Could COVID-19 have an impact on male fertility?

The pandemic caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to several hypotheses of functional alteration of different organs. The direct influence of this virus on the male urogenital organs is still to be evaluated. However some hypotheses can already be made, especially in the andrological field, for the biological similarity of the SARS-CoV and SARS-CoV2. As well as SARS-CoV, SARS CoV-2 uses the ‘Angiotensin Converting Enzyme-2’ (ACE2) as a receptor to enter human cells. It was found that ACE2, Angiotensin (1-7) and its MAS receptors are present, over in the lung, also in the testicles, in particular in Leydig and Sertoli cells. A first hypothesis is that the virus could enter the testicle and lead to alterations in testicular functionality. A second hypothesis is that the binding of the virus to the ACE2 receptor, could cause an excess of ACE2 and give rise to a typical inflammatory response. The inflammatory cells could interfere with the function of Leydig and Sertoli cells. Both hypotheses should be evaluated and confirmed, in order to possibly monitor fertility in patients COVID-19+.     

Decision-making impairment predicts 3-month hair-indexed cocaine relapse

Rationale

One of the key outstanding challenges in cocaine dependence research is determining who is at risk of relapsing during treatment.

Objectives

We examined whether cognitive decision-making profiles predict objectively (hair) indexed cocaine relapse at 3-month follow-up.

Methods

Thirty-three cocaine-dependent patients commencing outpatient treatment in a public clinic performed baseline decision-making assessments with the original and variant versions of the Iowa Gambling Task, and provided a 3-cm hair sample 3 months afterwards. Based on Iowa Gambling Tasks’ performance cut-offs, 5 patients had intact decision-making skills, 17 patients showed impaired sensitivity to reward or punishment (impairment in one of the tasks), and 9 patients showed insensitivity to future consequences (impairment in both tasks). Based on a 0.3 ng/mg cocaine cut-off, 23 patients were classified as relapsers and 10 as non-relapsers at the 3-month follow-up.

Results

Eighty percent of patients with intact decision-making were abstinent at follow-up, whereas 90 % of patients with insensitivity to future consequences had relapsed. The two subgroups (relapsers and non-relapsers) showed no significant differences on drug use, comorbidities, or psychosocial function, and significantly differed on verbal but not performance IQ. A regression model including decision-making scores and verbal IQ predicted abstinence status with high sensitivity (95 %) and moderately high specificity (81 %).

Conclusion

These preliminary findings demonstrate that decision-making profiles are associated with cocaine relapse. Moreover, combined decision-making and IQ assessments provide optimal predictive values over stimulant relapse, yielding significant opportunities for clinical translation.     

Functional differentiation of cytotoxic cancer drugs and targeted cancer therapeutics

There is no nationally or internationally binding definition of the term “cytotoxic drug” although this term is used in a variety of regulations for pharmaceutical development and manufacturing of drugs as well as in regulations for protecting medical personnel from occupational exposure in pharmacy, hospital, and other healthcare settings. The term “cytotoxic drug” is frequently used as a synonym for any and all oncology or antineoplastic drugs. Pharmaceutical companies generate and receive requests for assessments of the potential hazards of drugs regularly – including cytotoxicity. This publication is intended to provide functional definitions that help to differentiate between generically-cytotoxic cancer drugs of significant risk to normal human tissues, and targeted cancer therapeutics that pose much lesser risks. Together with specific assessments, it provides comprehensible guidance on how to assess the relevant properties of cancer drugs, and how targeted therapeutics discriminate between cancer and normal cells. The position of several regulatory agencies in the long-term is clearly to regulate all drugs regardless of classification, according to scientific risk based data. Despite ongoing discussions on how to replace the term “cytotoxic drugs” in current regulations, it is expected that its use will continue for the near future.     

Cancer risk of immunosuppressants in manufacturing

During the chemical and pharmaceutical production of active pharmaceutical substances which are intended for immunosuppressive therapy, the employees may be exposed to these substances via inhalation. Immunosuppressants are linked to development of certain types of cancers e.g., lymphoma or skin cancer in transplant patients. The development of these cancers in patients is linked to the level of immunosuppression needed for transplantation in order to avoid organ rejection. Below these levels, with the immune system functioning uninhibited, cancer is unlikely to develop.     

Arterial compression of the retro-olivary sulcus of the ventrolateral medulla in essential hypertension and diabetes

Pulsatile arterial compression in the retro-olivary sulcus along the surface of the ventrolateral medulla has been postulated as a mechanism in both essential hypertension and diabetes. The objective of this study was to test the independent effect of arterial compression in the retro-olivary sulcus on each of these diseases, using separate logistic regression models to control for other known risk factors. Study design was case-control. The study population consisted of 147 consecutive patients treated for neurological conditions requiring MRI of the posterior cranial fossa. Information on essential hypertension, diabetes, and risk factors for each disease was abstracted from medical records. Presence of arterial compression was determined by blinded review of magnetic resonance images. In the essential hypertension analysis, odds of arterial compression among hypertensive patients were 2.99-times the odds among normotensive subjects (P=0.04), controlling for hypertension risk factors such as age, body mass index, race, diabetes, and family history of hypertension. Of compressed hypertensive subjects, 56% were compressed on the left and 44% were compressed on the right. In the diabetes analysis, odds of arterial compression among diabetic subjects were 1.14-times the odds among nondiabetic subjects (P=0.83). Of compressed diabetic subjects, 60% were compressed on the left, and 40% were compressed on the right. Results suggest that arterial compression of the retro-olivary sulcus may be an independent risk factor for essential hypertension in this population, supporting the postulate for a treatable (with microvascular decompression) neural mechanism for essential hypertension. However, in the diabetic population, the slight increase in the odds of arterial compression was not significant.     

Myocardial perfusion grade and survival after percutaneous transluminal coronary angioplasty in patients with cardiogenic shock

We sought to evaluate myocardial reperfusion and its prognostic value after percutaneous transluminal coronary angioplasty (PTCA) in patients admitted for cardiogenic shock. Lack of myocardial reperfusion despite restored coronary flow affects the survival of patients with acute myocardial infarction (AMI). Myocardial blush grade (MBG) is an angiographic measure of myocardial perfusion. We assessed MBG in 41 consecutive patients admitted to our department within 12 hours from the onset of AMI and in cardiogenic shock. PTCA was successful in 83% of patients. Thrombolysis In Mycardial Infarction (TIMI) grade 3 flow was demonstrated in 22 patients (53%). MBG 2/3 was found in 14 patients (34%); among them, 12 had TIMI 3 flow. Compared with patients with MBG 2/3, those with MBG 0/1 were older (71 +/- 11 vs 57 +/- 13 years, p = 0.001), had a higher prevalence of diabetes (48% vs 14%, p = 0.04) and hypertension (63% vs 29%, p = 0.04), showed a trend toward longer ischemic time (6.1 +/- 2.4 vs 4.9 +/- 1.1), and had larger enzymatic infarct size (peak creatine kinase 7,690 +/- 3,516 vs 5,500 +/- 2,977 IU/L). Mortality was higher in patients with MBG 0/1 both in the hospital (81% vs 14%, p <0.001) and at follow-up (81% vs 29%, p = 0.001). After adjustment by multivariate analysis, MBG 0/1 (odds ratio 16, p = 0.01) and age (odds ratio 3.8/10 years, p = 0.04) were correlated with in-hospital mortality. MBG 2/3 was achieved in a few patients in cardiogenic shock after AMI who were treated with PTCA; this was a strong predictor of in-hospital survival. Also, risk stratification after mechanical revascularization should include assessment of restoration of myocardial reperfusion.