Transhiatal and transthoracic resection in adenocarcinoma of the esophagus: Does the operative approach have an influence on the long-term prognosis?

BACKGROUND: The goal of the present analysis was to investigate the long-term prognosis for adenocarcinoma of the esophagus treated with either the transhiatal (TH) or the transthoracic (TT) operative approach. METHODS: Between September 1985 and March 2004, esophageal resection due to carcinoma was performed on a total of 424 patients. This manuscript takes into account the 150 patients suffering from adenocarcinoma of the esophagus in whom a transhiatal resection of the esophagus was performed. In the event of transmural tumor growth and a justifiable risk of surgery, the transthoracic resection was selected. An extended mediastinal lymph node dissection, however, was only carried out in the course of the transthoracic approach. RESULTS: The transthoracic resection of the esophagus demonstrated a higher rate of general complications (p = 0.011) as well as a higher mortality rate (p = 0.011). The mediastinal dissection of the lymph nodes, however, revealed no prognostic influence. Considering all of the 150 patients with adenocarcinoma, as well as only those patients who had undergone curative resections (R0), the transhiatal approach was seen to demonstrate a better five-year survival rate of 32.1% versus 35.1%, with a median survival time of 24 versus 28 months, as compared with those who had undergone a transthoracic approach with a five-year survival rate of 13.6% (all patients) versus 17.7% (R0 resection) with a median survival time of 16 versus 17 months (p < 0.05). CONCLUSION: The prognosis in patients with adenocarcinoma of the esophagus is influenced by the depth of the tumor (pT) and the pM-category, as shown in the multivariate analysis. The present analysis did not demonstrate a relevant difference in survival for patients with N0 and N1 stages undergoing transhiatal or transthoracic esophagectomy. It is questionable, if a more extensive mediastinal lymph node dissection, in addition to the clearance of abdominal lymph nodes, offers prognostic advantages in adenocarcinoma of the esophagus. However, the morbidity and mortality associated with the transthoracic approach is higher

Excessive age-related decline in functional ovarian reserve in infertile women: prospective cohort of 15,500 women

Context: Whether infertile women exhibit accelerated ovarian aging and whether a low ovarian reserve is overrepresented in infertility populations is not known. Objective: To compare the age-related decline in antral follicle count (AFC), a biomarker of the ovarian reserve, in fertile and infertile women. Design: Cross-sectional data from a large prospective cohort study conducted from January 2013 to December 2014. Setting: Thirteen fertility centers across Spain. Patients or Other Participants: Consecutive women aged 18 to 45 years of age attending the fertility centers either seeking fertility treatment or as fertile women wishing to act as potential oocyte donors. Intervention(s): Standardized AFC assessment on day 2 to 4 of the cycle. Main Outcome Measure(s): Age-related decline of AFC for both fertile and infertile women. Results: A total of 15 500 women, of whom 5722 were potential donors and 9778 were patients seeking fertility treatment, participated in the study. Average AFC was greater in potential oocyte donors than in infertile women (20 [interquartile range, 16–24] vs 10 [interquartile range, 6–15], respectively; P &lt; .001), a difference that was maintained after adjustment for age (P &lt; .001) in a model predicting log(AFC) from donor vs infertility, adjusting for 2-year age bands. The age-related decline in AFC was much steeper in infertile women compared with that of potential oocyte donors, with an increased prevalence of a low ovarian reserve (AFC &lt; 5) at all ages in infertile women. Conclusions: The age-related decline in AFC was substantially greater in infertility patients than potential oocyte donors. Overrepresentation in infertility populations of women with low ovarian reserve may be an additional functional cause of infertility

Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial

Background: The DiRECT trial assessed remission of type 2 diabetes during a primary care-led weight-management programme. At 1 year, 68 (46%) of 149 intervention participants were in remission and 36 (24%) had achieved at least 15 kg weight loss. The aim of this 2-year analysis is to assess the durability of the intervention effect. Methods: DiRECT is an open-label, cluster-randomised, controlled trial done at primary care practices in the UK. Practices were randomly assigned (1:1) via a computer-generated list to provide an integrated structured weight-management programme (intervention) or best-practice care in accordance with guidelines (control), with stratification for study site (Tyneside or Scotland) and practice list size (&gt;5700 or ≤5700 people). Allocation was concealed from the study statisticians; participants, carers, and study research assistants were aware of allocation. We recruited individuals aged 20–65 years, with less than 6 years' duration of type 2 diabetes, BMI 27–45 kg/m2, and not receiving insulin between July 25, 2014, and Aug 5, 2016. The intervention consisted of withdrawal of antidiabetes and antihypertensive drugs, total diet replacement (825–853 kcal per day formula diet for 12–20 weeks), stepped food reintroduction (2–8 weeks), and then structured support for weight-loss maintenance. The coprimary outcomes, analysed hierarchically in the intention-to-treat population at 24 months, were weight loss of at least 15 kg, and remission of diabetes, defined as HbA1c less than 6·5% (48 mmol/mol) after withdrawal of antidiabetes drugs at baseline (remission was determined independently at 12 and 24 months). The trial is registered with the ISRCTN registry, number 03267836, and follow-up is ongoing. Findings: The intention-to-treat population consisted of 149 participants per group. At 24 months, 17 (11%) intervention participants and three (2%) control participants had weight loss of at least 15 kg (adjusted odds ratio [aOR] 7·49, 95% CI 2·05 to 27·32; p=0·0023) and 53 (36%) intervention participants and five (3%) control participants had remission of diabetes (aOR 25·82, 8·25 to 80·84; p&lt;0·0001). The adjusted mean difference between the control and intervention groups in change in bodyweight was −5·4 kg (95% CI −6·9 to −4·0; p&lt;0·0001) and in HbA1c was −4·8 mmol/mol (–8·3 to −1·4 [–0·44% (–0·76 to −0·13)]; p=0·0063), despite only 51 (40%) of 129 patients in the intervention group using anti-diabetes medication compared with 120 (84%) of 143 in the control group. In a post-hoc analysis of the whole study population, of those participants who maintained at least 10 kg weight loss (45 of 272 with data), 29 (64%) achieved remission; 36 (24%) of 149 participants in the intervention group maintained at least 10 kg weight loss. Serious adverse events were similar to those reported at 12 months, but were fewer in the intervention group than in the control group in the second year of the study (nine vs 22). Interpretation: The DiRECT programme sustained remissions at 24 months for more than a third of people with type 2 diabetes. Sustained remission was linked to the extent of sustained weight loss

Association Between Levothyroxine Treatment and Thyroid-Related Symptoms Among Adults Aged 80 Years and Older With Subclinical Hypothyroidism.

Importance It is unclear whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism. Objective To determine the association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older. Design, Setting, and Participants Prospectively planned combined analysis of data involving community-dwelling adults aged 80 years and older with subclinical hypothyroidism. Data from a randomized clinical trial were combined with a subgroup of participants aged 80 years and older from a second clinical trial. The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018. Exposures Participants were randomly assigned to receive levothyroxine (n = 112; 52 participants from the first trial and 60 from the second trial) or placebo (n = 139; 53 participants from the first trial and 86 from the second trial). Main Outcomes and Measures Co-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness at 1 year (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9). Results Of 251 participants (mean age, 85 years; 118 [47%] women), 105 were included from the first clinical trial and 146 were included from the second clinical trial. A total of 212 participants (84%) completed the study. The hypothyroid symptoms score decreased from 21.7 at baseline to 19.3 at 12 months in the levothyroxine group vs from 19.8 at baseline to 17.4 at 12 months in the placebo group (adjusted between-group difference, 1.3 [95% CI, -2.7 to 5.2]; P = .53). The tiredness score increased from 25.5 at baseline to 28.2 at 12 months in the levothyroxine group vs from 25.1 at baseline to 28.7 at 12 months in the placebo group (adjusted between-group difference, -0.1 [95% CI, -4.5 to 4.3]; P = .96). At least 1 adverse event occurred in 33 participants (29.5%) in the levothyroxine group (the most common adverse event was cerebrovascular accident, which occurred in 3 participants [2.2%]) and 40 participants (28.8%) in the placebo group (the most common adverse event was pneumonia, which occurred in 4 [3.6%] participants). Conclusions and Relevance In this prospectively planned analysis of data from 2 clinical trials involving adults aged 80 years and older with subclinical hypothyroidism, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in hypothyroid symptoms or fatigue. These findings do not support routine use of levothyroxine for treatment of subclinical hypothyroidism in adults aged 80 years and older. Trial Registration ClinicalTrials.gov Identifier: NCT01660126; Netherlands Trial Register: NTR3851

Association between Levothyroxine Treatment and Thyroid-Related Symptoms among Adults Aged 80 Years and Older with Subclinical Hypothyroidism

Importance: It is unclear whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism. Objective: To determine the association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older. Design, Setting, and Participants: Prospectively planned combined analysis of data involving community-dwelling adults aged 80 years and older with subclinical hypothyroidism. Data from a randomized clinical trial were combined with a subgroup of participants aged 80 years and older from a second clinical trial. The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018. Exposures: Participants were randomly assigned to receive levothyroxine (n = 112; 52 participants from the first trial and 60 from the second trial) or placebo (n = 139; 53 participants from the first trial and 86 from the second trial). Main Outcomes and Measures: Co-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness at 1 year (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9). Results: Of 251 participants (mean age, 85 years; 118 [47%] women), 105 were included from the first clinical trial and 146 were included from the second clinical trial. A total of 212 participants (84%) completed the study. The hypothyroid symptoms score decreased from 21.7 at baseline to 19.3 at 12 months in the levothyroxine group vs from 19.8 at baseline to 17.4 at 12 months in the placebo group (adjusted between-group difference, 1.3 [95% CI, -2.7 to 5.2]; P =.53). The tiredness score increased from 25.5 at baseline to 28.2 at 12 months in the levothyroxine group vs from 25.1 at baseline to 28.7 at 12 months in the placebo group (adjusted between-group difference, -0.1 [95% CI, -4.5 to 4.3]; P =.96). At least 1 adverse event occurred in 33 participants (29.5%) in the levothyroxine group (the most common adverse event was cerebrovascular accident, which occurred in 3 participants [2.2%]) and 40 participants (28.8%) in the placebo group (the most common adverse event was pneumonia, which occurred in 4 [3.6%] participants). Conclusions and Relevance: In this prospectively planned analysis of data from 2 clinical trials involving adults aged 80 years and older with subclinical hypothyroidism, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in hypothyroid symptoms or fatigue. These findings do not support routine use of levothyroxine for treatment of subclinical hypothyroidism in adults aged 80 years and older. Trial Registration: ClinicalTrials.gov Identifier: NCT01660126; Netherlands Trial Register: NTR3851

Selenium supplementation improves antioxidant capacity in vitro and in vivo in patients with coronary artery disease The SElenium Therapy in Coronary Artery Disease Patients (SETCAP) Study

&lt;b&gt;Background&lt;/b&gt; &lt;br&gt;Selenium is a central determinant of antioxidative glutathione peroxidase 1 (GPx-1) expression and activity. The relevance of selenium supplementation on GPx-1 in coronary artery disease (CAD) needs to be established. We assessed the effect of selenium supplementation on GPx-1 in cell culture and on endothelial function in a prospective clinical trial.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Methods&lt;/b&gt;&lt;/br&gt; &lt;br&gt;Human coronary artery endothelial cells were incubated with 5.78 to 578 nmol/L sodium selenite, Se-methyl-selenocysteine hydrochloride, or seleno-l-methionine. Glutathione peroxidase 1 mRNA and protein expression and activity were measured. Coronary artery disease patients (n = 465) with impaired endothelial function (flow-mediated dilation [FMD] &#x3C;8%) were randomly assigned to receive 200 or 500 μg sodium selenite daily or matching placebo during a 12-week period. We tested the effect on red blood cell GPx-1 activity and brachial artery FMD. Furthermore, differences in biomarkers of oxidative stress and inflammation were measured.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Results&lt;/b&gt;&lt;/br&gt; &lt;br&gt;Sodium selenite and Se-methyl-selenocysteine hydrochloride increased GPx-1 protein and activity in a dose-dependent manner (P &#x3C; .0001). The intention-to-treat groups comprised 433 CAD patients. Glutathione peroxidase 1 activity increased from 37.0 U/gHb (31.3-41.7) to 41.1 U/gHb (35.2-48.4) (P &#x3C; .0001) in the 200 μg and from 38.1 U/gHb (33.2-43.8) to 42.6 U/gHb (35.0-49.1) (P &#x3C; .0001) in the 500 μg sodium selenite group treated for 12-weeks. No relevant changes were observed for FMD or biomarkers of oxidative stress and inflammation.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Conclusions&lt;/b&gt;&lt;/br&gt; &lt;br&gt;Sodium selenite supplementation increases GPx-1 activity in endothelial cells and in CAD patients. Future studies have to demonstrate whether long-term CAD outcome can be improved.&lt;/br&gt

Healthy life-year costs of treatment speed from arrival to endovascular thrombectomy in patients with ischemic stroke

Importance The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known. Objective To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO). Data Sources PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020. Study Selection All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included. Data Extraction/Synthesis Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well–to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well–to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time. Main Outcomes and Measures Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics. Results Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP ≤4 hours) and 375 (48.0%) were late-treated (LKWTP &gt;4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P &lt; .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours. Conclusions and Relevance In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times