Designing Synthetic, Sulfated Glycosaminoglycan Mimetics That Are Orally Bioavailable and Exhibiting In Vivo Anticancer Activity.

Sulfated glycosaminoglycans (GAGs), or synthetic mimetics thereof, are not favorably viewed as orally bioavailable drugs owing to their high number of anionic sulfate groups. Devising an approach for oral delivery of such highly sulfated molecules would be very useful. This work presents the concept that conjugating cholesterol to synthetic sulfated GAG mimetics enables oral delivery. A focused library of sulfated GAG mimetics was synthesized and found to inhibit the growth of a colorectal cancer cell line under spheroid conditions with a wide range of potencies ( 0.8 to 46 µM). Specific analogues containing cholesterol, either alone or in combination with clinical utilized drugs, exhibited pronounced in vivo anticancer potential with intraperitoneal as well as oral administration, as assessed by ex vivo tertiary and quaternary spheroid growth, cancer stem cell (CSC) markers, and/or self-renewal factors. Overall, cholesterol derivatization of highly sulfated GAG mimetics affords an excellent approach for engineering oral activity.

The Role of Cost-Effectiveness Analysis in Patient-Centered Cancer Care in the Era of Precision Medicine.

Over the last few decades, changes in diagnostic and treatment paradigms have greatly advanced cancer care and improved outcomes [...].

Spontaneous coronary artery dissection in old patients: clinical features, angiographic findings, management and outcome.

AIMS: Spontaneous coronary artery dissection (SCAD) is a relatively rare but well-known cause of acute coronary syndrome. Clinical features, angiographic findings, management and outcomes of SCAD in old patients (>65 years of age) remain unknown. METHODS AND RESULTS: The Spanish multicentre prospective SCAD registry (NCT03607981), included 318 consecutive patients with SCAD. Data were collected between June 2015 and April 2019. All angiograms were analysed in a centralized corelab. For the purposes of this study, patients were classified according to age in two groups <65 and ≥65 years old and in-hospital outcomes were analysed. Fifty-five patients (17%) were ≥65 years old (95% women). Older patients had more often hypertension (76% vs. 29%, P < 0.01) and dyslipidaemia (56% vs. 30%, P < 0.01), and less previous (4% vs. 18%, P < 0.001) or current smoking habit (4% vs. 33%, P < 0.001). An identifiable trigger was less often present in old patients (27% vs. 43%, P = 0.028). They also had more often severe coronary tortuosity (36% vs. 11%, P = 0.036) and showed more frequently coronary ectasia (24% vs. 9%, P < 0.01). Older patients were more often managed conservatively (89% vs. 75%, P = 0.025), with no significant differences in major adverse cardiac events during index admission (7% vs. 8%, P = 0.858). There were no differences between groups in terms of in-hospital stay, new acute myocardial infarction, unplanned coronary angiography or heart failure. CONCLUSION: Older patients with SCAD show different clinical and angiographic characteristics compared with younger patients. Initial treatment strategy was different between groups, though in-hospital outcomes do not significantly differ (NCT03607981).

Coronary Plaque Erosion after Abemaciclib Treatment Onset: An Unknown Side Effect?

The current article describes a 72-year-old woman who suffered an acute myocardial infarction due to plaque erosion (PE) 2 weeks after abemaciclib treatment onset due to advanced breast cancer. Abemaciclib is a cyclin-dependent kinase 4 and 6 inhibitor that has recently demonstrated efficacy and safety in advanced breast cancer. Of major concern, however, reported thromboembolic rates in randomized clinical trials testing this drug range from 0.6 to 5%. To the best of our knowledge this is the first thrombotic coronary side effect ever reported. We suggest that a treatment that increases thromboembolic risk, such abemaciclib, may have triggered PE in our patient, 15 days after abemaciclib initiation. New molecules are promising in cancer treatment; however, care must be paid to their potential cardiotoxic effects.

Laser-interstitial thermal therapy compared to craniotomy for treatment of radiation necrosis or recurrent tumor in brain metastases failing radiosurgery.

PURPOSE: Many publications report laser-interstitial thermal therapy (LITT) as a viable alternative treatment to craniotomy for radiation necrosis (RN) and re-growing tumor occurring after stereotactic radiosurgery (SRS) for brain metastases. No studies to-date have compared the two options. The aim of this study was to retrospectively compare outcomes after LITT versus craniotomy for regrowing lesions in patients previously treated with SRS for brain metastases. METHODS: Data were collected from a single-institution chart review of patients treated with LITT or craniotomy for previously irradiated brain metastasis. RESULTS: Of 75 patients, 42 had recurrent tumor (56%) and 33 (44%) had RN. Of patients with tumor, 26 underwent craniotomy and 16 LITT. For RN, 15 had craniotomy and 18 LITT. There was no significant difference between LITT and craniotomy in ability to taper off steroids or neurological outcomes. Progression-free survival (PFS) and overall survival (OS) were similar for LITT versus craniotomy, respectively: %PFS-survival at 1-year = 72.2% versus 61.1%, %PFS-survival at 2-years = 60.0% versus 61.1%, p = 0.72; %OS-survival at 1-year = 69.0% versus 69.3%, %OS-survival at 2-years = 56.6% versus 49.5%, p = 0.90. Craniotomy resulted in higher rates of pre-operative deficit improvement than LITT (p < 0.01). On subgroup analysis, the single factor most significantly associated with OS and PFS was pathology of the lesion. About 40% of tumor lesions needed post-operative salvage with radiation after both craniotomy and LITT. CONCLUSIONS: LITT was as efficacious as craniotomy in achieving local control of recurrent irradiated brain metastases and facilitating steroid taper, regardless of pathology. Craniotomy appears to be more advantageous for providing symptom relief in those with pre-operative symptoms.

Situación del servicio de turno de farmacias y boticas / Situation of pharmacies and apothecaries service

El presente trabajo pretende llevar a cabo el dignóstico del servicio de turno que se realiza en farmacias y boticas a nivel de Lima Metropolitana, y que representan más del 50 por ciento de farmacias y boticas de las existentes en nuestro país. Se presentará una revisión histórica de este servicio enfocándose cómo, cuándo y porqué se organiza este tipo de servicio en nuestra comunidad, iniciando en la segunda mitad del siglo pasado; y de cómo ha ido evolucionando hasta nuestros días. En un segundo momento se analizará en forma comparativa los diferentes reglamentos que se han venido estableciendo a través de los años, hasta arribar en un análisis profundo al actual reglamento y al anteproyecto existente, donde se enfatizará la revisión de las normas legales que rigen su ejecución. Finalmente se presentará el análisis actual de la situación del servicio de turno precisándose puntos como: el uso del servicio de turno por la población, la seguridad en la prestación del servicio, grupos de medicamentos requeridos, así como otros aspectos muy importantes.