The Role of Lipoproteins in Mycoplasma-Mediated Immunomodulation

Mycoplasma infections, such as walking pneumonia or pelvic inflammatory diseases, are a major threat to public health. Despite their relatively small physical and genomic size, mycoplasmas are known to elicit strong host immune responses, generally inflammatory, while also being able to evade the immune system. The mycoplasma membrane is composed of approximately two-thirds protein and one-third lipid and contains several lipoproteins that are known to regulate host immune responses. Herein, the immunomodulatory effects of mycoplasma lipoproteins are reviewed. A better understanding of the immunomodulatory effects, both activating and evasive, of Mycoplasma surface lipoproteins will contribute to understanding mechanisms potentially relevant to mycoplasma disease vaccine development and treatment

Screening for renal cell carcinoma in renal transplant recipients: a single-centre retrospective study

Objectives The primary objective of our study was to evaluate the effectiveness of renal cell carcinoma (RCC) screening in renal transplant (RT) recipients.Design Single-centre retrospective study.Setting and participants 1998 RT recipients who underwent RT at Memorial Hermann Hospital (MHH) Texas Medical Center (TMC) between 1 January 1999 and 31 December 2019 were included and we identified 16 patients (0.8%) with RCC. An additional four patients with RCC who underwent RT elsewhere but received follow-up at MHH TMC were also included. Subject races included white (20%), black (50%), Hispanic (20%) and Asian (10%).Outcome measures The RCC stage at diagnosis and outcomes were compared between patients who were screening versus those who were not.Results We identified a total of 20 patients with post-RT RCC, 75% of whom were men. The median age at diagnosis was 56 years. RCC histologies included clear cell (75%), papillary (20%) and chromophobe (5%). Patients with post-RT RCC who had screening (n=12) underwent ultrasound or CT annually or every 2 years, whereas eight patients had no screening. All 12 patients who had screening had early-stage disease at diagnosis (stage I (n=11) or stage II (n=1)) and were cured by nephrectomy (n=10) or cryotherapy (n=2). In patients who had no screening, three (37.5%) had stage IV RCC at diagnosis and all of whom died of metastatic disease. There was a statistically significant difference in RCC-specific survival in patients who were screened (p=0.01) compared with those who were not screened.Conclusion All RT recipients who had RCC diagnosed based on screening had early-stage disease and there were no RCC-related deaths. Screening is an effective intervention in RT recipients to reduce RCC-related mortality

The Role of Lipoproteins in Mycoplasma-Mediated Immunomodulation.

Mycoplasma infections, such as walking pneumonia or pelvic inflammatory diseases, are a major threat to public health. Despite their relatively small physical and genomic size, mycoplasmas are known to elicit strong host immune responses, generally inflammatory, while also being able to evade the immune system. The mycoplasma membrane is composed of approximately two-thirds protein and one-third lipid and contains several lipoproteins that are known to regulate host immune responses. Herein, the immunomodulatory effects of mycoplasma lipoproteins are reviewed. A better understanding of the immunomodulatory effects, both activating and evasive, of Mycoplasma surface lipoproteins will contribute to understanding mechanisms potentially relevant to mycoplasma disease vaccine development and treatment

Hypophosphataemia after major hepatectomy and the risk of post-operative hepatic insufficiency and mortality: an analysis of 719 patients

AbstractBackgroundHypophosphataemia after a hepatectomy suggests hepatic regeneration. It was hypothesized that the absence of hypophosphataemia is associated with post-operative hepatic insufficiency (PHI) and complications.MethodsPatients who underwent a major hepatectomy from 2000–2012 at a single institution were identified. Post-operative serum phosphorus levels were assessed. Primary outcomes were PHI (peak bilirubin >7mg/dl), major complications, and 30- and 90-day mortality.ResultsSeven hundred and nineteen out of 749 patients had post-operative phosphorus levels available. PHI and major complications occurred in 63 (8.8%) and 169 (23.5%) patients, respectively. Thirty- and 90-day mortality were 4.0% and 5.4%, respectively. The median phosphorus level on post-operative-day (POD) 2 was 2.2mg/dl; 231 patients (32.1%) had phosphorus >2.4 on POD2.Patients with POD2 phosphorus >2.4 had a significantly higher incidence of PHI, major complications and mortality. On multivariate analysis, POD2 phosphorus >2.4 remained a significant risk factor for PHI [(hazard ratio HR):1.78; 95% confidence interval (CI):1.02–3.17; P = 0.048], major complications (HR:1.57; 95%CI:1.02–2.47; P = 0.049), 30-day mortality (HR:2.70; 95%CI:1.08–6.76; P = 0.034) and 90-day mortality (HR:2.51; 95%CI:1.03–6.15; P = 0.044). Similarly, patients whose phosphorus level reached nadir after POD3 had higher PHI, major complications and mortality.ConclusionElevated POD2 phosphorus levels >2.4mg/dl and a delayed nadir in phosphorus beyond POD3 are associated with increased post-operative hepatic insufficiency, major complications and early mortality. Failure to develop hypophosphataemia within 72h after a major hepatectomy may reflect insufficient liver remnant regeneration

Impact of hepatitis C treatment on long-term outcomes for patients with hepatocellular carcinoma: a United States Safety Net Collaborative Study

Widespread HCV treatment for hepatocellular carcinoma (HCC) patients remains limited. Our aim was to evaluate the association of HCV treatment with survival and assess barriers to treatment. Patients in the U.S. Safety Net Collaborative with HCV and HCC were included. Primary outcome was overall survival (OS). Secondary outcomes were recurrence-free survival (RFS) and barriers to receiving HCV treatment. Of 941 patients, 57% received care at tertiary referral centers (n=533), 74% did not receive HCV treatment (n=696), 6% underwent resection (n=54), 17% liver transplant (n=163), 50% liver-directed therapy (n=473), and 7% chemotherapy (n=60). HCV treatment was associated with improved OS compared to no HCV treatment (70 vs 21 months, p<0.01), persisting across clinical stages, HCC treatment modalities, and treatment facilities (all p<0.01). Surgical patients who received HCV treatment had improved RFS compared to those who did not (91 vs 80 months, p=0.03). On MVA, HCV treated patients had improved OS and RFS. On MVA, factors associated with failure to receive HCV treatment included Black race, higher MELD, and advanced clinical stage (all p<0.05). HCV treatment for HCC patients portends improved survival, regardless of clinical stage, HCC treatment, or facility type. Efforts must address barriers to HCV treatment

The Evolving Landscape of Hepatocellular Carcinoma : A US Safety Net Collaborative Analysis of Etiology of Cirrhosis

Hepatitis C virus (HCV) has historically been the most common cause of cirrhosis and hepatocellular carcinoma (HCC) in the United States. With improved HCV treatment, cirrhosis secondary to other etiologies is increasing. Given this changing epidemiology, our aim was to determine the impact of cirrhosis etiology on overall survival (OS) in patients with HCC. All patients with cirrhosis and primary HCC from the US Safety Net Collaborative (2012-2014) database were included. Patients were grouped into "safety net" and "academic" based on where they received their care. The primary outcome was the OS. 1479 patients were included. The average age was 60 years and 78% (n = 1156) were male. 56% (n = 649) received care at academic and 44% (n = 649) at safety net hospitals. The median model for end-stage liver disease (MELD) was 10 (IQR 8-16). Median OS was 23 months. Etiology of cirrhosis was viral hepatitis 56% (n = 612), alcohol abuse 14% (n = 152), alcohol and hepatitis 23% (n = 251), and other 7% (n = 85). Patients with alcohol-related cirrhosis (alcohol alone or with hepatitis) were younger (59 vs 62 years), more likely to be male (86% vs 75%), treated at a safety net facility (45% vs 35%), uninsured (17% vs 13%), and had a higher MELD (median 12 vs 10) (all < .003). They were less likely to have been screened for HCC within 1 year of diagnosis (20% vs 29%) and to receive treatment (69% vs 81%), and more likely to present with stage IV disease (21% vs 15%) (all < .001). Patients with alcohol-related cirrhosis had decreased OS (5-year OS 24% vs 40%, < .001), which persisted in a subset analysis of both academic and safety net populations. Although not significant on MVA, alcohol-related cirrhosis is associated with all factors that correlate with decreased survival from HCC. Efforts must focus on this vulnerable patient population to optimize screening, treatment, and outcomes

Dissecting disease, race, ethnicity, and socioeconomic factors for hepatocellular carcinoma: An analysis from the United States Safety Net Collaborative

Racial/ethnic and socioeconomic disparities are assumed to negatively affect treatment and outcomes for hepatocellular carcinoma (HCC). Our aim was to investigate the interaction of racial/ethnic and socioeconomic factors with stage of disease and type of treatment facility in receipt of treatment and overall survival (OS) of patients with HCC. All patients with primary HCC in the US Safety-Net Collaborative database (2012–2014) were included. Patients were categorized into “safety-net” or “tertiary referral center” based on where they received treatment. Socioeconomic factors were determined at the zip-code level and included median income and percent of adults who graduated from high-school. Primary outcomes were receipt of treatment and OS. On MV Cox regression, neither race/ethnicity, median income, nor care provided at a SNH were associated with decreased OS (all p > 0.05). Independent predictors of decreased OS included lack of insurance (HR 1.34), less educational attainment (HR 1.59) higher MELD score (HR 1.07), higher stage at diagnosis (II:HR 1.34, III:HR 2.87, IV:HR 3.23), and not receiving treatment (HR 3.94) (all p < 0.05). Factors associated with not receiving treatment included history of alcohol abuse (OR 0.682), increasing MELD (OR 0.874), higher stage at diagnosis (III: OR 0.234, IV: OR 0.210) and care at a safety net facility (OR 0.424) There were no racial/ethnic or socioeconomic disparities in receipt of treatment. There is no intrinsic or direct association of race/ethnicity, socioeconomic status, or being treated at select safety-net hospitals with worse outcomes. Poor liver function, no insurance, and advanced stage of presentation are the main determinants of not receiving treatment and decreased survival. •Racial and socioeconomic disparities are assumed to negatively affect treatment and outcomes.•Using a multi-institutional database, we investigated how these factors affect care for HCC.•We found no link between race, socioeconomics, or care at a safety-net hospital and worse outcomes

Vein involvement during pancreaticoduodenectomy: is there a need for redefinition of "borderline resectable disease"?

Current National Comprehensive Cancer Network guidelines recommend neoadjuvant therapy for borderline resectable pancreatic adenocarcinoma to increase the likelihood of achieving R0 resection. A consensus has not been reached on the degree of venous involvement that constitutes borderline resectability. This study compares the outcome of patients who underwent pancreaticoduodenectomy with or without vein resection without neoadjuvant therapy. A multi-institutional database of patients who underwent pancreaticoduodenectomy was reviewed. Patients who required vein resection due to gross vein involvement by tumor were compared to those without evidence of vein involvement. Of 492 patients undergoing pancreaticoduodenectomy, 70 (14 %) had vein resection and 422 (86 %) did not. There was no difference in R0 resection (66 vs. 75 %, p = NS). On multivariate analysis, vein involvement was not predictive of disease-free or overall survival. This is the largest modern series examining patients with or without isolated vein involvement by pancreas cancer, none of whom received neoadjuvant therapy. Oncological outcome was not different between the two groups. These data suggest that up-front surgical resection is an appropriate option and call into question the inclusion of isolated vein involvement in the definition of "borderline resectable disease.