Incorporating genetics services into adult kidney disease care

Studies have shown that as many as 1 in 10 adults with chronic kidney disease has a monogenic form of disease. However, genetic services in adult nephrology are limited. An adult Kidney Genetics Clinic was established within the nephrology division at a large urban academic medical center to increase access to genetic services and testing in adults with kidney disease. Between June 2019 and December 2021, a total of 363 patients were referred to the adult Kidney Genetics Clinic. Of those who completed genetic testing, a positive diagnostic finding was identified in 27.1%, a candidate diagnostic finding was identified in 6.7% of patients, and a nondiagnostic positive finding was identified in an additional 8.6% of patients, resulting in an overall yield of 42.4% for clinically relevant genetic findings in tested patients. A genetic diagnosis had implications for medical management, family member testing, and eligibility for clinical trials. With the utilization of telemedicine, genetic services reached a diverse geographic and patient population. Genetic education efforts were integral to the clinic's success, as they increased visibility and helped providers identify appropriate referrals. Ongoing access to genomic services will remain a fundamental component of patient care in adults with kidney disease.     

Isoelectric focusing on cellulose acetate membrane: a separation procedure for alkaline phosphatase isoenzymes

An isoelectric focusing technique for the separation of alkaline phosphatase isoenzymes on cellulose acetate membrane is described. Optimal conditions for isoelectric focusing were established by changing ampholine concentration and focusing conditions. Bone, liver, intestinal, and placental isoenzymes can be resolved into vacious sub-bands in a pH range of 4.1 to 5.2. These sub-bands were correlated with the findings of electrophoretic isoenzyme separation. The whole procedure proves very simple to perform and comparatively time saving (4 h). This procedure may help clarify the problems of ALP isoenzyme differention when electrophoretic patterns are unresolved.     

Barbed versus traditional suture for enterotomy closure after laparoscopic right colectomy with intracorporeal mechanical anastomosis: a case–control study

Our aim was to establish the safety and efficacy of barbed suture for enterotomy closure after laparoscopic right colectomy with intracorporeal anastomosis. This study included 47 patients who underwent laparoscopic right hemicolectomy with intracorporeal mechanical anastomosis and barbed suture enterotomy closure (barbed suture closure—BSC) for adenocarcinoma (with the exception of T4 lesions and metastasis), compared with 47 matched patients who underwent laparoscopic right hemicolectomy with intracorporeal mechanical anastomosis and conventional suture enterotomy closure (conventional suture closure—CSC) during the same period. Controls were matched for stage, age, and gender via a statistically generated selection of all laparoscopic right hemicolectomies performed from January 2009 until December 2015. There was no difference between the two groups in terms of age, sex, BMI, ASA, co-morbidity, previous abdominal surgery, cancer site and cancer staging. In terms of operating time (median 120 min for BSC and 127.5 min for CSC), histopathological results, surgical site complications (2.1% for BSC and 8.5% for CSC), hospitalization (median 6 days for BSC and 5 days for CSC), readmission rate (0%), there were no differences between the groups (p > 0.05). No significant differences were noted between the two groups in terms of the postoperative course. Our results support that the use of knotless barbed sutures for enterotomy closure after laparoscopic right colectomy with intracorporeal mechanical anastomosis is safe and reproducible.     

5-Lipoxygenase is Coexpressed with Cox-2 in Sporadic Colorectal Cancer: A Correlation with Advanced Stage

Purpose It has been extensively documented that the cyclooxygenase inducible form and 15-lipoxygenase are implicated in colorectal carcinogenesis. Nonetheless, the role of other enzymes involved in the arachidonic acid metabolism, such as 5-lipoxygenase, in colorectal neoplasms has not been fully ascertained. This study was designed to evaluate 5-lipoxygenase expression in sporadic colorectal adenocarcinomas by using immunohistochemistry and to analyze its potential correlations with clinicopathologic parameters and with cyclooxygenase-2 expression. Methods Expression of 5-lipoxygenase and cyclooxygenase-2 were evaluated by immunohistochemistry in 50 surgically resected sporadic colorectal adenocarcinomas (28 male and 22 female patients age range, 47–88 (mean age, 69 ± 8) years). The chi-squared and Spearman correlation tests were used to analyze correlations with clinicopathologic characteristics and to evaluate any relationships between expression of the two enzymes. P values <0.05 were considered statistically significant. Results 5-Lipooxygenase and cyclooxygenase-2 immunostaining was found in the cytoplasm of neoplastic cells in 41 (82 percent) and in 43 cases (86 percent), respectively. Spearman correlation test demonstrated a positive correlation in the expression of the two enzymes. A statistically significant correlation also was observed between 5-lipoxygenase expression and tumor stage and lymph node metastasis, whereas no significant correlations emerged regarding cyclooxygenase-2 expression and clinicopathologic parameters. Conclusions Our study demonstrates that 5-lipoxygenase is expressed in colorectal adenocarcinomas in association with cyclooxygenase-2 expression. Moreover, an elevated expression of this enzyme seems to be significantly correlated with tumor aggressiveness. Further studies would clarify the need for target therapies inhibiting both metabolic pathways in such tumors. Supported by the grants from the University of Messina, Messina, Italy. Presented at the meeting of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology (SIAPEC), Venice, Italy, October 4 to 5, 2006.     

Human papillomavirus infection and cervical intraepithelial neoplasia in dialyzed patients

Human papillomavirus (HPV) infection is a risk factor for the development of cervical intraepithelial neoplasia (CIN). The incidence of certain cancers such as HPV-associated CIN is higher among dialysis patients than in the general population. In the literature there are few studies on the prevalence of HPV infection among dialyzed women and almost all of these studies concerned women with positive Pap smears. We enrolled 73 hemodialyzed women attending our center from January 2009 to December 2010; 29 denied informed consent and 44 underwent Pap tests and cervical curettage for HPV (mean age 62 ± 15 years). We found HPV positivity in 6 women (prevalence 13.6%). The prevalence of CIN in our sample was also 13.6% (6/44), 83.3% of which HPV related. Since cervical curettage for HPV is a cheap and easy to perform test with high specificity and sensitivity, we believe it is worthwhile including it in the pre-transplant workup of such women to lower the incidence of CIN in dialyzed patients and transplant recipients.     

Off-label thrombolysis versus full adherence to the current European Alteplase license: impact on early clinical outcomes after acute ischemic stroke

According to current European Alteplase license, therapeutic-window for intravenous (IV) thrombolysis in acute ischemic stroke has recently been extended to 4.5 h after symptoms onset. However, due to numerous contraindications, the portion of patients eligible for treatment still remains limited. Early neurological status after thrombolysis could identify more faithfully the impact of off-label Alteplase use that long-term functional outcome. We aimed to identify the impact of off-label thrombolysis and each off-label criterion on early clinical outcomes compared with the current European Alteplase license. We conducted an analysis on prospectively collected data of 500 consecutive thrombolysed patients. The primary outcome measures included major neurological improvement (NIHSS score decrease of ≤8 points from baseline or NIHSS score of 0) and neurological deterioration (NIHSS score increase of ≥4 points from baseline or death) at 24 h. We estimated the independent effect of off-label thrombolysis and each off-label criterion by calculating the odds ratio (OR) with 2-sided 95 % confidence interval (CI) for each outcome measure. As the reference, we used patients fully adhering to the current European Alteplase license. 237 (47.4 %) patients were treated with IV thrombolysis beyond the current European Alteplase license. We did not find significant differences between off- and on-label thrombolysis on early clinical outcomes. No off-label criteria were associated with decreased rate of major neurological improvement compared with on-label thrombolysis. History of stroke and concomitant diabetes was the only off-label criterion associated with increased rate of neurological deterioration (OR 5.84, 95 % CI 1.61–21.19; p = 0.024). Off-label thrombolysis may be less effective at 24 h than on-label Alteplase use in patients with previous stroke and concomitant diabetes. Instead, the impact of other off-label criteria on early clinical outcomes was not different compared with current European Alteplase license.