Biomarkers in sarcoidosis

Introduction: Numerous biomarkers have been evaluated for the diagnosis, assessment of disease activity, prognosis, and response to treatment in sarcoidosis. In this report, we discuss the clinical and research utility of several biomarkers used to evaluate sarcoidosis.

Areas covered: The sarcoidosis biomarkers discussed include serologic tests, imaging studies, identification of inflammatory cells and genetic analyses. Literature was obtained from medical databases including PubMed and Web of Science.

Expert commentary: Most of the biomarkers examined in sarcoidosis are not adequately specific or sensitive to be used in isolation to make clinical decisions. However, several sarcoidosis biomarkers have an important role in the clinical management of sarcoidosis when they are coupled with clinical data including the results of other biomarkers.     

Single embryo transfer in preimplantation genetic diagnosis cycles for women <36 years does not reduce delivery rate

BACKGROUND: The Belgian legislation imposes single embryo transfer (SET) on women of <36 years in their first treatment cycle to avoid multiple pregnancies. The aim of this study is to assess the impact of this legislation on the outcome of preimplantation genetic diagnosis (PGD) for inherited diseases in young women undergoing SET. METHODS: A retrospective analysis of PGD cycles for monogenic disorders and translocations in women <36 years on their first treatment cycle. Two groups of patients were defined according to the implementation of the Belgian legislation: (i) double embryo transfer (DET), January 2001-June 2003 (ii) SET, July 2003-June 2005. The primary and secondary outcome measures were delivery per embryo transfer and multiple pregnancy rates, respectively. A subgroup analysis for monogenic disorders and translocations was performed. RESULTS: 62 cycles were included in the DET group and 73 cycles in the SET group. The mean age, number of cumulus-oocyte complexes, number of fertilized oocytes, number of biopsied and cryopreserved embryos were comparable between both groups. There was no significant difference in the delivery rates between the DET and the SET groups (33.9% versus 27.4%, respectively). Multiple pregnancies were avoided when SET was performed. When monogenic disorders and chromosomal translocations were separately evaluated, no significant difference in the delivery rate after SET was observed. CONCLUSIONS: The implementation of a SET policy in young women undergoing PGD for monogenic disorders and translocations enables a significant reduction of multiple pregnancies without significantly affecting the delivery rate.     

Effect of oral administration of dydrogestrone versus vaginal administration of natural micronized progesterone on the secretory transformation of endometrium and luteal endocrine profile in patients with premature ovarian failure: a proof of concept

BACKGROUND: We aimed to explore the endometrial histology and endocrine profiles on day 21 of an artificial cycle in patients with premature ovarian failure (POF) treated with oral dydrogesterone (DG) or vaginal micronized progesterone. METHODS: The study was designed as a prospective pilot study at an academic reproductive medicine unit. Six POF patients were included in the study. After estrogen endometrial priming, patients were randomized to receive DG or progesterone in two subsequent cycles. The main outcome measure was the endometrial histology and the endocrine profiles on day 21 of the cycle. RESULTS: Development of endometrial glands corresponded to an early secretory phase in five out of six cases supplemented with DG (out-phase). In contrast, five out of six cases treated with micronized progesterone showed an endometrium corresponding to a mid-luteal phase (in-phase) (P = 0.021 versus DG). There was a significant difference in the mean progesterone value [8.6 versus 0.3 microg l(-1) (P = 0.013)], the mean LH value [12.9 versus 22.5 IU l(-1) (P = 0.049)] and the mean FSH value [13.0 versus 23.9 IU l(-1) (P = 0.047)] between the progesterone and DG group, respectively, on day 21 of the cycle. CONCLUSIONS: After estrogen endometrial priming in POF patients, exogenous vaginal micronized progesterone is more effective than oral DG in creating an 'in-phase' secretory endometrium and induces significantly higher progesterone and lower LH and FSH serum concentrations on day 21 of the cycle.     

Preoperative Biliary Drainage of Severely Jaundiced Patients Increases Morbidity of Pancreaticoduodenectomy: Results of a Case-Control Study

Background

Recent studies have indicated that preoperative biliary drainage (PBD) should not be routinely performed in patients suffering from obstructive jaundice before surgery. The severity of jaundice that mandates PBD has yet to be defined. Our aim was to investigate whether PBD is truly justified in severely jaundiced patients before pancreaticoduodenectomy. The parameters evaluated were overall morbidity, length of hospital stay, and total in-hospital mortality.

Methods

From January 2000 to December 2012, a total of 240 patients underwent pancreaticoduodenectomy for periampullary tumors. Group A comprised 76 patients with preoperative serum bilirubin ≥15 mg/dl who did not undergo PBD before surgery. Group B comprised another 76 patients, matched for age and tumor localization (papillary vs. pancreatic head) who underwent PBD 2–4 weeks before pancreaticoduodenectomy and were identified from the same database.

Results

Less operative time was required in the ‘no PBD’ group compared with the ‘PBD’ group (210 vs. 240 min). Total intraoperative blood loss and blood transfusions were also significantly less in the ‘no PBD’ group. There was no difference detected in the rate of pancreatic fistula or biliary fistula formation. Group A patients demonstrated significantly lower morbidity than group B (24 vs. 36 %, respectively) and therefore required briefer hospitalization (11 vs. 16 days). Mild infectious complications appear to be the main factor that enhanced morbidity in the PBD group. However, total in-hospital mortality was not significantly different between the two groups.

Conclusions

Even severe jaundice should not be considered as an indication for PBD before pancreaticoduodenectomy, as PBD increases infections and postoperative morbidity, therefore delaying definite treatment.     

Focus on HPV Infection and the Molecular Mechanisms of Oral Carcinogenesis

This study is focused on the epidemiological characteristics and biomolecular mechanisms that lead to the development of precancerous and cancerous conditions of oral lesions related to Human Papilloma Virus (HPV) infections. Current evidence from the literature demonstrates the role of HPV in potentially malignant oral disorders. Therefore, the underlying biomolecular processes can give arise, or contribute to, benign lesions as well as to oral carcinogenesis.     

Predictors and Outcomes of Renal Replacement Therapy After Left Ventricular Assist Device Implantation

ObjectiveTo examine the frequency and outcomes of patients requiring renal replacement therapy (RRT) early after left ventricular assist device (LVAD) implantation.Patients and MethodsWe examined use of in-hospital RRT and outcomes in consecutive adults who underwent continuous-flow LVAD implantation from February 15, 2007, through August 8, 2017. Logistic regression was used to examine predictors of RRT. The associations of RRT with outcomes were examined using Cox proportional hazards regression.ResultsOf 354 patients who underwent LVAD implantation, 54 (15%) required in-hospital RRT. Patients receiving RRT had higher preoperative Charlson Comorbidity Index values (median, 5 vs 4; P=.03), Model for End-Stage Liver Disease scores (mean, 19.0 vs 14.5; P<.001), right atrial pressure (mean, 19.1 vs 13.4 mm Hg; P<.001), and estimated 24-hour urine protein levels (median, 357 vs 174 mg; P<.001) and lower preoperative estimated glomerular filtration rate (eGFR) (median, 43 vs 57 mL/min; P<.001) and measured GFR using ¹²⁵I-iothalamate clearance (median, 33 vs 51 mL/min; P=.001) than those who did not require RRT. Approximately 40% of patients with eGFR less than 45 mL/min/1.73 m² and 24-hour urine protein level greater than 400 mg required RRT vs 6% with eGFR greater than45 mL/min/1.73 m² and without significant proteinuria. Lower preoperative eGFR, higher estimated 24-hour urine protein level, higher right atrial pressure, and longer cardiopulmonary bypass time were independent predictors of RRT after LVAD implantation. Of patients requiring in-hospital RRT, 18 (33%) had renal recovery, 18 (33%) required outpatient hemodialysis, and 18 (33%) died before hospital discharge. After median (Q1, Q3) follow-up of 24.3 (8.9, 49.6) months, RRT was associated with increased risk of death (adjusted hazard ratio [HR], 2.86; 95% CI, 1.90-4.33; P<.001) and gastrointestinal bleeding (adjusted HR, 4.47; 95% CI, 2.57-7.75; P<.001).ConclusionIn-hospital RRT is associated with poor prognosis after LVAD. A detailed preoperative assessment of renal function before LVAD may be helpful in risk stratification and patient selection.     

Loss of cardioprotection induced by ischemic preconditioning after an initial ischemic period in isolated rat hearts

BACKGROUND:

The beneficial effect of ischemic preconditioning (PC) has been extensively studied in normal hearts but its effects on diseased hearts remain largely unknown. The effect of PC in the already ischemic myocardium has not been previously studied, although ischemia in varying intervals, which is difficult to assess, is often encountered in clinical practice.

OBJECTIVE:

To investigate whether the cardioprotective effect of PC is preserved when it is applied after a period of ischemia of varying duration.

METHODS:

Male Wistar rats were used for this study. Isolated normal rat hearts were perfused in Langendorff mode. Before 20 min of zero flow global ischemia followed by 45 min of reperfusion, hearts were subjected to an initial 20-min period of ischemia followed by 10 min of reperfusion (group A1); an initial 20-min period of ischemia followed by 10 min of reperfusion and two-cycle PC (3 min of ischemia, 5 min of reperfusion followed by 5 min of ischemia and 5 min of reperfusion) (group A2); and two-cycle PC followed by the initial 20-min period of ischemia and 10 min of reperfusion (group A3).Groups B and C were subjected to an initial ischemia of 15 min and 10 min, respectively, and subgroups 1, 2 and 3 were treated as above. Left ventricular end-diastolic pressure was measured at 45 min of reperfusion (LVEDP45 in mmHg). Postischemic recovery of left ventricular developed pressure was expressed as a percentage of the initial value (LVDP%).

RESULTS:

LVDP% and LVEDP45 were similar between groups A1 and A2, while when ischemic preconditioning preceded the two periods of ischemia (group A3), it resulted in significantly higher LVDP% and significantly lower LVEDP45 compared with groups A1 and A2. Left ventricular functional recovery was not increased in group B2 compared with group B1. LVDP% and LVEDP45 were similar among groups C1, C2 and C3.

CONCLUSION:

Ischemic preconditioning does not improve functional recovery in isolated rat hearts that have been initially subjected to 20 min or 15 min of zero-flow global ischemia, while an initial 10-min ischemic period seems to precondition the heart.     

Immune Modulation in Heart Failure: the Promise of Novel Biologics

Purpose of review

Immune system activation plays a central role in heart failure progression. Large-scale immune modulatory clinical trials targeting tumor necrosis factor-α and broad spectrum immune modulation have been negative. The objective of this review is to highlight past, present, and what is in the horizon for the immunomodulation in heart failure with a focus of biologics.

Recent findings

Strategies targeting interleukin-1 pathway are currently undergoing clinical evaluation and data from pilot studies are promising. The potential of cell therapy for immune modulation is increasingly recognized in clinical trials. Strategies targeting anti-cardiac antibodies such as immunoadsorption and intravenous immunoglobulin have been used in clinical practice with positive outcomes but large pragmatic clinical trials are lacking. The use of an aptamer to block anti-cardiac antibodies is undergoing phase 1 clinical evaluation. Promising targets include inflammasomes, toll-like receptors, chemokines, natural killer cells, and macrophages.

Summary

Large-scale immune modulatory clinical trials have been negative. Nevertheless, the experience gained from them along with increasing understanding of molecular mechanisms of immune pathophysiology in heart failure is leading to rapid recognition of new therapeutic targets and approaches.

     

Invasive techniques in diagnosis and staging of lung cancer

Aim-Background

During the staging process of lung cancer, accurate mediastinal lymph node staging is one of the more important factors to affect patient outcome. Accurate staging of the disease is important not only in determining prognosis but also in deciding the optimal treatment plan. The most significant treatment decision is establishing which patients can benefit from surgical resection and which should receive chemotherapy, radiation, or both. This paper reviews indications and current data regarding minimally invasive approaches for diagnosis and staging of lung cancer. In addition, current advances in diagnostic endoscopy for lung cancer will be reviewed.

Methods

A systematic literature search was performed to identify relevant reports. Studies and articles were identified using online searches of the U.S. National Library of Medicine via www.pubmed.com. We limited our bibliographic search to include only articles from 2008 onward.

Results

The thoracoscopic approach is currently considered the gold standard for the evaluation and treatment of suspected or known pleural effusion and in the diagnosis of indeterminate pulmonary nodules. It also has a complementary role to cervical mediastinoscopy in the invasive staging of mediastinal lymph nodes. Its role continues to evolve with regard to the management of lung cancer.

Conclusions

Mediastinoscopy has remained the ‘gold standard’ in invasive staging tests of the mediastinum. The classic way of invasively assessing the aortopulmonary window is the Chamberlain procedure, also known as an anterior mediastinotomy.