxicity offer promise in addressing some of the limitations associated with animal-based assessments. GIT NAMs vary in complexity, from two-dimensional monolayer cell line-based systems to sophisticated 3-dimensional organoid systems derived from human primary cells. Despite advances in GIT NAMs, challenges remain in fully replicating the complex interactions and pro­cesses occurring within the human GIT. Presentations and discussions addressed regulatory needs, challenges, and innovations in incorporating NAMs into risk assessment frameworks; explored the state of the science in using NAMs for evaluating systemic toxicity, understanding absorption and pharmacokinetics, evaluating GIT toxicity, and assessing potential allergenicity; and discussed strengths, limitations, and data gaps of GIT NAMs as well as steps needed to establish confidence in these models for use in the regulatory setting.

Non-animal methods to assess whether chemicals may be toxic to the human digestive tract promise to complement or improve on animal-based methods. These approaches, which are based on human or animal cells and/or computer models, are faced with their own technical challenges and need to be shown to predict adverse effects in humans. Regulators are tasked with evaluating submitted data to best protect human health and the environment. A webinar series and workshop brought together scientists from academia, industry, military, and regulatory authorities from dif­ferent countries to discuss how non-animal methods can be integrated into the risk assessment of drugs, food additives, dietary supplements, pesticides, and industrial chemicals for gastrointestinal toxicity.

Biomechanical Evaluation of Recurrent Dissociation of Modular Humeral Prostheses.

The purpose of the study was to evaluate the force and torque required to dissociate a humeral head from the unimplanted modular total shoulder replacement system from different manufacturers and to determine if load and torque to dissociation are reduced in the presence of bodily fluids. Impingement, taper contamination, lack of compressive forces, and interference of taper fixation by the proximal humerus have all been reported as possible causes for dissociation. Experimental values determined in this research were compared with literature estimates of dissociation force of the humeral head under various conditions to gain more understanding of the causes of recurrent dissociations of the humeral head. This study examined biomechanical properties under dry and wet conditions under clinically practiced methods. Mean load to dissociation (1513 N ± 508 N) was found to be greater than that exerted by the activities of daily living (578 N) for all implants studied. The mean torque to dissociation was (49.77 N·m ± 19.07 N·m). Analysis of R2 correlation coefficients and p-values (α = 0.05) did not show any significant correlation between dry/bovine, dry/wet, or wet/bovine for load, displacement, or torsional stiffness in the majority of tests performed. Wetting the taper with water or bovine serum did not reduce the dissociation force to a statistically significant degree. Torque and lack of compressive forces at the rotator cuff may be the cause of dissociation at values less than those of activities of daily living. Torque data are provided by this study, but further research is needed to fully appreciate the role of torque in recurrent dissociations.

Risk factors of instability following reverse total shoulder arthroplasty in patients with no history of shoulder surgery.

Introduction: As its indications expand, reverse total shoulder arthroplasty (rTSA) utilization continues to increase. Though relatively uncommon, instability following rTSA can be associated with significant morbidity and need for subsequent revision and treatment. This case control study aims to characterize factors leading to instability after rTSA, especially in those with no previous shoulder surgery. Methods: 194 rTSAs performed within the study period with appropriate operative indications and follow-up were included. Risk factors used in analysis included age, gender, BMI, ASA class, Charlson comorbidity index (CCI), glenosphere, tray, and liner size. Data was analyzed using a hierarchical binary logistical regression to create a predictive model for instability. Results: Seven patients sustained a post-operative dislocation. Mean time to dislocation was 60.4 weeks. Five required open reduction with placement of either a larger humeral tray or polyethylene spacer. One required open reduction with osteophyte removal, and one was converted to a resection arthroplasty. Dislocators were more likely to have a larger BMI (p = 0.002), higher ASA classification (p = 0.09), and larger liner size (p = 0.01). Conclusion: This study demonstrates a large series of patients successfully treated with rTSA. Dislocations were an uncommon complication, but were clearly associated with higher patient BMI, ASA classification, and increased liner size.

Evaluation of indoor PM2.5 concentrations in a Native American Community: a pilot study.

BACKGROUND: Indoor air pollution is associated with adverse health effects; however, few studies exist studying indoor air pollution on the Navajo Nation in the southwest U.S., a community with high rates of respiratory disease. METHODS: Indoor PM2.5 concentration was evaluated in 26 homes on the Navajo Nation using real-time PM2.5 monitors. Household risk factors and daily activities were evaluated with three metrics of indoor PM2.5: time-weighted average (TWA), 90th percentile of concentration, and daily minutes exceeding 100 µg/m3. A questionnaire and recall sheet were used to record baseline household characteristics and daily activities. RESULTS: The median TWA, 90th percentile, and daily minutes exceeding 100 µg/m3 were 7.9 µg/m3, 14.0 µg/m3, and 17 min, respectively. TWAs tended to be higher in autumn and in houses that used fuel the previous day. Other characteristics associated with elevated PM exposure in all metrics included overcrowded houses, nonmobile houses, and houses with current smokers, pets, and longer cooking time. CONCLUSIONS: Some residents of the Navajo Nation have higher risk of exposure to indoor air pollution by Environmental Protection Agency (EPA) standards. Efforts to identify the causes and associations with adverse health effects are needed to ensure that exposure to risks and possible health impacts are mitigated.

Balance of life and death in alveolar epithelial type II cells: proliferation, apoptosis, and the effects of cyclic stretch on wound healing.

After acute lung injury, repair of the alveolar epithelium occurs on a substrate undergoing cyclic mechanical deformation. While previous studies showed that mechanical stretch increased alveolar epithelial cell necrosis and apoptosis, the impact of cell death during repair was not determined. We examined epithelial repair during cyclic stretch (CS) in a scratch-wound model of primary rat alveolar type II (ATII) cells and found that CS altered the balance between proliferation and cell death. We measured cell migration, size, and density; intercellular gap formation; cell number, proliferation, and apoptosis; cytoskeletal organization; and focal adhesions in response to scratch wounding followed by CS for up to 24 h. Under static conditions, wounds were closed by 24 h, but repair was inhibited by CS. Wounding stimulated cell motility and proliferation, actin and vinculin redistribution, and focal adhesion formation at the wound edge, while CS impeded cell spreading, initiated apoptosis, stimulated cytoskeletal reorganization, and attenuated focal adhesion formation. CS also caused significant intercellular gap formation compared with static cells. Our results suggest that CS alters several mechanisms of epithelial repair and that an imbalance occurs between cell death and proliferation that must be overcome to restore the epithelial barrier.

Scapula fractures after reverse total shoulder arthroplasty: classification and treatment.

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) implants have been developed to treat patients with deficient rotator cuffs. The nature of this procedure's complications and how these complications should be managed continues to evolve. Fractures of the scapula after RTSA have been described, but the incidence and best methods of treatment are unclear. QUESTIONS/PURPOSES: We therefore (1) determined the incidence and (2) developed a classification system intended to suggest the best choice of treatment. PATIENTS AND METHODS: We reviewed the records of 400 patients treated with RTSA over 4.5 years and identified all patients with scapula fractures. We identified three discrete patterns: avulsion fractures of the anterior acromion (Type I); fractures of the acromion posterior to the acromioclavicular joint (Type II); and fractures of the scapular spine (Type III). RESULTS: Twenty-two patients (5.5%) had fractures. Eight (2.0%) had Type I fractures on the first followup radiographs; these patients were treated nonoperatively with resolution of symptoms. Ten (2.5%) had Type II fractures a mean of 10.8 months after RTSA; seven of the 10 were treated surgically with improvement in their clinical symptoms. Four (1%) had Type III fractures at a mean of 10.3 months; all four fractures were treated with surgical fixation with healing. CONCLUSIONS: Scapula fracture is a relatively common complication of RTSA. Our observations suggest Type I fractures can be observed with a likelihood of symptom relief. For Type II fractures, we recommend acromioclavicular joint resection if stable but open reduction internal fixation if unstable. We believe Type III fractures are best treated with open reduction internal fixation. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.