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Abstract Background Dupuytren disease, a chronic thickening and retraction of the palmar aponeurosis of the hands, may result in permanent and progressive flexion of one or more fingers. Percutaneous needle fasciotomy is a simple method that uses a hypodermic needle usually performed under local anaesthesia. The study aim was to report the postoperative results and complications using a percutaneous approach to treat Dupuytren contracture in a consecutive series of patients with advanced Dupuytren disease, also considering the relevant medico-legal implications. Methods Retrospective multicentre study of all patients with Tubiana stage 3–4 Dupuytren contracture treated with percutaneous needle aponeurotomy, with no ultrasound assistance, from 2012 to 2022. Patient demographics, disease severity, treatment-related complications, and the incidence of recurrence were identified. An overview of therapeutic treatment options has accounted for 52 relevant sources spanning the 2007–2023 time period. Results Overall, 41.7% (N = 200) of patients were females, the mean age was 72 years (60–89), the right hand was treated in 54.2% (N = 260) of patients. The little finger was involved in 50% of the patients. The 12 months mean PED was 9°, the mean quickDASH was 8, the mean URAM 6. Minor complications were reported in 18.7% (N = 90) of patients, typically skin lacerations (83.3%) with no clinical sequelae, and no major complications were reported. Recurrence occurred in 30% (N = 144) of patients. Conclusions Percutaneous needle fasciotomy is safe and reliable even in patients with advanced Dupuytren disease, resulting in predictably acceptable outcome with low risk of complications.

Objective: To present the surgical technique and outcomes of robotic ureteral reimplantation in ileal conduit (IC) and neobladder (NB) in patients with prior minimally-invasive radical cystectomy and intracorporeal urinary diversion, who developed benign uretero-ileal anastomotic strictures. Patients and surgical procedure: We report on a multiinstitutional cohort of 10 patients (7 IC, 3 NB) who had 12 uretero-ileal strictures (8 unilateral, 2 bilateral) causing hydronephrosis and renal function deterioration, who underwent robotic uretero-ileal reimplantation in referral centers for robotic surgery between 2016 and 2022. Median age was 67.5 years (Interquartile range [IQR]: 66–69). The stricture was diagnosed at a median of 6 months (IQR 5–10) from the initial surgery. All unilateral strictures were on the left side. Two patients received unsuccessful endoscopic dilatation before the reconstructive surgery. All patients underwent nephrostomy placement prior to the reconstructive procedure. Robotic uretero-ileal reanastomosis started with adhesiolysis, followed by the identification of the ureters and urinary diversion, facilitated by the use of intracavitary saline or ICG. When dissecting the ureters, a „no touch” technique was used, in order to minimize devascularization and ischemia. Localization of the ureteral stricture was critical. The excision of the entire ischemic segment was performed until signs indicative of adequate tissue trophism were found. At the same time, consideration was given to spare sufficient length of the ureteral stumps to allow for a tension-free anastomosis. Direct anastomosis using monofilament resorbable suture, with insertion of mono J or double J stent was performed with both ileal conduit and neobladder. Bricker technique was used in case of unilateral stricture. Results: The median operative time for robotic uretero-ileal reanastomosis was 152 min (IQR 120–180) and the median blood loss was 50 ml (IQR 40–70). No intraoperative complications occurred according to the ICARUS criteria. Median length of hospital stay was 4.5 days (IQR 3–6). Two Clavien-DIndo II (20 %) postoperative complications were registered (urinary tract infection and acute kidney injury). No patients required readmission or reoperation. The mean length of ureteral catheterization for reimplantation in IC was 20.7 days (± 4.29). For patients with NB, the mean ureteral and urethral catheterization times were 54.3 days (± 22.8) and 19.3 days (± 11.08), respectively. The ureteral stents were removed in all patients. At a median of 16 months follow-up (range 6–36 months), 2 patients (one IC and one NB, respectively) had persistent hydronephrosis. Conclusion: In patients requiring surgery for benign ureteral strictures following cystectomy, robotic surgery allows for safe and efficient ureteral reimplantation in urinary diversion.

(1) Background. A definition of healthcare-associated infections is essential also for the attribution of the restorative burden to healthcare facilities in case of harm and for clinical risk management strategies. Regarding M. chimaera infections, there remains several issues on the ecosystem and pathogenesis. We aim to review the scientific evidence on M. chimaera beyond cardiac surgery, and thus discuss its relationship with healthcare facilities. (2) Methods. A systematic review was conducted on PubMed and Web of Science on 7 May 2024 according to PRISMA 2020 guidelines for reporting systematic reviews, including databases searches with the keyword “Mycobacterium chimaera”. Article screening was conducted by tree authors independently. The criterion for inclusion was cases that were not, or were improperly, consistent with the in-situ deposition of aerosolised M. chimaera. (3) Results. The search yielded 290 eligible articles. After screening, 34 articles (377 patients) were included. In five articles, patients had undergone cardiac surgery and showed musculoskeletal involvement or disseminated infection without cardiac manifestations. In 11 articles, respiratory specimen reanalyses showed M. chimaera. Moreover, 10 articles reported lung involvement, 1 reported meninges involvement, 1 reported skin involvement, 1 reported kidney involvement after transplantation, 1 reported tendon involvement, and 1 reported the involvement of a central venous catheter; 3 articles reported disseminated cases with one concomitant spinal osteomyelitis. (4) Conclusions. The scarce data on environmental prevalence, the recent studies on M. chimaera ecology, and the medicalised sample selection bias, as well as the infrequent use of robust ascertainment of sub-species, need to be weighed up. The in-house aerosolization, inhalation, and haematogenous spread deserve experimental study, as M. chimaera cardiac localisation could depend to transient bacteraemia. Each case deserves specific ascertainment before tracing back to the facility, even if M. chimaera represents a core area for healthcare facilities within a framework of infection prevention and control policies.

Objective: To report the outcomes of intra- and extra-peritoneal robot-assisted radical prostatectomy (RARP) and robot-assisted radical cystectomy (RARC) with Hugo™ robot-assisted surgery (RAS) system (Medtronic, Minneapolis, MN, USA). Methods: Data of twenty patients who underwent RARP and one RARC at our institution between February 2022 and January 2023 were reported. The primary endpoint of the study was to report the surgical setting of Hugo™ RAS system to perform RARP and RARC. The secondary endpoint was to assess the feasibility of RARP and RARC with this novel robotic platform and report the outcomes. Results: Seventeen patients underwent RARP with a transperitoneal approach, and three with an extraperitoneal approach; and one patient underwent RARC with intracorporeal ileal conduit. No intraoperative complications occurred. Median docking and console time were 12 (interquartile range [IQR] 7–16) min and 185 (IQR 177–192) min for transperitoneal RARP, 15 (IQR 12–17) min and 170 (IQR 162–185) min for extraperitoneal RARP. No intraoperative complications occurred. One patient submitted to extraperitoneal RARP had a urinary tract infection in the postoperative period that required an antibiotic treatment (Clavien-Dindo Grade 2). In case of transperitoneal RARP, two minor complications occurred (one pelvic hematoma and one urinary tract infection; both Clavien-Dindo Grade 2). Conclusion: Hugo™ RAS system is a novel promising robotic platform that allows to perform major oncological pelvic surgery. We showed the feasibility of RARP both intra- and extra-peritoneally and RARC with intracorporeal ileal conduit with this novel platform.

Ostarine (enobasarm) is a selective androgen receptor modulator with great therapeutic potential. However, it is also used by athletes to promote muscle growth and enhance performances without the typical adverse effects of anabolic steroids. Ostarine popularity increased in recent years, and it is currently the most abused “other anabolic agent” (subclass S1.2. of the “anabolic agents” class S1) from the World Anti-Doping Agency’s (WADA) prohibited list. Several cases of liver toxicity were recently reported in regular users. Detecting ostarine or markers of intake in biological matrices is essential to document ostarine use in doping. Therefore, we sought to investigate ostarine metabolism to identify optimal markers of consumption. The substance was incubated with human hepatocytes, and urine samples from six ostarine-positive cases were screened. Analyses were performed via liquid chromatography–high-resolution tandem mass spectrometry (LC-HRMS/MS) and software-assisted data mining, with in silico metabolite predictions. Ten metabolites were identified with hydroxylation, ether cleavage, dealkylation, O-glucuronidation, and/or sulfation. The production of cyanophenol-sulfate might participate in the mechanism of ostarine liver toxicity. We suggest ostarine-glucuronide (C25H22O9N3F3, diagnostic fragments at m/z 118, 185, and 269) and hydroxybenzonitrile-ostarine-glucuronide (C25H22O10N3F3, diagnostic fragments at m/z 134, 185, and 269) in non-hydrolyzed urine and ostarine and hydroxybenzonitrile-ostarine (C19H14O4N3F3, diagnostic fragments at m/z 134, 185, and 269) in hydrolyzed urine as markers to document ostarine intake in doping.

ABSTRACT Introduction: Robotic approach has shown its feasibility and safety with respect to open approach for radical cystectomy (1). The performances of Hugo™ RAS system (Medtronic, Minneapolis, USA) have been demonstrated in several clinical scenarios (2-5). We report the feasibility and surgical settings of the first series of robot-assisted radical cystectomy (RARC) with intracorporeal ileal-conduit performed with Hugo™ RAS system. Methods: Two patients were submitted to RARC with ileal conduit at our institution. The trocar placement scheme and the operating room setting with docking angles of the four arms were already described (6). A 12-mm and a 5-mm trocar for the assistant were placed. In both cases, an ileal-conduit with a Wallace type-1 uretero-enteric derivation was performed intra-corporeally. Results: The first patient was a 71-year-old male with a very-high risk non-muscle invasive bladder cancer(BC), and the second patient was a 64-year-old male with a diagnosis of T2 high-grade BC. Operative times were 360 and 420 minutes with a docking time of 12 and 9 minutes, respectively. No intraoperative complications occurred. The estimated blood loss was 200ml and 400ml, respectively. The second patient developed an ileus on postoperative day 4 (Clavien-Dindo grade 2). No positive surgical margins were recorded. No recurrence nor progression occurred during follow-up. Conclusion: RARC with intracorporeal ileal conduit urinary diversion is feasible with Hugo™ RAS system. We provided insight into the surgical setting using this novel robotic platform to help new adopters to face this challenging procedure. These findings may help a wider distribution of robotic programs for BC treatment.

Although radical nephrectomy (RN) is the most common treatment for kidney cancer, no data on the learning curve for RN are available. In this study we investigated the effect of surgical experience (EXP) on RN outcomes using data for 1184 patients treated with RN for a cT1–3a cN0 cM0 renal mass. EXP was defined as the total number of RNs performed by each surgeon before the patient’s operation. The primary study outcomes were all-cause mortality, clinical progression, Clavien-Dindo grade ≥2 postoperative complications (CD ≥2), and the estimated glomerular filtration rate (eGFR). Secondary outcomes were operative time, estimated blood loss, and length of stay. Multivariable analyses adjusted for case mix revealed no evidence of association between EXP and all-cause mortality (p = 0.7), clinical progression (p = 0.2), CD ≥2 (p = 0.6), or 12-mo eGFR (p = 0.9). Conversely, EXP was associated with shorter operative time (estimate −0.9; p < 0.01). Mortality, cancer control, morbidity, and renal function might not be affected by EXP. The very large cohort examined and the extensive follow-up support the validity of these negative findings. Patient summary: For patients with kidney cancer undergoing surgical removal of a kidney, those treated by novice surgeons have similar clinical outcomes to those treated by experienced surgeons. Thus, this procedure represents a convenient scenario for surgical training if longer operating theatre time can be planned.

Drug abuse still represents a significant challenge for forensic pathologists; it must always be considered during the autopsy examination when the brain morphological alterations observed are not characteristic of any known disease of the central nervous system (CNS). Nonetheless, no specific brain lesions had been found to characterize the precise drug that caused the poisoning. In fact, a broad spectrum of changes affecting the CNS are seen in drug abusers. Thus, forensic pathology plays a key role in identifying the encephalic morphological alterations underlying the death. The aim of this review is to present an updated overview of the literature regarding the correlation between the main substances of abuse and the morphological alterations of the CNS to help the forensic pathologist to discriminate drug-induced alterations of the brain. The authors used the PRISMA criteriology to perform the bibliographic search for the present review. Among the articles identified according to the selected search criteria, 116 articles were chosen which allow us to define a picture of the main macroscopic and microscopic alterations of the brain in drug abuse.

The colloid cyst is a non-malignant tumor growth made of a gelatinous material covered by a membrane of epithelial tissue. It is usually located posterior to the foramen of Monro, in the anterior aspect of the third ventricle of the brain. Due to its location, it can cause obstructive hydrocephalus, increased intracranial pressure, and sudden cardiac death, catecholamine-mediated, through hypothalamus compression. All the mechanisms are still controversial, but the role of catecholamine has been confirmed with histological findings that highlighted myocardial injury (coagulative myocytolysis and contraction band necrosis, CBN). This study presents a case of sudden death in a previously healthy 22-year-old male due to a colloid cyst of the third ventricle. A complete autopsy was performed, highlighting in the brain an abundant quantity of cerebrospinal fluid (CSF) and a 2 cm pale grayish-green rounded cyst formation partially filling and distending the third ventricle. The diagnosis was confirmed through immunohistochemical investigation: positivity for Periodic acid-Schiff (PAS) staining and CK7 expression. In cases such as the one reported here, a combined approach of autopsy, histology, and immunohistochemistry is mandatory in order to identify the neoformation’s location and morpho-structural characteristics for a correct differential diagnosis, as well as to identify the cause of death.

Cancer of unknown primary (CUP) origin represents a diagnostic and therapeutic challenge. These tumours spread to different parts of the body even if the site of origin has not been identified. When renal metastases are observed without an obvious primary lesion, it is important to exclude the possibility of a primary kidney tumour that may be unknown or too small to be detected. The diagnosis of CUP is established after a careful clinical evaluation and diagnostic tests, including blood chemistry and laboratory tests, instrumental exams (CT, MRI, PET, bone scan), biopsy, and molecular and cytogenetic analysis. Once the diagnosis of CUP with kidney metastases is confirmed, treatment depends on the location of the metastases, the patient’s health status, and available treatment options. The latter includes surgery to remove metastases, radiation therapy, or systemic treatment such as chemotherapy or immunotherapy. It is important that patients with CUP are evaluated by a multidisciplinary team of specialists, who can contribute to planning the most appropriate treatment. In this article, we report the clinical case of a patient with a pathological fracture of the proximal humerus which occurred on metastases of probable renal origin in the absence of primary lesions.

In this report, we look at the relationship between prior circumcision and presenting stage of penile cancer. We performed an analysis of an international, multicenter database of 1254 penile cancer patients diagnosed from 1980 to 2019 in the United States, Europe, Brazil, and China, and analyzed the relationship between circumcision and presenting T and N stage. A total of 710 patients met the inclusion criteria and were statistically analyzed. We found that uncircumcised men with locally advanced tumors (T3–T4) had significantly higher risk of lymph node metastasis compared with circumcised men.

Highlights Anatomical variants of the intraarticular portion of the long head of the biceps tendon should be studied with MR arthrography. Some anatomical variants are more frequently associated with supraequatorial lesions. The higher frequency of lesions in the presence of certain anatomical variants is probably related to the limited excursion of the intraarticular long head biceps tendon.

Osteoarthritis (OA) is a degenerative and progressive joint disease. When all three compartments are involved, end-stage OA is treated with a total knee arthroplasty (TKA). Unicompartmental knee arthroplasty (UKA) is a primary treatment for isolated osteoarthritis. UKA has a quicker recovery time than TKA, as well as less morbidity and more tissue sparing. At the time of surgery, 17% of patients have a tricompartmental disease and most patients with a Kellegren–Lawrence grade >3 have an intact anterior cruciate ligament (ACL). Conventional TKA sacrifices the ACL. Patients with concurrent medial and lateral osteoarthritis and a functional ACL may receive a primary bi-unicondylar arthroplasty. Combined partial knee arthroplasty (CPKA) is an established practice either in bicompartmental femoro-tibial OA or in OA progression after UKA, with the addition of another UKA. A conversion of a lateral UKA to a tricompartmental joint replacement has been reported in the literature. In our case report, we describe a one-stage hypoallergenic tricompartmental UKA, with improved clinical score and no sign of early failure at the last follow-up.

Highlights Prosthetic joint infections (PJI) represent one of the major problems in orthopedic prosthetic surgery. The diagnosis of prosthetic infections requires a multispecialist approach, from accurate anamnestic collection, to clinical evaluation and biomarkers of inflammation, to the use of imaging techniques. The identification of the bacteria responsible for the infection is essential for the timely diagnostic setting and the correct antibiotic treatment. Risk management procedures, adherence to guidelines and good care practices, to prevent errors and complications.

Objectives: Lymph node invasion (LNI) is related to long-term survival in patients with muscle-invasive bladder cancer. However, in the case of variant histology (VH), data on pelvic lymph node dissection (PLND) and LNI are sparse. We described the pattern of care of PLND in patients with VHs of bladder cancer, exploring predictors of LNI. Methods: Using the 2001–2016 SEER registry, 20 767 bladder cancer patients who underwent PLND were identified. Included histological variants were pure urothelial carcinoma (UC), micropapillary UC, sarcomatoid UC, lymphoepithelioma-like UC, adenocarcinoma, sarcoma, giant and spindle cell carcinoma, squamous cell carcinoma (SCC), and neuroendocrine tumor. Uni- and multivariable logistic regression analyses tested for LNI predictors. Cox regression was used to test for predictors of overall mortality (OM) among both LNI positive and LNI negative patients. Results: Overall, 2464 (11.9%) harbored a VH. On multivariate analysis, only micropapillary UC was associated with higher risk (OR = 3.39) of LNI. This association was maintained when only the subset of patients treated without perioperative chemotherapy were analyzed (OR = 3.30). Similarly, higher T stage (T2 stage OR = 2.24; T3–4 stage OR = 9.44) and the use of chemotherapy (OR = 2.29) were associated with a higher risk of LNI. Among patients with LNI (5299, 25.5%), SCC (HR = 1.87), T3–4 stage (HR = 1.94), age at diagnosis (HR = 1.01) and geographic region (south) (HR = 1.22) were predictors of higher risk of OM. Conversely, chemotherapy (HR = 0.69) and number of removed LN (HR = −0.99) were associated with lower risk of OM. Finally, in a subgroup of patients without LNI, sarcomatoid UC (HR = 1.58) and giant and spindle cell carcinoma (HR = 1.83) were the only VH predictors of OM. Conclusions: We described different patterns of care in patients with VHs of bladder cancer. Micropapillary UC was an independent risk factor for LNI. Among patients harboring LNI, those with SCC VH had higher OM compared to pure UC. Conversely, sarcomatoid UC and giant and spindle cell carcinoma were predictors of OM in patients without nodal involvement.

Recreational use of Synthetic Cannabinoids (SCs), one of the largest groups of New Psychoactive Substances (NPS), has increased globally over the past few years. Driving is a structured process requiring the cooperation of several cognitive and psychomotor functions, organized in different levels of complexity. Each of these functions can be affected when Driving Under the Influence (DUI) of SCs. In order to reduce the likelihood of SC-related road accidents, it is essential to understand which areas of psychomotor performance are most affected by these substances, as well as the severity of impairment. For this purpose, a multiple database- literature review of recent experimental studies in humans and animals regarding the psychomotor effects of SCs has been performed. Despite the many limitations connected to experimental studies on humans, results showed a consistency between animal and human data. SCs appear to impair psychomotor performance in humans, affecting different domains related to safe driving even at low doses. Cases of DUI of SC have been repeatedly reported, although the exact prevalence is likely to be underestimated due to current analytical and interpretative issues. For this reason, an accurate physical examination performed by trained and experienced personnel has a primary role in recognizing signs of impairment in case of strong suspicion of SC consumption. The identification of a suspected case should be followed by reliable laboratory examination.

Anamorelin, developed for the treatment of cancer cachexia, is an orally active medication that improves appetite and food intake, thereby increasing body mass and physical functioning. It is classified as a growth hormone secretagogue and strictly monitored by the World Anti-Doping Agency (WADA), owing to its anabolic enhancing potential. Identifying anamorelin and/or metabolite biomarkers of consumption is critical in doping controls. However, there are currently no data available on anamorelin human metabolic fate. The aim of this study was to investigate and identify biomarkers characteristic of anamorelin intake using in silico metabolite predictions with GLORYx, in vitro incubation with 10-donor-pooled human hepatocytes, liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) analysis, and data processing with Thermo Scientific’s Compound Discoverer. In silico prediction resulted in N-acetylation at the methylalanyl group as the main transformation (score, 88%). Others including hydroxylation at the indole substructure, and oxidation and N-demethylation at the trimethylhydrazino group were predicted (score, ≤36%). Hepatocyte incubations resulted in 14 phase I metabolites formed through N-demethylation at the trimethylhydrazino group, N-dealkylation at the piperidine ring, and oxidation at the indole and methylalanyl groups; and two phase II glucuronide conjugates occurring at the indole. We propose four metabolites detected as specific biomarkers for toxicological screening.

This review article explores the possibility of developing an integrated approach to the management of the different needs of endometrial cancer (EC) patients seeking to become pregnant. Life preservation of the woman, health preservation of the baby, a precocious and—as much as possible—minimally invasive characterization of the health and fertility parameters of the patient, together with the concerns regarding the obstetric, neonatal, and adult health risks of the children conceived via assisted reproductive techniques (ART) are all essential aspects of the problem to be taken into consideration, yet the possibility to harmonize such needs through a concerted and integrated approach is still very challenging. This review aims to illustrate the main features of EC and how it affects the normal physiology of pre-menopausal women. We also focus on the prospect of a miR-based, molecular evaluation of patient health status, including both EC early diagnosis and staging and, similarly, the receptivity of the woman, discussing the possible evaluation of both aspects using a single specific panel of circulating miRs in the patient, thus allowing a relatively fast, non-invasive testing with a significantly reduced margin of error. Finally, the ethical and legal/regulatory aspects of such innovative techniques require not only a risk-benefit analysis; respect for patient autonomy and equitable health care access allocation are fundamental issues as well.

BackgroundAdult primary retroperitoneal sarcomas (RPSs) are a group of heterogeneous tumors with different histological subtypes. Comprehensive genomic profiling (CGP) analyses have recently provided significant insights into the biology of sarcomas by identifying genomic alterations (GAs) which could benefit from targeted therapies. MethodsRPS were evaluated by CGP using next-generation sequencing of up to 406 cancer-related genes. Tumor mutational burden (TMB) was determined on 0.83 to 1.14 mut/Mb of sequenced DNA. Finally, PD-L1 expression was determined. ResultsOverall, 296 cases of primary RPS were analyzed. Liposarcoma (LPS) subtype had more GA/tumor than leiomyosarcoma (LMS) subtypes, with follicular dendritic cell sarcomas harboring the highest and synovial sarcomas the lowest. TP53 and Rb1 alterations were the highest in LMS, and CDK4/6 and MDM2 in LPS. However, both the TMB and targetable GA rates were low across subtypes. PD-L1 immunostaining was low positive in 21% and high positive in 5% of patients, respectively. ConclusionsCGP analysis revealed that potentially actionable genomic targets were rare in our cohort of RPS. Moreover, RPSs seem less likely to respond to immune checkpoint inhibitors based on putative biomarkers status. Nevertheless, genomic stratification according to histological subtypes led to description of GAs that can inform future clinical trials design.

Infertility is a global health issue affecting women and men of reproductive age with increasing incidence worldwide, in part due to greater awareness and better diagnosis. Assisted reproduction technologies (ART) are considered the ultimate step in the treatment of infertility. Recently, artificial intelligence (AI) has been progressively used in the many fields of medicine, integrating knowledge and computer science through machine learning algorithms. AI has the potential to improve infertility diagnosis and ART outcomes estimated as pregnancy and/or live birth rate, especially with recurrent ART failure. A broad-ranging review has been conducted, focusing on clinical AI applications up until September 2022, which could be estimated in terms of possible applications, such as ultrasound monitoring of folliculogenesis, endometrial receptivity, embryo selection based on quality and viability, and prediction of post implantation embryo development, in order to eliminate potential contributing risk factors. Oocyte morphology assessment is highly relevant in terms of successful fertilization rate, as well as during oocyte freezing for fertility preservation, and substantially valuable in oocyte donation cycles. AI has great implications in the assessment of male infertility, with computerised semen analysis systems already in use and a broad spectrum of possible AI-based applications in environmental and lifestyle evaluation to predict semen quality. In addition, considerable progress has been made in terms of harnessing AI in cases of idiopathic infertility, to improve the stratification of infertile/fertile couples based on their biological and clinical signatures. With AI as a very powerful tool of the future, our review is meant to summarise current AI applications and investigations in contemporary reproduction medicine, mainly focusing on the nonsurgical aspects of it; in addition, the authors have briefly explored the frames of reference and guiding principles for the definition and implementation of legal, regulatory, and ethical standards for AI in healthcare.

Adulteration is a well-known practice of drug manufacturers at different stages of drug production. The intentional addition of active ingredients to adulterate the primary drug may enhance or mask pharmacological effects or may produce more potent drugs to increase the number of available doses and the dealer’s profit. Adulterants found in different drugs change over time in response to different factors. A systematic literature search in PubMed and Scopus databases and official international organizations’ websites according to PRISMA guidelines was performed. A total of 724 studies were initially screened, with 145 articles from PubMed and 462 from Scopus excluded according to the criteria described in the Method Section. The remaining 117 records were further assessed for eligibility to exclude articles without sufficient data. Finally, 79 studies were classified as “non-biological” (n = 35) or “biological” (n = 35 case reports; n = 9 case series) according to the samples investigated. Although the seized samples analyses revealed the presence of well-established adulterants such as levamisole for cocaine or paracetamol/acetaminophen for heroin, the reported data disclosed new adulteration practices, such as the use of NPS as cutting agents for classic drugs of abuse and other NPS. For example, heroin adulterated with synthetic cannabinoids or cocaine adulterated with fentanyl/fentalogues raised particular concern. Notably, adulterants play a role in some adverse effects commonly associated with the primary drug, such as levamisole-adulterated cocaine that may induce vasculitis via an autoimmune process. It is essential to constantly monitor adulterants due to their changing availability that may threaten drug consumers’ 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.

In recent years, the growing use of ART (assisted reproductive techniques) has led to a progressive improvement of protocols; embryo freezing is certainly one of the most important innovations. This technique is selectively offered as a tailored approach to reduce the incidence of multiple pregnancies and, most importantly, to lower the risk of developing ovarian hyperstimulation syndrome when used in conjunction with an ovulation-triggering GnRH antagonist. The increase in transfer cycles with frozen embryos made it possible to study the effects of the technique in children thus conceived. Particularly noteworthy is the increase in macrosomal and LGA (large for gestational age) newborns, in addition to a decrease in SGA (small for gestational age) and LBW (low birth weight) newborns. The authors aimed to outline a broad-ranging narrative review by summarizing and elaborating on the most important evidence regarding the neonatal outcome of children born from frozen embryos and provide information on the medium and long-term follow- up of these children. However, given the relatively recent large-scale implementation of such techniques, further studies are needed to provide more conclusive evidence on outcomes and implications.

Although the first discovery of a non-coding RNA (ncRNA) dates back to 1958, only in recent years has the complexity of the transcriptome started to be elucidated. However, its components are still under investigation and their identification is one of the challenges that scientists are presently facing. In addition, their function is still far from being fully understood. The non-coding portion of the genome is indeed the largest, both quantitatively and qualitatively. A large fraction of these ncRNAs have a regulatory role either in coding mRNAs or in other ncRNAs, creating an intracellular network of crossed interactions (competing endogenous RNA networks, or ceRNET) that fine-tune the gene expression in both health and disease. The alteration of the equilibrium among such interactions can be enough to cause a transition from health to disease, but the opposite is equally true, leading to the possibility of intervening based on these mechanisms to cure human conditions. In this review, we summarize the present knowledge on these mechanisms, illustrating how they can be used for disease treatment, the current challenges and pitfalls, and the roles of environmental and lifestyle-related contributing factors, in addition to the ethical, legal, and social issues arising from their (improper) use.

Colon cancer is the fourth most common malignancy in both incidence and mortality in developed countries. Infectious agents are among the risk factors for colon cancer. Variations in human endogenous retrovirus (HERV) transcript and protein levels are associated with several types of cancers, but few studies address HERV expression in colon cancer. Fifty-eight patients with advanced-stage colon cancer were enrolled in this study. HERV-H, -K (HML-2), -P LTRs, Alu, and LINE-1 methylation levels and transcription of HERV-H, -K (HML-2), and -P env and HERV-K pol genes in normal adjacent and tumor tissues were investigated by pyrosequencing and RT-qPCR, respectively. Expression of the HERV-K (HML-2) Pol and Env proteins in selected tissues was examined by Western blotting. Associations between HERV transcript expression and methylation levels and between clinical characteristics and HERV expression were evaluated. Compared to adjacent normal tissues, LINE-1 was hypomethylated in tumor tissues (p < 0.05), whereas Alu, HERV-K (HML-2), and -H LTRs showed a decreasing trend in tumor tissue compared to normal tissue, though without a significant difference. The transcription levels of HERV env and pol genes were similar. However, the HERV-K (HML-2) Pol protein was more highly expressed (p < 0.01) in surrounding normal tissues, but the HERV-K (HML-2) Env protein was only expressed in tumor tissues. Although HERV LTR methylation and gene expression did not show significant differences between tumor and normal tissues, HERV protein expression differed greatly. Pol protein expression in normal cells may induce reverse transcription and subsequent integration into the host genome, likely favoring cell transformation; in contrast, the Env protein in tumor tissue may contribute to cancer progression through cell-to-cell fusion.

The water drop penetration time (WDPT) technique was applied in 2018 to check persistence of soil water repellency (SWR) in a Sicilian mountain area affected by a wildfire on June 2016. A total of four sites, that were severely water repellent immediately after burning, were sampled. Depending on the site, wettable soil conditions, less SWR and maintenance of a noticeable SWR were detected two years later. At the site showing a near-constant SWR, WDPTs were particularly high in the top soil layer (0-0.03 m) and they appreciably decreased more in depth. Signs of decreasing SWR in drier soil conditions and in association with coarser soil particles were also detected at this site. High gradients of the WDPT can occur at very small vertical distances and a depth increment of approximately 0.01 m should be appropriate to capture small-scale vertical changes in SWR, especially close to the soil surface. Occurrence of SWR phenomena is easily perceivable and explainable if an inverse relationship between WDPTs and antecedent soil water content is obtained. A direct relationship between these two variables is more difficult to interpret because infiltration times that increase in wetter soil are expected according to the classical infiltration theory. A hypothesis that should be tested in the future is to verify if WDPTs that decrease in drier soil conditions signal less SWR as a consequence of a reduced biological activity of the soil. Finally, long-term monitoring projects on longevity of fire effects on SWR should be developed, even because an in depth knowledge of the involved processes is relevant for the civil protection system.

Infertile couples undergoing the use of assisted reproductive technology are a good study model to evaluate the microbiological signatures affecting reproductive health. We tested vaginal lavages, follicular fluids, embryo culture mediums, and seminal fluids from 47 couples for their microbiome composition and HPV infection. Twenty-five infertile couples were diagnosed with unexplained infertility, whereas 22 were diagnosed with explained infertility. Lactobacilli were dominant in the vaginal lavages of both patient groups, and the most abundant species was L. iners (CST III), which is linked to a decreased fertility rate. Besides this, L. gasseri—which is known to be associated with oocyte DNA fragmentation and decreased sperm mobility—was identified in the seminal fluids, follicular fluids, and embryo culture media of the unexplained infertility group. Prevotella was increased in the seminal fluids of the explained infertility group, along with HPV-positive seminal fluids: an infection commonly associated with infertility, especially male infertility. Prevotella has been described to negatively affect sperm motility. Taken together, these results suggest that the profiling of the reproductive tract microbiome can add new perspectives to human reproduction.

Human Polyomavirus (HPyV) infections are common, ranging from 60% to 100%. In kidney transplant (KTx) recipients, HPyVs have been associated with allograft nephropathy, progressive multifocal leukoencephalopathy, and skin cancer. Whether such complications are caused by viral reactivation or primary infection transmitted by the donor remains debated. This study aimed to investigate the replication pattern and genomic characterization of BK Polyomavirus (BKPyV), JC Polyomavirus (JCPyV), and Merkel Cell Polyomavirus (MCPyV) infections in KTx. Urine samples from 57 KTx donor/recipient pairs were collected immediately before organ retrieval/transplant and periodically up to post-operative day 540. Specimens were tested for the presence of BKPyV, JCPyV, and MCPyV genome by virus-specific Real-Time PCR and molecularly characterized. HPyVs genome was detected in 49.1% of donors and 77.2% of recipients. Sequences analysis revealed the archetypal strain for JCPyV, TU and Dunlop strains for BKPyV, and IIa-2 strain for MCPyV. VP1 genotyping showed a high frequency for JCPyV genotype 1 and BKPyV genotype I. Our experience demonstrates that after KTx, HPyVs genome remains stable over time with no emergence of quasi-species. HPyVs strains isolated in donor/recipient pairs are mostly identical, suggesting that viruses detected in the recipient may be transmitted by the allograft.

An incorrect food regimen from childhood is suggested to negatively impact the gut microbiome composition leading to obesity and perhaps to colon rectal cancer (CRC) in adults. In this study, we show that the obesity and cancer gut microbiota share a characteristic microbial profile with a high colonization by mucin degraders species, such as Hafnia alvei and Akkermansia muciniphila. In addition, the species Clostridium bolteae, a bacterium associated with insulin resistance, dyslipidemia, and inflammation, has been associated with the presence of oncogenic Human Polyomaviruses (HPyVs). Merkel cell Polyomavirus (MCPyV) and BK Polyomavirus (BKPyV) were the most frequently oncogenic viruses recovered in the gut of both obese and tumor patients. Considering the high seroprevalence of HPyVs in childhood, their association with specific bacterial species deserve to be further investigated. Data from the present study highlight the presence of a similar microbiome pattern in CRC and obese subjects, suggesting that obese microbiome may represent an opportunity for tumorigenic/driver bacteria and viruses to trigger cell transformation.