Drug‐Coated Balloons: A Safe and Effective Alternative to Drug‐Eluting Stents in Small Vessel Coronary Artery Disease

Background

Drug‐coated balloons (DCB) have been used to treat de novo small vessel coronary disease (SVD), with promising results and shorter dual antiplatelet therapy (DAPT) duration compared to drug‐eluting stents (DES). We compared safety and effectiveness of the two treatments at 1 year.

Methods

We reviewed 3,613 angioplasty cases retrospectively from 2011 to 2013 and identified 335 patients with SVD treated with device diameter of ≤2.5 mm. DCB‐only angioplasty was performed in 172 patients, whereas 163 patients were treated with second‐generation DES.

Results

DCB patients had smaller reference vessel diameter (2.22 ± 0.30 vs. 2.44 ± 0.19 mm, P < 0.001) and received smaller devices (median diameter 2.25 vs. 2.50 mm, P < 0.001) compared to the DES group. DES‐treated vessels had larger acute lumen gain (1.71 ± 0.48 mm) than DCB (1.00 ± 0.53 mm, P < 0.001). Half the patients had diabetes mellitus. While there were more patients presenting with acute coronary syndrome (ACS) in the DCB group (77.9% vs. 62.2%, P = 0.013), they received shorter DAPT (7.4 ± 4.7 vs. 11.8 ± 1.4 months, P < 0.001) than the DES group. The 1‐year composite major adverse cardiac event rate was 11.6% in the DCB arm and 11.7% in the DES arm (P = 1.000), with target lesion revascularization rate of 5.2% and 3.7%, respectively, (P = 0.601).

Conclusions

In this high‐risk cohort of patients, DCB‐only angioplasty delivered good clinical outcome at 1 year. The results were comparable with DES‐treated patients, but had the added benefit of a shorter DAPT regime.

     

Heat-shock protein expression in cisplatin-sensitive and -resistant human tumor cells

It has been suggested that the expression of certain heat-shock proteins (HSPs) may be prognostic markers in several tumor types. Since HSPs may be involved in determining cellular sensitivity to chemotherapeutic drugs, the possible relation between HSP expression and cisplatin (cDDP) sensitivity was studied. Three human germ-cell tumor cell lines, 1 human small-cell lung carcinoma (SCLC) cell line and 3 human colon carcinoma cell lines were used as a model for differences in intrinsic cDDP sensitivity. The constitutive expression of a panel of HSPs was studied by immunoblotting. No correlation was found between expression of HSP90, HSP73, HSP72, HSP60 and HSP27 and the extent of intrinsic cDDP sensitivity when all cell lines studied were considered. However, for the 3 cell lines derived from germ-cell carcinomas, HSP27 expression was inversely related to cDDP sensitivity, i.e. decreased HSP27 levels were associated with decreased sensitivity. Constitutive HSP expression was also studied in 2 sets of human cell lines with in vitro acquired cDDP resistance. In both resistant cell lines, decreased expression of HSP27 (as determined by Western blotting) was found as compared to the sensitive parent cell lines. Thus, acquired resistance to cDDP was also accompanied by decreased HSP27 expression. Interestingly, when basal HSP27 mRNA levels were measured in the SCLC cell line (GLC₄) and its subline with acquired resistance (GLC₄-cDDP), no significant differences were detected. Continuous cDDP incubation increased HSP27 levels and induced HSP27 phosphorylation in GLC₄ cells, but not in the resistant subline. Thus, although no general relationships between HSP expression and cDDP sensitivity are apparent, high HSP27 expression in vitro relates to high sensitivity to cDDP treatment in some tumor types. This is in accordance with reported clinical data on high HSP27 levels in tumors correlating with good prognosis. © 1996 Wiley-Liss, Inc.     

Multilayer Transducer for Acoustic Bladder Volume Assessment on the Basis of Nonlinear Wave Propagation

Catheterization remains the gold standard for bladder volume assessment, but it is invasive, uncomfortable to the patient and introduces the risk of infections and traumas. Acoustic measurement of the bladder volume reduces the need for a urinary catheter. Recently, a new method to non-invasively measure the volume of liquid filled cavities in vivo on the basis of nonlinear wave propagation has been introduced. To implement this method, two different multilayer ultrasound transducers were developed. Both transducers consisted of a first piezo-electric layer of lead zirconate titanate (PZT) to transmit waves at a fundamental frequency (2 MHz) and a second piezo-electric layer (copolymer) to receive a wide range of frequencies including harmonics. To suppress the inherent susceptibility of the film to electromagnetic waves, one of the two transducers, i.e., an “inverted” multilayer transducer, had the copolymer layer located inside the structure. The other multilayer transducer, i.e., a “normal” multilayer transducer, had the copolymer film located on the outside. Both transducers were compared with a commercially available broadband piezo-composite transducer, with respect to their transmit and receive transfer functions, their pulse-echo responses and their electromagnetic susceptibility (EMS) in reception. It was concluded that to measure up to at least the third harmonic frequency component with good sensitivity in combination with high transmit sensitivity at the fundamental frequency, a multilayer structure is preferred. To optimize for the EMS in reception, and hence also the signal-to-noise ratio, an inverted geometry, as proposed in this paper, was proven to be most effective. (E-mail: e.merks@erasmusmc.nl)     

Autosomal dominant adult neuronal ceroid lipofuscinosis: parkinsonism due to both striatal and nigral dysfunction.

We describe a family with adult neuronal ceroid lipofuscinosis, with apparent autosomal dominant inheritance, observed in six affected individuals in three generations. Disease onset was usually in the fifth decade, but was earlier in the youngest generation. Early symptoms consisted of myoclonus in face and arms, epilepsy, auditory symptoms, cognitive decline, or depression. Parkinsonism occurred a few years after disease onset, with stooped posture, shuffling gait, bradykinesia, and mask face. Four subjects deteriorated to a state of severe handicap, with severe dementia, contractures, dysphagia, and dysarthria. Leg weakness evolved to flaccid paraparesis in two patients. Diagnosis was confirmed by brain biopsy in one patient and full autopsy in two patients. Abundant intraneuronal storage of autofluorescent material was found throughout the brain. Electron microscopy showed granular osmiophilic deposits and scarce fingerprint profiles. Striking loss of neurons in the substantia nigra pars compacta and reticulata was found. (123)I-IBZM Single photon emission computed tomography in two patients showed loss of postsynaptic D2 receptor binding in the striatum. We conclude that parkinsonism in ANCL is likely to be caused by both presynaptic nigral cell loss and postsynaptic striatal degeneration.     

Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture

Groups of male Sprague-Dawley rats were administered orally the following chlorinated dibenzo-p-dioxins (CDDs) in corn oil/acetone (95/5; v/v): 30–60 μg/kg 2,3,7,8-tetrachlorodibenzo-dioxin (tetra-CDD), 160–270 μg/kg 1,2,3,7,8-pentachlorodibenzo-p-dioxins (penta-CDD), 630–1249 μg/kg 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (hexa-CDD) and 5000–8000 μg/kg 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (hepta-CDD) or a mixture of the four homologues such that each was present in the mixture at one quarter of its dose as a single compound. Animals were killed at 2 and 8 days after dosing. Livers were immediately removed, and aliquots frozen in liquid nitrogen. Storage occurred at ?80°C until further use. About 0.2 g of each lyophilized rat liver was extracted, the extract purified by column chromatography and analyzed by GC/MS for CDD content. Results obtained suggest that the absorption of CDDs after oral administration decreases in the order of tetra-CDD≥penta-CDD>hexa-CDD>hepta-CDD, indicating that the dose was an incomplete surrogate of exposure in parts I–III of this publication series (Stahl et al. 1992; Weber et al. 1992a,b). Moreover, data also support the notion that the pharmacokinetics of CDD mixtures at high doses are somewhat different from those expected based on single compound exposures. Our findings suggest that the intrinsic relative potency in terms of toxic equivalents (TEQ) of the higher chlorinated homologues is slightly greater (about a factor of 2) than suggested by Stahl et al. (1992), because of reduced absorption, whereas the contribution to total potency of the lower chlorinated homologues in mixtures is slightly higher (about a factor of 2) because of increased relative liver concentrations. This later finding appears to be due to altered pharmacokinetics of mixtures of CDDs, probably originating in changes of partial solubility of the lower chlorinated homologues in fat under conditions of near saturation.     

High-Level Pan-Azole-Resistant Aspergillosis

High-level pan-azole-resistant Aspergillus fumigatus was recovered from four patients with chronic lung disease. In one patient, the development of progressive resistance followed long-term azole therapy and switching between antifungal azoles. The high-level pan-azole-resistant phenotypes were not associated with a specific cyp51A gene mutation. New strategies that avoid the development of progressive azole resistance are needed.     

Which Radiographic Parameters Are Linked to Failure of a Dynamic Spinal Implant?

Background  

Knowledge about factors leading to failure of posterior dynamic stabilization implants is essential to design future implants and establish surgical indications. Therefore, we analyzed an implant for single-level or hybrid configuration (adjacent to spondylodesis), which was recalled due to high failure rates.     

Steroid-Responsive Rosai-Dorfman Disease

Nodular skin lesions on the lateral aspects of the legs of a female child were first noticed at the age of 6 days. A biopsy of the lesions was done at the age of 6 months when the child had also developed cervical and inguinal lymphadenopathy and angiomatous lesions on the face. The diagnosis of Rosai-Dorfman disease (RDD; also known as sinus histiocytosis with massive lymphadenopathy, SHML) was made. Increasing respiratory obstruction by lymphoid tissue prompted a 2-week trial with oral prednisolone. A dramatic response occurred, with complete resolution of all clinical findings within 5 days, but with recurrence of lymphadenopathy 6 weeks after stopping with medication. Further observations over the next 3 years established a consistent response to prednisolone and a pattern of steroid dependence.