Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced,Programmed Death Ligand 1–Expressing NSCLC

Introduction

In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.

Total lymphoid irradiation in chronic polyarthritis--a new therapeutic concept

Eleven patients with refractory rheumatoid arthritis were submitted to a total lymphoid irradiation up to a dose of 20 Gy. A constant improvement of clinical symptoms was observed in four out of the eleven patients already during the treatment and in the other patients not later than two months after. The frequency of attacks decreased and the number of joints involved in the attack was reduced. Morning rigidity and joint swellings decreased. One patient developed joint empyemas 4 and 26 months after the treatment. Four patients died in the meantime. In two patients the cause of death were renal insufficiency and a postoperative cardiogenic shock associated with generalized amyloidosis. The third patient died because of a toxically induced left cardiac decompensation with sepsis that could not be controlled by antibiotic drugs and multiple joint empyemas. The fourth patient developed an abscess after surgical treatment of a Kaposi syndrome. She died three months later from acute left cardiac decompensation. The therapy induced a lymphocytopenia with decrease of T helper lymphocytes and unchanged number of T suppressor lymphocytes. The constant therapy results of total lymphoid irradiation in primary chronic polyarthritis is probably due to this modification in the immune regulation.     

Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice

Cationic block copolymers spontaneously assemble via electrostatic interactions with DNA molecules in aqueous solution giving rise to micellar structures that protect the DNA from enzymatic degradation both in vitro and in vivo. In addition, we have previously shown that they are safe, not immunogenic and greatly increased antigen-specific CTL responses following six intramuscular inoculations of a very low dose (1 μg) of the vaccine DNA as compared to naked DNA. Nevertheless, they failed to elicit detectable humoral responses against the antigen. To gain further insight in the potential application of this technology, here we show that a shorter immunization protocol based on two DNA intramuscular inoculations of 1 μg of DNA delivered by these copolymers and a protein boost elicits in mice broad (both humoral and cellular) and long-lasting responses and increases the antigen-specific Th1-type T cell responses and CTLs as compared to priming with naked DNA. These results indicate that cationic block copolymers represent a promising adjuvant and delivery technology for DNA vaccination strategies aimed at combating intracellular pathogens.     

Tendon injuries of the knee joint extensor mechanism

Diagnosis, aetiology and therapy of injuries to the extensor mechanism of the knee joint are presented. 22 cases of ruptures and discisions of the lig. patellae or the quadriceps tendon could be reexamined. All cases but one, with operation within the first week after injury, suturing with absorbable or non absorbable material, immobilisation for 6 weeks and following physical therapy, had a good functional result. No rerupture occurred. In one case a limitation of the range of movement had to be seen afer an open discision of the lig. patellae. After transposition of the tuberositas tibiae, discission of the scares and functional therapy a good result could also be achieved.     

Treatment of fecal incontinence by temporary sacral nerve stimulation

Summary BACKGROUND: Sacral nerve stimulation (SNS) is an option for the treatment of fecal incontinence in patients with morphologically intact, but weak external anal sphincter. METHODS: In ten patients a percutaneous test-SNS was performed. Two patients suffered from fecal incontinence after surgery, one patient after incomplete leg palsy after traumatic spine injury and seven patients from idiopathic incontinence. Incontinence score, anorectal manometry and patient diary were performed before and after test-SNS. RESULTS: Intraoperative response (Bellows action) could be achieved in 90% of patients. Test-SNS was successful in 50% of patients. In these patients, resting pressure was increased by 100.1% and squeeze pressure by 84.5%. CONCLUSIONS: SNS is an effective therapy in a subset of patients with fecal incontinence. Fifty percent of patients tested are eligible for implantation of a permanent stimulation device.      

Screen sensitivity in photosensitive children and adolescents: patient-dependant and stimulus-dependant factors.

Television viewing is the most frequent cause of photogenic attacks in daily life. In the present study, we examined 48 photosensitive children and adolescents to find out: 1) whether hypersynchronous activity is induced less often by viewing a PC monitor than a television screen and 2) whether certain images are more likely to cause hypersynchronous activity than others. All subjects were tested for sensitivity to intermittent photic stimulation (IPS) and to a black and white striped pattern on cards. Additionally, all were subjected to stimuli from four different images (vertical black and white striped pattern, geometric figures, text, and a painting by Max Pechstein - 1913, Italian church), presented on a television screen (with an image regeneration frequency of 50 Hz) and on PC screens (with regeneration frequencies of 48 and 100 Hz). A total of 21 non-photosensitive, healthy children and adolescents served as controls. Of the 48 photosensitive subjects 13% were also pattern sensitive (cards), and 33% exhibited screen sensitivity. No differences were found between the three monitor types. However, the hypersynchronous reactivity to the four images presented was significantly different, with high contrast vertical striped pattern being the most provocative. Non-photosensitive subjects did not react to any of the stimuli. The results of the present study show that screen-dependant factors are less important than image-dependant factors.     

Combined sclerotherapy and operation for the treatment of bleeding oesophageal varices.

OBJECTIVE--To identify prognostic factors in a consecutive series of patients with bleeding oesophageal varices and develop an optimum regimen of treatment. DESIGN--Retrospective review. SETTING--I Department of Surgery, University Hospital, Vienna, Austria. PATIENTS--301 consecutive patients with bleeding oesophageal varices. OUTCOME MEASURES--Median survival and survival at one year after sclerotherapy alone (n = 213), or sclerotherapy with portosystemic shunt (n = 54), Hassab's devascularisation (n = 29), or liver transplantation (n = 5). RESULTS--Prognosis was dependent on the severity of liver damage at the start of treatment. Median survival for Child's class A was 47 months, for Child's class B 54 months, and for Child's class C 2 months. The overall one year survival for patients in Child's class C was 33%, for sclerotherapy alone 28%, and for sclerotherapy and portosystemic shunt 42%, Hassab's devascularisation 50%, and liver transplantation 80%. CONCLUSION--Despite the small number of patients who underwent liver transplantation and their poor initial prognosis (Child's class C, n = 4; class B, n = 1) our results suggest that liver transplantation should be considered for the treatment of patients with end stage cirrhosis and bleeding varices.     

Primary pulmonary hypertension in childhood--clinical course and morphologic correlations with particular reference to the endocrine heart

This is a case report of a 13-year-old girl who developed clinical symptoms of primary pulmonary hypertension (PPH). The prognosis is determined by progressive overloading of the right heart. Tissue from both the right and the left atria was examined using immunohistochemical methods. Cardiodilatin/alpha-ANP (atrial natriuretic peptide)-producing myoendocrine cells were analysed. As recent investigations have shown, the atrium and especially the atrial appendages of the heart function as an endocrine organ which is stimulated by pressure and volume overload, and which produces a natriuretic and vasodilatory peptide hormone from myoendocrine cells. In our case we found a general hyperplasia of the myoendocrine cells of the right atrium which is interpreted as a secondary reaction towards an increasing overload. This also means a temporary compensation of the progressive obstruction of the small pulmonary arteries, initiated by vasodilatory heart peptides. These investigations are in agreement with those of other groups who found an increased production of cardiac hormones in atrial overload. In the perinuclear area, electron microscopy shows zones of autophagolysis and the typical specific atrial granules which account for a dysfunction of atrial myoendocrine cells, as seen in other cardiac diseases. Our results may contribute to a better understanding of the pathogenesis of PPH and may help in diagnosis and therapy.