Specific transport of temozolomide does not override DNA repair-mediated chemoresistance.

Temozolomide (TMZ) a DNA alkylating agent, is the standard-of-care for brain tumors, such as glioblastoma multiforme (GBM). Although the physicochemical and pharmacokinetic properties of TMZ, such as chemical stability and the ability to cross the blood-brain barrier (BBB), have been questioned in the past, the acquired chemoresistance has been the main limiting factor of long-term clinical use of TMZ. In the present study, an L-type amino acid transporter 1 (LAT1)-utilizing prodrug of TMZ (TMZ-AA, 6) was prepared and studied for its cellular accumulation and cytotoxic properties in human squamous cell carcinoma, UT-SCC-28 and UT-SCC-42B cells, and TMZ-sensitive human glioma, U-87MG cells that expressed functional LAT1. TMZ-AA 6 accumulated more effectively than TMZ itself into those cancer cells that expressed LAT1 (UT-SCC-42B). However, this did not correlate with decreased viability of treated cells. Indeed, TMZ-AA 6, similarly to TMZ itself, required adjuvant inhibitor(s) of DNA-repair systems, O6-methylguanine-DNA methyl transferase (MGMT) and base excision repair (BER), as well as active DNA mismatch repair (MMR), for maximal growth inhibition. The present study shows that improving the delivery of this widely-used methylating agent is not the main barrier to improved chemotherapy, although utilizing a specific transporter overexpressed at the BBB or glioma cells can have targeting advantages. To obtain a more effective anticancer prodrug, the compound design focus should shift to altering the major DNA alkylation site or inhibiting DNA repair systems.

Long-term outcome after implementation of endovascular-first strategy to treat acute mesenteric ischemia.

OBJECTIVE: To evaluate the rationale of an aggressive endovascular-first strategy to treat elderly patients with acute mesenteric ischemia (AMI) by studying long-term survival, readmissions, and patients' discharge to home vs nursing facility a decade after an episode of AMI. METHODS: The retrospective study cohort included 66 consecutive patients (all-comers) treated for arterial occlusive AMI between 2009 and 2013. Endovascular revascularization (EVR) was attempted in 50 patients (EVR+), whereas 16 patients were treated without attempted revascularization (EVR-). All patients were followed until death or September 2022. Studied outcomes included discharge status, long-term survival and cause of death and readmissions related to AMI. RESULTS: The mean age of all 66 patients was 78 ± 10 years: 79 ± 9 years in the EVR+ group and 76 ± 12 years in the EVR- group. EVR was technically successful in 44 patients (88%); three patients underwent subsequent open revascularization after EVR failure. One-third required bowel resection after EVR. The 30-day mortality for all patients was 44%; 32% in the EVR+ group and 81% in the EVR- group. Only two survivors were permanently institutionalized, whereas all others were discharged to the same place they lived prior to the AMI episode. There were four AMI-related readmissions during the follow-up; all were in the EVR+ group. Two patients underwent reinterventions for recurrent AMI. One-year survival was 52% for EVR+ and 19% for EVR- patients. Five-year survival rates were 18% and 13%, respectively. The causes of deaths were mesenteric ischemia in 22, other cardiovascular event in 21, and non-cardiovascular cause in 19 patients. Four patients were alive at the end of the follow-up. CONCLUSIONS: In this unselected elderly population with AMI, the aggressive strategy to attempt EVR resulted in a high revascularization rate and favorable outcomes. The high proportion of patients returning to their prior living status and low readmission rate after survival from AMI encourages active treatment of high-functioning elderly patients.

Friendly Neck Anatomy Does Not Prevent Neck-Related Adverse Events After EVAR.

BACKGROUND: Life-long follow-up after endovascular aneurysm repair (EVAR) is costly and burdensome to the patient. Follow-up should be stratified based on the risk of EVAR failure. Aneurysm neck is thought to be the single most important risk factor. This study investigated neck anatomy as a predictor of neck-related adverse events after EVAR. METHODS: This retrospective single-center study included consecutive patients undergoing elective EVAR for infrarenal abdominal aortic aneurysms between 2011 and 2016 (n = 222) who were followed with yearly imaging until December 2020. Hostile neck was defined as neck length ≤15 mm, width ≥28 mm, angulation ≥60°, calcification, or thrombus ≥50% of circumference or conical neck based on preoperative computed tomography angiography. Neck-related adverse event was defined as aneurysm rupture, any neck-related reintervention or type 1a endoleak during follow-up. RESULTS: Ninety (41%) patients had hostile neck and 132 (59%) had friendly neck. There were no differences in 30-day mortality (1% vs. 1%, P = 0.78), major adverse events (20% vs. 16%, P = 0.43) or reinterventions during the hospital stay (8% vs. 4%, P = 0.20) between patients with hostile and friendly neck. Estimated survival at 1 year was 89 ± 3% for hostile neck and 95 ± 2% for friendly neck patients (P < 0.01). Five-year survival estimates were 51 ± 6% and 66 ± 4%, respectively. Aneurysm-related mortality was higher after 6 years in patients with hostile neck (P < 0.01). Twenty-four patients (11%) suffered neck-related adverse events with mean time-to-event of 3.3 ± 2.8 years; there were no differences between the groups stratified by neck anatomy. Incidentally, preoperative aneurysm diameter was found to be an independent risk factor for neck-related adverse events and aneurysm-related mortality; 53 patients (24%) had aneurysm diameter ≥70 mm, which was associated with nearly 4-fold risk of neck-related complications during the follow-up. CONCLUSIONS: Friendly neck anatomy may not protect from neck-related adverse events after EVAR in the long-term. Especially patients with large aneurysms should be followed closely.

Percutaneous coronary intervention with drug-coated balloon-only strategy combined with single antiplatelet treatment in patients at high bleeding risk: Single center experience of a novel concept.

OBJECTIVES: At least 1 month of dual antiplatelet therapy is required after coronary stenting. The aim of this all-comers retrospective registry study was to assess the efficacy and safety of percutaneous coronary intervention (PCI) using drug-coated balloon (DCB) with single antiplatelet treatment (SAPT). METHODS: Between 2011 and 2020, 232 PCIs were performed in 172 patients using the DCB-only strategy and discharged with SAPT. RESULTS: The mean age of the patients was 75 ± 11 years and 59% were male. The clinical presentation was stable coronary artery disease (CAD) in 42% of the patients and acute coronary syndrome (ACS) in 58%. The lesions were mainly de novo (96%). The majority (58%) of treated lesions were in large coronary arteries (≥3.0 mm). Most (87%) of the patients were at high bleeding risk (HBR) with at least one major or two minor Academic Research Consortium (ARC) risk factors for bleeding. Periprocedural DAPT was used in 49% of the patients. The 12-month major adverse cardiac events (MACE, the composition of cardiovascular death, nonfatal myocardial infarction, and target-lesion revascularization) rate was 1.4% in stable CAD and 7.1% in ACS. The 12-month all-cause mortality after DBC only + SAPT strategy was 4.1% in stable CAD and 12.1% in ACS. The rate of ischemia-driven target lesion revascularisation (TLR) was 0% in stable CAD and 3.0% in ACS at 12 months. The 12-month rate of significant bleeding (BARC type 2-5) was 10.5%. There were no acute or subacute vessel closures. CONCLUSIONS: Despite the aged patient population with comorbidities, the TLR, MACE, and bleeding rates were low with DCB-only PCI combined with SAPT. This novel approach could reduce the post-PCI bleeding risk in patients with CAD and HBR compared to stenting.

Drug-coated balloon-only strategy for percutaneous coronary intervention of de novo left main coronary artery disease: the importance of proper lesion preparation.

This retrospective single-center registry study included all consecutive patients who underwent percutaneous coronary intervention (PCI) for a de novo left main coronary artery lesion using drug coated-balloon (DCB)-only strategy between August 2011 and December 2018. To best of our knowledge, no previous studies of DCB-only strategy of treating de novo left main coronary artery disease, exist. The primary endpoint was major adverse cardiovascular events (MACEs) including cardiac death, non-fatal myocardial infarction, and target lesion revascularization (TLR). The cohort was divided into two groups depending on weather the lesion preparation was done according to the international consensus group guidelines. Sixty-six patients (mean age 75±8.6, 72% male), 52% of whom had acute coronary syndrome, underwent left main PCI with the DCB-only strategy. No procedural mortality and no acute closures of the treated left main occurred. At 12 months, MACE and TLR occurred in 24% and 6% of the whole cohort, respectively. If the lesion preparation was done according to the guidelines, the MACE and TLR rates were 21.2% and 1.9%. Left main PCI with the DCB only-strategy is safe leading to acceptable MACE and low TLR rates at one year, if the lesion preparation is done according to the guidelines.

Multivariable Analysis of Pre-operative Brain Atrophy as a Predictor of Long Term Mortality After Carotid Endarterectomy.

OBJECTIVE: Brain atrophy is associated with an increased mortality rate in elderly trauma patients and in patients treated with mechanical thrombectomy for acute ischaemic stroke. In the setting of ischaemic stroke, the association between brain atrophy and death is stronger than that of sarcopenia. It has previously been shown that lower masseter area, as a marker of sarcopenia, is linked to lower survival after carotid endarterectomy (CEA). The aim of this study was to investigate whether brain atrophy is also associated with long term mortality in patients undergoing CEA. METHODS: A cohort of patients treated with CEA between 2004 and 2010 was retrieved from the Tampere University Hospital vascular registry and those with available pre-operative computed tomography (CT) imaging were analysed retrospectively. CT images were evaluated for brain atrophy index (BAI) and masseter muscle surface area and density. The association between BAI and mortality was investigated with Cox regression. RESULTS: Two hundred and thirty-three patients with a median (interquartile range [IQR]) age of 71 years (64.0, 77.0) were included. Most patients were operated on for symptomatic stenosis (n = 203; 87.1%). The median (IQR) duration of follow up was 115.0 months (66.0, 153.0), and 155 patients (66.5%) died during follow up. BAI was statistically significantly correlated with age (r = .489), average masseter density (r = -.202), and smoking (r = -.186; all p <.005). Increased BAI was statistically significantly associated with overall mortality (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.25 - 1.68, per one standard deviation [SD] increase) in the univariable analysis, and the association remained (HR 1.23, 95% CI 1.04 - 1.46, per one SD increase) in the multivariable models. Age, peripheral artery disease, and chronic obstructive pulmonary disease were also independently associated with mortality. The optimal cutoff value for BAI was 0.133. CONCLUSION: Brain atrophy independently predicts the long term post-operative mortality rate after CEA in a cohort containing mainly symptomatic patients. Future studies are needed to validate the results in prospective settings and in asymptomatic patients.

Technical success, clinical efficacy, and insight into the causes of restenosis after the percutaneous coronary intervention of de novo coronary artery lesions using a paclitaxel-coated balloon with citrate ester excipient.

Objectives: The aim of this all-comers registry study was to investigate the technical success, clinical efficacy, and safety of a drug-coated balloon (DCB) with paclitaxel combined with citrate ester excipient (CEE) in percutaneous coronary intervention (PCI) of de novo coronary lesions in an all-comers population. Materials and methods: A total of 338 consecutive PCIs using the DCB (CEE)-only approach comprising 406 de novo lesions were included in the study. Technical success was determined by the successful delivery of the device and no need for bailout stenting. Results: The mean follow-up time was 25 ± 12 months. The mean age of patients was 71 ± 11 years, and 48% had the acute coronary syndrome. A total of 55% of the patients were at risk of factor bleeding. The delivery of DCB was successful in 98% of cases. The overall technical success rate was 83%. Bailout stenting was used in 9% of lesions. Rotational atherectomy was used in 11% of cases before the DCB-only approach. The mean diameter of the DCBs used was 2.7 ± 0.5 mm and 38% of DCBs were large (≥3.0 mm). The 12-month MACE rates were 5.4 ± 1.7 and 18.3 ± 3.1% in stable CAD and in ACS, respectively. The respective target lesion revascularization (TLR) rates were 3.0 ± 1.3 and 8.5 ± 2.3%. Unacceptable acute recoil (>30%) was found in 74% of cases that needed repeat revascularization. No acute vessel closures occurred after DCB treatment. Conclusion: The DCB-only strategy using a paclitaxel-coated (CEE) device was technically feasible, safe, and effective in an all-comers population. Acute recoil was found as a significant cause of restenosis after the DCB-only strategy.

Effect of patient frailty status on outcomes of fenestrated-branched endovascular aortic repair for complex abdominal and thoracoabdominal aortic aneurysms.

OBJECTIVE: In the present study, we assessed the effects of patient frailty status on the early outcomes and late survival after fenestrated-branched endovascular aortic repair (FB-EVAR) for complex abdominal and thoracoabdominal aortic aneurysms. METHODS: We retrospectively reviewed the clinical data and outcomes of consecutive patients who had undergone elective FB-EVAR from 2007 to 2019 in a single institution. A previously validated 11-item modified frailty index (mFI-11) was derived from the comorbidity and preoperative functional status data. An mFI-11 <0.3 was defined as low risk, 0.3 to 0.5 as medium risk, and >0.5 as high risk. The studied outcomes were 90-day mortality, major adverse events (MAE), and long-term survival. Multivariate analyses were performed to identify the independent predictors of these outcomes. RESULTS: A total of 592 patients (155 women, mean age, 75 ± 8 years) had undergone FB-EVAR. Using the mFI-11, 310 patients (52%) were included in the low-risk, 199 (34%) in the medium-risk, and 83 (14%) in the high-risk group. The 90-day mortality was significantly higher in the high-risk group than in the medium- and low-risk groups (13%, 4%, and 3%, respectively; P < .01). The corresponding MAE rates were 27%, 18%, and 19% (P = .23). As a subgroup, 44 patients in the high-risk group had had chronic kidney disease (CKD). The 90-day mortality for these patients was as high as 23%, and 32% had experienced MAE. On multivariable analysis, the independent risk factors for 90-day mortality were CKD, respiratory disease, and a high mFI-11. The independent risk factors for MAE were female sex, CKD, larger aneurysm diameter, and the high-risk subgroup with CKD. The independent risk factors for long-term mortality were age, a low body mass index, CKD, larger aneurysm diameter, extent I-III thoracoabdominal aortic aneurysm, respiratory disease, congestive heart failure, a history of cerebrovascular problems, and higher mFI-11. The estimated survival at 1 year was 91% ± 2% in the low-risk, 88% ± 2% in the medium-risk, and 78% ± 5% in the high-risk group (P < .001). The corresponding 5-year survival estimates were 60% ± 4%, 52% ± 5%, and 32% ± 6%. The mean follow-up time was 2.9 ± 2.3 years. The patients treated during the first quartile of the study period were significantly more frail than were those in the later quartiles. Also, the outcomes of FB-EVAR had improved over time. CONCLUSIONS: Greater frailty was significantly associated with early mortality. Together with CKD, frailty was also associated with MAE and lower patient survival after FB-EVAR. The mFI-11 represents the accumulation of comorbidities and can be used to assist in better patient selection for FB-EVAR.

Use of paclitaxel-coated balloons in clinical setting is not associated with increased mortality compared with plain balloon angioplasty in femoropopliteal lesions.

OBJECTIVE: To investigate mortality and causes of death associated with the use of paclitaxel-coated balloon (PCB) compared with plain balloon (PB) angioplasty in the treatment of femoropopliteal artery lesions in real-world clinical setting. METHODS: This retrospective, single-center study included patients who underwent percutaneous femoropopliteal artery angioplasty without stenting between years 2014 and 2020. Patients were stratified into PCB and PB groups according to the index procedure. Those who had undergone any prior or subsequent intervention using drug-eluting technology were excluded from the PB group. Long-term survival was estimated up to 5 years using the Kaplan-Meier method, and risk factors for all-cause mortality were assessed in a multivariable analysis. Causes of death were retrieved from a national registry. RESULTS: The study included 139 patients treated with PB and 190 with PCB. Patients treated with PCB had a higher prevalence of chronic pulmonary disease (27% vs 17%; P = .02) and were less often on anticoagulant therapy (34% vs 48%; P = .01) compared with patients in the PB group. Those treated with PB were more likely to have chronic limb-threatening ischemia (CLTI; 82% vs 72%; P = .04). Ipsilateral perioperative amputation rate was significantly higher in the PB group (7% vs 1%; P = .01). There were no major differences in other 30-day outcomes between the groups and no differences in the rates of reinterventions and ipsilateral amputations during a mean follow-up time of 2.7 ± 1.9 years. Survival at 1 year in the PCB group was 83% ± 3% compared with 73% ± 4% in the PB group (P = .0001). The 5-year survival estimates were 56% ± 5% and 37% ± 5%, respectively. PCB use was independently associated with decreased risk of mortality (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.50-0.97). Independent risk factors for increased mortality were age (HR, 1.04 per year; 95% CI, 1.02-1.06), cardiac insufficiency (HR, 1.60; 95% CI, 1.12-2.27), chronic renal insufficiency (HR, 2.04; 95% CI, 1.47-2.85), anticoagulation therapy (HR, 1.65, 95% CI, 1.16-2.34), and CLTI (HR, 2.85; 95% CI, 1.51-5.39). In the PCB group, 63% of deaths were due to cardiovascular causes compared with 42% in the PB group (P < .01). CONCLUSIONS: The use of PCB is safe, and there is no concern of increased mortality after the procedure based on the 5-year survival estimates.

Radiographically quantified sarcopenia and traditional cardiovascular risk assessment in predicting long-term mortality after endovascular aortic repair.

OBJECTIVE: This study evaluated radiographically quantified sarcopenia and the patient's comorbidity burden based on traditional cardiovascular risk assessment as potential predictors of long-term mortality after endovascular aortic repair (EVAR). METHODS: The study included 480 patients treated with standard EVAR for intact infrarenal abdominal aortic aneurysms. Patient characteristics, comorbidities, aneurysm dimensions, and other preoperative risk factors were collected retrospectively. Preoperative computed tomography was used to measure psoas muscle area (PMA) at the L3 level. Patients were divided into three groups based on American Society of Anesthesiologists (ASA) score and PMA. In the high-risk group, patients had sarcopenia (PMA <8.0 cm2 for males and <5.5 cm2 for females) and an ASA score of 4. In the medium-risk group, patients had either sarcopenia or an ASA score of 4. Patients in the low-risk group had no sarcopenia and the ASA score was less than 4. Risk factors for long-term mortality were determined using multivariable analysis. Kaplan-Meier survival estimates were calculated for all-cause mortality. RESULTS: Patients in the high- and medium-risk groups were older than those in the low-risk group (77 ± 7, 76 ± 6, and 74 ± 8 years, respectively, P < .01). Patients in the high-risk group had higher prevalence of coronary artery disease, pulmonary disease, and chronic kidney disease. There were no differences in 30-day or 90-day mortality between the groups. The independent predictors of long-term mortality were age, ASA score, PMA, chronic kidney disease, and maximum aneurysm sac diameter. The estimated 1-year mortality rates were 5% ± 2% for the low-risk, 5% ± 2% for the medium-risk, and 18% ± 5% for the high-risk group (P < .01). Five-year mortality estimates were 23% ± 4%, 36% ± 3%, and 60% ± 6%, respectively (P < .01). The mean follow-up time was 5.0 ± 2.8 years. CONCLUSIONS: Both ASA and PMA were strong predictors of increased mortality after elective EVAR. The combination of these two can be used as a simple risk stratification tool to identify patients in whom aneurysm repair or the intensive long-term surveillance after EVAR may be unwarranted.

Long-term outcomes of transaxillary versus video-assisted first rib resection for neurogenic thoracic outlet syndrome.

OBJECTIVES: This study compared the long-term outcomes in terms of clinical examinations and patient-reported outcome measures, between transaxillary and video-assisted thoracoscopic techniques for first rib resection in patients with neurogenic thoracic outlet syndrome. METHODS: The study population comprised patients who underwent first rib resection for neurogenic thoracic outlet syndrome at our institution between 2009 and 2016. All patients were recruited in a follow-up assessment in 2019, and those who agreed to participate were included in this study. Outcomes included examinations at the outpatient clinic and patient-reported outcome measures: Disabilities of Arm Shoulder and Hand Score and Cervical Brachial Symptom Questionnaire. The completeness of the rib resection was assessed on chest X-rays. RESULTS: :A total of 60 first rib resections (30 transaxillary + 30 video-assisted fully thoracoscopic approaches) were performed for neurogenic thoracic outlet syndrome in 47 patients between 2009 and 2016. Of these, 32 patients participated in the study including 18 who had transaxillary and 22 who had video-assisted thoracoscopic procedures. The mean follow-up was 5.9 (standard deviation: 2.2) years. The outcome was good or excellent after 15 (83.3%) and 17 (77.3%) procedures in the transaxillary and video-assisted thoracoscopic surgery groups, respectively (P = 0.709). There were no differences in patient-reported outcome measures between the 2 groups. Furthermore, the length of the residual first rib stump was similar in both groups. CONCLUSIONS: We found no differences in the long-term outcomes between the study groups. These results indicate that both transaxillary and purely thoracoscopic approaches offer favourable long-term outcomes following first rib resection in patients with neurogenic thoracic outlet syndrome.

Discontinuing low-dose acetylsalicylic acid after gastrointestinal bleeding is associated with increased mortality.

BACKGROUND: Gastrointestinal bleeding is a common clinical problem in patients using low-dose acetylsalicylic acid (ASA). It is uncertain whether aspirin should continue to be used in patients who develop acute gastrointestinal bleeding during low-dose ASA therapy. AIMS: To assess whether ASA should be continued in patients who develop GI bleeding during low-dose ASA. METHODS: All patients admitted to an academic hospital for acute gastrointestinal bleeding between 2009 and 2011 were reviewed retrospectively. Clinical characteristics, comorbidities, medications and treatments were recorded from the patient records. Patients were divided into two groups based on continuing or discontinuing ASA after discharge. RESULTS: A total of 548 patients were included. ASA was continued in 282 (51.5%) (ASAc group) and discontinued in 266 (48.5%) patients (ASAd group). ASAc patients had more often coronary artery disease (57.8% vs. 42.5%, p < .001) and peripheral artery disease (17.4% vs. 9.0%, p = .004) than ASAd patients, whereas no differences were found in other comorbidities. There was no difference in 30-day all-cause mortality between ASAd and ASAc groups. However, after adjustment for age, gender and comorbidities, one-year all-cause mortality was double in the ASAd group (hazard ratio 2.16, 95% confidence interval 1.39-3.35). ASAd and ASAc groups did not differ with respect to cardiovascular mortality (4.9% vs. 5.3%, p = .811, respectively) or re-bleeding (10.2% vs. 9.2%, p = .713, respectively). CONCLUSION: Continuing low-dose ASA after gastrointestinal bleeding was associated with lower all-cause mortality during the first year without increasing the risk of re-bleeding.

Prospective Assessment of a Protocol Using Neuromonitoring, Early Limb Reperfusion, and Selective Temporary Aneurysm Sac Perfusion to Prevent Spinal Cord Injury During Fenestrated-branched Endovascular Aortic Repair.

OBJECTIVE: The aim of this study was to analyze the outcomes of a standardized protocol using routine CSFD, neuromonitoring, LL reperfusion, and selective TASP to prevent SCI during F-BEVAR. BACKGROUND: SCI is to be the most devastating complication for the patient, family, and surgeon, with impact on patient's quality of life and long-term prognosis. An optimal standardized protocol may be used to improve outcomes. METHODS: Patients enrolled in a prospective, nonrandomized single-center study between 2013 and 2018. A SCI prevention protocol was used for TAAAS or complex abdominal aneurysms with ≥5-cm supraceliac coverage including CSFD, neuromonitoring, LL reperfusion, and selective TASP. Endpoints included mortality and rates of SCI. RESULTS: SCI prevention protocol was used in 170 of 232 patients (73%) treated by F-BEVAR. Ninety-one patients (55%) had changes in neuromonitoring, which improved with maneuvers in all except for 9 patients (10%) who had TASP. There was one 30-day or in-hospital mortality (0.4%). Ten patients (4%) developed SCIs including in 1% (1/79) of patients with normal neuromonitoring and 10% (9/91) of those who had decline in neuromonitoring ( P = 0.02). Permanent paraplegia occurred in 2 patients (1%). Factors associated with SCI included total operating time (odds ratio 1.5, 95% confidence interval 1.1-2.2, P = 0.02) and persistent changes in neuromonitoring requiring TASP (odds ratio 15.7, 95% confidence interval 2.9-86.2, P = 0.001). CONCLUSION: This prospective nonrandomized study using a standardized strategy to prevent SCI was associated with low incidence of the SCI during F-BEVAR. Permanent paraplegia occurred in 1%.

Prevention of Atrial Fibrillation After Cardiac Surgery: A Review of Literature and Comparison of Different Treatment Modalities.

Atrial fibrillation is the most common arrhythmia to occur after cardiac surgery, with an incidence of 10% to 50%. It is associated with postoperative complications including increased risk of stroke, prolonged hospital stays and increased costs. Despite new insights into the mechanisms of atrial fibrillation, no specific etiologic factor has been identified as the sole perpetrator of the arrhythmia. Current evidence suggests that the pathophysiology of atrial fibrillation in general, as well as after cardiac surgery, is multifactorial. Studies have also shown that new-onset postoperative atrial fibrillation following cardiac surgery is associated with a higher risk of short-term and long-term mortality. Furthermore, it has been demonstrated that prophylactic medical therapy decreases the incidence of postoperative atrial fibrillation after cardiac surgery. Of note, the incidence of postoperative atrial fibrillation has not changed during the last decades despite the numerous preventive strategies and operative techniques proposed, although the perioperative and postoperative care of cardiac patients as such has improved.

Long-term outcome over a decade after first rib resection for neurogenic thoracic outlet syndrome.

OBJECTIVES: The aim was to determine long-term outcomes over a decade after first rib resection (FRR) in patients with neurogenic thoracic outlet syndrome (NTOS). A secondary aim was to investigate correlation of residual rib stump with long-term symptoms. METHODS: This ambispective cohort included patients who underwent transaxillary FRRs for NTOS between 1998 and 2007. Short-term outcomes at 3-month clinical follow-up were retrospectively collected from medical records. Patients who agreed to participate in the study were invited to a long-term clinical follow-up in 2019. Disabilities of Arm, Shoulder, and Hand Score and Cervical Brachial Symptom Questionnaire were used. A chest X-ray limited to a clavicular projection was taken, and the length of the residual first rib was measured. RESULTS: Twenty patients {mean age 41.8 [standard deviation (SD): 10.3 years]} who underwent 27 FRRs participated in the study. The mean follow-up time was 14.9 (SD: 3.6) years. Excellent or good recovery was noted after 16 (59.3% of operated arms) operations in the short-term follow-up and 22 (81.5%) operations in the long-term follow-up. No reoperations were necessary for residual symptoms. The mean Cervical Brachial Symptom Questionnaire score was 26.7 (SD: 28.2) (maximum 120), and the Disabilities of Arm, Shoulder, and Hand Score was 21.1 (SD: 18.4) (maximum 100) points. Twenty-six patients (96.3%) had a noticeable residual first rib stump. The mean length of the residual first rib was 28.9 (SD: 9.5) mm. More than 30-mm rib stump did not indicate a worse long-term outcome. CONCLUSIONS: This study showed good long-term outcome without symptom recurrence after FRR for NTOS. In most patients, after surgery, quality of life and ability to work improved. Residual rib stump length was not associated with the treatment outcome.

Molecular characteristics supporting l-Type amino acid transporter 1 (LAT1)-mediated translocation.

l-Type amino acid transporter 1 (LAT1) is an interesting protein due to its peculiar expression profile. It can be utilized not only as a carrier for improved or targeted drug delivery, e.g., into the brain but also as a target protein by which amino acid supply can be restricted, e.g., from the cancer cells. The recognition and binding processes of LAT1-ligands, such as amino acids and clinically used small molecules, including l-dopa, gabapentin, and melphalan, are today well-known. Binding to LAT1 is crucial, particularly when designing the LAT1-inhibitors. However, it will not guarantee effective translocation across the cell membrane via LAT1, which is a definite requirement for LAT1-substrates, such as drugs that elicit their pharmacological effects inside the cells. Therefore, in the present study, the accumulation of known LAT1-utilizing compounds into the selected LAT1-expressing cancer cells (MCF-7) was explored experimentally over a time period. The differences found among the transport efficiency and affinity of the studied compounds for LAT1 were subsequently explained by docking the ligands into the human LAT1 model (based on the recent cryo-electron microscopy structure). Thus, the findings of this study clarify the favorable structural requirements of the size, shape, and polarity of the ligands that support the translocation and effective transport across the cell membrane via LAT1. This knowledge can be applied in future drug design to attain improved or targeted drug delivery and hence, successful LAT1-utilizing drugs with increased therapeutic effects.

Patient Self-Assessment and Acoustic Voice Analysis in Screening of Postoperative Vocal Fold Paresis and Paralysis.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the utility of two items in vocal fold paresis and paralysis screening after thyroid and parathyroid surgery: patient self-assessment of voice using the Voice Handicap Index and computer-based acoustic voice analysis using the Multi-Dimensional Voice Program. METHODS: This was a prospective study of 181 patients who underwent thyroid or parathyroid surgery over a 1-year study period (2017). Preoperatively, all patients underwent laryngoscopic vocal fold inspection and acoustic voice analysis, and they completed the Voice Handicap Index questionnaire. Postoperatively, all patients underwent laryngoscopy prior to hospital discharge; 2 weeks after the surgery, they completed the Voice Handicap Index questionnaire a second time. Two weeks postoperatively, patients with vocal fold paresis or paralysis and 20 randomly selected controls without vocal fold paresis or paralysis underwent a follow-up acoustic voice analysis. RESULTS: Fourteen patients had a new postoperative vocal fold paresis or paralysis. Postoperatively, the total Voice Handicap Index score was significantly higher (p = 0.040) and the change between preoperative and postoperative scores was greater (p = 0.028) in vocal fold paresis or paralysis patients. A total postoperative Voice Handicap Index score > 30 had 55% sensitivity, and 90% specificity, for vocal fold paresis or paralysis. In the postoperative Multi-Dimensional Voice Program analysis, vocal fold paresis or paralysis patients had significantly more jitter (p = 0.044). Postoperative jitter > 1.33 corresponded to 55% sensitivity, and 95% specificity, for vocal fold paresis or paralysis. CONCLUSIONS: In identifying postoperative vocal fold paresis or paralysis, patient self-assessment and jitter in acoustic voice analysis have high specificity but poor sensitivity. Without routine laryngoscopy, approximately half of the patients with postoperative vocal fold paresis or paralysis could be overlooked. However, if the patient has no complaints of voice disturbance 2 weeks after thyroid or parathyroid surgery, the likelihood of vocal fold paresis or paralysis is low.

Current Indications and Long-Term Outcomes of Surgical Portosystemic Shunts in Adults.

BACKGROUND: Surgical portosystemic shunts are rare. We reviewed indications, operative details, and outcomes of patients undergoing surgical portosystemic shunt procedures. METHODS: We retrospectively reviewed clinical data of consecutive patients between 1997 and 2018 from a single institution. Clinical characteristics and outcomes were compared between two groups: patients with portomesenteric venous thrombosis (PMVT) vs those with cirrhosis. Endpoints included 30-day mortality, shunt-related complications, patency, and survival. RESULTS: There were 99 patients, 45 male and 54 female, with a mean age of 46 ± 18 years, enrolled in the study. There were 63 patients (63%) with PMVT and 36 patients (36%) with cirrhosis. Both groups had similar demographics, cardiovascular risk factors, and aneurysm extent, except for more diabetes among those with cirrhosis (p < 0.05). There were no significant differences in procedural metrics and intra-procedure complications between groups, except that patients with PMVT underwent more non-selective shunts than those with cirrhosis (63% vs. 30%, p < 0.001). There were two 30-day deaths (2%), with no difference in mortality and MAEs between groups. On univariate analysis, cholangiopathy and PMVT were associated with graft thrombosis (HR = 9.22, 95% CI 1.22-70.27) while race, smoking, cardiac comorbidity, type of operative shunt, configuration of the shunt, and use of conduit were not (p > 0.05). Patients with PMVT had significantly lower 1-, 5-, and 10-year primary (77%, 71%, and 71% vs. 97%, p = 0.009) and secondary patency (88%, 76%, and 72% vs. 96%, p = 0.027) compared with those with cirrhosis. The 1-, 5-, and 10-year survival rates were 94%, 84%, and 61% for patients with PMVT compared with 88%, 58%, and 26% for those with cirrhosis (non-adjusted HR 0.40, 95% CI 0.19-0.84, p = 0.01, age-adjusted HR 0.51, 95% CI 0.24-1.09, p = 0.08). The survival of patients with PMVT without liver disease trended higher than those with liver disease; however, when adjusted for age, the survival gap narrowed, and the difference was not statistically significant (p = 0.19), survival being lowest for those with PMVT and liver disease. CONCLUSIONS: Surgical portosystemic shunts are safe and effective for symptom relief in selected patients with portal hypertension. The odds of graft thrombosis is 9 times higher in patients with PMVT. Overall survival is similar in patients with PMVT or cirrhosis.

Perceptual Assessment and Acoustic Voice Analysis as Screening Tests for Vocal Fold Paresis After Thyroid or Parathyroid Surgery.

BACKGROUND: The aim of this study was to evaluate the reliability of clinician-based perceptual assessment of voice and computerized acoustic voice analysis as screening tests for vocal fold paresis or paralysis (VFP) after thyroid and parathyroid surgery. METHODS: This was a prospective study of 181 patients undergoing thyroid or parathyroid procedure with pre and postoperative laryngoscopic vocal fold inspection, perceptual voice assessment using grade, roughness, breathiness, asthenia, and strain (GRBAS) scale and acoustic voice analysis using the multi-dimensional voice program (MDVP). Patients were divided into 2 groups for comparison; those with new postoperative VFP and those without. Potential screening tools were evaluated using the receiving operating characteristic (ROC) analysis. RESULTS: Fourteen (6.6%) patients had a new postoperative VFP. Postoperative GRBAS scores were significantly (P < 0.05) higher in patients with VFP compared to those without. However, there were no statistically significant differences in MDVP values between the groups. Postoperative GRBAS grade score (cut off > 0) had the best sensitivity, 93%, for predicting VFP, but the specificity was only 50%. Postoperative jitter (cut off > 1.60) in MDVP had a good specificity, 90%, but only 50% sensitivity. Combining all the GRBAS and MDVP variables with P < 0.05 in the ROC analysis yielded a test with 100% sensitivity and 55% specificity. CONCLUSIONS: Physician-based perceptual voice assessment has a high sensitivity for detecting postoperative VFP, but the specificity is poor. The risk of VFP is low in patients with completely normal voice at discharge. However, routine laryngoscopy after thyroid and parathyroid surgery is still the most reliable exam for VFP screening.

Long-term symptom improvement and health-related quality of life after operative management of median arcuate ligament syndrome.

OBJECTIVE: To investigate long-term symptom improvement and health-related quality of life (HRQOL) after operative intervention for median arcuate ligament syndrome (MALS). METHODS: Clinical data of all consecutive patients treated by operative management of MALS from 1999 to 2018 were reviewed. A cross-sectional questionnaire using the Visick score, the Gastrointestinal Quality of Life Index, and Short Form (SF)-12v2 questionnaires was performed to assess long-term outcomes. The SF-12 HRQOL domains were compared between symptom-free and symptomatic patient groups and to averages for the US general population. Treatment failure was defined as no relief after surgery and Visick category 3 to 4 symptoms. Freedom from symptoms was estimated at 5 years. RESULTS: A total of 100 patients were treated for MALS (mean age, 38 ± 18 years; 75% female). Open surgical release was performed in 81 and laparoscopic release in 19 patients. The most common presenting symptom was abdominal pain in 99 patients with postprandial exacerbation in 85. There was no mortality. Major adverse events at 30 days had occurred in 21 patients (open 19, laparoscopic 2) including myocardial infarction (n = 1), pancreatitis (n = 2), respiratory failure (n = 4), estimated blood loss of more than 1 L (n = 8), and postoperative ileus (n = 8). One patient treated by laparoscopic release required conversion for an aortic injury, which was treated by primary repair and splenectomy. Forty-six patients responded to the questionnaire with a mean follow-up of 8 ± 4 years. Initial symptom resolution or improvement was reported by 38 patients (83%), whereas 8 patients (17%) reported treatment failure. Seven of the 38 patients (18%) with initial treatment success reported symptom recurrence. The estimated 5-year freedom from symptoms was 67 ± 7%. All SF-12 HRQOL domains were significantly lower and below the average population range in symptomatic patients compared with those who were symptom free, in which all domains were within the average population range. The Gastrointestinal Quality of Life Index scores were also significantly lower in symptomatic patients. Forty respondents (87%) reported that they would still undergo operative management if given the choice, including all respondents who reported symptom recurrence. CONCLUSIONS: The operative management of MALS can be performed with a low rate of complications. Approximately two-thirds of respondents were free of symptoms 5 years after the procedure. Treatment success in symptom-free patients was associated with an improved HRQOL on par with the population average compared with symptomatic patients. The vast majority of respondents would opt to have the operation again if given a choice. However, patients should be well-informed about the possibility of failure to relieve symptoms and symptom recurrence.