The Value of Claims-Based Nontraditional Risk Factors in Predicting Long-term Mortality After MitraClip Procedure

Background

We sought to identify nontraditional risk factors coded in administrative claims data and evaluate their ability to improve prediction of long-term mortality in patients undergoing percutaneous mitral valve repair.

HLA class 1 associations in Henoch Schonlein purpura: increased and decreased frequencies

Henoch Schonlein purpura (HSP) is the most common vasculitis of childhood. Susceptibility to HSP and associated clinical heterogeneity in HSP may be conferred by a number of genetic loci, including the major histocompatibility complex. We aimed to investigate the implications of the human leukocyte antigen (HLA) class 1 alleles in susceptibility to HSP and determine the possible associations with renal, gastrointestinal (GI), and joint manifestations of the disease. 110 children with HSP (66 boys, 44 girls) and 250 unrelated healthy controls were enrolled in the study. The mean age was 8.65 ± 3.59 years. HSP was diagnosed on the basis of clinical and laboratory data according to the American College of Rheumatology classification. The diagnosis was supported with skin and/or kidney in most of the patients. Clinical and laboratory findings revealed: skin involvement in 110 (100%), joint manifestations in 82 (74.5%), GI symptoms in 58 (52.7%), and hematuria and/or proteinuria in 36 (32.7%) patients. HLA class 1 alleles were identified by DNA amplification, hybridized with specific primer sequences. Comparison of frequencies between patients and controls were made by using the Fisher’s exact test. Odds ratio (OR) was used as the measure of association. HLA A2, A11, and B35 antigens showed an increased risk for predisposition to HSP (OR = 1.714, 95%CI = 1.088–2.700, p = 0.020; OR = 2.185, 95%CI = 1.289–3.703, p = 0.003; and OR = 2.292, 95%CI = 1.451–3.619, p = 0.000, respectively), while HLA A1, B49, and B50 antigens revealed decreased risk for predisposition to HSP (OR = 4.739, 95%CI = 1.828–12.345, p = 0.001; OR = 3.268, 95%CI = 0.955–11.236, p = 0.047; and OR = 7.462, 95%CI = 0.975–55.555, p = 0.024, respectively). Considering the renal involvement and severity of proteinuria, there was no association with HLA class 1 alleles. Our results suggest that the increased frequency of HLA A2, A11, and B35 alleles in unselected pediatric HSP patient population and miscarrying of HLA A1, B49, and B50 could be considered as a risk factor for susceptibility to HSP.     

L-carnitine alleviates sciatic nerve crush injury in rats：functional and electron microscopy assessments

Several studies have demonstrated that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats with diabetes mellitus. It is hypothesized that L-carnitine exhibits neuro-protective effects on injured sciatic nerve of rats. Rat sciatic nerve was crush injured by a forceps and exhibited degenerative changes. After intragastric administration of 50 and 100 mg/kg L-carnitine for 30 days, axon area, myelin sheath area, axon diameter, myelin sheath diameter, and numerical density of the myelinated axons of injured sciatic nerve were similar to normal, and the function of injured sciatic nerve also improved signiifcantly. These ifndings suggest that L-carnitine exhibits neuroprotective effects on sciatic nerve crush injury in rats.     

Bayesian random effects selection in mixed accelerated failure time model for interval‐censored data

In many medical problems that collect multiple observations per subject, the time to an event is often of interest. Sometimes, the occurrence of the event can be recorded at regular intervals leading to interval‐censored data. It is further desirable to obtain the most parsimonious model in order to increase predictive power and to obtain ease of interpretation. Variable selection and often random effects selection in case of clustered data become crucial in such applications. We propose a Bayesian method for random effects selection in mixed effects accelerated failure time (AFT) models. The proposed method relies on the Cholesky decomposition on the random effects covariance matrix and the parameter‐expansion method for the selection of random effects. The Dirichlet prior is used to model the uncertainty in the random effects. The error distribution for the accelerated failure time model has been specified using a Gaussian mixture to allow flexible error density and prediction of the survival and hazard functions. We demonstrate the model using extensive simulations and the Signal Tandmobiel Study^®. Copyright © 2013 John Wiley & Sons, Ltd.     

Tocilizumab challenge: A series of cytokine storm therapy experiences in hospitalized COVID-19 pneumonia patients

To recognize the period of exaggerated cytokine response in patients with coronavirus disease 2019 (COVID-19) pneumonia, and to describe the clinical outcomes of using tocilizumab as a treatment option. The data of 12 adult COVID-19 pneumonia patients who were followed in the inpatient clinics of Biruni University Medical Faculty Hospital (Istanbul, Turkey) were retrospectively analyzed. Diagnostic tests, laboratory examinations, clinical findings, and computed tomography of the thorax imaging results were evaluated. A dramatic laboratory and clinical improvement was observed in 83% (10 out of 12) of patients after tocilizumab. In 17% (2 out of 12) of our patients, short-term ventilator support was required in the intensive care unit. The longest hospital stay was 18 days. However, in the end, all of our patients were discharged home with good health. Although arterial oxygen saturations (87.58 ± 3.12%) dropped in room air in the pre-tocilizumab period, post-tocilizumab they normalized in all patients (94.42 ± 1%). None of them had fever after tocilizumab treatment and the levels of C-reactive protein (13.08 ± 12.89) were almost within normal limits. Eosinophil values were quite low at the time of diagnosis (10 ± 17.06), but increased significantly post-tocilizumab (155.33 ± 192.69). There is currently no proven treatment for COVID-19 induced by novel coronavirus SARS-CoV-2. Based on our experience with twelve adult COVID-19 pneumonia patients, we can say that tocilizumab, an IL-6 inhibitor, is more beneficial in preventing the damage caused by excessive cytokine response in the body if administered at the right time and provides clinical and radiological recovery.     

Tumour growth stimulation following partial hepatectomy in mice is associated with increased upregulation of c-Met

Hepatic resection is the preferred option for curative treatment of colorectal liver metastasis (CLM). However, this is associated with significant recurrence rates in both hepatic and extrahepatic sites. The upregulation of growth factors required for liver regeneration after resection is thought to stimulate the growth of micrometastases. The current study describes temporal changes in the expression of hepatocyte growth factor receptor (c-Met), epidermal growth factor receptor (EGFR) and insulin growth factor I receptor (IGF-IR) in an orthotopic mouse model of liver resection and tumour induction. Mice underwent 70 % hepatectomy and induction of liver metastases through intrasplenic injection of colorectal cancer cells. Control groups included sham-operated mice and 70 % hepatectomy alone. The expression levels of liver and tumour c-Met, EGFR and IGF-IR were quantified by quantitative RT-PCR at different time points. 70 % liver resection stimulates tumour growth; increases the expression of c-Met within established tumours and surrounding liver parenchyma; downregulates EGFR expression and increases IGF-IR expression within the liver parenchyma. In conclusion, we demonstrate in our mouse model that major hepatectomy stimulates engraftment and growth of CLM and that this effect is probably due to the upregulation of c-Met as a result of the liver regeneration process. Liver IGF-IR may also contribute to this phenomenon through a paracrine effect on tumour growth. This study provides support for the role of c-Met in the stimulation of tumour growth after resection possibly through the promotion of tumour cell proliferation.     

Does gradual detorsion protect the ovary against ischemia–reperfusion injury in rats?

Aim

Adnexal torsion is an infrequent and serious gynecologic surgical emergency. Adnexal torsion may result from pre-existing tubal or ovarian pathology or hyperstimulation of the ovary during ovulation. Early diagnosis and emergency surgical treatment (detorsion) are important to preserve fertility and to prevent peritonitis or loss of the adnexa. However, during reperfusion, tissue damage is more severe than during ischemia because of oxygen-derived radicals. The present study aimed to investigate the protective effect of gradual detorsion on adnexal torsion.

Materials and methods

Twenty-one adult female rats were divided into three groups as sham-operated (Sh group, n = 7); torsion + detorsion (TD group, n = 7); and torsion + gradual detorsion (TGD group, n = 7). A midline laparotomy was performed under anesthesia. In the TD and TGD groups, the left adnexa along with tubal and ovarian vessels were twisted three times in a clockwise direction and fixed to the abdominal wall. After 30 h, detorsion was performed on the mesenteries of both TD and TGD groups. In the TGD group, however, detorsion was performed gradually: the ovarian mesentery was detorsioned 360°, followed by a 5-min pause, then a repeat of the cycle until full detorsion was achieved. Rats were killed 1 week later. Left ovaries were removed and evaluated histopathologically.

Results

The histopathological mean grade was significantly higher in the TD than in the TGD group (p < 0.05).

Conclusion

Gradual detorsion can reduce reperfusion injury in a rat model of ovarian torsion. This method is easily applicable and may be a useful method for human patients with ovarian torsion.     

Protein Energy Wasting in a Cohort of Maintenance Hemodialysis Patients in Dhaka,Bangladesh

Malnutrition is associated with high rates of mortality among patients with end stage kidney disease (ESKD). There is a paucity of data from Bangladesh, where around 35,000–40,000 people reach ESKD annually. We assessed protein-energy wasting (PEW) amongst 133 patients at a single hemodialysis setting in Dhaka. Patients were 49% male, age 50 ± 13 years, 62% were on twice-weekly hemodialysis. Anthropometric, biochemical, and laboratory evaluations revealed: BMI 24.1 ± 5.2 kg/m², mid-arm muscle circumference (MAMC) 21.6 ± 3.6 cm, and serum albumin 3.7 ± 0.6 g/dL. Based on published criteria, 18% patients had PEW and for these patients, BMI (19.8 ± 2.4 vs. 25.2 ± 5.2 kg/m²), MAMC (19.4 ± 2.4 vs. 22.2 ± 3.8 cm), serum albumin (3.5 ± 0.7 vs. 3.8 ± 0.5 g/dL), and total cholesterol (135 ± 34 vs. 159 ± 40 mg/dL), were significantly lower as compared to non-PEW patients, while hand grip strength was similar (19.5 ± 7.6 vs. 19.7 ± 7.3 kg). Inflammatory C-reactive protein levels tended to be higher in the PEW group (20.0 ± 34.8 vs. 10.0 ± 13.9 p = 0.065). Lipoprotein analyses revealed PEW patients had significantly lower low density lipoprotein cholesterol (71 ± 29 vs. 88 ± 31 mg/dL, p < 0.05) and plasma triglyceride (132 ± 51 vs. 189 ± 103 mg/dL, p < 0.05), while high density lipoprotein cholesterol was similar. Nutritional assessments using a single 24 h recall were possible from 115 of the patients, but only 66 of these were acceptable reporters. Amongst these, while no major differences were noted between PEW and non-PEW patients, the majority of patients did not meet dietary recommendations for energy, protein, fiber, and several micronutrients (in some cases intakes were 60–90% below recommendations). Malnutrition Inflammation Scores were significantly higher in PEW patients (7.6 ± 3.1 vs. 5.3 ± 2.7 p < 0.004). No discernible differences were apparent in measured parameters between patients on twice- vs. thrice-weekly dialysis. Data from a larger cohort are needed prior to establishing patient-management guidelines for PEW in this population.     

Promising role of preoperative neutrophil-to-lymphocyte ratio in patients treated with radical nephroureterectomy

Objective

Several retrospective studies with small cohorts reported neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). We aimed at validating the predictive and prognostic role of NLR in a large multi-institutional cohort.

Methods

Preoperative NLR was assessed in a multi-institutional cohort of 2477 patients with UTUC treated with RNU. Altered NLR was defined by a ratio >2.7. Logistic regression analyses were performed to assess the association between NLR and lymph node metastasis, muscle-invasive and non-organ-confined disease. The association of altered NLR with recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Cox proportional hazards regression models.

Results

Altered NLR was observed in 1428 (62.8 %) patients and associated with more advanced pathological tumor stage, lymph node metastasis, lymphovascular invasion, tumor necrosis and sessile tumor architecture. In a preoperative model that included age, gender, tumor location and architecture, NLR was an independent predictive factor for the presence of lymph node metastasis, muscle-invasive and non-organ-confined disease (p < 0.001). Within a median follow-up of 40 months (IQR 20–76 months), 548 (24.1 %) patients experienced disease recurrence and 453 patients (19.9 %) died from their cancer. Compared to patients with normal NLR, those with altered NLR had worse RFS (0.003) and CSS (p = 0.002). In multivariable analyses that adjusted for the effects of standard clinicopathologic features, altered NLR did not retain an independent value. In the subgroup of patients treated with lymphadenectomy in addition to RNU, NLR was independently associated with CSS (p = 0.03).

Conclusion

In UTUC, preoperative NLR is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC such as lymph node metastasis, muscle-invasive or non-organ-confined status. NLR may help better risk stratify patients with regard to lymphadenectomy and conservative therapy.