Perioperative complications of minor and major reinterventions for peripheral arterial disease.

INTRODUCTION: Patients with peripheral arterial disease (PAD) frequently require reinterventions after lower-extremity revascularization (LER) to maintain perfusion. Current Society for Vascular Surgery guidelines define reinterventions as major or minor based on the magnitude of the procedure. While prior studies have compared primary LER procedures of different magnitudes, similar studies for reinterventions have not been performed. The objective of this study is to compare perioperative outcomes associated with major and minor reinterventions. METHODS: Patients undergoing LER for PAD at a tertiary care center from 2013 to 2017 were included. A retrospective review of electronic medical records was performed, and reinterventions were categorized as major or minor based on the procedure magnitude. Minor reinterventions included endovascular procedures and open revision with patch angioplasty, while major reinterventions were characterized by open surgical or endovascular LER with catheter-directed thrombolysis (CDT). Perioperative outcomes following LER were captured and compared for major and minor reinterventions. An additional subgroup analysis was performed comparing outcomes associated with major reinterventions stratified into open major surgical reinterventions and CDT. RESULTS: This study included 713 patients over a mean follow-up of 2.5 years. A total of 291 patients underwent 696 ipsilateral reinterventions (range = 1-12 reinterventions). Most reinterventions were minor (72.1%, N = 502) and 27.9% (N = 194) were major. Patients receiving reinterventions had an average age of 67.2 ± 11.5 and most were white (73.5%) males (60.1%) initially treated for claudication (58.2%) and CLTI (41.8%). There was significantly higher post-operative bleeding (9.8% vs 3.4%, p = .001), arterial thrombosis (3.1% vs 1.0%, p = .047), and acute renal failure (6.2% vs 2.4%, p = .014) after major reinterventions than minor. Additionally, major reinterventions had significantly higher return to the OR (17.0% vs 11.3%, p = .046) and longer hospital stays (7.5 vs 4.3 days, p = <.0001). Overall, major reinterventions were associated with significantly increased perioperative morbidity (37.6% vs 19.7%, p ≤ .001) with no difference in perioperative mortality. In the subgroup analysis, open reinterventions resulted in significantly longer hospital stays (8.6 days vs 5.5 days, p ≤ .001) and more wound infections than CDT (11.0% vs 0%, p = .017). However, there was no other significant difference in morbidity or mortality following treatment with open surgical reinterventions or CDT. CONCLUSIONS: In this study, major reinterventions after LER were associated with greater perioperative morbidity than minor reinterventions, with no difference in mortality. Major reinterventions performed via open surgery and CDT had similar morbidity and mortality.

The Impact of Ejection Fraction on Major Adverse Limb Events after Lower Extremity Revascularization.

BACKGROUND: Peripheral arterial disease (PAD) is commonly associated with coronary artery disease, and echocardiography is frequently performed before lower extremity revascularization (LER). However, the incidence of various echocardiographic findings in patients with PAD and their impact on the outcomes of LER has not been well studied. Reduced ejection fraction (EF) ≤ 40% is associated with increased major adverse limb events (MALE) after LER. METHODS: The electronic medical records of patients undergoing LER in a single center were reviewed. Patients were divided based on the presence or absence of reduced EF. Patient, transthoracic echocardiogram, procedural characteristics, and outcomes were compared between the 2 groups. RESULTS: A total of 1,114 patients (N = 131, 11.8% with reduced EF) underwent LER between 2013 and 2019. Patients with reduced EF were more likely to be male and have a history of coronary artery disease and heart failure. Furthermore, they were more likely to have diastolic dysfunction with moderate to severe mitral and tricuspid valve regurgitation. Patients with reduced EF were more likely to undergo LER for chronic limb-threatening ischemia, and to be treated with endovascular procedures. Perioperatively, patients with reduced EF were more likely to develop myocardial infarction. Lastly, the 2 groups had no difference in overall MALE or major amputation. However, on Kaplan-Meier curves, MALE-free survival was significantly lower for patients with reduced EF. Regression analysis demonstrated that indication and not EF was associated with MALE and MALE-free survival. CONCLUSIONS: Reduced EF is associated with decreased MALE-free survival for patients with PAD undergoing LER.

Season of Conception and Risk of Cerebral Palsy.

Importance: Cerebral palsy (CP) is the most prevalent neuromotor disability in childhood, but for most cases the etiology remains unexplained. Seasonal variation in the conception of CP may provide clues for their potential etiological risk factors that vary across seasons. Objective: To evaluate whether the month or season of conception is associated with CP occurrence. Design, Setting, and Participants: This statewide cohort study examined more than 4 million live births that were registered in the California birth records during 2007 to 2015 and were linked to CP diagnostic records (up to year 2021). Statistical analyses were conducted between March 2022 and January 2023. Exposures: The month and season of conception were estimated based on the child's date of birth and the length of gestation recorded in the California birth records. Main Outcomes and Measures: CP status was ascertained from the diagnostic records obtained from the Department of Developmental Services in California. Poisson regression was used to estimate the relative risk (RR) and 95% CI for CP according to the month or the season of conception, adjusting for maternal- and neighborhood-level factors. Stratified analyses were conducted by child's sex and neighborhood social vulnerability measures, and the mediating role of preterm birth was evaluated. Results: Records of 4 468 109 children (51.2% male; maternal age: 28.3% aged 19 to 25 years, 27.5% aged 26 to 30 years; maternal race and ethnicity: 5.6% African American or Black, 13.5% Asian, 49.8% Hispanic or Latinx of any race, and 28.3% non-Hispanic White) and 4697 with CP (55.1% male; maternal age: 28.3% aged 19 to 25 years, 26.0% aged 26 to 30 years; maternal race and ethnicity: 8.3% African American or Black, 8.6% Asian, 54.3% Hispanic or Latinx of any race, and 25.8% non-Hispanic White) were analyzed. Children conceived in winter (January to March) or spring (April to June) were associated with a 9% to 10% increased risk of CP (winter: RR, 1.09 [95% CI, 1.01-1.19]; spring: RR, 1.10 [95% CI, 1.02-1.20]) compared with summer (July to September) conceptions. Analyses for specific months showed similar results with children conceived in January, February, and May being at higher risk of CP. The associations were slightly stronger for mothers who lived in neighborhoods with a high social vulnerability index, but no child sex differences were observed. Only a small portion of the estimated association was mediated through preterm birth. Conclusions and Relevance: In this cohort study in California, children conceived in winter and spring had a small increase in CP risk. These findings suggest that seasonally varying environmental factors should be considered in the etiological research of CP.

Incidence and Significance of Deep Venous Reflux in Patients Treated with Saphenous Vein Ablation.

BACKGROUND: Venous ablation (VA) of the saphenous vein is the most common procedure performed for venous insufficiency. The incidence of concomitant deep venous reflux (DVR) in patients undergoing VA is unknown. Our hypothesis is that patients undergoing saphenous VA with concomitant DVR exhibit a higher clinical, etiology, anatomy, and pathophysiology (CEAP) stage and less relief after VA compared to patients without DVR. METHODS: Electronic medical records of patients treated with saphenous VA at a tertiary care center from March 2012 to June 2016 were reviewed. Patients were divided into 2 groups based on presence or absence of DVR on initial ultrasound (US) before saphenous VA. Patient characteristics and outcomes were compared. A telephone survey was conducted to assess long-term symptomatic relief, compliance with compression, and pain medication use. Subgroup analysis of patients with post-thrombotic versus primary DVR was performed. RESULTS: 362 patients underwent 497 ablations, and the incidence of DVR (>1 sec) was 20% (N = 71). Patients with DVR were significantly more likely to be male (46.4% vs. 32.1%, P = 0.021) and of Black race (21.2% vs. 5.5%, P = 0.0001) compared to patients without DVR. Patients with DVR were more likely to have a history of deep vein thrombosis (DVT) (15.1% vs. 7.9%, P = 0.045), but there was no difference in other comorbidities. There was no significant difference in presenting symptoms, CEAP stage, or symptom severity based on numeric rating scale (NRS) (0-10) for pain and swelling. Clinical success of saphenous VA was comparable between the 2 groups, but patients with DVR were more likely to develop endovenous heat-induced thrombosis (EHIT) II-IV (6% vs. 1%, P = 0.002). After a mean follow-up of 26 months, there was still no difference in pain or swelling scores, but patients with DVR were more likely to use compression stockings and used them more frequently. Only 11 of 71 patients with DVR had a history of DVT. Patients with post-thrombotic DVR were significantly older than patients with primary DVR (67.3 vs. 57.2, P = 0.038) and exhibited a trend toward more advanced venous disease (C4-C6: 45.4% vs. 33.3%, P = 0.439). CONCLUSIONS: In this study, 20% of patients undergoing saphenous VA demonstrated DVR, which was more common in Black men. Presence of DVR is associated with increased risk of EHIT after saphenous VA but does not seem to impact disease severity or clinical relief after ablation. Larger studies are needed to understand outcome differences between post-thrombotic and primary DVR.

Sex differences in long-term outcomes of patients with deep vein thrombosis.

OBJECTIVE: Sex differences in short-term outcomes of patients with deep vein thrombosis (DVT) have been reported, but differences in long-term outcomes remain poorly characterized. This study aimed to evaluate sex differences in long-term mortality, venous thromboembolism (VTE)-related mortality, and bleeding-related mortality in patients with DVT at a tertiary care center. METHODS: A retrospective chart review from 2012 to 2018 of all consecutive patients diagnosed with DVT was performed. Patients were grouped by sex, and baseline characteristics and treatment modalities were compared. Long-term outcomes of recurrent VTE, bleeding, and related mortalities were analyzed. Multivariable regression analysis was performed to determine factors associated with overall mortality. RESULTS: A total of 1043 (female = 521 and male = 522) patients with DVT were captured in this study period. Female patients were older (64.7 vs 61.6 years old, p = 0.01) and less likely to be obese (68.2% vs. 71.1%, p = 0.04),but had a higher average Caprini score (6.73 vs 6.35, p = 0.04). There was no difference in anatomic extent of DVT, association with PE, and severity of PE between sexes. Most patients (80.5%) were treated with anticoagulation, with no differences in choice of anticoagulant or duration of anticoagulation between females and males. Male patients were more likely to undergo catheter-directed thrombolysis (CDT) for DVT (4.2% vs 1.7%, p = 0.02) and PE (2.7% vs 0.9%, p = 0.04). Female patients were more likely to receive systemic thrombolysis for PE (2.9% vs 1.1%, p = 0.05). After an average 2.3 years follow-up, there was significantly higher bleeding complications among females (22.2% vs 16.7%, p = 0.027). The overall mortality rate was 33.5% and not different between males and females. Females were more likely to experience VTE-related mortality compared to males (3.3% vs 0.6%, p = 0.002). On regression analysis, older age (OR = 1.04 [1.03-1.06]), cancer (OR = 7.64 [5.45-10.7]), and congestive heart failure (OR = 3.84 [2.15-6.86]) were independently associated with overall mortality. CONCLUSIONS: In this study, there was no difference in overall long-term mortality between sexes for patients presenting with DVT. However, females had increased risk of long-term bleeding and VTE-related mortality compared to males.

Developmental Milestones of Infancy and Associations with Later Childhood Neurodevelopmental Outcomes in the Adolescent Brain Cognitive Development (ABCD) Study.

The age at attaining infancy developmental milestones has been associated with later neurodevelopmental outcomes, but evidence from large and diverse samples is lacking. We investigated this by analyzing data of 5360 singleton children aged 9-10 from 17 states in the US enrolled in the Adolescent Brain Cognitive Development (ABCD) study during 2016-2020. Delays in four milestones (first roll over, unaided sitting, unaided walking, and speaking first words) were defined using the 90th percentile of age at attainment reported by children's biological mothers. Childhood neurocognitive function was measured by research assistants using the NIH toolbox, and children reported their behavioral problems using the Brief Problem Monitor. Linear mixed-effects models were employed to investigate the association between delays in single or multiple milestones and childhood neurobehavioral outcomes. Delays in first roll over, unaided sitting, or walking were associated with poorer childhood neurocognitive function, while delay in speaking first words was associated with both poorer neurocognitive function and behavioral problems. Children who had delays in both motor and language milestones had the worst neurocognitive function and behavioral outcomes. Our results suggest that delays in motor and language milestone attainment during infancy are predictive of childhood neurobehavioral outcomes.

Impact of bowel preparation on elective colectomies for diverticulitis: analysis of the NSQIP database.

BACKGROUND: Recent data based on large databases show that bowel preparation (BP) is associated with improved outcomes in patients undergoing elective colorectal surgery. However, it remains unclear whether BP in elective colectomies would lead to similar results in patients with diverticulitis. The purpose of this study was to investigate whether bowel preparation affected the surgical site infections (SSI) and anastomotic leakage (AL) in patients with diverticulitis undergoing elective colectomies. STUDY DESIGN: We identified 16,380 diverticulitis patients who underwent elective colectomies from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) colectomy targeted database (2012-2017). Multivariate logistic regression models were employed to investigate the impact of different bowel preparation strategies on postoperative complications, including SSI and AL. RESULTS: In the identified population, a total of 2524 patients (15.4%) received no preparation (NP), 4715 (28.8%) mechanical bowel preparation (MBP) alone, 739 (4.5%) antibiotic bowel preparation (ABP) alone, and 8402 (51.3%) MBP + ABP. Compared to NP, patients who received any type of bowel preparations showed a significantly decreased risk of SSI and AL after adjustment for potential confounders (SSI: MBP [OR = 0.82, 95%CI: 0.70-0.96], ABP [0.69, 95%CI: 0.52-0.92]; AL: MBP [OR = 0.66, 95%CI: 0.51-0.86], ABP [0.56, 95%CI: 0.34-0.93]), where the combination type of MBP + ABP had the strongest effect (SSI:OR = 0.58, 95%CI:0.50-0.67; AL:OR = 0.46, 95%CI:0.36-0.59). The significantly decreased risk of 30-day mortality was observed in the bowel preparation of MBP + ABP only (OR = 0.32, 95%CI: 0.13-0.79). After the further stratification by surgery procedures, patients who received MBP + ABP showed consistently lower risk for both SSI and AL when undergoing open and laparoscopic surgeries (Open: SSI [OR = 0.51, 95%CI: 0.37-0.69], AL [OR = 0.47, 95%CI: 0.25-0.91]; Laparoscopic: SSI [OR = 0.58, 95%CI: 0.47-0.72, AL [OR = 0.49, 95%CI: 0.35-0.68]). CONCLUSIONS: MBP + ABP for diverticulitis patients undergoing elective open or laparoscopic colectomies was associated with decreased risk of SSI, AL, and 30-day mortality. Benefits of MBP + ABP for diverticulitis patients underwent robotic surgeries warrant further investigation.

The Impact of Clinical Follow-Up After Revascularization on the Outcomes of Patients with Chronic Limb Threatening Ischemia.

BACKGROUND: Guidelines for optimal follow-up for patients undergoing lower extremity revascularization (LER) for peripheral arterial disease recommend multiple visits with imaging during the first year followed by yearly monitoring thereafter. Critical limb-threatening ischemia (CLTI) patients are at a greater risk for mortality and limb amputation than claudicants and thus necessitate closer monitoring. The goal of this article is to study the effects of compliance with follow-up after revascularization for patients with CLTI on major amputation rates and mortality. METHODS: A single-center retrospective chart review of consecutive patients undergoing LER for CLTI was performed. Patients were stratified based on compliance with follow-up to compliant or noncompliant cohorts. Patient characteristics, reinterventions, and perioperative and long-term outcomes were compared between the 2 groups. RESULTS: There were 356 patients undergoing LER and 61% (N = 218) were compliant. There was no significant difference in baseline characteristics between the 2 groups. Noncompliant patients were more likely to undergo endovascular interventions compared to compliant patients (92.8% vs. 79.4%, P = 0.03). There was no difference in perioperative outcomes between the 2 groups with overall 30-day mortality of 0.6%. After mean follow-up of 2.7 years, compliant patients had greater ipsilateral reintervention rates (49.1% vs. 34.1%, P = 0.005) and overall reintervention rates (61% vs. 44.2%, P = 0.002) compared to noncompliant patients. There was no significant difference in mortality or ipsilateral major amputations between the 2 groups. CONCLUSIONS: Patients who were compliant with follow-up after LER for CLTI underwent more reinterventions with no difference in mortality or major limb amputation. Further research regarding the threshold for reintervention and the optimal schedule for follow-up in patients with CLTI is needed.

A nested case-control study of serum polychlorinated biphenyls and papillary thyroid cancer risk among U.S. military service members.

BACKGROUND AND OBJECTIVES: Although polychlorinated biphenyls (PCBs) were banned decades ago, populations are continuously exposed to PCBs due to their persistence and bioaccumulation/biomagnification in the environment. Results from limited epidemiologic studies linking PCBs to thyroid cancer have been inconclusive. This study aimed to investigate the association between individual PCBs and PCB mixture and papillary thyroid cancer (PTC), the most common thyroid cancer histologic subtype. METHODS: We carried out a nested case-control study including 742 histologically confirmed PTC cases diagnosed in 2000-2013 and 742 individually matched controls among U.S. military service members. Pre-diagnostic serum samples that were collected on average nine years before PTC diagnosis were used to measure PCB congeners by gas chromatography isotope dilution high resolution mass spectrometry (GC/ID-HRMS). Conditional logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression were employed to estimate the association between single PCB congeners as well as their mixture and PTC. RESULTS: Four PCB congeners (PCB-74, PCB-99, PCB-105, PCB-118) had significant associations and dose-response relationships with increased risk of PTC in single congener models. When considering the effects from all measured PCBs and their potential interactions in the BKMR model, PCB-118 showed positive trends of association with PTC. Increased exposure to the PCB congeners as a mixturewas also associated with an increased risk of PTC in the WQS model, with the mixture dominated by PCB-118, followed by PCB-74 and PCB-99. One PCB congener, PCB-187, showed an inverse trend of association with PTC in the mixture analysis. DISCUSSION: This study suggests that exposure to certain PCBs as well as a mixture of PCBs were associated with an increased risk of PTC. The observed association was mainly driven by PCB-118, and to a lesser extent by PCB-74 and PCB-99. The findings warrant further investigation.

Eligibility of Patients with Chronic Limb Threatening Ischemia for Deep Venous Arterialization.

BACKGROUND: Percutaneous deep venous arterialization (pDVA) has emerged as a new modality for limb salvage in patients with chronic limb threatening ischemia (CLTI) and no standard option for revascularization. The proportion of patients facing major amputation who are eligible for this technology remains unknown. This study aims to provide a real-life estimate of patient eligibility for pDVA to reduce major amputations. METHODS: Electronic medical records of 100 consecutive patients with peripheral arterial disease (PAD) who underwent major amputation of 106 limbs were reviewed. Angiograms performed ≤6 months before amputation were assessed by two vascular surgeons. Disease severity was categorized using the Global Limb Anatomic Staging System (GLASS) and patients were classified as ideal, possible, or not candidates for pDVA. Ideal candidates had ≥1 patent tibial artery, no target in the foot, and no proximal disease. Possible candidates had ≥1 patent tibial artery with PAD, no target in the foot, and proximal disease amenable to endovascular therapy. Patients were not eligible if there was no patent tibial artery, extensive PAD, or an arterial target in the foot for bypass. RESULTS: Of 106 limbs reviewed, 35 (33%) did not undergo angiography ≤6 months before amputation because of infection (n = 14), advanced tissue loss (n = 10), failed revascularizations (n = 8), advanced limb ischemia (n = 2), and refusing revascularization (n = 1). Thus, 69 lower extremity angiograms (2 incomplete excluded) in 68 patients were analyzed. A total of 15 patients with 16 limbs (23.2%) were identified as candidates for pDVA (ideal = 7, possible = 9). There were no differences in demographics between the two groups, but candidates for pDVA were less likely to have hyperlipidemia and congestive heart failure than those who were not candidates. The pDVA candidates underwent significantly fewer interventions before major amputation compared to patients who were not candidates (1.50 ± 0.73 vs. 2.61 ± 2.57, P = 0.007). Angiographically, patients who were pDVA candidates had significantly higher Inframalleolar GLASS grades (1.81 ± 0.40 vs. 0.86 ± 0.41, P < 0.0001) but lower Femoropopliteal Glass grades (0.73 ± 1.10 vs. 2.43 ± 1.71, P < 0.0001) than patients who were not candidates. There was no significant difference in GLASS stage between these two groups (P = 0.368). After mean follow-up of 48 months, there was no difference in mortality between both groups (40% vs. 32.1%, P = 0.567). CONCLUSIONS: Among patients considered for revascularization, 23.2% had favorable angiography and 14.7% could have benefited for pDVA as a new therapeutic modality for limb salvage. 33% of major amputations were performed for clinically-deemed unsalvageable CLTI.

Vein ablation is an effective treatment for patients with bleeding varicose veins.

BACKGROUND: Bleeding is a rare but potentially life-threatening complication of varicose veins. There is paucity of literature about patients with varicose veins that present with bleeding and the effectiveness of vein ablation as therapy to prevent recurrent bleeding. This study compares patients treated with vein ablation for bleeding varicose veins with patients treated for venous symptoms other than bleeding. We hypothesize that vein ablation is safe and effective in preventing recurrence of bleeding from varicose veins. METHODS: A retrospective single-centre review of consecutive patients undergoing vein ablation using radiofrequency in an outpatient office was performed. Patients presenting with bleeding were identified. A random (3:1) group of patients undergoing vein ablation for other venous symptoms and no bleeding was selected as a comparative group (control). The medical records were reviewed for patient characteristics and outcomes. A telephone survey inquiring about intensity of symptoms on a numeric rating scale of 0 to 10 prior and after treatment as well as recurrence of bleeding was also conducted. Patient characteristics and outcomes were compared between the two groups. RESULTS: The incidence of patients with bleeding varicose veins was 3.6% (13/362) of all patients undergoing vein ablation at our center. A total of 26 ablations and 60 ablations were performed in patients with bleeding (n = 13) and controls (n = 39), respectively. There was no difference in age and race, but there was a trend for bleeding to occur more commonly in male patients (61.5% vs 33.3%; P = .073). Patients with bleeding from varicose veins were more likely to have congestive heart failure (P = .013) and present with more advanced venous disease based on CEAP classification (P = .005) compared with the control group. There was no difference between the 2 groups in vein closure (P = .246) or complications (P = .299) after vein ablation. With mean follow-up of 2.26 ± 1.17 years, 85% of patients (n = 11) remained free from bleeding episodes. One patient with recurrent bleeding required additional vein ablation and the second patient had a concomitant ulcer that was treated with compression therapy. CONCLUSIONS: Bleeding from varicose veins is rare and more common in patients with congestive heart failure. Bleeding affects patients with higher CEAP scores. Vein ablation is a safe and effective treatment to prevent the recurrence of bleeding.

Environmental risk factors for non-Hodgkin's lymphoma: umbrella review and comparison of meta-analyses of summary and individual participant data.

Objectives: To summarise the range, strength, and validity of reported associations between environmental risk factors and non-Hodgkin's lymphoma, and to evaluate the concordance between associations reported in meta-analyses of summary level data and meta-analyses of individual participant data. Design: Umbrella review and comparison of meta-analyses of summary and individual participant level data. Data sources: Medline, Embase, Scopus, Web of Science Core Collection, Cochrane Library, and Epistemonikos, from inception to 23 July 2021. Eligibility criteria for selecting studies: English language meta-analyses of summary level data and of individual participant data evaluating associations between environmental risk factors and incident non-Hodgkin's lymphoma (overall and subtypes). Data extraction and synthesis: Summary effect estimates from meta-analyses of summary level data comparing ever versus never exposure that were adjusted for the largest number of potential confounders were re-estimated using a random effects model and classified as presenting evidence that was non-significant, weak (P<0.05), suggestive (P<0.001 and >1000 cases), highly suggestive (P<0.000001, >1000 cases, largest study reporting a significant association), or convincing (P<0.000001, >1000 cases, largest study reporting a significant association, I2 <50%, 95% prediction interval excluding the null value, and no evidence of small study effects and excess significance bias) evidence. When the same exposures, exposure contrast levels, and outcomes were evaluated in meta-analyses of summary level data and meta-analyses of individual participant data from the International Lymphoma Epidemiology (InterLymph) Consortium, concordance in terms of direction, level of significance, and overlap of 95% confidence intervals was examined. Methodological quality of the meta-analyses of summary level data was assessed by the AMSTAR 2 tool. Results: We identified 85 meta-analyses of summary level data reporting 257 associations for 134 unique environmental risk factors and 10 subtypes of non-Hodgkin's lymphoma nearly all (79, 93%) were classified as having critically low quality. Most associations (225, 88%) presented either non-significant or weak evidence. The 11 (4%) associations presenting highly suggestive evidence were primarily for autoimmune or infectious disease related risk factors. Only one association, between history of coeliac disease and risk of non-Hodgkin's lymphoma, presented convincing evidence. Of 40 associations reported in meta-analyses of summary level data that were also evaluated in InterLymph meta-analyses of individual participant data, 22 (55%) pairs were in the same direction, had the same level of statistical significance, and had overlapping 95% confidence intervals; 28 (70%) pairs had summary effect sizes from the meta-analyses of individual participant data that were more conservative. Conclusion: This umbrella review suggests evidence of many meta-analyses of summary level data reporting weak associations between environmental risk factors and non-Hodgkin's lymphoma. Improvements to primary studies as well as evidence synthesis in evaluations of evironmental risk factors and non-Hodgkin's lymphoma are needed. Review registration number: PROSPERO CRD42020178010.

Reinterventions in Patients with Claudication and Chronic Limb Threatening Ischemia.

BACKGROUND: Patients with peripheral artery disease (PAD) present with claudication or chronic limb threatening ischemia (CLTI). CLTI patients have a more advanced stage of atherosclerosis and increased comorbidities compared to claudicants, and are at an elevated risk of major amputation and mortality after lower extremity revascularization (LER). However, the frequency of reinterventions for claudication and CLTI have not been compared. Our hypothesis is that patients with CLTI undergo more frequent reinterventions to prevent major amputation. METHODS: A single-center retrospective chart review of consecutive patients undergoing lower extremity revascularization (LER) for PAD in 2013-2015 was performed. Patients were stratified based on indication for revascularization into claudication or CLTI. Patient characteristics, outcomes, and reinterventions were compared between the 2 groups. RESULTS: There were 826 patients undergoing LER and 44% (N = 361) had CLTI. Patients treated for CLTI were more likely to be smokers (P < 0.001), to have diabetes (P< 0.001), chronic renal insufficiency (P< 0.001), end stage renal disease (P< 0.001), and cardiac disease (P< 0.001). CLTI patients were less likely to be on optimal medical management as reflected by decreased rate of aspirin (P< 0.001), ADP receptor/P2Y12 inhibitors (P< 0.001), and statins (P< 0.001) compared to patients with claudication. Patients with CLTI had significantly higher major amputation (3.7% vs. 0.2%, P< 0.001) and mortality (1.4% vs. 0.2%, P = 0.092) at 30 days. At long-term follow up, patients with CLTI had higher rates of major amputation (15.5% vs. 1.3%, P < 0.001) and mortality (37.1% vs. 18.1%, P < 0.001) compared to patients with claudication. There was a significant difference in mean follow-up time between the 2 cohorts (claudication: 3.7 ± 1.5 years versus CLTI: 2.6 ± 1.8 years, P < 0.001). There was no significant difference in the ipsilateral reintervention rate between the 2 groups (claudication: 39.6% vs. CLTI: 42.7%, P = 0.37) or the mean number of ipsilateral reinterventions (claudication: 2.0 ± 1.6 vs. CLTI: 2.0 ± 1.7). However, after adjusting for follow-up time, the mean number of reinterventions per year was significantly higher for CLTI patients compared to patients with claudication (1.4 ± 2.2 vs. .6 ± 0.7 intervention per year, P < 0.001). CONCLUSIONS: Patients undergoing LER for CLTI undergo more frequent reinterventions over time compared to patients treated for claudication. Research on reinterventions after LER should include reporting of the frequency of reintervention adjusted for the follow up period in addition to the reintervention rate defined as the percentage of patients undergoing reintervention.

Alcohol consumption and risk of stomach cancer: A meta-analysis.

Stomach cancer is one of the most common cancers in the world. The relationship between alcohol consumption and the risk of stomach cancer remains unclear. Epidemiology studies investigating this relationship have shown inconsistent findings. A meta-analysis was performed to explore the association between alcohol consumption and increased stomach cancer risk. Eighty-one epidemiology studies, including 68 case-control studies and 13 cohort studies, were included in this study. A significant association was found between alcohol consumption and increased risk of stomach cancer (OR = 1.20, 95% CI 1.12-1.27). To explore the source of the significant heterogeneity (p < 0.05, I2 = 86%), analysis was stratified by study type (case-control study and cohort study), control type (hospital-based control and population-based control), gender (male, female, and mix), race (White and Asian), region (United States, Sweden, China, Japan), subsite of stomach cancer, and type of alcohol. The stratified analyses found that region and cancer subsite are major sources of the high heterogeneity. The inconsistent results in different regions and different subsites might be related to smoking rates, Helicobacter pylori infection, obesity, and potential genetic susceptibility. The positive association between drinking and increased risk of stomach cancer is consistent in stratified analyses. The dose-response analysis showed a clear trend that a higher daily intake of alcohol is associated with a higher risk of stomach cancer.

Cooking stoves and risk of birth defects in urban China.

INTRODUCTION: Birth defects are a leading cause of infant death. Pregnant women spend a large amount of time indoors, and little research from population-based studies has investigated the association between indoor air pollution and birth defects. We aimed to examine whether using coal, biomass, or electromagnetic stoves for cooking is associated with risk of birth defects compared to using gas stoves. METHODS: A birth cohort study was conducted from 2010 to 2012 in Lanzhou, China. Cases (n = 264) were singleton births with birth defects, which were defined as abnormalities of structure or function, including metabolism, presented at birth based on the International Classification of Diseases (ICD)-10 codes. Controls (n = 9926) were defined as singleton live births without birth defects. Unconditional logistic regression models were employed to estimate the association adjusting for confounding variables. RESULTS: Compared to gas stoves for cooking, biomass (OR = 2.66, 95%CI: 1.38-5.13), and electromagnetic stove (OR = 1.90, 95%CI: 1.26-2.88) for cooking were associated with an increased risk of birth defects. The significant associations remained among non-congenital heart disease (CHD) defects but not CHDs. CONCLUSIONS: Using biomass or electromagnetic stoves for cooking during pregnancy was associated with an increased risk of birth defects. Additional studies are warranted to confirm these novel findings. Studies with larger sample size or greater statistical power are also warranted to better estimate the associations for individual birth defects.

Surgical Outcomes of Mastectomy with Immediate Autologous Reconstruction Followed by Radiation.

INTRODUCTION: Timing of autologous reconstruction relative to postmastectomy radiation therapy (PMRT) is debated. Benefits of immediate reconstruction must be weighed against a possibly heightened risk of complications from flap irradiation. We reviewed flap outcomes after single operation plus PMRT in a large institutional cohort. METHODS: Medical records were reviewed for women who underwent simultaneous mastectomy-autologous reconstruction with PMRT from 2007 to 2016. Primary endpoints were rates and types of radiation-related flap complications and reoperations, whose predictors were assessed by multivariable analysis. A p value < 0.10 was deemed significant to avoid type II error. Non-parametric logistic regression generated a model of PMRT timing associated with probabilities of complications and reoperations. RESULTS: One-hundred and thirty women underwent 208 mastectomy reconstruction operations, with a median follow up of 35.1 months (interquartile range 23.6-56.5). Forty-seven (36.2%) women experienced radiation-related complications, commonly fat necrosis (44.1%) and chest wall asymmetry (28.8%). Complications were higher among women who received PMRT < 3 months after surgery (46.8% for < 3 months vs. 29.3% for ≥ 3 months; p = 0.06), most of whom received neoadjuvant chemotherapy, and among women treated with internal mammary nodal (IMN) radiation (65.2% vs. 26.4%; p < 0.01); IMN radiation remained strongly associated in multivariable analysis (odds ratio [OR] 5.24; p < 0.01). Thirty-two (24.6%) women underwent 70 reoperations, commonly fat grafting (51.9%) and fat necrosis excision (17.1%). Reoperations were higher among women who received PMRT < 3 months after surgery (48.9 for < 3 months vs. 36.6 for ≥ 3 months; p = 0.19), which was significantly associated in multivariable analysis (OR 0.42; p = 0.08 for ≥ 3 months). The probabilities of complications and reoperations were lowest when PMRT was administered ≥ 3 months after surgery. CONCLUSIONS: Among a large institutional cohort, immediate autologous reconstruction was associated with similar rates of adverse flap outcomes as historically reported alternatively sequenced protocols. IMN radiation increased risk, while PMRT ≥ 3 months after surgery decreased risk. Additional studies are needed to elaborate the impact of IMN radiation and early PMRT in immediate versus delayed autologous reconstruction.

Association of Race/Ethnicity with Surgical Route and Perioperative Outcomes of Hysterectomy for Leiomyomas.

STUDY OBJECTIVE: To evaluate the associations among race/ethnicity, route of surgery, and perioperative outcomes for women undergoing hysterectomy for uterine leiomyomas. DESIGN: Retrospective cohort study. SETTING: Multistate. PATIENTS: Women who underwent hysterectomies for leiomyomas from the American College of Surgeons National Surgical Quality Improvement Program database, 2014 to 2017. INTERVENTIONS: None. Exposures of interest were race/ethnicity and route of surgery. MEASUREMENTS AND MAIN RESULTS: Racial/ethnic variation in route of surgery and perioperative outcomes. Propensity score matching was employed to control for possible confounders. We identified 20 133 women who underwent nonemergent abdominal hysterectomy (AH), laparoscopic hysterectomy (LH), or vaginal hysterectomy (VH) for leiomyomas. We defined minimally invasive hysterectomy (MIH) as LH or VH. Black women were more likely to have open surgery (AH vs MIH adjusted odds ratio [aOR], 2.22; 95% confidence interval [CI], 2.07-2.38; AH vs VH aOR, 1.79; 95% CI, 1.54-2.08; AH vs LH aOR, 2.27; 95% CI, 2.13-2.44) than white women. Likewise, Hispanic women were more likely to have open surgery (AH vs MIH aOR, 1.76; 95% CI, 1.58-1.96; AH vs LH aOR, 1.82; 95% CI, 1.61-2.00) than white women. Black women were more likely to experience any complication after hysterectomy (AH aOR, 1.54; 95% CI, 1.31-1.80; VH aOR, 1.65; 95% CI, 1.02-2.68; LH aOR, 1.37; 95% CI, 1.13-1.66) than white women. Hispanic women were less likely than white women to experience major complications after VH (aOR, 0.28; 95% CI, 0.08-0.98). Compared with white women, the mean length of stay was longer for black women who underwent AH or LH. The mean total operation time was higher for all minority groups (except for Asian/other undergoing AH) regardless of surgical approach. CONCLUSION: Women of minority race/ethnicity were more likely to undergo abdominal rather than MIH for leiomyomas. Even when controlling for route of surgery, they were more likely to experience perioperative complications.

Location of reflux in the saphenous vein does not affect outcomes of vein ablation.

BACKGROUND: Varicose veins are commonly caused by valvular reflux in the saphenous vein. Most insurance companies will approve venous ablation (VA) for the treatment of junctional reflux only and will deny coverage for symptomatic patients with significant nonjunctional reflux of the saphenous vein at the deep system. The present study compared the outcomes of VA for patients with junctional reflux and patients with nonjunctional reflux. METHODS: A retrospective, single-center review of consecutive patients who had undergone VA using radiofrequency in an outpatient office was performed from 2012 to 2016. The patients' electronic medical records were reviewed for the characteristics, imaging findings, and outcomes. A telephone survey inquiring about the intensity of symptoms using a numeric rating scale of 0 to 10 before and after treatment was also conducted, with higher number correlating with increasing symptom severity. Patients were grouped according to the location of reflux, either at the saphenofemoral-saphenopopliteal junction or below the junction (nonjunctional). The patient characteristics and outcomes were compared between the two groups. Clinical success was defined by symptom improvement or resolution. Technical success was defined by vein closure on duplex ultrasonography. RESULTS: A total of 265 patients (224 with junctional reflux [84.5%] and 41 with nonjunctional reflux [15.5%]) had undergone VA of 343 veins. The mean patient age was 58.8 ± 15 years. No differences in age, sex, or race were present between the two groups. Patients with junctional reflux were significantly more likely to have undergone bilateral treatment (33.3% vs 12.2%; P = .006). No difference was found in CEAP (clinical, etiologic, anatomic, pathophysiologic) class, laterality, or type of vein treated. On ultrasonography, the veins with junctional reflux had significantly larger diameters (5.8 ± 2.1 mm vs 4.8 ± 1.8 mm; P = .004). However, the veins with nonjunctional reflux had a longer reflux time (5.5 ± 0.6 seconds vs 4 ± 1.7 seconds; P < .0001). The clinical success rates, technical success rates, and incidence of complications were not different between patients with junctional reflux and those with nonjunctional reflux. The telephone survey was completed by 217 patients after a mean follow-up of 24.9 ± 11.3 months. The survey results demonstrated no differences in improvement in pain or swelling or recurrence of pain or swelling after 2 years. CONCLUSIONS: Junctional reflux in the saphenous vein is more likely to be bilateral compared with nonjunctional reflux. The location of reflux did not affect patient presentation or outcomes after VA.

The association of maternal age with adverse neonatal outcomes in Lusaka, Zambia: a prospective cohort study.

BACKGROUND: Pregnancy among adolescents, whether intended or not, is a public health concern as it is generally considered high risk for both mothers and their newborns. In Zambia, where many women engage in early sexual behaviour or marry at a young age, 28.5% of girls aged 15-19 years were pregnant with their first child in the year 2013-2014. This study sought to explore associations between maternal age and neonatal outcomes among pregnant women in Lusaka, Zambia. METHODS: This was a secondary analysis of data nested within a larger population-based prospective cohort study which was implemented in three government health facilities-two first level hospitals and one clinic in Lusaka, Zambia. Women presenting to the study sites for antenatal care were enrolled into the study and followed up for collection of maternal and neonatal outcomes at 7, 28 and 42 days postpartum. The study's primary outcomes were the incidence of maternal and newborn complications and factors associated with adverse neonatal outcomes. Statistical significance was evaluated at a significance level of P < 0.05. RESULTS: The study included 11,501 women, 15.6% of whom were adolescents aged 10-19 years. Generally, adolescence did not have statistically significant associations with poor maternal health outcomes. However, the risk of experiencing obstructed labour, premature rupture of membranes and postpartum hemorrhage was higher among adolescents than women aged 20-24 years while the risk of severe infection was lower and non-significant. Adolescents also had 1.36 times the odds of having a low birthweight baby (95% CI 1.12, 1.66) and were at risk of preterm birth (aOR = 1.40, 95% CI 1.06, 1.84). Their newborns were in need of bag and mask resuscitation at birth (aOR = 0.62, 95% CI 0.41, 0.93). Advanced maternal age was significantly associated with increased odds of hypertension/ pre-eclampsia (95% CI 1.54, 5.89) and preterm labour (aOR = 2.78, 95% CI 1.24, 6.21). CONCLUSIONS: Adolescence is a risk factor for selected pregnancy outcomes in urban health facilities in Lusaka, Zambia. Health care workers should intensify the provision of targeted services to improve neonatal health outcomes. TRIAL REGISTRATION: Clinical trial number and URL:  NCT03923023 (Retrospectively registered). Clinical trial registration date: April 22, 2019.