Diabetes was the only comorbid condition associated with mortality of invasive pneumococcal infection in ICU patients: a multicenter observational study from the Outcomerea research group

Purposes

Streptococcus pneumoniae is a leading pathogen of severe community, hospital or nursing facility infections. We sought to describe characteristics of invasive pneumococcal infection (IPI) and pneumonia (due to the high mortality of intensive care-associated pneumonia) and to report outcomes according to various types of comorbidity.

Methods

Multicenter observational cohort study on the prospective Outcomerea database, including adult patients, with a hospital stay?<?48 h before ICU admission and a documented IPI within the first 72 h of ICU admission. Comorbid conditions were defined according to the Knaus and Charlson classification.

Results

Of the 20,235 patients, 5310 (26.4%) had an invasive infection, including 560/5,310 (10.6%) who had an IPI. The ICU 28-day mortality was 109/560 (19.8%). Four factors were independently associated with mortality: SOFA day 1–2: [hazard ratio (HR) 1.21; 95% confidence interval (95% CI) 1.15–1.27, p?<?0.001]; maximum lactate level day 1–2: (HR 1.07, 95% CI 1.02–1.12, p?=?0.006); diabetes mellitus: (HR 1.91, 95% CI 1.23–3.03, p?=?0.006) and appropriate antibiotics (HR 0.28, 95% CI 0.15–0.50, p?<?0.001). Comparable results were obtained when other comorbid conditions were forced into the model. Diabetes impact was more pronounced in case of micro- or macro-angiopathy (HR 4.17, 95%CI 1.68–10.54, p?=?0.003), in patients?≥?65 years old (HR 2.59, 95% CI 1.56–4.28, <?0.001) and in those with body mass index (BMI)?<?25 kg/m² (HR 2.11, 95% CI 1.10–4.06, p?=?0.025).

Conclusions

Diabetes mellitus was the only comorbid condition which independently influenced mortality in patients with IPI. Its impact was more pronounced in patients with complications, aged?≥?65 years and with BMI?<?25 kg/m².

     

Alcohol-related acute-on-chronic liver failure—Comparison of various prognostic scores in predicting outcome

Background and Aims

Various prognostic scores are available for predicting outcome in acute-on-chronic liver failure (ACLF). We compared the available prognostic models as predictors of outcome in alcohol-related ACLF patients.

Methods

All consecutive patients with alcohol-related ACLF were included. At admission, prognostic indices-acute physiology and chronic health evaluation score (APACHE II), model for end-stage liver disease (MELD), MELD-Na, Maddrey’s discriminant function (DF), age-bilirubin-INR-creatinine (ABIC), and Chronic Liver Failure Consortium (CLIF-C) ACLF score (CLIF-C ACLF) score were calculated. Receiver operator characteristic (ROC) curves were plotted for all prognostic scores with in-hospital, 90-day, and 1-year mortality as outcome.

Results

Of the 171 patients, 170 were males, and grade 1 ACLF in 20 (11.7%), grade 2 in 52 (30.4%), and grade 3 in 99 (57.9%) patients. One hundred and nineteen (69.6%) died in-hospital. The median (IQR) Maddrey’s score, MELD, MELD-Na, ABIC, APACHE II, and CLIF-C ACLF were 87.8 (66.5–123.0), 33.1 (27.6–40.0), 34.4 (29.5–40.0), 8.5 (7.3–9.6), 15 (12–21), and 51.1 (44.1–56.4), respectively. On multivariate Cox regression analysis, independent predictors of in-hospital outcome were presence of hepatic encephalopathy (early HR, 2.078; 95%CI, 1.173–3.682, p?=?0.012 and advanced, HR, 2.330; 95% CI, 1.270–4.276, p?=?0.006), elevated serum creatinine (HR, 1.140; 95% CI, 1.023–1.270, p?=?0.018), and infection at admission (HR, 1.874; 95% CI, 1.160–23.029, p?=?0.010). On comparison of ROC curves, APACHE II and CLIF-C ACLF AUROC were significantly higher than MELD, MELD-Na, DF, and ABIC (p?<?0.05) for predicting in-hospital, 90-day, and 1-year mortality. The AUROC was highest for APACHE II followed by CLIF-C ACLF (Hanley and McNeil, p?=?0.660).

Conclusions

Alcohol-related ACLF has high in-hospital mortality. Among the available prognostic scores, CLIF-C ACLF and APACHE II perform best.

     

Non-driver mutations in patients with <Emphasis Type="Italic">JAK2</Emphasis>V617F-mutated polycythemia vera or essential thrombocythemia with long-term molecular follow-up

JAK2V617F monitoring and NGS of non-driver genes was performed in 100 patients with polycythemia vera (PV) or essential thrombocythemia (ET) with long molecular follow-up. Patients who did not progress to myelofibrosis (MF) or acute myeloid leukemia (AML) after more than 10 years (n?=?50) showed a low frequency of mutations at first sample (18%) and an incidence rate of 1.7 new mutations?×?100 person-years. Mutations were detected at first sample in 83% of PV/ET patients who later progressed to AML (n?=?12) with these patients having a rate of 25.6 mutations?×?100 person-years. Presence of mutations at diagnosis was the unique risk factor for acquiring a new genetic event (HR 2.7, 95% CI 1.1–6.8, p?=?0.03) after correction for age, PV diagnosis, and total duration of hydroxyurea (HU) exposure. Patients with additional mutation at first sample showed a higher probability of developing cytopenia under HU therapy and a higher risk of AML (HR 12.2, 95% CI 2.6–57.1, p?=?0.001) with mutations in ASXL1 (p?<?0.0001), TP53 (p?=?0.01), SRSF2 (p?<?0.0001), IDH1/2 (p?<?0.0001), and RUNX1 (p?<?0.0001) being associated with a higher probability of AML. Myelofibrotic transformation was more frequent in patients with additional mutations, especially in SF3B1 (p?=?0.02) and IDH1/2 (p?<?0.0001) although a persistently high or a progressive increase of the JAK2V617F allele burden while receiving cytoreduction was the strongest predictor of MF transformation (HR 10.8, 95% CI 2.4–49.1, p?=?0.002). In conclusion, NGS may be useful to identify a minority of PV and ET patients with high genetic instability and increased risk of AML transformation.     

The prognostic value of signet ring cell histology in stage I/II colon cancer—a population-based,propensity score-matched analysis

Background

Previous research associated signet ring cell histology in colon cancer patients with poor survival outcomes. The aim of this study was to analyze the prognostic significance of signet ring cell histology on overall and cancer-specific survival in patients with localized colon cancer.

Methods

Stage I and II colon cancer patients treated with surgical resection between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were assessed using risk-adjusted Cox proportional hazards regression models and propensity score methods.

Results

Eighty-eight thousand nine hundred fifty-eight stage I–II colon cancer patients were identified. Overall, 446 (0.5%) showed signet ring cell histology. In unadjusted analyses, the 5-year OS and CSS rates of patients with signet ring cell histology were 65.8 and 83.1%, respectively, compared with 74.3 and 88.7% in patients with non-signet ring cell adenocarcinoma (p values: OS, p?<?0.001; CSS, p?<?0.001). Neither in risk-adjusted Cox proportional hazard regression analysis (OS: hazard ratio (HR), 0.96 (95% CI, 0.82–1.12%) p?=?0.616; CSS: HR, 1.01 (95% CI, 0.79–1.28%) p?=?0.946) nor with propensity score matching (OS: HR, 0.96 (95% CI, 0.82–1.14%) p?=?0.669 and CSS: HR: 1.09 (95% CI: 0.84–1.40%) p?=?0.529), a survival disadvantage was found for signet ring cell histology.

Conclusion

This is the first propensity score-adjusted population-based investigation on exclusively stage I and II colon cancer patients providing compelling evidence that signet ring cell histology does not negatively impact survival in stage I and II colon cancer after risk-adjusting for known prognostic factors. Therefore, standard treatment strategies can be applied in these patients.

     

Major adverse cardiovascular events in non-valvular atrial fibrillation with chronic obstructive pulmonary disease: the ARAPACIS study

Chronic obstructive pulmonary disease (COPD) increases the risk of mortality in non-valvular atrial fibrillation (NVAF) patients. Data on the relationship of COPD to major cardiovascular events (MACE) in AF have not been defined. The aim of the study is to assess the predictive value of COPD on incident MACE in NVAF patients over a 3-year follow-up. In the Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study (ARAPACIS) cohort, we evaluate the impact of COPD on the following clinical endpoints: MACE (including vascular death, fatal/non-fatal MI and stroke/TIA), cardiovascular (CV) death and all-cause mortality. Among 2027 NVAF patients, patients with COPD (9%) are more commonly male, elderly and at higher thromboembolic risk. During a median 36.0 months follow-up, 186 patients experienced MACE: vascular death (n?=?72), MI (n?=?57), stroke/TIA (n?=?57). All major outcomes (including stroke/TIA, MI, vascular death, and all-cause death) are centrally adjudicated. Kaplan–Meier curves show that NVAF patients with COPD are at higher risk for MACE (p?<?0.001), CV death (p?<?0.001) and all-cause death (p?<?0.001). On Cox proportional hazard analysis, COPD is an independent predictor of MACE (Hazard ratio [HR] 1.77, 95% Confidence Intervals [CI] 1.20–2.61; p?=?0.004), CV death (HR 2.73, 95% CI 1.76–4.23; p?<?0.0001) and all-cause death (HR 2.16, 95% CI 1.48–3.16; p?<?0.0001). COPD is an independent predictor of MACE, CV death and all-cause death during a long-term follow-up of NVAF patients.     

Tumor necrosis could reflect advanced disease status in patients with diffuse large B cell lymphoma treated with R-CHOP therapy

Tumor necrosis (TN) can lower responsiveness to chemotherapy and confer basic resistance to anti-cancer therapy. We investigated the association of TN with poor clinical features and outcome in diffuse large B cell lymphoma (DLBCL). We examined the presence or absence of TN in 476 DLBCL patients of who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Eighty-nine (18.7 %) patients had TN at diagnosis. Patients with TN had a progression-free survival (PFS) and overall survival (OS) of 39.3 and 46.7 %, whereas patients without TN had a PFS and OS of 73.4 and 82.6 %. Adverse clinical factors of poor Eastern Cooperative Oncology Group performance status ≥ grade 2 (p?=?0.005), elevated lactate dehydrogenase ratio >1 (p?<?0.001), advanced Ann Arbor stage (p?=?0.002), and bulky disease (p?=?0.026) were more prevalent in the TN group than the non-TN group. Cox regression model analysis revealed TN as an independent prognostic factor for PFS and OS in DLBCL (PFS, hazard ratio [HR]?=?1.967, 95 % confidence interval [CI]?=?1.399–2.765, p?<?0.001; OS, HR?=?2.445, 95 % CI?=?1.689–3.640, p?<?0.001). The results indicate that TN could reflect adverse clinical features and worse prognosis in DLBCL patients receiving R-CHOP therapy.     

Baricitinib,a Janus kinase inhibitor,in the treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials

Janus kinases (JAKs) play an important role in intracellular signaling for multiple cytokines in the pathogenesis of RA. Baricitinib is an oral, selective JAK 1 and 2 inhibitor which has been shown to be effective in the treatment of RA in several clinical trials. This meta-analysis aims to aggregate currently available data to assess the overall efficacy and safety of baricitinib in RA. We searched PubMed, EMBASE, and Cochrane CENTRAL from inception through 09/24/17 with restriction to English language. We excluded meeting abstracts without full text publication. We used RevMan 5.3 to perform meta-analysis between groups on baricitinib (2 and 4 mg daily) and placebo using random effect model calculating odds ratio (OR) as well as 95% confidence interval (CI). Compared to placebo, 2 mg of baricitinib was more effective in achieving ACR20 [54 vs. 36.6%; OR 2.09; 95% CI 1.60–2.71; p?<?0.00001; I² 0%], ACR50 [31.6 vs. 10.3%; OR 2.3; 95% CI 1.68–3.15; p?<?0.00001; I² 0%], and ACR70 responses [18.7 vs. 5.1%; OR 4.05; 95% CI 2.54–6.44; p?<?0.00001; I² 0%]. Similarly, 4 mg of baricitinib daily was more effective than placebo. Baricitinib 2 mg once daily did not increase any adverse events [65.3 vs. 62.4%; OR 1.03; 95% CI 0.80–1.34; p?=?0.8; I² 0%], serious adverse events [3.5 vs. 5%; OR 0.68; 95% CI 0.37–1.27; p?=?0.22; I² 0%], and herpes zoster [1.2 vs. 0.4%; OR 2.34; 95% CI 0.27–20.47; p?=?0.44; I² 37%] as compared to placebo. Similarly, 4 mg of baricitinib did not increase the risk of serious adverse events but increased herpes zoster infection [OR 3.88; 95% CI 1.36–11.06; p?=?0.01; I² 0%] when compared to placebo. Baricitinib is effective in treatment of RA, and did not appear to have significant safety concerns during the first 6 months of treatment.     

Association between susceptibility to rheumatoid arthritis and <Emphasis Type="Italic">PADI4</Emphasis> polymorphisms: a meta-analysis

The objective of the study was to determine by meta-analysis whether polymorphisms of the gene encoding peptidylarginine deiminase 4 (PADI4) are associated with susceptibility to rheumatoid arthritis (RA). A literature review was conducted to identify data sets that described analyses of genetic association between PADI4 polymorphisms and RA. Data sets were collated and a meta-analysis was performed, with a specific focus on associations within Caucasian and Asian populations. A total of 15,947 RA cases and 22,696 controls that were taken from 28 studies in 24 papers were included in this study. Meta-analysis showed a significant association between allele 2 of the PADI4_94 polymorphism and RA in the overall population (odds ratio [OR]?=?1.155, 95 % confidence interval [CI]?=?1.069–1.249, p?=?2.7?×?10^?5). Stratification by ethnicity revealed an association between PADI4_94 allele 2 and RA in Asians (OR?=?1.273, 95 % CI?=?1.193–1.359, p?<?1.0?×?10^?9), but not in Caucasians (OR?=?1.024, 95 % CI?=?0.973–1.078, p?=?0.358). However, meta-analysis using homozygote contrast showed an association between PADI4_94 allele 2 and RA in both Asians (OR?=?2.311, 95 % CI?=?1.1.858–2.875, p?<?1.0?×?10^?9) and Caucasians (OR?=?1.523, 95 % CI?=?1.157–2.004, p?=?0.008). Meta-analysis also revealed an association between allele 2 of the PADI4_104 polymorphism and RA in both Asians (OR?=?1.547, 95 % CI?=?1.247–1.919, p?=?7.1?×?10^?6) and Caucasians (OR?=?1.096, 95 % CI?=?1.025–1.172, p?=?0.008). Finally, meta-analysis showed an association between allele 2 of the PADI4_92 polymorphism and RA in Asians (OR?=?1.263, 95 % CI?=?1.153–1.384, p?=?5.8?×?10^?8), but not in Caucasians (OR?=?1.123, 95 % CI?=?0.980–1.287, p?=?0.095). Meta-analysis indicated no association between allele 2 of either the PADI4_90 or PADI4_89 polymorphisms and RA in Asians. This meta-analysis revealed that the PADI4_94 and PADI_104 polymorphisms are associated with susceptibility to RA in Asians and Caucasians, and that the PADI4_92 polymorphism is associated with susceptibility to RA in Asians, but not in Caucasians.     

Surgical Resection for Pulmonary Carcinoid: Long-Term Results of Multicentric Study—The Importance of Pathological N Status,More Than We Thought

Background

Histological subdivision into typical (TC) and atypical (AC) is crucial for treatment and prognosis of lung carcinoids but can be also very challenging, even for experts. In this study, we aimed to strengthen or reduce the prognostic value of several pathological, clinical, or per-operative factors some of which are still controversial.

Methods

We retrospectively reviewed clinical records related to 195 patients affected by TC (159) or AC (36) surgically treated between 2000 and 2014, in three different centers. Survival and subtypes comparison analyses were performed to identify potential prognostic factors.

Results

TCs showed a lower rate of nodal involvement than ACs (N0 = 94.9%; N1 = 1.9%; N2 = 3.2% in typical and N0 = 63.8%; N1 = 16.6%; N2 = 19.4% in atypical carcinoids, respectively, p < 0.0001). Long-term oncological results of resected carcinoids were significantly better in TCs than ACs with higher 5- and 10-year overall survival rates (97.2 and 88.2% vs. 77.9 and 68.2%, respectively; p = 0.001) and disease-free survival rates (98.2 and 90.3% in typical and 80.8 and 70.7% atypical carcinoids, respectively; p = 0.001). Risk factors analysis revealed that AC subtype [HR 4.33 (95% CI 1.72–8.03), p = 0.002], pathological nodal involvement [HR 3.05 (95% CI 1.77–5.26), p < 0.0001], and higher SUV_max [HR 4.33 (95% CI 1.03–7.18), p = 0.002] were independently and pejoratively associated with overall survival. Factors associated with a higher risk of recurrence were AC subtype [HR 6.13 (95% CI 1.13–18.86), p = 0.002]; nodal involvement [HR 5.48 (95% CI 2.85–10.51), p < 0.0001]; higher Ki67 expression level [HR 1.09 (95% CI 1.01–1.20), p = 0.047]; and SUV_max [HR 1.83 (95% CI 1.04–3.23), p = 0.035].

Conclusion

Surgery for lung carcinoids allows satisfactory oncological results which mainly depend on carcinoid subtype dichotomy, pathological nodal status, and SUV_max.

     

Association between the functional <Emphasis Type="Italic">MHC2TA</Emphasis> −168 A/G polymorphism and susceptibility to rheumatoid arthritis: a meta-analysis

The aim of this study was to determine whether the functional major histocompatibility complex II transactivator (MHC2TA) ?168 A/G polymorphism is associated with susceptibility to rheumatoid arthritis (RA). A meta-analysis was conducted to estimate the association between the MHC2TA?168 A/G polymorphism and RA. A total of 15 comparative studies, which included 14,158 patients and 13,642 controls, were included in the meta-analysis. Based on the meta-analysis, there was no association between RA and the MHC2TA ?168 G allele in the study subjects (OR?=?1.046, 95 % CI?=?0.987–1.108, p?=?0.130) or Caucasians (OR?=?1.027, 95 % CI?=?0.986–1.070, p?=?0.193). However, the country-specific meta-analysis revealed an association between the MHC2TA ?168 G allele and RA in the Swedish population (OR?=?1.131, 95 % CI?=?1.023–1.250, p?=?0.016). A direct comparison between rheumatoid factor (RF)-positive and RF-negative patients revealed that the frequency of the G allele was significantly lower in RF-positive patients (OR?=?0.783, 95 % CI?=?0.628–0.975, p?=?0.029) than in RF-negative patients. This meta-analysis demonstrated that the MHC2TA ?168 A/G polymorphism is not associated with susceptibility to RA in Caucasians.     

Malnutrition and sarcopenia in a large cohort of patients with systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease which may lead to malnutrition. Previous studies have defined it with different criteria. No thorough evaluations of sarcopenia in SSc are available. The aim of the present study was to assess the prevalence and the potential association of malnutrition and sarcopenia in a large cohort of SSc cases. A total of 141 SSc consecutive outpatients were enrolled. Body composition was analyzed by densitometry. Malnutrition was defined according to recently published ESPEN criteria, whereas sarcopenia was diagnosed in patients with reduced skeletal muscle index. Malnutrition was diagnosed in 9.2% of patients (95% CI, 4.4–14.0%). Malnourished patients had worse gastrointestinal symptoms according to UCLA SCTC GIT 2.0 questionnaire (p?=?0.007), lower physical activity (p?=?0.028), longer disease duration (p?=?0.019), worse predicted DLCO/VA and FVC (p?=?0.009, respectively), worse disease severity according to Medsger severity score (p?<?0.001), lower hemoglobin (p?=?0.023), and fat-free mass (p?<?0.001) and were more often sarcopenic (p?<?0.001). In multivariate analysis, only FVC (p?=?0.006) and disease severity (p?=?0.003), in particular for the lungs (p?=?0.013), were confirmed to be worse in malnourished patients. Sarcopenia was diagnosed in 29\140 patients (20.7%; 95% CI, 14.0–27.4%); 11\29 were also malnourished. In multivariate analysis, sarcopenic patients had longer disease duration (p?=?0.049), worse DLCO/VA (p?=?0.002), and lung (p?=?0.006) and skin (p?=?0.014) involvement. In SSc, malnutrition defined with ESPEN criteria was found to be lower than previously reported. Sarcopenia was found to be somewhat common. Lung involvement was significantly associated with nutritional status and may not be explained only by muscle weakness.     

Statin Use,Diabetes Incidence and Overall Mortality in Normoglycemic and Impaired Fasting Glucose Patients

BACKGROUND

The association between the use of statins and the risk of diabetes and increased mortality within the same population has been a source of controversy, and may underestimate the value of statins for patients at risk.

OBJECTIVE

We aimed to assess whether statin use increases the risk of developing diabetes or affects overall mortality among normoglycemic patients and patients with impaired fasting glucose (IFG).

DESIGN AND PARTICIPANTS

Observational cohort study of 13,508 normoglycemic patients (n?=?4460; 33 % taking statins) and 4563 IFG patients (n?=?1865; 41 % taking statin) among residents of Olmsted County, Minnesota, with clinical data in the Mayo Clinic electronic medical record and at least one outpatient fasting glucose test between 1999 and 2004. Demographics, vital signs, tobacco use, laboratory results, medications and comorbidities were obtained by electronic search for the period 1999–2004. Results were analyzed by Cox proportional hazards models, and the risk of incident diabetes and mortality were analyzed by survival curves using the Kaplan–Meier method.

MAIN MEASURES

The main endpoints were new clinical diagnosis of diabetes mellitus and total mortality.

KEY RESULTS

After a mean of 6 years of follow-up, statin use was found to be associated with an increased risk of incident diabetes in the normoglycemic (HR 1.19; 95 % CI, 1.05 to 1.35; p?=?0.007) and IFG groups (HR 1.24; 95%CI, 1.11 to 1.38; p?=?0.0001). At the same time, overall mortality decreased in both normoglycemic (HR 0.70; 95 % CI, 0.66 to 0.80; p?<?0.0001) and IFG patients (HR 0.77, 95 % CI, 0.64 to 0.91; p?=?0.0029) with statin use.

CONCLUSION

In general, recommendations for statin use should not be affected by concerns over an increased risk of developing diabetes, since the benefit of reduced mortality clearly outweighs this small (19–24 %) risk.

     

Impact of front line relative dose intensity for methotrexate and comorbidities in immunocompetent elderly patients with primary central nervous system lymphoma

Primary central nervous system lymphomas (PCNSL) are non-Hodgkin lymphomas strictly localized to the CNS, occurring mainly in elderly patients with comorbidities. Current treatment in fit patients relies on high-dose methotrexate and high-dose cytarabine. The aim of this study was to evaluate the efficacy and feasibility of this treatment in elderly patients and to assess potential prognostic factors associated with survival. We conducted a retrospective study in two centers between January 2008 and September 2015 including 35 elderly immunocompetent patients who received first-line treatment with high-dose methotrexate. With a median follow-up of 19.8 months (range: 1.7–73.4 months), median overall survival (OS) was 39.5 months (95% confidence interval (95% CI): 18.3–60.7) and median progression-free survival (PFS) was 25.8 months (95% CI: 5.2–46.4). In univariate analysis, administration of high-dose cytarabine and achieving a relative dose intensity for methotrexate >?75% were associated with increased OS (p?=?0.006 and p?=?0.003, respectively) and PFS (p?=?0.003 and p?=?0.04, respectively) whereas comorbidities, defined by a CIRS-G score ≥?8, were associated with decreased OS and PFS (p?=?0.02 and p?=?0.04, respectively). A high MSKCC score was associated with decreased OS (p?=?0.02). In multivariate analysis, administration of high-dose cytarabine was associated with increased OS and PFS (p?=?0.02 and p?=?0.007, respectively). Comorbidities and relative dose intensity for methotrexate are important for the prognosis of elderly patients with PCNSL. These results must be confirmed in prospective trials.     

Prognostic Factors in Adult Patients with Non-Cystic Fibrosis Bronchiectasis

Background

Non-cystic fibrosis bronchiectasis (NCFB) is a heterogeneous disease. There are few studies about prognostic factors in these patients. Our study aims to assess mortality rates and related factors in a cohort of patients and test the ability of the BSI and FACED scores in predicting mortality in this cohort.

Methods

This was a prospective cohort analysis of 70 patients with NCFB recruited from May 2008 to August 2010. At baseline, patients underwent clinical evaluation, pulmonary function tests, 6-min walk test, and quality of life assessment. Outcomes were defined as favorable (survivors) and unfavorable (survivors who underwent lung transplantation and death from all causes). Baseline records provided data for determination of BSI and FACED.

Results

Twenty-seven patients (38.57%) died and 1 (1.43%) underwent lung transplantation. Mean time for occurrence of unfavorable outcomes was 74.67?±?4.00 months. Main cause of death was an acute infectious exacerbation of bronchiectasis (60.7). Cox regression identified age (p?=?0.035; HR 1.04; CI 1.01–1.08), FEV₁ % of predicted (p?=?0.045; HR 0.97; CI 0.93–0.99), and MEP (p?=?0.016; HR 0.96; CI 0.94–0.99) as independent predictors of unfavorable outcomes. FACED was better at predicting unfavorable outcomes in our cohort (log-rank test, FACED p?=?0.001 and BSI p?=?0.286). In ROC analysis, both scores were similar in predicting unfavorable outcomes (BSI 0.65; FACED 0.66).

Conclusions

Older age, lower FEV₁ % of predicted, and lower MEP were independently linked to unfavorable outcomes. FACED and BSI were not accurate in predicting mortality in our cohort.

     

Self-reported obstructive sleep apnea,simple snoring,and various markers of sleep-disordered breathing as predictors of cardiovascular risk

Purpose

Our objective was to investigate whether self-reported obstructive sleep apnea (OSA), simple snoring, and various markers of sleep-disordered breathing (SDB) are associated with cardiovascular risk.

Methods

We examined a representative nationwide cohort of 5177 Finnish adults aged ≥30 years. The participants underwent measurement of traditional cardiovascular risk factors and answered SDB-related questions derived from the Basic Nordic Sleep Questionnaire, which were used to operationalize self-reported OSA. The primary end point was incidence of a cardiovascular event (cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, or coronary interventions).

Results

During a median follow-up of 11.2 years and 52,910 person-years of follow-up, 634 participants suffered a cardiovascular event. In multivariable-adjusted Cox models, self-reported OSA (hazard ratio [HR] 1.34; 95 % confidence interval [CI] 1.04–1.73; p?=?0.03) was an independent predictor of cardiovascular events. Self-reported simple snoring by itself was not associated with future cardiovascular events (HR 0.88 versus non-snorers, 95 % CI 0.75–1.04, p?=?0.15). However, among snorers (n?=?3152), frequent breathing cessations (HR 2.19, 95 % CI 1.26–3.81, p?=?0.006) and very loud and irregular snoring (HR 1.82, 95 % CI 1.31–2.54, p?<?0.001) were associated with cardiovascular risk.

Conclusions

Self-reported OSA and SDB-related snoring variables are associated with cardiovascular risk, whereas simple snoring is not. In clinical practice and in surveys, questions concerning only habitual snoring should be amended with questions focusing on respiratory pauses and snoring stertorousness, which can be used to estimate the risk of OSA and cardiovascular events.

     

Time from colorectal cancer diagnosis to laparoscopic curative surgery—is there a safe window for prehabilitation?

Background

There is a growing interest in the adoption of formal prehabilitation programmes prior to elective surgery but regulatory targets mandate prompt treatment following cancer diagnosis. We aimed to investigate if time from diagnosis to surgery is linked to short- and long-term outcomes.

Methods

An exploratory analysis was performed utilising a dedicated, prospectively populated database. Inclusion criteria were biopsy-proven colorectal adenocarcinoma undergoing elective laparoscopic surgery with curative intent. Demographics, date of diagnosis and surgery was captured with patients dichotomised using 4-, 8- and 12-week time points. All patients were followed in a standardised pathway for 5 years. Overall survival was assessed with the Kaplan-Meier log-rank method.

Results

Six hundred sixty-eight consecutive patients met inclusion criteria. Mean time from diagnosis to surgery was 53 days (95% CI 48.3–57.8). Identified risk factors for longer time to surgery were males (OR 1.92 [1.2–3.1], p?=?0.008), age?≤?65 (OR 1.9 [1.2–3], p?=?0.01), higher ASA scores (p?=?0.01) stoma formation (OR 6.9 [4.1–11], p?<?0.001) and neoadjuvant treatment (OR 5.06 [3.1–8.3], p?<?0.001). There was no association between time to surgery and BMI (p?=?0.36), conversion (16.3%, p?=?0.5), length of stay (p?=?0.33) and readmission or reoperation (p?=?0.3). No differences in five-year survival were seen in those operated within 4, 8 and 12 weeks (p?=?0.397, p?=?0.962 and p?=?0.611, respectively). Multivariate analysis showed time from diagnosis to surgery was not associated with five-year overall survival (HR 0.99, p?=?0.52).

Conclusion

Time from colorectal cancer diagnosis to curative laparoscopic surgery did not impact on overall survival. This finding may allow preoperative pathway alteration without compromising safety.

     

The Association Between Receipt of Guideline-Concordant Long-Term Opioid Therapy and All-Cause Mortality

Purpose

For patients receiving long-term opioid therapy (LtOT), the impact of guideline-concordant care on important clinical outcomes—notably mortality—is largely unknown, even among patients with a high comorbidity and mortality burden (e.g., HIV-infected patients). Our objective was to determine the association between receipt of guideline-concordant LtOT and 1-year all-cause mortality.

Methods

Among HIV-infected and uninfected patients initiating LtOT between 2000 and 2010 through the Department of Veterans Affairs, we used Cox regression with time-updated covariates and propensity-score matched analyses to examine the association between receipt of guideline-concordant care and 1-year all-cause mortality.

Results

Of 17,044 patients initiating LtOT between 2000 and 2010, 1048 patients (6%) died during 1 year of follow-up. Patients receiving psychotherapeutic co-interventions (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.51–0.75; P?<?0.001) or physical rehabilitative therapies (HR 0.81; 95% CI 0.67–0.98; P?=?0.03) had a decreased risk of all-cause mortality compared to patients not receiving these services, whereas patients prescribed benzodiazepines concurrent with opioids had a higher risk of mortality (HR 1.39; 95% CI 1.12–1.66; P?<?0.001). Among patients with a current substance use disorder (SUD), those receiving SUD treatment had a lower risk of mortality than untreated patients (HR 0.47; 95% CI 0.32–0.68; P?=?< 0.001). No association was found between all-cause mortality and primary care visits (HR 1.12; 95% CI 0.90–1.26; P?=?0.32) or urine drug testing (HR 0.96; 95% CI 0.78–1.17; P?=?0.67).

Conclusions

Providers should use caution in initiating LtOT in conjunction with benzodiazepines and untreated SUDs. Patients receiving LtOT may benefit from multi-modal treatment that addresses chronic pain and its associated comorbidities across multiple disciplines.

     

Identifying Subpopulations with Distinct Response to Treatment Using Plasma Biomarkers in Acute Heart Failure: Results from the PROTECT Trial

Background

Over the last 50 years, clinical trials of novel interventions for acute heart failure (AHF) have, with few exceptions, been neutral or shown harm. We hypothesize that this might be related to a differential response to pharmacological therapy.

Methods

We studied the magnitude of treatment effect of rolofylline across clinical characteristics and plasma biomarkers in 2033 AHF patients and derived a biomarker-based responder sum score model. Treatment response was survival from all-cause mortality through day 180.

Results

In the overall study population, rolofylline had no effect on mortality (HR 1.03, 95% CI 0.82–1.28, p = 0.808). We found no treatment interaction across clinical characteristics, but we found interactions between several biomarkers and rolofylline. The biomarker-based sum score model included TNF-R1α, ST2, WAP four-disulfide core domain protein HE4 (WAP-4C), and total cholesterol, and the score ranged between 0 and 4. In patients with score 4 (those with increased TNF-R1α, ST2, WAP-4C, and low total cholesterol), treatment with rolofylline was beneficial (HR 0.61, 95% CI 0.40–0.92, p = 0.019). In patients with score 0, treatment with rolofylline was harmful (HR 5.52, 95% CI 1.68–18.13, p = 0.005; treatment by score interaction p < 0.001). Internal validation estimated similar hazard ratio estimates (0 points: HR 5.56, 95% CI 5.27–7–5.87; 1 point: HR 1.31, 95% CI 1.25–1.33; 2 points: HR 0.75, 95% CI 0.74–0.76; 3 points: HR 1.13, 95% CI 1.11–1.15; 4 points, HR 0.61, 95% CI 0.61–0.62) compared to the original data.

Conclusion

Biomarkers are superior to clinical characteristics to study treatment heterogeneity in acute heart failure.

     

Prognostic Impact of Node-Spreading Pattern in Surgically Treated Small-Cell Lung Cancer: A Multicentric Analysis

Objective

Although surgery in selected small-cell lung cancer (SCLC) patients has been proposed as a part of multimodality therapy, so far, the prognostic impact of node-spreading pattern has not been fully elucidated. To investigate this issue, a retrospective analysis was performed.

Methods

From 01/1996 to 12/2012, clinico-pathological, surgical, and oncological features were retrospectively reviewed in a multicentric cohort of 154 surgically treated SCLC patients. A multivariate Cox proportional hazard model was developed using stepwise regression, in order to identify independent outcome predictors. Overall (OS), cancer-specific (CSS), and Relapse-free survival (RFS) were calculated by Kaplan-Meier method.

Results

Overall, median OS, CSS, and RFS were 29 (95 % CI 18–39), 48 (95 % CI 19–78), and 22 (95 % CI 17–27) months, respectively. Lymphadenectomy was performed in 140 (90.9 %) patients (median number of harvested nodes: 11.5). Sixty-seven (47.9 %) pN0-cases experienced the best long-term survival (CSS: 71, RFS: 62 months; p < 0.0001). Among node-positive patients, no prognostic differences were found between pN1 and pN2 involvement (CSS: 22 vs. 15, and RFS: 14 vs. 10 months, respectively; p = 0.99). By splitting node-positive SCLC according to concurrent N1-invasion, N0N2-patients showed a worse CSS compared to those cases with combined N1N2-involvement (N0N2: 8 months vs. N1N2: 22 months; p = 0.04). On the other hand, the number of metastatic stations (p = 0.80) and the specific node-level (p = 0.85) did not affect CSS. At multivariate analysis, pN+ (HR: 3.05, 95 % CI 1.21–7.67, p = 0.02) and ratio between metastatic and resected lymph-nodes (RL, HR: 1.02, 95 % CI 1.00–1.04, p = 0.03) were independent predictors of CSS. Moreover, node-positive patients (HR: 3.60, 95 % CI 1.95–6.63, p < 0.0001) with tumor size ≥5 cm (HR: 1.85, 95 % CI 0.88–3.88, p = 0.10) experienced a worse RFS.

Conclusions

In selected surgically treated SCLC, the long-term survival may be stratified according to the node-spreading pattern.