COVID-19 and female fertility: the flaws of Italian Law 40/2004 on assisted procreation in pandemic times.

BACKGROUND AND AIM: SARS-CoV-2 has infected over 614 million people worldwide, killing more than 6.5 million. COVID-19 impact on fertility may have far-reaching ramifications, considering that only in Italy, over 20 million people have been infected, many more considering unconfirmed cases. METHODS: The authors aimed to outline the repercussions of COVID-19 on female reproductive capabilities, through an analysis of underlying mechanisms and dynamics liable to cause long-term COVID-19 complications and sequelae, including direct virus-induced tissue damage. RESULTS: The entry receptor for SARS-CoV-2, Angiotensin-converting enzyme 2 (ACE2) can be found in several tissues and organs within the human body, including ovaries, oocytes and placenta. In order to assess the fertility-damaging potential of the disease, it is necessary to clarify highly complex mechanisms such as the ovarian renin-angiotensin system (OVRAS) affecting ovarian physiology and dysfunction. COVID-19 and its potential to undermine the fertility prospects of millions cannot be underestimated. It is therefore essential for lawmakers to solve inconsistencies such as those in Italy's Law 40/2004, which has been all but dismantled by Constitutional Court and European Court of Human Rights rulings, and cannot therefore offer a sufficient degree of certainty and reliability. CONCLUSIONS: When crafting novel, updated standards, norms and regulations to govern access to medically-assisted procreation, national leaders need to take into account the grave threat to fertility in a country such as Italy, which already has one of the world's lowest birth rates, posed by COVID-19 in light of currently available research findings outlining its impact on reproductive capacity.

Telemedicine, Telepsychiatry and COVID-19 Pandemic: Future Prospects for Global Health.

There is no denying that demand for telemedicine and telepsychiatry services has been on the rise, as the COVID-19 pandemic engulfed the world and upset the daily lives and certainties of us all. Such growth, however, calls for a comprehensive analysis and assessment of the strengths and weaknesses inherent in such innovative approaches, which are bound to change and evolve as the fourth industrial revolution unfolds before our eyes. The authors have set out to analyze the complexities and distinctive features of telemedicine and telepsychiatry by focusing on the strengths and weaknesses of such approaches and analyzing research findings, recommendations, and guidelines by scientific societies and institutions, for the ultimate purpose of striking a tenable balance between technological innovations and the ethics and moral imperative of guaranteeing equal access to care for everyone, irrespective of social and financial status. The European regulatory and legislative scenario has been briefly outlined, and the standards for the medicolegal sustainability of such practices have been explored. Ultimately, in order to improve accessibility without compromising the quality of care, new broadly shared ethical standards, best practices, and guidelines need to be prioritized. National legislative initiatives and the international sharing of information need to be encouraged, for the ultimate purpose of optimizing and harmonizing telemedicine-based care for the sake of all patients. As technology moves forward and evolves, so must the normative standards and guidelines on which professionals must be able to rely when delivering telemedicine-based care in an ethically and legally viable fashion. From that perspective, addressing the digital divide means enabling more people to receive care and should therefore be seen as part and parcel of the effort to uphold the universal human right to health.

New Psychoactive Substances and receding COVID-19 pandemic: really going back to "normal"?

To the Editor, The ongoing rise of New Psychoactive Substances (NPS), i.e. psychotropic molecules devised and synthesized to replicate the effects of traditional drugs of abuse in order to circumvent banned substances schedules, has been posing a challenge of enormous magnitude to substance detection systems and law enforcement worldwide. Still, it would be remiss to ignore the role played by the unprecedented public health emergency relating to the COVID-19 pandemic in the exacerbation of the NPS crisis. The diversion of resources has in fact hindered conventional approaches to drug monitoring, surveillance, control, and public health responses. The dangerous path ahead in our struggle against NPS abuse is best exemplified by the rather recent emergence of isotonitazene, an analogue of a benzimidazole class of analgesic compounds, powerful synthetic opioid and full mu-opioid receptor agonist belonging to the 2-benzylbenzimidazole group of compounds, which comprises the structurally different clonitazene, metonitazene and etonitazene (1). Isonitazene has reportedly been detected on European markets in at least five different forms and could even supplant fentanyl derivatives (2). Currently available data on isonitazene-related abuse and fatalities seem to be emblematic of the volatile, elusive nature of NPS: deaths in which isotonitazene was involved in fact presented substantial differences from casualties arising from synthetic opioids abuse. Case reports have highlighted how flualprazolam was detected in most fatalities associated with isotonitazene whereas flualprazolam was involved in only 8% of other synthetic opioid overdose deaths (3). Rather than rising background use, such a finding seems to suggest likely co-use or co-distribution of flualprazolam and isotonitazene. The key element of polysubstance involvement is rife in synthetic opioid overdose deaths. That being said, significantly more substances were implicated in isotonitazene-related deaths than fatalities linked to other synthetic opioid overdose (4, 5). Such dynamics and mortality patterns further stress the urgency of expanding health services for those suffering from opioid addiction disorders. Fine-tuned and standardized detection mechanisms relying on specialized assays based on sensitive instrumentation are essential for the timely and accurate characterization of such novel synthetic opioids (6-8). Isotonitazene in fact cannot be detected by common fentanyl testing strips (9). Hence, the essential nature of clinical and toxicological cannot be overstated, if we are to effectively deal with the public health risks arising from new substances or classes, along with the healthcare and social costs thereof (10). As new substances appear on illicit markets and are detected, their distinctive traits can only be identified by user experience, in the early stages (11-13). Nonetheless, the pandemic scenario has brought about a profound alteration of substance abuse patterns, and opened up new avenues of supply and demand for which our surveillance/detection systems may not be fully prepared or well-suited. As the pandemic appears to recede and hopefully turn into an endemic context based on coexistence with the SARS-CoV-2 and its less harmful variants, it would be a mistake to take for granted that drug abuse/trafficking dynamics will also get back to where they were before the pandemic. Putting in place policies aimed at monitoring web-based platforms and social media can potentially constitute a valuable tool in terms of keeping in check emerging substances, given how during the COVID-19 pandemic many interactions between traffickers and buyers have moved online (14). After all, social media have been playing an increasingly relevant role as interacting platforms, which users and drug dealers can take advantage of in order to discuss drug prices, substance purity, distinctive traits of the "high" (i.e. desired drug effects) they are seeking, ways of taking the substances, dosages, and characteristics of any new NPS becoming available on such back-alley marketing channels (15). Softwares designed and specifically programmed to sift through and analyze all detectable online information in that regard may prove valuable to figure out evolving dynamics of trafficking, purchases and use. Probing social media users has proven effective tool for public health concerns, e.g. drug checking services which have been harnessed due to their harm reduction potential in places estimated to be at risk, with large crowds gathering (concerts, clubs and the like). Nonetheless, research efforts need to be directed towards the new realm of criminality, the "Dark Web", in which all sorts of illegal exchanges and interactions are known to take place. A 2020 study has highlighted the appalling risks for drug users who choose to pursue that option in order to buy drugs (16). Three dealers were selected on a specific "Dark Web" marketplace, and NPS were ordered through such a channel. All these exchanges were thoroughly documented, and an analysis was undertaken of all the substances thus bought, totaling nine samples, by NMR, HRMS, LC-UV, and two also by x-ray diffraction. It was ultimately concluded that four out of five substances bought had been labeled with NPS names that did not match the actual substance, and two out of three samples of substances sold as new (i.e. unscheduled) NPS were instead found to be already documented substances, mislabeled and peddled under false pretenses. Drug dealers were therefore either deceiving their clients or were unaware as to the actual substances which they were selling. In light of such extremely worrisome findings, it is not hard to understand the implications and the major public health risks that such new trends of trafficking and abuse may entail. It is therefore incumbent upon the scientific community and law enforcement agencies to adapt and strive to meet the new challenges brought by the new criminal ecosystems in terms of drug enforcement, first and foremost the impervious environment known as "Dark Web" relying on untraceable cryptocurrencies for illegal transactions.

A global approach to improving penile cancer care.

Rare tumours such as penile carcinoma have been largely neglected by the urology scientific community in favour of more common - and, therefore, more easily fundable - diseases. Nevertheless, penile cancer represents a rising burden for health-care systems around the world, because a lack of widespread expertise, ineffective centralization of care and absence of research funds have hampered our ability to improve the global care of these patients. Moreover, a dichotomy has arisen in the field of penile cancer, further impeding care: the countries that are mainly supporting research on this topic through the development of epidemiological studies and design of clinical trials are not the countries that have the highest prevalence of the disease. This situation means that randomized controlled trials in developed countries often do not meet the minimum accrual and are intended to close before reaching their end points, whereas trials are almost completely absent in those areas with the highest disease prevalence and probability of successful recruitment, such as Africa, South America and South Asia. The scientific and organizational inaction that arises owing to this mismatch translates into a burdensome cost for our patients. A global effort to gather experts and pull together scientific data from around the world may be the best way to boost clinical research, to change clinical practice and, ultimately, to improve care for patients and their families.

The epidemiology of proximal femur fractures during COVID-19 emergency in Italy: a multicentric study.

BACKGROUND AND AIM: After the first Italian case of Covid-19, the Government imposed the complete closure of all areas involved by the spread of the virus to contain transmissions. There was a massive reorganization of Hospitals, a stop of all elective activities and a convertion of many hospitals in "Covid Centers''. AITOG (Associazione Italiana Traumatologia e Ortopedia Geriatrica) conducted a retrospective study on all proximal femur fractures surgeries that occurred in this period, to find out whether the pandemic and the correlated lockdown somehow changed the incidence of these events.  Methods: 10 Italian orthopedic centers were involved in the study. Considering the geographic location, three groups were created (North, Centre and South). The considered period is the Italian "Phase 1" (February 23rd - May 3rd 2020). RESULTS: the cohort is composed of 412 patients, 116 male and 296 female (mean age 81.1 ± 9.1 years). The same period of 2019 has been used as control group, with 558 patients, 156 male and 402 female (mean age 84.2 ± 8.0 years). In 2020 we counted 323 (78.4%) fractures occurred at home, 61 (14.8%) in retirement houses and 28 (6.8%) in different locations. We mainly treated fractures with intramedullary nails (n.237 57.5%). Among all patients we had 46 (11.1%) Covid-19 positive. The mortality rate within 30 days was of 51 patients (12.4%); 23 of these died because of complications related to Covid-19 while 31 of  these were in treatment with anticoagulant/antiaggregant. CONCLUSIONS: AITOG analysis demonstrates a decrease in surgical interventions for proximal femur fractures from 2019 to 2020, a reduction in patients mean age and an increase in trauma occurred in domestic environment. We also registered a consistent difference between the North, Center and South of the Country.

A seven week observational analysis of clinical activities in a North Italian orthopaedic hospital during the second wave of SARS-CoV-2 pandemic: far from usual volumes, but different from the first wave.

PURPOSE: We previously described the radical changes occurred in an orthopaedic hospital in Milan (Italy) during the first SARS-CoV-2 pandemic outbreak. Currently, during the second wave, the situation is still far from normality. Here we describe the changes that took place, and are still ongoing, in the clinical practice. METHODS: Number and type of admissions, outpatients activity, ER and urgent procedures in SARS-CoV-2 negative and positive patients have been analyzed over seven weeks (October 26th-December 13th, 2020) and compared with the correspondent period in 2019 and the same timeframe during the first wave (February 24th-April 10th). RESULTS: 2019 vs. 2020: Overall admissions decreased by 39.8%; however, while admissions for elective surgery dropped by 42.0%, urgent surgeries increased by 117.0%. Rehabilitation admissions declined by 85.2%. White and green priority ER consultations declined by 41.6% and 52.0%, respectively; yellow and red increased by 766.7% and 400.0%, respectively. Second vs. first wave: Overall admissions increased by 58.6% with a smoother decrement in weekly admissions than during the first wave. Disparity of acute admissions vs. rehabilitation expanded: Acute cases increased by 63.6% while rehabilitation cases decreased by 8.7%. Admissions to triage procedures increased by 72.3%. CONCLUSIONS: Activity levels are far from normality during the second COVID-19 wave. Elective surgery and outpatients-related activities are still strongly limited compared to 2019 while the number of urgent cases treated increased consistently. SARS-CoV-2 positive emergencies are slightly higher than during the first wave. These important changes are expected to impact on health service and hospital budget for long.