Progress in clinical trial of histone deacetylase （HDAC） inhibitors for non-small cell lung cancers

Histone deacetylase （HDAC） inhibitors, which represent a structurally diverse group of molecules, have emerged as a novel therapeutic class of molecules with significant anticancer potential. Vorinostat and romidepsin, known as the first generation of HDAC inhibitors, were approved in the United States for the treatment of T-cell lymphomas. Preliminary activity of HDAC inhibitors has also been observed in non-small cell lung cancer （NSCLC） in combination with the existing treatment regimens, of which is the focus of the current review.     

Comparison of homeopathic globules prepared from high and ultra-high dilutions of various starting materials by ultraviolet light spectroscopy

ObjectiveHomeopathic globules are commonly used in clinical practice, while research focuses on liquid potencies. Sequential dilution and succussion in their production process has been proposed to change the physico-chemical properties of the solvent(s). It has been reported that aqueous potencies of various starting materials showed significant differences in ultraviolet light transmission compared to controls and between different dilution levels. The aim of the present study was to repeat and expand these experiments to homeopathic globules.MethodsGlobules were specially produced for this study by Spagyros AG (Gümligen, Switzerland) from 6 starting materials (Aconitum napellus, Atropa belladonna, phosphorus, sulfur, Apis mellifica, quartz) and for 6 dilution levels (6x, 12x, 30c, 200c, 200CF (centesimal discontinuous fluxion), 10,000CF). Native globules and globules impregnated with solvents were used as controls. Globules were dissolved in ultrapure water, and absorbance in the ultraviolet range was measured. The average absorbance from 200 to 340 nm was calculated and corrected for differences between measurement days and instrumental drift.ResultsStatistically significant differences were found for A. napellus, sulfur, and A. mellifica when normalized average absorbance of the various dilution levels from the same starting material (including control and solvent control globules) was compared. Additionally, absorbance within dilution levels was compared among the various starting materials. Statistically significant differences were found among 30c, 200c and 200CF dilutions.ConclusionThis study has expanded previous findings from aqueous potencies to globules and may indicate that characteristics of aqueous high dilutions may be preserved and detectable in dissolved globules.     

Adverse events related to the new psychoactive substance 3-fluorophenmetrazine – results from the Swedish STRIDA project

Background: New psychoactive substances (NPS) are often poorly pharmacologically documented and the production is unregulated, implying high risks for toxic side effects. This report from the STRIDA project describes analytically confirmed non-fatal intoxications involving the phenmetrazine analogue 3-fluorophenmetrazine (3-FPM).

Study design and methods: Observational case series of patients with suspected acute NPS exposure requiring hospital care. Blood and urine samples were collected from patients presenting in emergency departments (ED) or intensive care units (ICU), after consultation with the Swedish Poisons Information Centre (PIC). Laboratory analysis was performed by multi-component liquid chromatography–mass spectrometry. Clinical data were collected during PIC consultations and retrieved from medical records.

Results: From November 2014 to October 2015, eight cases were registered as 3-FPM or “phenmetrazine” intoxications at the PIC after consultation. During the same period, analysis of STRIDA project samples confirmed 3-FPM use in a total of 19 patients (84% men) aged 22–54 (median 30) years. 3-FPM was detected in 15 out of 19 serum (2.7–1416?ng/mL) and in 14 out of 14 urine (1.0–6857?μg/mmol creatinine) samples. All patients were also tested positive for other psychoactive substances, with benzodiazepines being most common (57% of the cases). Ten patients were monitored in the ED for <4?h, while six needed ICU monitoring of which five were graded as severe intoxications (Poisoning Severity Score 3). Prominent clinical signs were tachycardia (47%), depressed consciousness (42%), agitation/anxiety (37%), delirium (37%), dilated pupils (26%), and seizures (16%). All patients survived.

Conclusion: In 19 patients testing positive for 3-FPM, a high incidence of severe clinical features was demonstrated. However, as all patients had also used other psychoactive substances, it was difficult to identify a unique toxidrome for 3-FPM. The results further showed that many 3-FPM intoxications would have been missed, if relying solely on information from PIC consultations. These results emphasize the importance of performing bioanalytical investigation in cases of suspected NPS intoxication.     

Single-cell analysis of CTCs with diagnostic precision: opportunities and challenges for personalized medicine

The generation of variant cancer cells is the major cause of acquired resistance against systemic therapies and consequently, of our inability to cure advanced cancer patients. Circulating tumor cells are gaining increasing clinical attention because they may enable the monitoring cancer progression and adjustment of treatment. In recent years multiple technologies for enrichment, isolation as well as molecular and functional analysis of circulating tumor cells have been developed. Implementation of these technologies in standardized and automated workflows in clinical diagnostics could provide valuable information for real-time monitoring of cancer and eventually new therapeutic strategies for the benefit of patients.     

The Impact of Psychosis on Sexual Functioning: A Systematic Review

BackgroundSexual dysfunction among psychotic patients is highly prevalent. However, most research has focused on antipsychotic side effects on sexual functioning.AimTo provide evidence by means of a systematic review of the literature about the impact of psychosis on sexual functioning among unmedicated patients.MethodsSystematic search of MEDLINE (PubMed), Scopus, and Google Scholar for studies that reported sexual functioning among psychotic patients, who were drug-naïve or drug-free for at least 3 weeks before the study. Studies were published in English language between January 1994 and October 2019. We used the approach recommended by PRISMA, and the selection process was carried out by 2 reviewers.OutcomesThe outcome measures were sexual function and sexual dysfunctions.ResultsA total of 734 articles were obtained, 658 were obtained after duplicates were removed, 612 were excluded after reading the title and abstract, and 46 were included for a complete review of the articles. 5 papers were finally included. A total of 770 cases were included in the systematic review. The prevalence of sexual dysfunction in psychosis varied from 16.8% to 70% and in ultra-high state was 50%. It is noteworthy that those ultra–high-risk (prodromal) patients who develop psychosis had higher rates of sexual impairment. Therefore, we found higher rates of sexual dysfunction among untreated patients, both psychotic and ultra-high risk patients, than healthy controls.Clinical ImplicationsThe assessment of sexual behavior should be a part of routine psychiatric examination not only in psychotic but also in ultra–high-risk patients.Strengths & LimitationsThis is the first systematic review about the impact of psychosis on sexual functioning among unmedicated patients. However, scarce and heterogeneous studies were identified.ConclusionsImpaired sexual functioning is common in the onset of psychosis (or during ultra–high-risk state) and prior to the beginning of treatment. This suggests that psychotic symptoms and sexual dysfunction may have common etiological pathways at the psychosocial and neurobiological levels.Vargas-Cáceres S, Cera N, Nobre P, et al. The Impact of Psychosis on Sexual Functioning: A Systematic Review. J Sex Med 2021;18:457–466.