GPER deficiency impedes murine myocutaneous revascularization and wound healing.

Estrogens regulate numerous physiological and pathological processes, including wide-ranging effects in wound healing. The effects of estrogens are mediated through multiple estrogen receptors (ERs), including the classical nuclear ERs (ERα and ER ß ), that typically regulate gene expression, and the 7-transmembrane G protein-coupled estrogen receptor (GPER), that predominantly mediates rapid "non-genomic" signaling. Estrogen modulates the expression of various genes involved in epidermal function and regeneration, inflammation, matrix production, and protease inhibition, all critical to wound healing. Our previous work demonstrated improved myocutaneous wound healing in female mice compared to male mice. In the current study, we employed male and female GPER knockout mice to investigate the role of this estrogen receptor in wound revascularization and tissue viability. Using a murine myocutaneous flap model of graded ischemia, we measured real-time flap perfusion via laser speckle perfusion imaging. We conducted histologic and immunohistochemical analyses to assess skin and muscle viability, microvascular density and vessel morphology. Our results demonstrate that GPER is crucial in wound healing, mediating effects that are both dependent and independent of sex. Lack of GPER expression is associated with increased skin necrosis, reduced flap perfusion and altered vessel morphology. These findings contribute to understanding GPER signaling in wound healing and suggest possible therapeutic opportunities by targeting GPER.

Endovascular repair of bilateral common iliac artery aneurysms using intraoperative positioning system.

Intraoperative positioning system (IOPS; Centerline Biomedical, Inc) is a novel technology that allows for real-time intravascular navigation of endovascular devices using an electromagnetic field. In this report, we describe the use of IOPS for effective treatment of bilateral common iliac artery aneurysms with endovascular aortoiliac repair using iliac branch endoprostheses. Our experience suggests that this technology has the potential to reduce radiation and contrast use in endovascular procedures, although its application is currently limited. To the best of our knowledge, this is the first reported case of bilateral internal iliac cannulations for iliac branch endoprosthesis placement using IOPS.

Racial and sex disparities in inpatient outcomes of patients with ruptured abdominal aortic aneurysms in the United States.

BACKGROUND: Ruptured abdominal aortic aneurysm (AAA) is a medical emergency that requires immediate surgical intervention. The aim of this analysis was to identify the sex- and race-specific disparities that exist in outcomes of patients hospitalized with this condition in the United States using the National Inpatient Sample (NIS) to identify targets for improvement and support of specific patient populations. METHODS: In this descriptive, retrospective study, we analyzed the patients admitted with a primary diagnosis of ruptured AAA between January 1, 2016, and December 31, 2020, using the NIS database. We compared demographics, comorbidities, and in-hospital outcomes in AAA patients, and compared these results between different racial groups and sexes. RESULTS: A total of 22,395 patients with ruptured AAA were included for analysis. Of these, 16,125 patients (72.0%) were male, and 6270 were female (28.0%). The majority of patients (18,655 [83.3%]) identified as Caucasian, with the remaining patients identifying as African American (1555 [6.9%]), Hispanic (1095 [4.9%]), Asian or Pacific Islander (470 [2.1%]), or Native American (80 [0.5%]). Females had a higher risk of mortality than males (OR, 1.7; 95% confidence interval [CI], 1.45-1.96; P < .001) and were less likely to undergo endovascular aortic repair (OR, 0.70; 95% CI, 0.61-0.81; P < .001) or fenestrated endovascular aortic repair (OR, 0.71; 95% CI, 0.55-0.91; P = .007). Relative to Caucasian race, patients who identified as African American had a lower risk of inpatient mortality (OR, 0.50; 95% CI, 0.37-0.68; P < .001). CONCLUSIONS: In this retrospective study of the NIS database from 2016 to 2020, females were less likely to undergo endovascular intervention and more likely to die during their initial hospitalization. African American patients had lower rates in-hospital mortality than Caucasian patients, despite a higher burden of comorbidities. Future studies are needed to elucidate the potential factors affecting racial and sex disparities in ruptured AAA outcomes, including screening practices, rupture risk stratification, and more personalized guidelines for both elective and emergent intervention.

A hybrid approach to previously excluded, expanding internal iliac artery aneurysms.

Previously excluded internal iliac artery (IIA) aneurysms can continue to expand and pose a risk of rupture. In this case series, we present three patients with previously excluded, expanding IIA aneurysms after endovascular stent coverage or open surgical ligation of the proximal IIA. We describe a hybrid approach to treat these patients safely and effectively.

A novel, microvascular evaluation method and device for early diagnosis of peripheral artery disease and chronic limb-threatening ischemia in individuals with diabetes.

Objective: A novel transdermal arterial gasotransmitter sensor (TAGS) has been tested as a diagnostic tool for lower limb microvascular disease in individuals with and without diabetes mellitus (DM). Methods: The TAGS system noninvasively measures hydrogen sulfide (H2S) emitted from the skin. Measurements were made on the forearm and lower limbs of individuals from three cohorts, including subjects with DM and chronic limb-threatening ischemia, to evaluate skin microvascular integrity. These measurements were compared with diagnosis of peripheral artery disease (PAD) using the standard approach of the toe brachial index. Other measures of vascular health were made in some subjects including fasting blood glucose, hemoglobin A1c, plasma lipids, blood pressure, estimated glomerular filtration, and body mass index. Results: The leg:arm ratio of H2S emissions correlated with risk factors for microvascular disease (ie, high-density lipoprotein levels, estimated glomerular filtration rate, systolic blood pressure, and hemoglobin A1c). The ratios were significantly lower in symptomatic DM subjects being treated for chronic limb-threatening ischemia (n = 8, 0.48 ± 0.21) compared with healthy controls (n = 5, 1.08 ± 0.30; P = .0001) and with asymptomatic DM subjects (n = 4, 0.79 ± 0.08; P = .0086). The asymptomatic DM group ratios were also significantly lower than the healthy controls (P = .0194). Using ratios of leg:arm transdermal H2S measurement (17 subjects, 34 ratios), the overall accuracy to identify limbs with severe PAD had an area under the curve of the receiver operating curve of 0.93. Conclusions: Ratios of transdermal H2S measurements are lower in legs with impaired microvascular function, and the decrease in ratio precedes clinically apparent severe microvascular disease and diabetic ulcers. The TAGS instrument is a novel, sensitive tool that may aid in the early detection and monitoring of PAD complications and efforts for limb salvage.

Long-Term Outcomes of Open and Endovascular Axillosubclavian Interventions After Traumatic Injury Reveal High Rates of Limb Dysfunction.

BACKGROUND: Arterial axillosubclavian injuries (ASIs) are currently managed with open repair (OR) and endovascular stenting (ES). The long-term prognosis of patients with these and associated brachial plexus injuries is poorly understood. We hypothesize that OR and ES for ASI have similar long-term patency rates and that brachial plexus injuries would confer high long-term morbidity. METHODS: All patients at a level-1 trauma center who underwent procedures for ASI over a 12-year period (2010 to 2022) were identified. Long-term outcomes of patency rates, types of reintervention, rates of brachial plexus injury, and functional outcomes were then investigated. RESULTS: Thirty-three patients underwent operations for ASI. OR was performed in 72.7% (n = 24) and ES in 27.3% (n = 9). ES patency was 85.7% (n = 6/7) and OR patency was 75% (n = 12/16), at a median follow-up of 20 and 5.5 months respectively. In subclavian artery injuries, ES patency was 100% (n = 4/4) and OR patency was 50% (n = 4/8) at a median follow-up of 24 and 12 months respectively. Long-term patency rates were similar between OR and ES (P = 1.0). Brachial plexus injuries occurred in 42.9% (n = 12/28) of patients. Ninety percent (n = 9/10) of patients with brachial plexus injuries who were followed postdischarge had persistent motor deficits at median follow-up of 12 months, occurring at significantly higher rates in patients with brachial plexus injuries (90%) compared to those without brachial plexus injuries (14.3%) (P = 0.0005). CONCLUSIONS: Multiyear follow-up demonstrates similar OR and ES patency rates for ASI. Subclavian ES patency was excellent (100%) and prosthetic subclavian bypass patency was poor (25%). brachial plexus injuries were common (42.9%) and devastating, with a significant portion of patients having persistent limb motor deficits (45.8%) on long-term follow-up. Algorithms to optimize brachial plexus injuries management for patients with ASI are high-yield, and likely to influence long-term outcomes more than the technique of initial revascularization.

Clinical Interpretability of Quadriceps Strength and Gait Speed Performance in Total Knee Arthroplasty: A Longitudinal Study.

OBJECTIVE: After a total knee arthroplasty, physical assessments of quadriceps strength and gait speed performance are often undertaken during rehabilitation. Our study aimed to improve their clinical interpretability by examining trajectory curves across levels of self-reported walking and stair climbing function. DESIGN: A sample of 2624 patients with primary total knee arthroplasty participated in this retrospective longitudinal study. Monthly, for 4 mos after surgery, quadriceps strength and gait speed were quantified. At the month-6 time point, self-reported walking and stair climbing function was measured. RESULTS: All physical measures improved nonlinearly over time. In mixed-effects models, greater quadriceps strength and gait speed over time were associated with higher month-6 self-reported walking and stair climbing function ( P < 0.001). Steeper gains in quadriceps strength and gait speed were associated with higher levels of walking and stair-climbing function (interaction P < 0.001). Among female patients who had great difficulty with stair ascent and ambulation, quadriceps strength trajectory curves plateaued after 8 wks after total knee arthroplasty. CONCLUSIONS: By stratifying trajectory curves across clinically interpretable functional levels, our findings potentially provide patients and clinicians a means to better interpret the continuous-scaled quadriceps strength and gait speed values. This information may be valuable when engaging patients in shared decision making and expectation setting. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Understand how self-reported walking and stair climbing abilities improved from baseline before total knee arthroplasty (total knee arthroplasty) to 6 mos postoperatively; (2) Describe the time course of the 2 performance-based measures of quadriceps strength and walking speed after a total knee arthroplasty; and (3) Relate the trajectories of post-total knee arthroplasty quadriceps strength and walking speed measurements across distinct levels of self-reported walking and stair climbing function. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Vascular Surgery Role in Vascular Trauma: 11-Year Analysis of Peripheral Vascular Trauma Management at a Level-1 Trauma Center.

BACKGROUND: Vascular surgeons are increasingly relied upon in the management of complex peripheral vascular trauma. The degree however that vascular surgery (VS) is involved in vascular trauma care is not well established. We hypothesize that VS consultation is required in a high portion of complex lower extremity vascular trauma. METHODS: A single-center retrospective review of all consecutive patients who sustained traumatic arterial injury of the lower extremity requiring open operative repair at a level-1 trauma center (from February 2009 to May 2020) was performed. Patients who underwent surgical repair were stratified by the service that performed the operation (VS versus trauma surgery [TS]). Secondary outcomes assessed included location of arterial injury, type of repair, and clinical outcomes. RESULTS: A total of 111 patients underwent operative repair of lower extremity arterial injury (mean age 34.5 ± 15.5 years, 89% male). The most common vessels requiring intervention were the superficial femoral artery (n = 42, 38%), popliteal artery (n = 35, 31.5%), and tibial vessels (n = 19, 17.1%). The most common intervention required in patients was an autologous bypass (n = 85, 76.5%), followed by ligation (n = 9, 8.1%) and primary repair (n = 6, 5.4%). Most interventions overall required VS involvement (n = 95, 86%). VS performed a higher proportion of autologous graft procedures compared to TS (n = 79, 92.9% vs. n = 6, 7.1%). VS case load overall was likewise predominantly autologous grafts (n = 79/95, 83.2%). TS operated on a higher proportion of injuries to the tibial vessels (44% vs. 13%, P = 0.01), whereas VS intervened more frequently on popliteal injuries (36% vs. 6%, P = 0.02). With regard to the method of arterial repair, TS was more likely to perform ligation (38% vs. 3 %, P < 0.001) or primary repair (13% vs. 3%, P = 0.04) compared to VS. However, VS was more likely to perform repair with autologous graft (83% vs. 38%, P < 0.001). There were no significant differences in rates of mortality, limb loss, transfusions requirement, fasciotomy, deep venous thrombosis, hematoma formation, or length of stay between groups. Although, surgical site infections were more common in the TS group (38% vs. 15%, P = 0.04). CONCLUSIONS: Vascular surgeons play a large role in managing complex lower extremity vascular trauma. In particular, VS remains integral for the management of more difficult injuries (e.g., popliteal injuries) and is more likely to provide more complex repairs (e.g., autologous grafts).

Assessment of association between lower ureteric excision technique and oncological outcomes for upper urinary tract urothelial carcinoma: retrospective analysis from the Scottish Renal Cancer Consortium.

PURPOSE: Nephroureterectomy(NU) remains the gold-standard surgical option for the management of upper urinary tract urothelial carcinoma(UTUC). Controversy exists regarding the optimal excision technique of the lower ureter. We sought to compare post-UTUC bladder tumour recurrence across the Scottish Renal Cancer Consortium(SRCC). METHODS: Patients who underwent NU for UTUC across the SRCC 2012-2019 were identified. The impact of lower-end surgical technique along with T-stage, N-stage, tumour location and focality, positive surgical margin, pre-NU ureteroscopy, upper-end technique and adjuvant mitomycin C administration were assessed by Kaplan-Meier and Cox-regression. The primary outcome was intra-vesical recurrence-free survival (B-RFS). RESULTS: In 402 patients, the median follow-up was 29 months. The lower ureter was managed by open transvesical excision in 90 individuals, transurethral and laparoscopic dissection in 76, laparoscopic or open extra-vesical excision in 31 and 42 respectively, and transurethral dissection and pluck in 163. 114(28.4%) patients had a bladder recurrence during follow-up. There was no difference in B-RFS between lower-end techniques by Kaplan-Meier (p = 0.94). When all factors were taken into account by adjusted Cox-regression, preceding ureteroscopy (HR 2.65, p = 0.001), lower ureteric tumour location (HR 2.16, p = 0.02), previous bladder cancer (HR 1.75, p = 0.01) and male gender (HR 1.61, p = 0.03) were associated with B-RFS. CONCLUSION: These data suggest in appropriately selected patients, lower ureteric management technique does not affect B-RFS. Along with lower ureteric tumour location, male gender and previous bladder cancer, preceding ureteroscopy was associated with a higher recurrence rate following NU, and the indication for this should be carefully considered.

Sit-to-Stand Weight-Bearing Symmetry Performance in Total Knee Arthroplasty: Recovery Curves, Correlates, and Predictive Validity With Gait Speed.

OBJECTIVE: After total knee arthroplasty, the ability to weight bear symmetrically during the sit-to-stand task provides important information regarding altered movement patterns. Despite this, comprehensive recovery curves and validity data for sit-to-stand weight-bearing symmetry are lacking in the total knee arthroplasty population. Our study aimed to (1) develop recovery curves with reference ranges, (2) identify the correlates of standard and constrained sit-to-stand weight-bearing symmetry, and (3) evaluate their predictive validity with gait speed. DESIGN: We performed a retrospective longitudinal study of 706 patients with primary unilateral total knee arthroplasty. Monthly, for 4 mos after surgery, sit-to-stand weight-bearing symmetry, knee pain, knee range of motion, quadriceps strength, and gait speed were quantified. RESULTS: Standard and constrained sit-to-stand weight-bearing symmetry measures improved nonlinearly over time. Standard sit-to-stand weight-bearing symmetry was most strongly associated with bilateral quadriceps strength, whereas constrained sit-to-stand weight-bearing symmetry was most strongly associated with ipsilateral quadriceps strength. Knee range of motion and contralateral knee pain were additional correlates. Both standard sit-to-stand and constrained sit-to-stand weight-bearing symmetry were independently and nonlinearly associated with gait speed in multivariable models. CONCLUSIONS: Our study provided recovery curves and validity data to support routine clinical measurement of sit-to-stand weight-bearing symmetry in total knee arthroplasty. Our results also indicate that constrained sit-to-stand may promote greater use of the operated limb than standard sit-to-stand.

The effect of preoperative embolization on surgical outcomes for carotid body tumor resection.

OBJECTIVE: Compare the effects of preoperative embolization for carotid body tumor resection on surgical outcomes to carotid body tumor resections without preoperative embolization. METHODS: Single-center retrospective review of all consecutive patients who underwent carotid body tumor resection from 2001 to 2019. Surgical outcomes with emphasis on operative time (estimated blood loss and cranial nerve injury) of patients undergoing carotid body tumor resection following preoperative embolization were compared to those undergoing resection alone using unpaired Student's t-test and Fisher's exact test. RESULTS: Forty-six patients (15% male, mean age 50 ± 15 years) underwent resection of 49 carotid body tumors. Patients undergoing preoperative embolization (n = 20 (40%)) had larger mean tumor size (4.0 ± 0.7 vs 3.2 ± 1 cm, p = 0.006), increased Shamblin II/III tumor classification (18 (90%) vs 22 (76%), p < 0.001), operative time (337 ± 195 vs 199 ± 100 min, p = 0.004), and cranial nerve injuries overall (8 (40%) vs 2 (10%), p = 0.01) compared to patients undergoing resection without preoperative embolization (n = 29 (60%)). In subgroup analysis of Shamblin II/III classification tumors (n = 40), preoperative embolization (n = 18) was associated with increased tumor size (4.1 ± 0.6 vs 3.5 ± 0.9 cm, p = 0.01), operative time (351 ± 191 vs 244 ± 105 min, p = 0.02), and cranial nerve injury overall (8 (44%) vs 2 (9%), p = 0.03) compared to resections alone (n = 19). In further subgroup analysis of large (⩾ 3 cm) tumors (n = 37), preoperative embolization (n = 18) was associated with increased operative time (350 ± 191 vs 198 ± 99 min, p = 0.006) and cranial nerve injury overall (8 (44%) vs 2 (11%), p = 0.03) compared to resections alone (n = 19). There were no significant differences in estimated blood loss, transfusion requirement, or hematoma formation between any of the embolization and non-embolization subgroups. CONCLUSION: After controlling for tumor Shamblin classification and size, carotid body tumor resections following preoperative embolization were associated with increased operative time and inferior surgical outcomes compared to those tumors undergoing resection alone. Nonetheless, such results remain susceptible to the confounding effects of individual tumor characteristics often used in the decision to perform preoperative embolization, underscoring the need for prospective studies evaluating the utility of preoperative embolization for carotid body tumors.

Knee performance and self-efficacy trajectory curves after ACL reconstruction: A longitudinal study.

OBJECTIVES: To examine knee flexion range-of-motion, quadriceps strength, and knee self-efficacy trajectory curves over 6 months after anterior cruciate ligament reconstruction (ACLR), stratified by patients' Month-6 sports activity level. DESIGN: Prospective longitudinal study. SETTING: Hospital outpatient physiotherapy department. PARTICIPANTS: 595 individuals after unilateral ACLR (mean age, 27 years). MAIN OUTCOME MEASURES: At 2-, 3-, and 6-months post-surgery, knee flexion range-of-motion, quadriceps strength, and self-efficacy were quantified. Flexion range-of-motion was additionally measured at 2- and 4-weeks post-surgery. Sports activity levels were assessed using the Tegner Activity Score at 6-months post ACLR. RESULTS: The various measures improved nonlinearly over time, with substantial improvements observed in the first 2-4 months post-surgery. In multivariable generalized least squares models, greater knee flexion range-of-motion, quadriceps strength, and self-efficacy over time were significantly associated with higher Month-6 Tegner levels (all P values < 0.01). Additionally, receiving a bone-patellar-tendon-bone graft or meniscal repair was associated with lower quadriceps strength trajectories (P-values<0.001) while female sex was associated with lower knee self-efficacy trajectories (P = 0.02). CONCLUSIONS: Greater knee flexion range-of-motion, quadriceps strength, and self-efficacy were associated with higher Month-6 Tegner levels. The derived trajectory curves may be useful for effective management decision making and adequate results interpretation during the rehabilitation process.

Initial Outcomes Following Introduction of Percutaneous Arteriovenous Fistula Program with Comparison to Historical Surgically Created Fistulas.

BACKGROUND: Recently, there has been an abundance of encouraging data regarding the creation of percutaneous arteriovenous fistulas. Despite promising data regarding their clinical maturation, a paucity of data exists which provides direct comparison between percutaneously created AVFs (pAVF) and open surgically created AVFs (sAVF). This study has 2 primary objectives: First, to compare clinical outcomes of pAVFs to sAVFs, with emphasis on clinical maturation and frequency of postoperative interventions to facilitate maturation. Second, to contribute toward the evidence-based incorporation of the pAVF procedure into the hemodialysis access algorithm. METHODS: A single-center retrospective review was performed on all consecutive patients undergoing surgically created brachiocephalic arteriovenous fistula (BC-AVF, sAVF group) from January 1, 2018 to December 31, 2018 and Ellipsys-created percutaneous arteriovenous fistula (pAVF group) from January 1, 2019 to December 31, 2019. Comparative analysis between groups was performed. RESULTS: A total of 24 patients underwent Ellipsys-created pAVF with mean age of 56.7 ± 22.6 years (12 males [50%], 12 females [50%]) and 62 patients underwent surgically created BC-AVF with mean age of 62.5 ± 13.2 years (32 males [52%], 30 females [48%]). Both the pAVF and sAVF groups had comparable mean operating times (60 ± 40 vs. 56 ± 25 min, P = 0.67) and frequency of procedural technical success (23 [96%] vs. 62 [100%], P = 0.28), respectively. The pAVF group had a lower clinical maturation rate (12 [52%] vs. 54 [87%], P = 0.003) and a higher primary failure rate (9 [39%] vs. 6 [10%], P = 0.003) when compared to the sAVF group. The pAVF group had an increased overall rate of undergoing a postoperative intervention (18 [78%] vs. 13 [21%], P< 0.001), as well as an increased number of total postoperative interventions (1.1 ± 0.9 vs. 0.3 ± 0.6 interventions, P< 0.001) compared to the sAVF group. Percutaneous transluminal angioplasty of the juxta anastomotic segment was the most prevalent postoperative intervention performed in the pAVF group and occurred at a significantly increased frequency when compared to the sAVF group rate (13 [57%] vs. 5 [8%], P< 0.001). CONCLUSIONS: In our single-center retrospective review, patients undergoing Ellipsys-created pAVF in the first year following introduction of percutaneous endovascular had inferior rates of clinical maturation and underwent more postoperative interventions when compared to historical patients undergoing surgically created BC-AVF. Outcome discrepancies compared to previously reported Ellipsys data demonstrate a need for further studies examining the practical translatability of the pAVF.

Developing a coordinate-based strategy to support cognitive targeted prostate biopsies and correlative spatial-histopathological outcome analysis.

Lack of investment for magnetic resonance (MR) fusion systems is an obstacle to deliver targeted prostate biopsies within the prostate cancer diagnostic pathway. We developed a coordinate-based method to support cognitive targeted prostate biopsies and then performed an audit on cancer detection and the location of lesions. In each patient, the prostate is considered as two separate hemiprostates, and each hemiprostate is divided into 4 × 4 × 4 units. Each unit is therefore defined by a three-dimensional coordinate. We prospectively applied our coordinates approach to target 106 prostatic lesions in 93 men. Among 45 (of 106; 42.5%) lesions positive for cancer, 27 lesions (60.0%) harbored clinically significant disease. PSA density was significantly higher in patients with proven cancer (median: 0.264 ng ml-2) when compared to the noncancer group (median: 0.145 ng ml-2; P = 0.003, Wilcoxon rank-sum test). Lesions with Prostate Imaging-Reporting and Data System (PIRADS) score of 5 were found to have a cancer incidence of 65.2%, while PIRADS 4 and 3 lesions have a lower risk of cancer detection, as expected, at 37.3% and 31.3%, respectively. The probability of a lesion being cancerous in our series significantly decreases as we go from the "apex-to-base" dimension (odds ratio [OR]: 2.62, 95% confidence interval [CI]: 1.55-4.44, P = 0.00034). Our analysis also indicates that the probability of cancer decreases as the prostate volume increases (OR: 1.03, 95% CI: 1.01-1.05, P = 0.00327). Based on this feasibility study, the use of coordinates to guide cognitive targeted prostate biopsies warrants future validation study in additional centers.

Sex differences in murine myocutaneous flap revascularization.

Sex differences in susceptibility to ischemia/reperfusion injury have been documented in humans. Premenopausal women have a lower risk of ischemic heart disease than age-matched men, whereas after menopause, the risk is similar or even higher in women. However, little is known about the effects of sex on myocutaneous ischemia/reperfusion. To explore sex differences in wound revascularization, we utilized a murine myocutaneous flap model of graded ischemia. A cranial-based, peninsular-shaped, myocutaneous flap was surgically created on the dorsum of male and female mice. Physiological, pathological, immunohistochemical, and molecular parameters were analyzed. Flaps created on female mice were re-attached to the recipient site resulting in nearly complete viability at post-operative day 10. In contrast, distal full-thickness myocutaneous necrosis was evident at 10 days post-surgery in male mice. Over the 10 day study interval, laser speckle imaging documented functional revascularization in all flap regions in female mice, but minimal distal flap reperfusion in male mice. Day 10 immunostained histologic sections confirmed significant increases in distal flap vessel count and vascular surface area in female compared to male mice. RT-PCR demonstrated significant differences in growth factor and metabolic gene expression between female and male mice at day 10. In conclusion, in a graded-ischemia wound healing model, flap revascularization was more effective in female mice. The recognition and identification of sex-specific wound healing differences may lead to a better understanding of the underlying mechanisms of myocutaneous revascularization and drive novel discovery to improve soft tissue wound healing following tissue transfer for traumatic injury and cancer resection.

Pneumothorax, pneumomediastinum, and dysphonia complicating awake transcarotid artery revascularization.

A 59-year-old woman presented with advanced, symptomatic carotid artery stenosis in the setting of severe medical comorbidities including coronary artery disease, congestive heart failure with recent admission for exacerbation, and diabetes mellitus. She underwent awake transcarotid artery revascularization because of her medically high-risk status. Postoperatively, she was noted to have developed pneumothorax, pneumomediastinum, and dysphonia, thought to be secondary to entrained air during the course of low neck dissection for carotid artery exposure in the setting of partial airway obstruction and high negative intrathoracic pressures during the procedure. After conservative treatment, she ultimately enjoyed complete clinical resolution. This case demonstrates an unusual complication of awake transcarotid artery revascularization.

Machine learning methods are comparable to logistic regression techniques in predicting severe walking limitation following total knee arthroplasty.

PURPOSE: Machine-learning methods are flexible prediction algorithms with potential advantages over conventional regression. This study aimed to use machine learning methods to predict post-total knee arthroplasty (TKA) walking limitation, and to compare their performance with that of logistic regression. METHODS: From the department's clinical registry, a cohort of 4026 patients who underwent elective, primary TKA between July 2013 and July 2017 was identified. Candidate predictors included demographics and preoperative clinical, psychosocial, and outcome measures. The primary outcome was severe walking limitation at 6 months post-TKA, defined as a maximum walk time ≤ 15 min. Eight common regression (logistic, penalized logistic, and ordinal logistic with natural splines) and ensemble machine learning (random forest, extreme gradient boosting, and SuperLearner) methods were implemented to predict the probability of severe walking limitation. Models were compared on discrimination and calibration metrics. RESULTS: At 6 months post-TKA, 13% of patients had severe walking limitation. Machine learning and logistic regression models performed moderately [mean area under the ROC curves (AUC) 0.73-0.75]. Overall, the ordinal logistic regression model performed best while the SuperLearner performed best among machine learning methods, with negligible differences between them (Brier score difference, < 0.001; 95% CI [- 0.0025, 0.002]). CONCLUSIONS: When predicting post-TKA physical function, several machine learning methods did not outperform logistic regression-in particular, ordinal logistic regression that does not assume linearity in its predictors. LEVEL OF EVIDENCE: Prognostic level II.

Physical Activity Levels Are Low in Inoperable Lung Cancer: Exploratory Analyses from a Randomised Controlled Trial.

BACKGROUND: In inoperable lung cancer, evidence is limited regarding physical activity (PA) and associations with other outcomes. AIMS: in the usual care (UC) group of an RCT to (1) explore whether baseline PA was associated with improved follow-up outcomes, (2) identify baseline variables associated with higher follow-up PA and in all RCT participants, to (3) analyse patterns of objectively measured PA, and (4) report on characteristics of those who were able to maintain or increase PA levels. METHODS: exploratory analyses of an assessor-blinded RCT. Outcomes, assessed at baseline, nine weeks and six months, included PA (seven-days of accelerometry), six-minute walk distance (6MWD), muscle strength, symptoms, mood and health-related quality of life (HRQoL). RESULTS: 92 participants were randomised, 80 completed baseline accelerometry (39 intervention group (IG), 41 UC), characteristics: mean (SD) age 63.0 (12.3) years, 56% male, 51% stage IV disease. Baseline PA: median (IQR) steps/day 2859.6 (2034.0-3849.2) IG versus 3195.2 (2161.2-4839.0) UC. Associations between baseline PA and six-month outcomes were significant for HRQoL and 6MWD. PA at six months was significantly associated with baseline age, 6MWD and quadriceps strength. Between-group change score (steps/day) mean differences (95% CI) at nine weeks (174.5 (-1504.7 to 1853.7), p = 0.84) and six months (574.0 (-1162.3 to 2310.3), p = 0.52). CONCLUSIONS: further research is required to determine patient subgroups deriving the greatest benefits from PA interventions.

Multidisciplinary home-based rehabilitation in inoperable lung cancer: a randomised controlled trial.

BACKGROUND: Lung cancer is associated with poor health-related quality of life (HRQoL) and high symptom burden. This trial aimed to assess the efficacy of home-based rehabilitation versus usual care in inoperable lung cancer. METHODS: A parallel-group, assessor-blinded, allocation-concealed, randomised controlled trial. Eligible participants were allocated (1:1) to usual care (UC) plus 8 weeks of aerobic and resistance exercise with behaviour change strategies and symptom support (intervention group (IG)) or UC alone. Assessments occurred at baseline, 9 weeks and 6 months. The primary outcome, change in between-group 6 min walk distance (6MWD), was analysed using intention-to-treat (ITT). Subsequent analyses involved modified ITT (mITT) and included participants with at least one follow-up outcome measure. Secondary outcomes included HRQoL and symptoms. RESULTS: Ninety-two participants were recruited. Characteristics of participants (UC=47, IG=45): mean (SD) age 64 (12) years; men 55%; disease stage n (%) III=35 (38) and IV=48 (52); radical treatment 46%. There were no significant between-group differences for the 6MWD (n=92) at 9 weeks (p=0.308) or 6 months (p=0.979). The mITT analyses of 6MWD between-group differences were again non-significant (mean difference (95% CI): 9 weeks: -25.4 m (-64.0 to 13.3), p=0.198 and 6 months: 41.3 m (-26.7 to 109.4), p=0.232). Significant 6-month differences, favouring the IG, were found for HRQoL (Functional Assessment of Cancer Therapy-Lung: 13.0 (3.9 to 22.1), p=0.005) and symptom severity (MD Anderson Symptom Inventory-Lung Cancer: -2.2 (-3.6 to -0.9), p=0.001). CONCLUSIONS: Home-based rehabilitation did not improve functional exercise capacity but there were improvements in patient-reported exploratory secondary outcomes measures observed at 6 months. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12614001268639).

Predicting individual knee range of motion, knee pain, and walking limitation outcomes following total knee arthroplasty.

Background and purpose - Up to 20% of patients are dissatisfied after total knee arthroplasty (TKA), mainly because of pain and restricted physical function. We developed a prediction model for 6-month knee range of motion, knee pain, and walking limitations in patients undergoing TKA surgery. Patients and methods - We performed a prospective cohort study of 4,026 patients who underwent elective, primary TKA between July 2013 and July 2017. Candidate predictors included demographic, clinical, psychosocial, and preoperative outcome measures. The outcomes of interest were (i) knee extension and flexion range of motion, (ii) knee pain rated on a 5-point ordinal scale, and (iii) self-reported maximum walk time at 6 months post TKA. For each outcome, we fitted a multivariable proportional odds regression model with bootstrap internal validation. Results - At 6 months post TKA, around 5% to 20% of patients had a flexion contracture ³ 10°, range of motion < 90°, moderate to severe knee pain, or a maximum walk time £â€¯15 minutes. The model c-indices (the probabilities to correctly discriminate between 2 patients with different levels of follow-up TKA outcomes) when evaluating these patients were 0.71, 0.79, 0.65, and 0.76, respectively. Each postoperative outcome was strongly influenced by the same outcome measure obtained preoperatively (all p-values < 0.001). Additional statistically significant predictors were age, sex, race, education level, diabetes mellitus, preoperative use of gait aids, contralateral knee pain, and psychological distress (all p-values < 0.001). Interpretation - We have developed models to predict, for individual patients, their likely post-TKA levels of knee extension and flexion range of motion, knee pain, and walking limitations. After external validation, they can potentially be used preoperatively to identify at-risk patients and to help patients set more realistic expectations about surgical outcomes.