Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR

Severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) are inborn errors of immune function that require prompt diagnosis and treatment to prevent life-threatening infections. The lack of functional T or B lymphocytes in these diseases serves as a diagnostic criterion and can be applied to neonatal screening. A robust triplex PCR method for quantitation of T-cell receptor excision circles (TRECs) and κ-deleting recombination excision circles (KRECs), using a single Guthrie card punch, was developed and validated in a cohort of 2560 anonymized newborn screening cards and in 49 original stored Guthrie cards from patients diagnosed with SCID, XLA, ataxia-telangiectasia, Nijmegen-breakage-syndrome, common variable immunodeficiency, immunoglobulin A deficiency, or X-linked hyper-IgM syndrome. Simultaneous measurement of TREC and KREC copy numbers in Guthrie card samples readily identified patients with SCID, XLA, ataxia-telangiectasia and Nijmegen-breakage-syndrome and thus facilitates effective newborn screening for severe immunodeficiency syndromes characterized by the absence of T or B cells.     

The meaning of hypokalemia in heart failure

Maintenance of normal potassium (K(+)) homeostasis has become an increasingly important limiting factor in the therapy of heart failure (HF). With the application of loop diuretics and digoxin, hypokalemia has become a frequent and feared side effect of treatment. Low serum K(+) in HF may be also a marker of increased neurohormonal activity and disease progression. To gain the maximum benefit from treatment, we need to individualize drug use and carefully monitor electrolytes. Symptomatic HF patients (New York Heart Association class III-IV) should be prescribed the lowest dose of diuretic necessary to maintain euvolemia. Mild hypokalemia may be corrected by the use of aldosterone receptor antagonists such as spironolactone or eplerenone. However, a more severe hypokalemia should preferably be corrected using K(+) supplement. Serum K levels should be frequently checked and maintained between 4.0 and 5.5 mEq/l (mmol/l).     

The Role of the Epiglottis in the Swallow Process after a Partial or Total Glossectomy Due to a Neoplasm

Repeatable epiglottic movement patterns were recorded during a videofluoroscopic swallow evaluation of 95 patients who had undergone a total or partial glossectomy due to a neoplasm. Because no epiglottic function assessment was performed preoperatively, for the purpose of this study it was assumed that epiglottic mobility was “normal” during this time and that all abnormalities found afterward resulted from the growth of the neoplasm and the glossectomy. It was noted that in the early postoperative period, absence of epiglottic movement was accompanied by aspiration and made swallowing incompetent in a majority of cases (9 of 10). A correlation of movement between the epiglottis and the extent of oral tissue excision was found. Epiglottic mobility was evaluated as “normal” in 72% of the patients, i.e., in 67 of 91 (74%) patients after a partial or nearly total glossectomy and in 1 of 4 people who underwent a total glossectomy. In the subgroup (16%) of patients who underwent a total or nearly total glossectomy and then had videofluoroscopic examinations, 60% of the cases had normal epiglottic movements and 40% had an immobile epiglottis. Compensatory mechanisms implemented by the patients on their own initiative, such as additional swallows and prolonged apnea during deglutition, enabled them to avoid aspiration. However, upward head movement and downward chin tilting during deglutition as compensatory mechanisms used by patients with no epiglottic movement did not reduce the aspiration risk in the early postoperative period and were found to accompany incompetent swallowing attempts.     

Variations in non-pharmacological anti-infective measures in childhood leukemia - results of an international survey

Background Standardization in clinical practice may lead to improved outcomes. Unfortunately, little is known about the variability of non-pharmacological anti-infective measures in children with cancer. DESIGN AND METHODS: A web-based survey assessed institutional recommendations regarding restrictions of social contacts, pets and food and instructions on wearing face masks in public for children with standard- risk acute lymphoblastic leuk emia and acute myeloid leukemia during intensive chemotherapy. RESULTS: A total of 336 institutions in 27 countries responded to the survey (range, 1-76 institutions per country; overall response rate 61%). Most institutions recommend that patients with acute myeloid leukemia avoid indoor public places and daycare, kindergarten and school, whereas recommendations for patients with acute lymphoblastic leukemia differ considerably by institution. In terms of restrictions related to pets, there was a wide variability between institutions for both acute lymphoblastic and acute myeloid leukemia patients. Most, but not all institutions do not allow children with either acute lymphoblastic or acute myeloid leukemia to eat raw meat, raw seafood or unpasteurized milk. Whereas most institutions do not routinely recommend that patients with acute lymphoblastic leukemia wear face masks in public, advice on this matter varies for patients with acute myeloid leukemia. Conclusions The survey demonstrates that there is a wide variation in recommendations on non-pharmacological anti-infective measures between different institutions, countries and continents. This information may be used to encourage harmonization of supportive care practices and future clinical trials.     

Application of biochemical markers CA 19-9, CEA and C-reactive protein in diagnosis of malicious and benign pancreatic tumors

Introduction

We would save many lives and spare a lot of suffering if we could only detect and accurately determine the character and TMN staging of pancreatic tumors (PTs). With improved diagnosis, we could offer specific treatment that would result in better treatment outcome. The aim of study was to determine the significance of neoplastic markers CA 19-9 and CEA for prognosis in inflammatory and carcinomatous PTs.

Material and methods

We based our research upon a group of 170 patients. The patients were treated in our Oncologic Surgery Department from January 2007 to December 2010 for PTs. The patients were divided into four groups depending on the character of the tumor and underwent the following treatments: group 1 – 34 patients with carcinoma of the ampulla of Vater, group 2 – 64 patients with PTs at different stages (1, 2, 3) according to TMN classification, group 3 – 62 patients with PTs at stage 4 on the TMN scale (unresectable tumors), group 4 – 28 patients with inflammatory PTs.

Results

The results of Ca 19-9 in group 2 were 736.00 (25–75% 220.40–4285.00) ng/ml before surgery, 53.00 (25–75% 12.60–84.00) ng/ml in the 7 days after surgery, 29.4 (25–75% 7.90–113.00) ng/ml at day 30, and 119.00 (25–75% 96.30–621.00) ng/ml 3 months after the operation. These results were significantly higher than the control group but were significantly lower than the results for group 3 (unresectable tumors). The highest average concentration and median for CA 19-9 and CEA were noted in patients with unresectable PTs (the 3^rd group). The average concentration for CEA was lowest in group 4, but much higher than the lab limits.

Conclusions

The sensitivity of the CA 19-9 marker may be as high as 88%. Values of CA 19-9 above 852 U/ml may indicate TNM stage 4, consistent with an unresectable PT. In the cases where CA 19-9 is within normal limits but C-reactive protein is above normal limits (often thirty times the upper limit), in comparison to the control group and to patients with pancreatic neoplasms, strong consideration should be given towards the inflammatory characteristics of the pancreatic changes and conservative treatment should be applied.     

Treatment of non-ST-elevation myocardial infarction and ST-elevation myocardial infarction in patients with chronic kidney disease

Renal dysfunction is frequent in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Chronic kidney disease (CKD) is associated with very poor prognosis and is an independent predictor of early and late mortality and major bleeding in patients with NSTE-ACS. Patients with NSTE-ACS and CKD are still rarely treated according to guidelines. Medical registers reveal that patients with CKD are usually treated with too high doses of antithrombotics, especially anticoagulants and inhibitors of platelet glycoprotein (GP) IIb/IIIa receptors, and therefore they are more prone to bleeding. Drugs which are excreted mainly or exclusively by the kidney should be administered in a reduced dose or discontinued in patients with CKD. These drugs include enoxaparin, fondaparinux, bivalirudin, and small molecule inhibitors of GP IIb/IIIa inhibitors. In long-term treatment of patients after myocardial infarction, anti-platelet therapy, lipid-lowering therapy and β-blockers are used. Chronic kidney disease patients before qualification for coronary interventions should be carefully selected in order to avoid their use in the group of patients who could not benefit from such procedures. This paper presents schemes of non-ST and ST-segment elevation myocardial infarction treatment in CKD patients in accordance with the current recommendations of the European Society of Cardiology (ESC).     

Operative field temperature during transnasal endoscopic cranial base procedures

Background

Data regarding the safety of endoscopic skull base exploration are very scarce. With this method, fragile vital structures (cranial nerves, the optic complex, brainstem, hypothalamus or cerebral ventricles) are exposed to direct illumination within a closed space. Also, high-speed drills, cauterization and ultrasonic aspiration deliver a significant load of thermal energy. The aim of this study was to record the temperature close to the structures of the skull base and in the intradural space during the procedures performed using extended endoscopic transnasal approaches.

Methods

The temperature of the skull base was continuously recorded during six transnasal endoscopic procedures. Implantable copper-constantan thermocouples were inserted: one into the esophagus and another through the nostril to reach the operative field at the skull base.

Results

At the beginning of the procedure, the temperature of the operative field was on average 36.8 °C?±?0.80 °C, i.e. only 1 °C higher than the esophageal temperature. Then it grew continuously during the whole procedure, to eventually reach a level of 42–43 °C at the final stage, whereas the esophageal temperature remained stable. Occasionally, the temperature increased up to 45 °C during cauterization and ultrasonic aspiration, and even up to 62 °C during high-speed drilling.

Conclusion

Endoscopic skull base surgery is associated with an incessant increase of the temperature of the intraoperative field. The temperature can peak suddenly to levels which can potentially harm neural structures and influence the rate of postoperative complications.