Infection and venous thromboembolism in patients undergoing colorectal surgery: what is the relationship?

BACKGROUND: There is evidence demonstrating an association between infection and venous thromboembolism. We recently identified this association in the postoperative setting; however, the temporal relationship between infection and venous thromboembolism is not well defined OBJECTIVE: We sought to determine the temporal relationship between venous thromboembolism and postoperative infectious complications in patients undergoing colorectal surgery. DESIGN, SETTING, AND PATIENTS: A retrospective cohort analysis was performed using data for patients undergoing colorectal surgery in the National Surgical Quality Improvement Project 2010 database. MAIN OUTCOME MEASURES: The primary outcome measures were the rate and timing of venous thromboembolism and postoperative infection among patients undergoing colorectal surgery during 30 postoperative days. RESULTS: Of 39,831 patients who underwent colorectal surgery, the overall rate of venous thromboembolism was 2.4% (n = 948); 729 (1.8%) patients were diagnosed with deep vein thrombosis, and 307 (0.77%) patients were diagnosed with pulmonary embolism. Eighty-eight (0.22%) patients were reported as developing both deep vein thrombosis and pulmonary embolism. Following colorectal surgery, the development of a urinary tract infection, pneumonia, organ space surgical site infection, or deep surgical site infection was associated with a significantly increased risk for venous thromboembolism. The majority (52%-85%) of venous thromboembolisms in this population occurred the same day or a median of 3.5 to 8 days following the diagnosis of infection. The approximate relative risk for developing any venous thromboembolism increased each day following the development of each type of infection (range, 0.40%-1.0%) in comparison with patients not developing an infection. LIMITATIONS: We are unable to account for differences in data collection, prophylaxis, and venous thromboembolism surveillance between hospitals in the database. Additionally, there is limited patient follow-up. CONCLUSIONS: These findings of a temporal association between infection and venous thromboembolism suggest a potential early indicator for using certain postoperative infectious complications as clinical warning signs that a patient is more likely to develop venous thromboembolism. Further studies into best practices for prevention are warranted

Bacterial peptidoglycan stimulates adipocyte lipolysis via NOD1.

Obesity is associated with inflammation that can drive metabolic defects such as hyperlipidemia and insulin resistance. Specific metabolites can contribute to inflammation, but nutrient intake and obesity are also associated with altered bacterial load in metabolic tissues (i.e. metabolic endotoxemia). These bacterial cues can contribute to obesity-induced inflammation. The specific bacterial components and host receptors that underpin altered metabolic responses are emerging. We previously showed that Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) activation with bacterial peptidoglycan (PGN) caused insulin resistance in mice. We now show that PGN induces cell-autonomous lipolysis in adipocytes via NOD1. Specific bacterial PGN motifs stimulated lipolysis in white adipose tissue (WAT) explants from WT, but not NOD1⁻/⁻mice. NOD1-activating PGN stimulated mitogen activated protein kinases (MAPK),protein kinase A (PKA), and NF-κB in 3T3-L1 adipocytes. The NOD1-mediated lipolysis response was partially reduced by inhibition of ERK1/2 or PKA alone, but not c-Jun N-terminal kinase (JNK). NOD1-stimulated lipolysis was partially dependent on NF-κB and was completely suppressed by inhibiting ERK1/2 and PKA simultaneously or hormone sensitive lipase (HSL). Our results demonstrate that bacterial PGN stimulates lipolysis in adipocytes by engaging a stress kinase, PKA, NF-κB-dependent lipolytic program. Bacterial NOD1 activation is positioned as a component of metabolic endotoxemia that can contribute to hyperlipidemia, systemic inflammation and insulin resistance by acting directly on adipocytes

Temporal trends in gender-affirming surgery among transgender patients in the United States

Importance: Little is known about the incidence of gender-affirming surgical procedures for transgender patients in the United States.Objectives: To investigate the incidence and trends over time of gender-affirming surgical procedures and to analyze characteristics and payer status of transgender patients seeking these operations.Design, setting, and participants: In this descriptive observational study from 2000 to 2014, data were analyzed from the National Inpatient Sample, a representative pool of inpatient visits across the United States. The initial analyses were done from June to August 2015. Patients of interest were identified by International Classification of Diseases, Ninth Revision, diagnosis codes for transsexualism or gender identity disorder. Subanalysis focused on patients with procedure codes for surgery related to gender affirmation.Main outcomes and measures: Demographics, health insurance plan, and type of surgery for patients who sought gender-affirming surgery were compared between 2000-2005 and 2006-2011, as well as annually from 2012 to 2014.Results: This study included 37 827 encounters (median [interquartile range] patient age, 38 [26-49] years) identified by a diagnosis code of transsexualism or gender identity disorder. Of all encounters, 4118 (10.9%) involved gender-affirming surgery. The incidence of genital surgery increased over time: in 2000-2005, 72.0% of patients who underwent gender-affirming procedures had genital surgery; in 2006-2011, 83.9% of patients who underwent gender-affirming procedures had genital surgery. Most patients (2319 of 4118 [56.3%]) undergoing these procedures were not covered by any health insurance plan. The number of patients seeking these procedures who were covered by Medicare or Medicaid increased by 3-fold in 2014 (to 70) compared with 2012-2013 (from 25). No patients who underwent inpatient gender-affirming surgery died in the hospital.Conclusions and relevance: Most transgender patients in this national sample undergoing inpatient gender-affirming surgery were classified as self-pay; however, an increasing number of transgender patients are being covered by private insurance, Medicare, or Medicaid. As coverage for these procedures increases, likely so will demand for qualified surgeons to perform them

Collecting sexual orientation and gender identity information in the emergency department : The divide between patient and provider perspectives

Background: In the USA, The Joint Commission and Institute of Medicine have called for collection of patient sexual orientation (SO) and gender identity (GI) information in healthcare. In a recent study, we reported that ED clinicians believe patients will refuse to provide this information; however, very few patients say they would refuse to provide SO/GI. As part of this study, we interviewed patients and providers regarding the importance of collecting this information. While these interviews were briefly summarised in our prior report, the qualitative data warranted a more thorough analysis and exposition to explore provider and patient views as well as risks and benefits of collecting SO/GI. Methods: A purposive sample of 79 participants was recruited for semi-structured interviews between August 2014 and January 2015. Participants included community members who had a previous ED encounter and ED providers from 3 community and 2 academic centres in a major US metropolitan area. Interviews were conducted one-on-one in person, audio-recorded and transcribed verbatim. Data were analysed using the constant comparative method. Results: Fifty-three patients and 26 ED providers participated. Patients perceived collection of SO/GI to be important in most clinical circumstances because SO/GI is relevant to their identity and allows providers to treat the whole person. However, many providers felt SO/GI was not relevant in most clinical circumstances because similar care is provided to all patients regardless of SO/GI. Patients and providers agreed there are risks associated with collecting SO/GI in the ED. Conclusions: ED clinicians do not perceive routine collection of SO/GI to be medically relevant in most circumstances. However, patients feel routine SO/GI collection allows for recognition of individual identity and improved therapeutic relationships in the ED. These discordant perspectives may be hindering patient-centred care, especially for sexual and gender minority patients

NOD1-mediated lipolysis occurs via both ERK and PKA.

<p>Glycerol release rate over 48-L1 adipocytes, which were incubated without or with FK565 (10 µg/mL) and various concentrations of the PKA inhibitor, PKI (14–22) (A). Glycerol release rate over 48 h was calculated in 3T3-L1 adipocytes, which were incubated without or with FK565 (10 µg/mL) and various combinations of H89 (20 µM, PKA inhibitor), and U0126 (10 µM, ERK1/2 inhibitor) or SP600125 (20 µM, JNK inhibitor) (B). 3T3-L1 adipocytes were incubated with or without FK565 (10 µg/mL) for 6 h and phosphorylated ERK1/2^{Thr202/Tyr204} (pERK) relative to total ERK was determined in the presence or absence of the PKA inhibitors PKI and H89 (C). n = 6–16 experiments per condition, values are mean <u>+</u> SEM. *Significantly different from control without FK565. #Significantly different from control with FK565. φSignificantly different from H89 or U0126 alone with FK565.</p

Avoiding Weight Gain in Cardiometabolic Disease: A Systematic Review

Patients with cardiometabolic disease are at higher risk for obesity-related adverse effects. Even without weight loss, weight maintenance may be beneficial. We performed a systematic review to identify the effect of nonweight loss-focused lifestyle interventions in adults with cardiometabolic disease. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify comparative studies of lifestyle interventions (self-management, diet, exercise, or their combination) without a weight loss focus in adults with or at risk for diabetes and cardiovascular disease. Weight, BMI, and waist circumference at ≥12 months were the primary outcomes. Of 24,870 citations, we included 12 trials (self-management, n=2; diet, n=2; exercise, n=2; combination, n=6) studying 4,206 participants. Self-management plus physical activity ± diet versus minimal/no intervention avoided meaningful weight (−0.65 to −1.3 kg) and BMI (−0.4 to −0.7 kg/m2) increases. Self-management and/or physical activity prevented meaningful waist circumference increases versus control (−2 to −4 cm). In patients with cardiometabolic disease, self-management plus exercise may prevent weight and BMI increases and self-management and/or exercise may prevent waist circumference increases versus minimal/no intervention. Future studies should confirm these findings and evaluate additional risk factors and clinical outcomes

NF-κB is involved in NOD1-mediated lipolysis.

<p>NF-κB activity in 3T3-L1 adipocytes after various exposure times of FK565 (10 µg/mL) (A). NF-κB activity in 3T3-L1 adipocytes without and with 6h exposure to FK565 (10 µg/mL) in the presence and absence of PKI (20 µM) and H89 (20 µM) (B). NF-κB activity in 3T3-L1 adipocytes without and with 6h exposure to FK565 (10 µg/mL) with various doses of U0126 (C). n = 4-6 experiments per condition for NF-κB activity. Glycerol release rate over 48 h in 3T3-L1 adipocytes incubated without or with FK565 (10 µg/mL) with various concentrations of NF-κB inhibitors, PDTC (D) and CAY10470 (E). Glycerol release rate over 48 h in 3T3-L1 adipocytes incubated without or with FK565 (10 µg/mL) with various combinations of H89 (20 µM, PKA inhibitor), and U0126 (20 µM, ERK1/2 inhibitor) or CAY10470 (NF-κB inhibitor, 5 nM) (F). n = 12–24 experiments per condition of lipolysis. Values are mean <u>+</u> SEM. *Significantly different from control without FK565. #Significantly different from control with FK565. φSignificantly different from CAY10470 or U0126 or H89 alone with FK565. εSignificantly different from CAY10470 plus U0126 or CAY10470 plus H89 with FK565.</p

NOD1-activating PGN causes adipocyte-autonomous lipolysis.

<p>Differentiated 3T3-L1 adipocytes were incubated with FK565 (10 µg/mL) and glycerol (A) and NEFA (B) concentration in the media determined at 0, 24, 48 h. Glycerol release rate over 48 h was calculated in 3T3-L1 adipocytes, which were incubated with vehicle (control), c12-iEDAP (10 µg/mL), FK565 (10 µg/mL) and various doses of MDP (C). Glycerol release rate over 48 h in 3T3-L1 adipocytes without and with FK565 (10 µg/mL) in the absence or presence of the NOD1 inhibitor ML130 (1-[(4-Methylphenyl)sulfonyl]-1H-benzimidazol-2-amine) at various concentrations (D). Glycerol release rate in 3T3-L1 adipocytes that were incubated with or without FK565 (10 µg/mL) and various concentrations of the HSL inhibitor CAY10499 (E). n = 5–16 experiments per condition, values are mean <u>+</u> SEM. *Significantly different from control or control at a given time point. #Significantly different from c12-iEDAP.</p