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The primary aim of this study was to evaluate epidemiological characteristics and prevalence of lung disease among e-cigarettes users in the United States. A population-based, cross-sectional survey was performed using the National Health and Nutrition Examination Survey (NHANES) of 2015–2018. Adults using e-cigarettes (SMQ900), traditional smoking (SMQ020: > 100 cigarettes in lifetime or SMQ040: current cigarettes use), and dual smoking (e-cigarettes and traditional smoking) were identified and compared in their sociodemographic characteristics and prevalence of lung diseases (Asthma: MCQ010 and COPD: MCQ160O). We used the chi square test (categorical variables) and Mann–Whitney test and unpaired-student t test (continuous variables). p-value

Objectives: Irreparable rotator cuff tears can be challenging to manage in younger patients who are not well indicated for reverse total shoulder replacement. Treatment options in this patient population include both marginal convergence (MC) and superior capsular reconstruction (SCR). While both treatment options have demonstrated good short term outcomes, they have vastly different associated costs and operative times. Thus, the purpose of this study was to compare range of motion (ROM), patient reported outcomes, and re-operation rates following MC and SCR. We hypothesized that SCR would outperform MC regarding functional and subjective outcomes. Methods: A retrospective review was conducted on 44 patients from two surgeons with irreparable rotator cuff tears that underwent either MC (28 patients, 28 shoulders) or SCR (16 patients, 16 shoulders) from 2014-2019 at a single academic center. Patient inclusion criteria were the following: failed conservative or prior surgical management, no or mild glenohumeral arthritis, Goutallier grade 3 or 4 fatty infiltration of the involved muscles, Hamada grade 1 or 2 rotator cuff arthropathy, intact or repairable subscapularis tear and minimum of 1 year follow-up. Visual Analogue Scale (VAS) for pain, active forward flexion (FF) and external rotation (ER) range of motion, reoperation rate, and rate of conversion to reverse total shoulder arthroplasty were evaluated. For statistical analysis, t-tests were used to determine differences in functional outcomes and VAS, while Chi-Squared tests were used to determine differences in the rate of re-operation and conversion to arthroplasty (*p < 0.05). Results: The mean age at the time of surgery for the MC and SCR groups was 64.4 and 58.5 years, respectively, with an average follow-up of 31.5 months for the MC group and 17.8 months for the SCR group. There were no significant differences in the mean age at the time of surgery, gender, body mass index, pre-operative FF and ER, and pre-operative VAS between the groups. The MC group did not have a significant improvement FF with a mean pre-operative FF of 144.4°(range: 30-170°) and post-operative FF of 150.5°(range: 90-180). The same was true for the SCR group, with a mean pre-operative FF 127.5°(range: 40-170°) and post-operative FF of 146.3°(range: 40-170). There was also no significant improvement in ER post-operatively in either group. Both the MC and SCR group had significant improvements in VAS for pain from an average of 7.3 (range: 1-10) pre-operatively to 2.5 (range: 0-10) post-operative for the MC group (p < 0.01) and from 7.3 (range: 3-10) pre-operatively to 1 (range: 0-4) post-operative for the SCR group (p < 0.01). There were no significant differences in the post-operative FF or ER, change in FF or ER, post-operative VAS, or change in VAS between the two treatment groups. The rate of conversion to arthroplasty was not significantly different between the groups at 3.6% for the MC group and 12.5% for the SCR group. Additionally, the overall reoperation rate was not significantly different between the MR and SCR groups at 10.7% and 12.5%, respectively. Conclusions: There were no significant differences between the MC and SCR treatment groups. While both MC and SCR were effective in improving VAS for pain, neither treatment consistently resulted in significant improvement in ROM. Further studies with long term outcomes are needed to determine if there are certain indications for which one treatment results in better outcomes.

Objectives: While rotator cuff tears often require repair of the supraspinatus, patients can also have a concurrent tear of the subscapularis requiring repair. Previous smaller studies have shown good clinical outcomes following the repair of the subscapularis and rotator cuff during the same procedure.1 The purpose of this study was to compare clinical outcome measures between patients who had isolated supraspinatus repairs versus those who had a supraspinatus tear with a concurrent subscapularis repair. Methods: A retrospective review of 166 patients who underwent arthroscopic supraspinatus repair with or without a concurrent subscapularis repair between 2013-2018 with a minimum of one-year follow up was performed. Patients were separated into two groups based on their treatment: 100 had an isolated supraspinatus repair (SP) and 66 had both a supraspinatus and subscapularis repair (SB). The primary outcome was revision rotator cuff repair. Secondary outcomes were objective measures such as range of motion (ROM) and strength testing, including flexion (FF), external rotation (ER), and internal rotation (IR), as well as patient-reported outcome measures (PROs) including visual analog pain scale (VAS) and subjective shoulder value (SSV). Outcomes were compared using the Mann- Whitney Test and Fisher’s Exact Test with pResults: There was no significant difference in the rate of revision surgery required following isolated supraspinatus repair versus those with a subscapularis repair. Additionally, there were no significant differences between groups for all PROs, all ROM parameters, and all strength parameters (all p > 0.05) (Table 1). Conclusions: The data from this study demonstrated that patients who require a subscapularis repair at the time of their rotator cuff repair can expect similar short term outcomes to those patients who only required repair of their supraspinatus.

Background: In anterior cruciate ligament–deficient (ACL-D) knees, injury pattern and bony morphologic features have been shown to influence both static anterior tibial subluxation relative to the femur and dynamic rotatory knee laxity. Therefore, the relationship between static anterior tibial subluxation and dynamic rotatory knee laxity was investigated. Purpose: To determine whether static tibial subluxation as measured on magnetic resonance imaging (MRI) is associated with the grade of rotatory knee laxity in ACL-D knees. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Two-hundred fifty-eight knees underwent preoperative, image-guided assessment of lateral knee compartment translation during quantitative pivot shift (QPS). Subluxations of the medial and lateral tibial plateaus were measured on preoperative MRI in a subset of primary ACL-D knees meeting criteria for high-grade (QPS > 5.2 mm) and low-grade (QPS < 2.4 mm) rotatory laxity. Tibial subluxations on MRI were compared between patients with high- and low-grade rotatory laxity through use of pairwise t test and were analyzed via univariate and multivariate logistic regression. Significance was set at P < .05. Results: On MRI, greater anterior subluxation of the lateral tibial plateau was observed in patients with high-grade compared with low-grade rotatory knee laxity (4.5 mm vs 2.3 mm; P < .05). No similar relationship was observed for the medial tibial plateau (−0.9 mm vs −0.4 mm; P > .05). Univariate logistic regression demonstrated that static subluxation of the lateral tibial plateau was associated with high-grade rotatory knee laxity (odds ratio [OR], 1.2; P < .05). An optimal cutoff of 2.95 mm of static lateral tibial subluxation was associated with high-grade rotatory knee laxity (sensitivity, 75%; specificity, 63%). Lateral meniscal injury was the first variable entered into a multivariate regression analysis and proved to be most associated with high-grade rotatory knee laxity (OR, 6.8; P < .05). When lateral meniscal injury was excluded from multivariate regression analysis, static anterior subluxation of the lateral tibial plateau alone was associated with high-grade rotatory knee laxity (OR, 1.2; P < .05). Conclusion: Data from this MRI study of two distinct rotatory knee laxity groups showed that static anterior subluxation of the lateral tibial plateau of 2.95 mm or greater was associated with high-grade rotatory knee laxity, and each millimeter increase of lateral tibial plateau subluxation was associated with a 1.2-fold odds of high-grade rotatory knee laxity. Anterior subluxation of the lateral tibial plateau on MRI was not independently associated with high-grade rotatory knee laxity in the presence of concomitant lateral meniscal injury. Static measurements made preoperatively may aid in predicting high-grade rotatory knee laxity and refining the indications for individualized knee surgery.

Atezolizumab is a monoclonal antibody that targets programmed death ligand-1. Treatments with this drug may cause immune-related adverse events by creating an exaggerated inflammatory response. The most common side effects are fatigue, rash, and gastrointestinal symptoms. Cases of central nervous system toxicity such as encephalitis and encephalopathy are uncommon. We present the case of a 53-year-old female with metastatic squamous cell carcinoma of the cervix who presented to the emergency room 13 days after receiving atezolizumab with altered mental status, headache, and meningeal signs. She was admitted to the intensive care unit. Infectious, anatomical, and neoplastic etiologies were ruled out. Auto-immune meningoencephalitis was diagnosed and treated with high-dose steroids. Within 10 days of the diagnosis, she had clinical, radiological, and laboratory improvement. Given the increasing use of novel immunotherapies and life-threatening side effects associated with them, healthcare providers in the intensive care unit should be aware of their diagnosis and management.

Objectives: High ankle sprains are a common injury that occur in up to 11% of ankle sprains. Injury to the structures of the syndesmosis, the anterior inferior tibiofibular ligament (AITFL), posterior inferior tibiofibular ligament (PITFL), and interosseous membrane (IOM), has been shown to be predictive of residual symptoms after ankle injury. When the syndesmosis is unstable, it is typically treated surgically with cortical screw fixation or suture button fixation. Studies have shown that a 1 mm lateral shift of the talus relative to the tibia significantly decreases the tibiotalar contact area by 42%. Thus, restoring the tibiotalar kinematics to those of the intact ankle with appropriate fixation is important to avoid accelerated tibiotalar arthritis. The objective of this study was to quantify tibiotalar joint motion after syndesmotic screw and suture button fixation compared to the intact ankle. Methods: Nine fresh-frozen human cadaveric specimens (mean age 60 yrs.; range 38-73 yrs.) were tested using a six degree-of-freedom robotic testing system. The subtalar joint was fused and the tibia and calcaneus were rigidly fixed to a robotic manipulator, while fibular length was maintained and fibular motion was unconstrained. Talar motion with respect to the tibia was measured using the robotic testing system. A 5 Nm external rotation moment and 5 Nm inversion moment were applied independently to the ankle at 0°, 15°, and 30° plantarflexion and 10° dorsiflexion. Outcome variables included talar medial-lateral (ML) translation, anterior-posterior (AP) translation, and internal/external rotation relative to the tibia in the following syndesmosis states: 1) intact, 2) AITFL transected, 3) AITFL, PITFL, and IOM transected, 4) 3.5 mm cannulated tricortical screw fixation, and 5) suture button fixation. An ANOVA with a post-hoc Tukey analysis was performed for statistical analysis. Statistical significance was set at p < 0.05. Results: There were significant differences in ML translation of the talus relative to the tibia between the tricortical screw fixation and the intact ankle. These significant changes were only present during states with no loads applied. Tricotical screw fixation resulted in a significant decrease in medial translation of the talus compared to the intact ankle at 30° plantarflexion and increased lateral translation at 0° flexion (p < 0.05) (Figure 1). The talus moved 1.1 mm less medially at 30° plantarflexion and 0.4 mm more laterally at 0° flexion in the tricortical screw fixation state compared to the intact ankle. The total medial translation of the talus relative to the tibia during plantarflexion decreased from 1.1 mm to only 0.4 mm. No significant difference in AP translation or external rotation of the talus existed between the tricortical screw fixation and the intact ankle. No significant differences existed in translation or rotation of the talus between the suture button fixation and intact ankle at any ankle positions. Conclusion: Suture button fixation restored tibiotalar motion in all planes, with no significant differences compared to the intact ankle. Tricortical screw fixation significantly increased lateral shift of the talus in a neutral ankle position and constrained motion during plantarflexion compared to the intact ankle, which can lead to accelerated tibiotalar arthritis. Thus, physicians should consider hardware removal after tricortical screw fixation for syndesmotic repair to avoid post-traumatic arthritis. [Figure: see text]

Objectives: In anterior cruciate ligament-deficient (ACL-D) knees, injury pattern and bony morphology have been shown to influence both static anterior tibial subluxation relative to the femur and dynamic rotatory knee laxity. Therefore, the relationship between static anterior tibial subluxation and dynamic rotatory knee laxity was investigated. The goal of this study was to determine if static tibial subluxation as measured on magnetic resonance imaging (MRI) was associated with the grade of rotatory knee laxity in ACL-D knees. Methods: Two-hundred and fifty-eight knees underwent preoperative, image-guided assessment of lateral knee compartment translation during quantitative pivot shift (QPS). Subluxations of the medial and lateral tibial plateaus were measured on preoperative MRI in a subset of primary ACL-D knees meeting criteria for high-grade (QPS > 5.2 mm) and low-grade (QPS < 2.4 mm) rotatory laxity. Tibial subluxations on MRI were compared between patients with high- and low-grade rotatory laxity using pairwise t-test, and analyzed using uni- and multivariate logistic regression. Significance was set at pResults: On MRI, greater anterior subluxation of the lateral tibial plateau was observed in patients with high-grade compared to low-grade rotatory knee laxity (4.5 mm vs. 2.3 mm; p0.05). Univariate logistic regression demonstrated that static subluxation of the lateral tibial plateau was associated with high-grade rotatory knee laxity (Odds ratio [OR] 1.2; pConclusion: Data from this MRI study of two distinct rotatory knee laxity groups showed that static anterior subluxation of the lateral tibial plateau of 2.95 mm or greater was associated with high-grade rotatory knee laxity, and each millimeter increase of lateral tibial plateau subluxation was associated with a 1.2-fold odds of high-grade rotatory knee laxity. Anterior subluxation of the lateral tibial plateau on MRI was not independently associated with high-grade rotatory knee laxity in the presence of concomitant lateral meniscus injury. Static measurements made pre-operatively may aid in predicting high-grade rotatory knee laxity and refining the indications for individualized knee surgery.

The Yersinia outer protein (Yop) M effector from the Yersinia pestis bacterium is well-known for being a critical virulence determinant; however, structural insight vis-à-vis its role in Y. pestis pathogenesis has been elusive. Here, we investigate the intact sequence of the YopM protein through our recently developed fold identification and homology modeling tools, and analyze the immune modulatory potential of its constituent domains. We identify a putative novel E3 ligase (NEL) domain towards the C-terminal tail of YopM and characterize its active site, to show that YopM could function as an autoregulated bacterial type E3 ubiquitin ligase. We further identify unreported NEL domains in several other bacteria and note remarkable similarity in sequence, structure, surface, and electrostatics for the family of NEL-containing bacterial effectors that suggests conserved function and potentially similar host targets for these proteins. Based on these observations and recent empirical evidence for degradation of the human proteins HLA-DR, thioredoxin, and NEMO/IKKγ by other members of the NEL-containing bacterial family, we discuss the potential for YopM to modulate a wide spectrum of immune signal transduction pathways. The key immune modulatory effects highlighted are suppression of MHC class II antigen presentation, dampening of nuclear factor (NF)-κB mediated inflammatory response, and intonation of mitogen-activated protein kinase (MAPK) signaling. Additionally, our analysis of the modeled YopM LRR domain reveals structural features akin to the Toll-like receptor 4 (TLR4) LRR motif. We propose that YopM LRR could be a ‘molecular mimic’ of TLR4 LRR, permitting reduced immunogenicity and potentially mitigating bacterial lipopolysaccharide surveillance of the innate immune system. Our identification and characterization of the YopM NEL domain, taken together with our analysis of the YopM LRR domain, provides plausible insight into subversion of host immunity by Y. pestis YopM and perhaps could set the stage for design of new therapeutic opportunities.

Category: Ankle Introduction/Purpose: Injury to the anterior inferior tibiofibular ligament (AITFL), posterior inferior tibiofibular ligament (PITFL), and interosseous membrane (IOM) of the syndesmosis is a predictive measure of residual symptoms after an ankle injury. Unstable syndesmotic injuries are typically treated surgically with constructs consisting of cortical screw and/or suture button fixation. Previous studies have shown contradicting findings regarding the effects of different surgical fixation methods on tibiofibular kinematics. Thus, the objective of this study was to quantify tibiofibular joint motion with different syndesmotic screw and suture button fixation constructs after disruption of the syndesmosis compared to the intact ankle during simulated weight bearing. Methods: Five fresh-frozen human cadaveric specimens were tested using a six degree-of-freedom robotic testing system. After subtalar joint fusion, the tibia and calcaneus were rigidly fixed to a robotic manipulator, while complete fibular length was maintained and fibular motion was unconstrained. A constant 200 N compressive load was applied to the ankle while an additional 5 Nm external rotation and 5 Nm inversion moment applied independently to the ankle at 0°, 15°, and 30° plantarflexion and 10° dorsiflexion. Fibular motion with respect to the tibia was tracked using an optical tracking system. Outcome variables included fibular medial-lateral (ML) translation, anterior-posterior (AP) translation, and external rotation (ER) in the following states: intact ankle, complete injury (AITFL, PITFL, and IOM transected), single tricortical screw fixation double tricortical screw fixation, hybrid fixation (single tricortical screw and single suture button), suture button fixation, and divergent suture button fixation. Repeated measures ANOVA was performed for statistical analysis. Results: The external rotation moment produced significant differences in fibular motion between the injury and fixation states compared to the intact state. A complete syndesmotic injury caused significantly increased fibular lateral translation, posterior translation, and external rotation in all ankle positions except 30° plantarflexion compared to the intact ankle. Single suture button and single screw fixation resulted in significantly higher fibular lateral translation at 10° dorsiflexion compared the intact ankle, while single suture button fixation also resulted in significantly higher external rotation at 10° dorsiflexion compared the intact ankle. Fibular posterior translation was significantly higher with hybrid, suture button, and divergent suture button fixation at 0° flexion and with single tricortical screw and double screw fixation at 10° dorsiflexion compared to the intact ankle (Figure 1). Conclusion: Complete injury to the syndesmosis results in significantly higher fibular lateral translation, external rotation, and posterior translation compared to the intact ankle. Hybrid or divergent suture button fixation would be recommended to restore tibiofibular motion without over-constraint. However, none of the fixation methods were able to restore AP translation in all ankle positions. Thus, it is important to evaluate syndesmotic stability in the sagittal plane at different ankle positions. Findings of this study suggest that physicians should evaluate fibular AP translation in a neutral position when using suture button fixation constructs and in dorsiflexion when using tricortical screw fixation constructs.

Objectives: Anterior inferior tibiofibular ligament (AITFL), posterior inferior tibiofibular ligament (PITFL), and interosseous membrane (IOM) disruption is a predictive measure of residual symptoms after an ankle injury. Unstable syndesmotic injuries are typically treated surgically with cortical screw or suture button fixation. Previous studies have shown contradicting findings regarding the effects of partial syndesmotic injuries and different surgical fixation methods on tibiofibular kinematics. Thus, the objective of this study was to quantify tibiofibular joint motion with sequential disruption of the syndesmosis and with syndesmotic screw and suture button fixation compared to the intact ankle. Methods: Nine fresh-frozen human cadaveric specimens (mean age 60 yrs.; range 38-73 yrs.) were tested using a six degree-of-freedom robotic testing system. The subtalar joint was fused and the tibia and calcaneus were rigidly fixed to a robotic manipulator, while complete fibular length was maintained and fibular motion was unconstrained. A 5 Nm external rotation moment and 5 Nm inversion moment were independently applied to the ankle at 0°, 15°, and 30° plantarflexion and 10° dorsiflexion. Fibular motion with respect to the tibia was tracked by a 3D optical tracking system. Outcome variables included fibular medial-lateral (ML) translation, anterior-posterior (AP) translation, and external rotation (ER) in the following states: 1) intact ankle, 2) AITFL transected, 3) AITFL, PITFL, and IOM transected (complete injury), 4) 3.5 mm cannulated tricortical screw fixation, 5) suture button fixation. An ANOVA with a post-hoc Tukey analysis was performed for statistical analysis (*p < 0.05). Results: All significant differences in fibular motion between ankle states occurred during the inversion moment. An isolated AITFL injury caused significant increases in fibular posterior translation at 15° and 30° plantarflexion compared to the intact ankle. A complete syndesmotic injury caused significant increases in fibular posterior translation in all 4 ankle positions and in fibular ER at 0° flexion and 15° plantarflexion compared to the intact ankle. No significant differences were detected in fibular motion between an isolated AITFL injury and complete injury at any ankle positions. No significant differences existed between the tricortical screw fixation and the intact ankle. Significantly higher fibular posterior translation was observed with the suture button compared to the intact ankle at 0° flexion, 30° and 15° plantarflexion. (Figure 1) Conclusion: An isolated AITFL injury resulted in a significant increase in fibular posterior translation relative to the tibia, comparable to that a complete injury, especially in positions of plantarflexion. Current diagnostic protocols after injury focus on the evaluation of fibular ML translation. However, these findings show that it is important to also evaluate syndesmotic stability in the sagittal plane and at different ankle positions. Restoration of native tibiofibular kinematics is essential to prevent post-traumatic arthritis. Tricortical screw fixation was able to restore tibiofibular kinematics in all planes. However, suture button fixation was not able to restore tibiofibular AP translation, which suggests that physicians should critically evaluate fibular AP translation and individualize treatment of unstable ankle injuries when reconstructing the syndesmosis with suture button fixation. Figure 1. Posterior translation of the fibula relative to the tibia (mean ± standard deviation) during a 5Nm inversion moment at 0° flexion, 15° and 30° plantarflexion, and 10° dorsiflexion in different ankle states: intact ankle, isolated AITFL injury, complete injury, tricortical screw flixation using a 3.5mm screw, suture button fixation. *p < 0.05

The increasing complexity of cancer chemotherapy makes it mandatory that pharmacists be familiar with these highly toxic agents. This column reviews various issues related to the preparation, dispensing, and administration of cancer chemotherapy, both commercially available and investigational.