A Pilot Study of Hypofractionated Radiosurgery for Trigeminal Neuralgia.

The primary late toxicity of radiosurgery treatment for trigeminal neuralgia (TN) is facial numbness due to trigeminal nerve dysfunction. Although most patients prefer loss of facial sensation to TN, severe loss of facial sensation can be debilitating. In order to try to obtain high pain control rates while minimizing the risk of late facial numbness, we elected to treat patients on the distal trigeminal nerve with a three-fraction regimen over consecutive days instead of one fraction. Our goal was to relieve the pain while also allowing the trigeminal nerve time to repair radiation damage between treatments in an attempt to minimize the risk of permanent facial numbness. Patients in a pilot study, approved by an Institutional Review Board (IRB), received a treatment regimen of 99 Gy, administered in three consecutive daily fractions of 33 Gy each, with the dosage targeted to the 80% line. This dose was selected to approximate a biologically equivalent dose of 80 Gy maximal dose to the trigeminal nerve. Forty-eight patients were treated with CyberKnife Radiosurgery (CKRS; 99 Gy/3 fractions) for TN from 2016 to 2022, with at least one year of follow-up. The Barrow Neurological Institute (BNI) scale was used to assess facial pain, and Kaplan-Meier analysis was used to assess adequate pain relief. Thirty-eight (84%) patients experienced adequate pain relief, defined as a BNI score of I-IIIb, after a median of 1.5 months following CKRS. Treatment failure (BNI=IV-V) occurred in 12 (25%) patients after a median of 6 months following initial pain relief. The actuarial probability of pain relief at 6, 12, and 24 months post-CKRS were 87.4%, 83.7%, and 83.7%, respectively. Facial numbness was experienced in 24 (50%) cases after a median of 10 months following CKRS. Typical facial pain (p=0.034) and vascular compression (p=0.039) were the only predictors of better treatment outcomes using univariate Cox survival analysis, and vascular compression (p= 0.037) was the only predictor in multivariate Cox survival analysis. Hypofractionated treatment to the distal trigeminal nerve segment does not appear to offer an advantage in treating TN, due to similar rates of pain relief but with an unacceptably high rate of late facial numbness.

Chronic aryl hydrocarbon receptor activity impairs muscle mitochondrial function with tobacco smoking.

BACKGROUND: Accumulating evidence has demonstrated that chronic tobacco smoking directly contributes to skeletal muscle dysfunction independent of its pathological impact to the cardiorespiratory systems. The mechanisms underlying tobacco smoke toxicity in skeletal muscle are not fully resolved. In this study, the role of the aryl hydrocarbon receptor (AHR), a transcription factor known to be activated with tobacco smoke, was investigated. METHODS: AHR related gene (mRNA) expression was quantified in skeletal muscle from adult controls and patients with chronic obstructive pulmonary disease (COPD), as well as mice with and without cigarette smoke exposure. Utilizing both skeletal muscle-specific AHR knockout mice exposed to chronic repeated (5 days per week for 16 weeks) cigarette smoke and skeletal muscle-specific expression of a constitutively active mutant AHR in healthy mice, a battery of assessments interrogating muscle size, contractile function, mitochondrial energetics, and RNA sequencing were employed. RESULTS: Skeletal muscle from COPD patients (N = 79, age = 67.0 ± 8.4 years) had higher levels of AHR (P = 0.0451) and CYP1B1 (P < 0.0001) compared to healthy adult controls (N = 16, age = 66.5 ± 6.5 years). Mice exposed to cigarette smoke displayed higher expression of Ahr (P = 0.008), Cyp1b1 (P < 0.0001), and Cyp1a1 (P < 0.0001) in skeletal muscle compared to air controls. Cigarette smoke exposure was found to impair skeletal muscle mitochondrial oxidative phosphorylation by ~50% in littermate controls (Treatment effect, P < 0.001), which was attenuated by deletion of the AHR in muscle in male (P = 0.001), but not female, mice (P = 0.37), indicating there are sex-dependent pathological effects of smoking-induced AHR activation in skeletal muscle. Viral mediated expression of a constitutively active mutant AHR in the muscle of healthy mice recapitulated the effects of cigarette smoking by decreasing muscle mitochondrial oxidative phosphorylation by ~40% (P = 0.003). CONCLUSIONS: These findings provide evidence linking chronic AHR activation secondary to cigarette smoke exposure to skeletal muscle bioenergetic deficits in male, but not female, mice. AHR activation is a likely contributor to the decline in muscle oxidative capacity observed in smokers and AHR antagonism may provide a therapeutic avenue aimed to improve muscle function in COPD.

Efficacy of Dose-Escalated Hypofractionated Radiosurgery for Arteriovenous Malformations.

There is considerable controversy about the management of arteriovenous malformations (AVMs) that are high risk for surgical resection. Stereotactic radiosurgery (SRS) has a reported success rate of less than 50% with unacceptably high rates of radiation necrosis with larger AVM volumes. Neither volume staging nor hypo-fractionated SRS have conclusively been demonstrated to improve results. We hypothesized that the failure of previous hypo-fractionation SRS trials was due to an insufficient biologically effective dose (BED) of radiation. We initiated a pilot study of treating AVM patients with a total dose divided into three or five fractions designed to deliver the equivalent BED of 20 Gy in a single fraction (α/ß =3). We performed a retrospective analysis of 37 AVM patients who had a minimum of two years of follow-up or underwent obliteration. Patients were treated with 30 Gy/3 fractions, 33 Gy/3 fractions, or 40 Gy/5 fractions using a CyberKnife device (Accuracy Incorporated, Madison, Wisconsin, United States). The primary endpoint was complete AVM obliteration, determined by MRA imaging. Most obliterations were confirmed with diagnostic cerebral angiography. Secondary endpoints were post-radiosurgery hemorrhage and radiation-related necrosis. Kaplan-Meier analysis was used to determine obliteration rates. From 2013 to 2021, 37 patients fitting inclusion criteria were identified (62% male, average age at treatment = 48.88 years). Fifteen (41%) patients had prior treatment (surgery, radiosurgery, embolization) for their AVM, 32 (86%) had AVMs in eloquent locations, 17 (46%) had high-risk features, and 14 (38%) experienced AVM rupture prior to treatment. The average modified radiosurgery-based AVM score (mRBAS) was 1.81 (standard deviation (SD)= 0.52), and the mean AVM volume was 6.77 ccs (SD = 6.09). Complete AVM obliteration was achieved in 100% of patients after an average of 26.13 (SD = 14.62) months. The Kaplan-Meier analysis showed AVM obliteration rates at one, two, and three years to be 16.2%, 46.9%, and 81.1%, respectively. Post-operative AVM rupture or hemorrhage occurred in one (2.7%) patient, after nine months. Radiation necrosis occurred in four (11%) patients after an average period of 17.3 (SD =14.7) months. The SRS dose used in this study is the highest BED of any AVM hypofractionation trial in the published literature. This study suggests that dose-escalated hypofractionated radiosurgery can be a successful strategy for AVMs with acceptable long-term complication rates. Further investigation of this treatment regimen should be performed to assess its efficacy.

The Effect of Postoperative Naloxone in Certain Otolaryngologic Surgeries.

OBJECTIVE: To evaluate the association of postoperative naloxone with the development of new substance use disorder (SUD), overdose, and death within 6 months of otolaryngologic surgery. STUDY DESIGN: Retrospective cohort database study on TriNetX. METHODS: Adult patients who underwent tonsil surgery (noncancerous), thyroid/parathyroid, septorhinoplasty, otology/neurotology, sinus/anterior skull base, and head and neck cancer surgeries between January 2003 and April 2023. Patients were excluded if they had an instance of SUD or overdose recorded in their charts prior to surgery, or had undergone another surgery within that 6-month time frame. We hypothesized that patients prescribed naloxone postoperatively would have decreased odds for experiencing new SUD, overdose, and/or death within 6 months of surgery compared to patients who did not receive naloxone. P < .01 was considered statistically significant. RESULTS: There were 2,305,655 patients in this study. The average age was 36.7 ± 19.5 years old, with 46% female patients. Before matching, cohorts showed equivocal odds for developing new SUD, increased odds for overdose, and mixed odds for dying. After matching for demographic variables and comorbidities such as other substance use, opioid use for other pathologies, and psychiatric conditions, these effects diminished (P > .01). CONCLUSION: Our results suggest that postoperative naloxone may not significantly affect development of new SUD and incident overdose and death in certain otolaryngologic surgeries after controlling for prior SUD and psychiatric conditions. Clinicians should be aware of these comorbidities when considering their postoperative pain management protocol, which may or may not include naloxone.

Targeting F-actin stress fibers to suppress the dedifferentiated phenotype in chondrocytes.

Actin is a central mediator of the chondrocyte phenotype. Monolayer expansion of articular chondrocytes on tissue culture polystyrene, for cell-based repair therapies, leads to chondrocyte dedifferentiation. During dedifferentiation, chondrocytes spread and filamentous (F-)actin reorganizes from a cortical to a stress fiber arrangement causing a reduction in cartilage matrix expression and an increase in fibroblastic matrix and contractile molecule expression. While the downstream mechanisms regulating chondrocyte molecular expression by alterations in F-actin organization have become elucidated, the critical upstream regulators of F-actin networks in chondrocytes are not completely known. Tropomyosin (TPM) and the RhoGTPases are known regulators of F-actin networks. The purpose of this study is to elucidate the regulation of passaged chondrocyte F-actin stress fiber networks and cell phenotype by the specific TPM, TPM3.1, and the RhoGTPase, CDC42. Our results demonstrated that TPM3.1 associates with cortical F-actin and stress fiber F-actin in primary and passaged chondrocytes, respectively. In passaged cells, we found that TPM3.1 inhibition causes F-actin reorganization from stress fibers back to cortical F-actin and also causes an increase in G/F-actin. CDC42 inhibition also causes formation of cortical F-actin. However, CDC42 inhibition, but not TPM3.1 inhibition, leads to the re-association of TPM3.1 with cortical F-actin. Both TPM3.1 and CDC42 inhibition reduces nuclear localization of myocardin related transcription factor, which is known to suppress dedifferentiated molecule expression. We confirmed that TPM3.1 or CDC42 inhibition partially redifferentiates passaged cells by reducing fibroblast matrix and contractile expression, and increasing chondrogenic SOX9 expression. A further understanding on the regulation of F-actin in passaged cells may lead into new insights to stimulate cartilage matrix expression in cells for regenerative therapies.

Penthrox® (Methoxyflurane) as an Analgesic for Removal of Circular External Fixators and Minor Procedures during the COVID-19 Pandemic.

Introduction: Methoxyflurane has excellent analgesic properties and is approved for use in the United Kingdom and Ireland since 2015. It is currently used in emergency departments for analgesia during fracture reductions. During the COVID-19 pandemic, with theatre access severely restricted, Penthrox® had the potential to provide adequate pain relief to aid frame and wire removal in the clinic setting. Materials and methods: Patients presenting to the limb reconstruction service elective clinic and requiring frame removal or minor procedures were included in the study. Patients with renal, cardiac or hepatic disease, a history of sensitivity to fluorinated anaesthetic agents and those on any nephrotoxic or enzyme-inducing drugs were excluded. All procedures were performed in an appropriate isolated room in the clinic. Patient demographics, procedure details, visual analogue score, Richmond Agitation Scale and patient satisfaction were recorded. Results: A total of 39 patients were included in the study of which 17 had Ilizarov frames removed, 10 had hexapod removals, nine had heel rings removed and three had an external fixator removed. Eleven patients received additional pain relief in the form of oral analgesia. All patients were satisfied or very satisfied with the experience. One patient required a general anaesthetic for the removal of a wire that could not be removed in the clinic due to bony overgrowth. Conclusion: Patient satisfaction was very high (>95%), and it was possible to perform frame removals and minor procedures in the clinic environment during the COVID-19 pandemic. We see potential for regular use of Penthrox® in the future for the removal of external fixation outside of the operating theatre. Clinical significance: Penthrox as an analgesic for frame adjustments and removals is safe and has the potential for significant financial savings for the National Health Service (NHS). How to cite this article: Debuka E, Birkenhead P, Shah S, et al. Penthrox® (Methoxyflurane) as an Analgesic for Removal of Circular External Fixators and Minor Procedures during the COVID-19 Pandemic. Strategies Trauma Limb Reconstr 2023;18(2):82-86.

Salvage Radiosurgery for Recurrent Cardiac Sarcoma: A Case Report.

Primary cardiac sarcoma is a rare malignant tumor that arises from the cardiac myocardium. Surgical resection is the standard of care, and median survival ranges from 6 to 12 months. The role of salvage chemotherapy and radiation is not well defined. A 53-year-old female presented with acute congestive heart failure and underwent complete surgical resection of an undifferentiated pleomorphic sarcoma of the left atrium, followed by six cycles of adjuvant doxorubicin/hydroxydaunorubicin and ifosfamide. An MRI scan demonstrated an asymptomatic, 24 mm, recurrent atrial mass. The patient was treated with frameless robotic radiation therapy over three weeks. The tumor was treated with a dose of 72 Gy in 15 fractions to the 84% isodose line. A repeat cardiac MRI at four weeks showed in-field local progression with greater protrusion into the left atrium and invasion of the left ventricle. The patient therefore elected to proceed with salvage single-fraction frameless robotic radiosurgery. 25 Gy in one fraction was prescribed to the 76% isodose line. She tolerated treatment well without any acute toxicity and was subsequently treated with a variety of chemotherapy regimens, including tyrosine kinase inhibitors (TKIs) and immunotherapy. Unfortunately, the patient relapsed with metastases in the spine and pelvis. She underwent palliative radiation therapy at multiple bony sites with a partial response. She resumed chemotherapy treatment with TKIs but passed away due to septic shock without evidence of local failure. Fractionated SBRT was ineffective at controlling our patient's cardiac sarcoma. Our patient demonstrated local control of disease at 12 months after salvage of 25 Gy in one fraction of radiosurgery without any evidence of cardiac toxicity. High-dose single-fraction radiosurgery is a reasonable palliative option for long-term local control of unresectable cardiac sarcomas.

Concurrent Radiation and Targeted Therapy for Papillary Craniopharyngioma: A Case Report.

Craniopharyngiomas are rare epithelial malformations in the sellar or suprasellar regions of the craniopharyngeal ducts. Complete surgical resection is difficult due to the location of the base of the skull and the risk of injury to vital neurological structures. Fractionated radiation is effective in controlling residual tumors, but craniopharyngiomas can progress during treatment. The papillary subtype is driven by BRAF V600E mutations. Treatment with BRAF and MEK inhibitors alone has a response rate of 90% but a median progression-free survival of only 12 months. A 57-year-old female presented in May 2017 with complaints of headaches and blurriness in her right eye. Brain MRI demonstrated a 2 cm suprasellar mass engulfing the right optic nerve and optic chiasm. The patient underwent a transsphenoidal hypophysectomy with pathology consistent with a benign pituitary adenoma. Follow-up imaging in August, however, showed recurrence, and a re-resection was performed which surprisingly demonstrated papillary craniopharyngioma. Due to subtotal resection, the patient elected to proceed with intensity-modulated radiation therapy (IMRT) to the tumor bed in April of 2018 with an intended dose of 5400 cGy. After treatment with 2160 cGy in 12 fractions, the patient experienced visual deterioration and progression of the cystic tumor. The patient underwent another debulking procedure but due to rapid recurrence, an endoscopic transsphenoidal fenestration was performed. On postoperative imaging, a cystic mass was still engulfing the right optic nerve and chiasm. Due to the extended break and limited radiation tolerance of the optic chiasm, we elected to re-treat the tumor with an additional 3780 cGy IMRT in conjunction with one cycle of Taflinar and Mekinist, which was completed in August 2018. The cumulative dose to the optic chiasm was 5940 cGy.The patient had an excellent clinical response to treatment with the improvement of vision in her right eye. A brain MRI on 3/29/2019 demonstrated no residual craniopharyngioma. Four-year follow-on CT scan showed no evidence of tumor recurrence. The patient had preservation of vision and did not suffer any late neurological toxicity or new endocrine deficiency. Surgical resection and radiation were ineffective at treating our patient's craniopharyngioma due to rapid cystic progression. This is the first case report in the literature detailing concurrent radiation therapy with BRAF and MEK inhibitors for papillary craniopharyngioma. Despite a suboptimal dose of radiation, our patient had no tumor recurrence and no late toxicity four years after treatment. This represents a potentially novel treatment strategy in this challenging entity.

Gender Diversity in Urology Residency Program Leadership Is Associated With Gender Diversity in Residency Cohort.

OBJECTIVE: To evaluate the association of program director (PD) gender on the proportion of female residents in urology residency programs. METHODS: Demographics for program faculty and current residents matched in the 2017-2022 cycles at United States' accredited urology residency programs were collected from institutional websites. Data verification was completed using the American Urological Association's (AUA) list of accredited programs and the programs' official social media channels. Proportion of female residents across cohorts was compared using two-tailed Student's t-tests. RESULTS: One hundred forty-three accredited programs were studied, and 6 were excluded for lack of data. Thirty (22%) of the 137 programs studied have female PDs. Of 1799 residents, 571 (32%) are women. There has been an upward trend in the proportion of females matched from 26% in 2018 to 30% in 2019, 33% in 2020, 32% in 2021, to 38% in 2022. When compared to programs with male PDs, those with female PDs had a significantly higher proportion of female residents (36.2% vs 28.8%, p = .02). CONCLUSION: Nearly one-quarter of urology residency PDs are female, and approximately one-third of current urology residents are women, a proportion that has been increasing. Programs with female PDs are more likely to match female residents, whether those programs with female leadership rank female applicants more favorably or female applicants rank those programs higher. Given the ongoing gender disparities in urology, these findings indicate notable benefit in supporting female urologists in academic leadership positions.

Sternal fractures and thoracic injury: an analysis of 288 sternal fractures attending a major trauma centre.

INTRODUCTION: Sternal fractures (SF) are uncommon injuries usually associated with a significant mechanism of injury. Concomitant injury is likely, and a risk of mortality is substantial. AIM: Our aim in this study was to identify the risk factors for mortality in patients who had sustained sternal fractures. METHODS: We conducted a single centre retrospective review of the trust's Trauma Audit and Research Network Database, from May 2014 to July 2021. Our inclusion criteria were any patients who had sustained a sternal fracture. The regions of injury were defined using the Abbreviated Injury Score. Pearson Chi-Squared, Fisher Exact tests and multivariate regression analyses were performed using IBM SPSS. RESULTS: A total of 249 patients were identified to have sustained a SF. There were 19 patients (7.63%) who had died. The most common concomitant injuries with SF were Rib fractures (56%), Lung Contusions (31.15%) and Haemothorax (21.88%). There was a significant increase in age (59.93 vs 70.06, p = .037) and admission troponin (36.34 vs. 100.50, p = .003) in those who died. There was a significantly lower GCS in those who died (10.05 vs. 14.01, p < .001). On multi regression analysis, bilateral rib injury (p = 0.037, OR 1.104) was the only nominal variable which showed significance in mortality. CONCLUSION: Sternal Fractures are uncommon but serious injuries. Our review has identified that bilateral rib injuries, increase in age, low GCS, and high admission troponin in the context of SF, were associated with mortality.

The effect of renin-angiotensin system blockers on spinal cord dysfunction and imaging features of spinal cord compression in patients with symptomatic cervical spondylosis.

BACKGROUND CONTEXT: Cervical spondylosis may lead to spinal cord compression, poor vascular perfusion, and ultimately, cervical myelopathy. Studies suggest a neuroprotective effect of renin-angiotensin system (RAS) inhibitors in the brain, but limited data exist regarding their impact on the spinal cord. PURPOSE: To investigate whether RAS blockers and other antihypertensive drugs are correlated with preoperative functional status and imaging markers of cord compression in patients with symptomatic cervical spondylosis. STUDY DESIGN: Retrospective observational study. PATIENT SAMPLE: Individuals with symptomatic degenerative cervical stenosis who underwent surgery. OUTCOME MEASURES: Imaging features of spinal cord compression and functional status (modified Japanese Orthopedic Association [mJOA] and Nurick grading scales). METHODS: Two hundred sixty-six operative patients with symptomatic degenerative cervical stenosis were included. Demographic data, comorbidities, antihypertensive medications, and functional status (including mJOA and Nurick grading scales) were collected. We evaluated canal compromise, cord compromise, surface area of T2 signal cord change, and pixel intensity of signal cord change compared with normal cord on T2-weighted magnetic resonance imaging sequences. RESULTS: Of 266 patients, 41.7% were women, 58.3% were men; median age was 57.2 years; 20.6% smoked tobacco; 24.7% had diabetes mellitus. One hundred forty-nine patients (55.8%) had hypertension, 142 (95.3%) of these were taking antihypertensive medications (37 angiotensin-II receptor blockers [ARBs], 44 angiotensin-converting enzyme inhibitors, and 61 other medications). Patients treated with ARBs displayed a higher signal intensity ratio (ie, less signal intensity change in the compressed cord area) compared with untreated patients without hypertension (p=.004). Patients with hypertension had worse preoperative mJOA and Nurick scores than those without (p<.001). In the multivariate analysis, ARBs remained an independent beneficial factor for lower signal intensity change (p=.04), whereas hypertension remained a risk factor for worse preoperative neurological status (p<.01). CONCLUSIONS: In our study, patients with hypertension who were treated with RAS inhibitors had decreased T2-weighted signal intensity change than untreated patients without hypertension. Patients with hypertension also had worse preoperative functional status. Prospective case-control studies may deepen understanding of RAS modulators in the imaging and functional status of chronic spinal cord compression.

Early Surgical Stabilization of Complex Chest Wall Injuries Improves Short-Term Patient Outcomes.

BACKGROUND: This study aimed to assess the outcome of patients undergoing internal fixation of complex rib fractures in a U.K. major trauma center. METHODS: A retrospective analysis was performed on all patients undergoing operative fixation of rib fractures from March 2014 to May 2016. Outcome measures included hospital length of stay, intensive care unit (ICU) admission, mechanical ventilation, infection, and mortality. RESULTS: One hundred and two patients (66 male patients and 36 female patients, with a median age of 62 years) underwent rib fracture fixation during the study period. The causes of trauma were road traffic accidents in 39 patients (38%), a fall from a substantial height in 38 patients (37%), and a fall down stairs in 21 patients (21%). Thirty-eight patients (37%) had isolated chest trauma, and 64 patients (63%) had additional injuries. Fifty-three patients (52%) required ICU admission with a mean ICU stay of 4.7 days (range, 1 to 34 days). The median hospital length of stay was 10.6 days (range, 3 to 51 days). Patients with additional injuries (p = 0.01) and those requiring mechanical ventilation (p < 0.0001) stayed significantly longer. Sixty-five patients (64%) underwent rib fixation within 48 hours of the injury, and 37 patients (36%) underwent the surgical procedure after 48 hours. A surgical procedure within 48 hours resulted in a shorter ICU stay (p = 0.01), fewer cases of pneumonia (p = 0.001), reduced duration of mechanical ventilation (p = 0.03) and fewer tracheostomies (p = 0.02), and shorter hospital length of stay (11.5 compared with 17.3 days; p = 0.008). CONCLUSIONS: Surgical stabilization of multiple rib fractures may improve the outcome in patients with multiple injuries and isolated chest wall trauma. Early surgical fixation leads to shorter length of stay and better outcomes. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Evidence-based analysis of peripheral arterial disease screening based on the WHO criteria.

INTRODUCTION: Peripheral arterial disease (PAD) is an increasingly prevalent condition caused by atherosclerosis of the lower limb arteries. The majority of patients with PAD also have atherosclerosis of the coronary and cerebral vessels, therefore screening for PAD may detect patients at risk of myocardial infarction and/or stroke, but the clinical benefit of mass screening for PAD is uncertain. EVIDENCE ACQUISITION: Using the ten WHO criteria for evaluation of a screening program, we analyzed the potential merits of conducting PAD screening, using ABPI, by reviewing the evidence within the domain of each individual criterion. A comprehensive literature search was systematically carried out in order to identify relevant articles in relation to PAD screening. An evaluation and critical overview of all evidence in favor of and against the implementation of PAD screening was undertaken. EVIDENCE SYNTHESIS: Screening for PAD fits most of the WHO criteria. On current evidence, and generally in line with current guidelines, a potential target population could include anybody aged 70 years or older and those aged 45-69 with at least one risk factor for PAD. However, evidence on the cost-effectiveness of screening is based purely on theoretical modelling. Furthermore, the benefits of some secondary prevention measures, such as antiplatelet therapy and statin therapy, in asymptomatic patients are uncertain. CONCLUSIONS: Randomized trials evaluating PAD screening in asymptomatic individuals at risk are needed before widespread implementation can be advocated. Further studies assessing the merits of commencing anti-platelet and statin therapy are also required.

Prognostic significance of ankle brachial pressure index: A systematic review and meta-analysis.

Purpose To synthesize and quantify the excess risk of morbidity and mortality in individuals with low ankle-brachial pressure index. Methods Electronic databases were searched to identify studies investigating morbidity and mortality outcomes in individuals undergoing ankle-brachial pressure index measurement. Meta-analysis of the outcomes was performed using fixed- or random-effects models. Uncertainties related to varying follow-up periods among the studies were resolved by meta-analysis of time-to-event outcomes. Results Forty-three observational cohort studies, enrolling 94,254 participants, were selected. A low ankle-brachial pressure index (<0.9) was associated with a significant risk of all-cause mortality (risk ratio: 2.52, 95% CI 2.26-2.82, P < 0.00001); cardiovascular mortality (risk ratio: 2.94, 95% CI 2.72-3.18, P < 0.00001); cerebrovascular event (risk ratio: 2.17, 95% CI 1.90-2.47, P < 0.00001); myocardial infarction (risk ratio: 2.28, 95% CI 2.07-2.51, P < 0.00001); fatal myocardial infarction (risk ratio: 2.81, 95% CI 2.33-3.40, P < 0.00001); fatal stroke (risk ratio: 2.28, 95% CI 1.80-2.89, P < 0.00001); and the composite of myocardial infarction, stroke, and death (risk ratio: 2.29, 95% CI 1.87-2.81, P < 0.00001). Similar findings resulted from analyses of individuals with asymptomatic PAD, individuals with cardiovascular or cerebrovascular co-morbidity, and patients with diabetes. Conclusions A low ankle-brachial pressure index is associated with an increased risk of subsequent cardiovascular and cerebrovascular morbidity and mortality. Randomised controlled trials are required to investigate the effectiveness of screening for PAD in asymptomatic and undiagnosed individuals and to evaluate benefits of early treatment of screen-detected PAD.