Rare patients in routine care: Treatment and outcome in advanced papillary renal cell carcinoma in the prospective German clinical RCC-Registry

Non-clear cell renal cell carcinoma is a very rare malignancy that includes several histological subtypes. Each subtype may need to be addressed separately regarding prognosis and treatment; however, no Phase III clinical trial data exist. Thus, treatment recommendations for patients with non-clear cell metastatic RCC (mRCC) remain unclear. We present first prospective data on choice of first- and second-line treatment in routine practice and outcome of patients with papillary mRCC. From the prospective German clinical cohort study (RCC-Registry), 99 patients with papillary mRCC treated with systemic first-line therapy between December 2007 and May 2017 were included. Prospectively enrolled patients who had started first-line treatment until May 15, 2016, were included into the outcome analyses (n = 82). Treatment was similar to therapies used for clear cell mRCC and consisted of tyrosine kinase inhibitors, mechanistic target of rapamycin inhibitors and recently checkpoint inhibitors. Median progression-free survival from start of first-line treatment was 5.4 months (95% confidence interval [CI], 4.1–9.2) and median overall survival was 12.0 months (95% CI, 8.1–20.0). At data cutoff, 73% of the patients died, 6% were still observed, 12% were lost to follow-up, and 9% were alive at the end of the individual 3-year observation period. Despite the lack of prospective Phase III evidence in patients with papillary mRCC, our real-world data reveal effectiveness of systemic clear cell mRCC therapy in papillary mRCC. The prognosis seems to be inferior for papillary compared to clear cell mRCC. Further studies are needed to identify drivers of effectiveness of systemic therapy for papillary mRCC.     

Patient Safety Through RFID: Vulnerabilities in Recently Proposed Grouping Protocols

As RFID-tagged systems become ubiquitous, acceptance of this technology by the general public necessitates addressing related security/privacy issues. The past eight years have seen an increasing number of publications in this direction, specifically using cryptographic approaches. Recently, the Journal of Medical Systems published two papers addressing security/privacy issues through cryptographic protocols. We consider the proposed protocols and identify some existing vulnerabilities.     

Ring chromosome 20 epilepsy syndrome in children: electroclinical features

Ring chromosome 20 mosaicism is associated with dysmorphic features, mental retardation, and intractable seizures, including recurrent episodes of nonconvulsive status epilepticus. The authors' findings in four children, all without dysmorphic features, indicate that mental deterioration and frequent subtle nocturnal frontal lobe seizures, associated with a characteristic EEG pattern, represent prominent additional clinical features not previously described in this syndrome. This emphasizes the importance of full-night video-EEG in children with frontal lobe seizures and cognitive deterioration.     

Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)

The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) have come to consensus definitions for the terms epileptic seizure and epilepsy. An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure.     

Acute promyelocytic leukemia and pregnancy

In acute promyelocytic leukemia (APL), the use of all-trans-retinoic acid (ATRA) as a differentiating agent induces complete remission in a high percentage of patients. In pregnancy, however, this drug bears the risk of severe teratogenicity to the child. We report the case of a 23-yr-old woman at 21 weeks' gestation suffering from APL. She was treated with ATRA (45 mg/m2) for 40 d and two courses of standard chemotherapy. The mother achieved complete remission within 22 d of treatment. Fetal development was normal, and a healthy premature girl was born in the 35th week of pregnancy. In a review of the literature we have identified 14 cases of APL in pregnancy treated with ATRA alone or in combination with chemotherapy. ATRA has been used as early as in the 3rd week of gestation and in no case have malformations or other teratogenic effects occurred. Side-effects, however, ranged from fetal cardiac arrhythmias to induction of labour. Although known to exhibit severe teratogenic effects during the first trimester of pregnancy, ATRA seems to be reasonably safe during the second and third trimesters in the treatment of APL. However, careful obstetric follow-up is mandatory regarding fetal cardiac complications.     

Anatomical connections of auditory and lateral line areas of the dorsal telencephalon (Dm) in the osteoglossomorph teleost, Gnathonemus petersii

Local field potentials evoked either by auditory or by mechanosensory (water displacement) lateral line stimuli were recorded in sensory subregions of the telencephalic nucleus dorsalis pars medialis (Dm) in the weakly electric fish Gnathonemus petersii. The neural tracer Neurobiotin was injected into these two physiologically defined subregions. A reciprocal connection between the two subregions of Dm, as well as cell bodies and terminals in other telencephalic regions, whose distribution was somewhat different for the two injection types, were found. The course of labeled fibers outside the telencephalon was similar after injections in both Dm regions. Fibers were seen running through the lateral forebrain bundle (lfb) to the ventral surface area of the brain within the diencephalic preglomerular region (PGv). Within a narrow streak along the ventral side of the brain densely arranged cell bodies were labeled. The locations of labeled cells within PGv were indistinguishable after tracer was injected into either acoustical or lateral line areas of Dm. Only after injection into the mechanosensory Dm region labeled cell bodies were found in the anterior preglomerular nucleus (PGa), in addition. When crystals of the fluorescent tracer DiI were inserted in the ventral part of PGv, a path of labeled fibers similar to that after telencephalic injections was found. Labeled terminals, but no cell bodies, were located both in the acoustical and in the mechanosensory regions of Dm as well as in several other telencephalic areas. Even though sensory regions in Dm that process acoustical and mechanical stimuli are segregated and unimodal, they both receive input from neurons of PGv. The specificity of the mechanosensory region of Dm might originate from the additional input from PGa and from other endbrain areas.     

Die Prognose der totalen kavopulmonalen Anastomose in Abhängigkeit vom Operationsalter

The purpose of this study was to evaluate the relations between the age of surgery and the postoperative results in children after a total cavopulmonary anastomosis (TCPA). Between February 1990 and August 1995, 53 patients underwent a TCPA in our institution. At the time of the operation 26 of the patients were younger than 4 years, 27 patients were more than 4 years old. The perioperative mortality for all patients was 9.4%. Among the young children the perioperative mortality was higher than in the older patients (15.4% vs 3.7%). The only 2 patients who died late after surgery (2.8 and 2.6 years postoperatively) had been 8.3 and 9.0 years old at the time of their TCPA and represent 7.7% of the initially surviving patients of that group. The follow-up was based on routine heart catheterizations in 25 of our patients carried out 3.6 +/- 0.7 (m +/- SD) years postoperatively. Sixteen patients underwent a bicycle exercise test 4.0 +/- 1.0 years postoperatively and in 32 patients a Holter-ECG was obtained 3.2 +/- 1.2 years postoperatively (Table 1). The systemic cardiac index (CI), obtained at the catheterization laboratory, was only slightly reduced with 3.0 +/- 1.0 l/min/m2 (normal 3.5-5.5 l/min/m2). We saw a weak but significant negative correlation between the CI and the age at the TCPA (r = -0.43; p = 0.03; Figure 1). The maximal work load at the exercise test also showed a weak negative correlation to the age of surgery (r = -0.50; p = 0.05; Figure 2). Only 43.75% of our patients had no arrhythmias at the Holter-ECG. Again the group of children with no arrhythmias had been operated on at a significant lower age than the group of patients with arrhythmias (3.9 vs 7.3 years; p = 0.02; Figure 3). At follow-up the patients were all in good condition. Patients who had the TCPA in a relatively young age showed a better cardiac output, a higher work load at exercise testing and less arrhythmias than patients who were operated on when they were older. Therefore in suitable patients we recommend to carry out the TCPA at the 3rd or 4th year of life. The higher intraoperative mortality in young children should be overcome by excluding patients with additional preoperative risk factors.     

The effect of a calcium carbonate-bismuth subsalicylate combination on intragastric acidity over the course of 24 hours. A randomized study of healthy probands

Bismuth salts are successfully used for the treatment of campylobacter-pylori-associated gastritis. It cannot be excluded, however, that calcium carbonate, which is present in one of the recommended preparations (calcium carbonate/bismuth subsalicylate, Jatrox), may have an additional therapeutic effect due to an increase of intragastric pH. Therefore, the in-vitro H+ buffering capacity of Jatrox was determined in comparison to other antacids using the pH-stat technique, and its effect on intragastric acidity was tested in 15 healthy volunteers using ambulatory 24-hour pH-metry (combined glass electrode in gastric corpus, solid state memory recorder, sampling rate 30/min). At two study sessions, the volunteers received standardized normal meals (8:00 a.m., 12:00 noon, 6:00 p.m.) and, in randomized order, either Jatrox (three times 2 tablets one hour before meals) or no medication. Under in-vitro conditions, the buffering capacity of Jatrox amounts to 7.82 mmol H+ per tablet (equivalent to 47 mmol H+/24 h at recommended dosage), which is relatively low. Under in-vivo conditions, gastric pH only increases significantly during the first hour after medication. This short-lasting effect, however, has no influence on the 24-hour median pH. It is concluded from these results that the calcium carbonate contained in Jatrox probably does not contribute directly towards its therapeutic effect in promoting the healing of gastritis.