Combining telemedicine and in-person visits to deliver care to patients with severe chronic kidney disease (CKD): Lessons learned from COVID-19.

BACKGROUND: Telemedicine has been widely used to deliver healthcare to outpatients during the COVID-19 pandemic. The effectiveness of this modality is unclear in patients with a pre-dialysis stage of chronic kidney disease (CKD). This study aims to describe the clinical characteristics and management of CKD patients receiving telemedicine care during the COVID-19 pandemic. MATERIALS AND METHODS: A retrospective single-center cohort study enrolled outpatients with pre-dialytic stage of CKD from March 9 to June 21, 2020. Telemedicine was proposed for all patients with a stable CKD to reduce the risk of in-hospital transmission whereas in-person visit was performed for patients requiring urgent evaluation. RESULTS: In a 15-week period, 97 patients received 116 nephrological visits. According to the modality of healthcare delivery, the patients were subdivided into telemedicine (66%) and in-person visit (34%) groups. Mean age of all CKD patients was 72.8 ± 12.5 years and males were 50.5% of the population. The average estimated glomerular filtration rate (eGFR) was 14.6 ± 6 mL/min. Patients evaluated by telemedicine had better kidney function (GFR, 16.2 ± 6.4 vs. 13.6 ± 5.9 mL/min/1.73m2; p = 0.037), a lower body mass index (BMI) (24.1 ± 1.7 vs. 30.6 ± 5.7; p = 0.019), and a lower risk of CKD progression (51.1 vs. 25.4%, p = 0.017) than patients requiring in-person visit. Telemedicine-visit patients experienced a significantly lower number of pharmacological changes than patients managed in the ambulatory setting. Telemedicine was also used to conduct 20% of educational meetings on the choice of dialysis modality and 18.9% of pre-eligibility visits for kidney transplantation. CONCLUSION: Telemedicine made it possible to provide care to and maintain close monitoring of 2/3 of patients with pre-dialytic stage of CKD during the COVID-19 pandemic.

The risks associated with percutaneous native kidney biopsies: a prospective study.

BACKGROUND: The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy. METHODS: The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression. RESULTS: Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08-1.17], liver disease (OR 2.27, 95% CI 1.21-4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07-1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92-0.99) were protective. CONCLUSIONS: This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes.

Prevalence, clinical course and outcomes of COVID-19 in peritoneal dialysis (PD) patients: a single-center experience.

INTRODUCTION: There are limited data on the effects of COVID-19 on peritoneal dialysis (PD) patients. This study aimed to describe the impact of COVID-19 on the PD population. METHODS: A monocentric retrospective observational study was conducted on 146 consecutive PD patients followed from January 2020 to March 2022 at the University Hospital of Modena, Italy. RESULTS: Twenty-seven (18.4%) PD patients experienced 29 episodes of SARS-CoV-2 infection, corresponding to an incidence rate of 0.16 episodes/patient-year. Median age of COVID-19 patients was 60.4 (interquartile range [IQR] 50.2-66.5) years. In unvaccinated patients (n. 9), COVID-19 was always symptomatic and manifested with fever (100%) and cough (77.7%). COVID-19 caused hospital admission of three (33.3%) patients and two (22.2%) died of septic shock. COVID-19 was symptomatic in 83.3% of vaccinated subjects (n.18) and manifested with fever (61.1%) and cough (55.6%). Hospital admission occurred in 27.8% of the subjects but all were discharged home. Median SARS-CoV-2 shedding was 32 and 26 days in the unvaccinated and vaccinated groups, respectively. At the end of the follow-up, COVID-19 triggered the shift from PD to HD in two subjects without affecting the residual renal function of the remaining patients. Overall, COVID-19 caused an excess death of 22.2%. COVID-19 vaccination refusal accounted for only 1.6% in this cohort of patients. CONCLUSION: COVID-19 incident rate was 0.16 episodes/patient-year in the PD population. About one-third of the patients were hospitalized for severe infection. Fatal outcome occurred in two (7.4%) unvaccinated patients. A low vaccination refusal rate was observed in this population.

Molecular detection of SARS-CoV-2 from indoor air samples in environmental monitoring needs adequate temporal coverage and infectivity assessment.

The relevance of airborne exposure to SARS-CoV-2 in indoor environments is a matter of research and debate, with special importance for healthcare low-risk settings. Experimental approaches to the bioaerosol sampling are neither standardized nor optimized yet, leading in some cases to limited representativity of the temporal and spatial variability of viral presence in aerosols. Airborne viral viability moreover needs to be assessed. A study has been conducted collecting five 24-h PM10 samples in a COVID-19 geriatric ward in late June 2020, and detecting E and RdRp genes by RT-qPCR with a Ct between 36 and 39. The viral RNA detection at Ct = 36 was related to the maximal numerosity of infected patients hosted in the ward. Lacking a direct infectivity assessment for the collected samples an experimental model has been defined, by seeding twelve nasopharyngeal swab extracts from COVID-19 positive patients on Vero E6 cells; only the four extracts with a viral load above E+10 viral copies (approximately Ct<24) have been able to establish a persistent infection in vitro. Therefore, the cytopathic effect, a key feature of residual infectivity, could be considered unlikely for the environmental PM10 samples showing amplification of viral RNA at Ct = 36 or higher. A standardization of airborne SARS-CoV-2 long-term monitoring and of environmental infectivity assessment is urgently needed.

Incidence, risk factors and outcome of acute kidney injury (AKI) in patients with COVID-19.

BACKGROUND: Acute kidney injury (AKI) is a severe complication of coronavirus disease-2019 (COVID-19). This study aims to evaluate incidence, risk factors and case-fatality rate of AKI in patients with COVID-19. METHODS: We reviewed the health medical records of 307 consecutive patients with COVID-19 hospitalized at the University Hospital of Modena, Italy. RESULTS: AKI was diagnosed in 69 out of 307 (22.4%) COVID-19 patients. Stages 1, 2, or 3 AKI accounted for 57.9%, 24.6% and 17.3%, respectively. AKI patients had a mean age of 74.7 ± 9.9 years. These patients showed higher serum levels of the main markers of inflammation and higher rate of severe pneumonia than non-AKI patients. Kidney injury was associated with a higher rate of urinary abnormalities including proteinuria (0.44 ± 0.85 vs 0.18 ± 0.29 mg/mg; P = < 0.0001) and microscopic hematuria (P = 0.032) compared to non-AKI patients. Hemodialysis was performed in 7.2% of the subjects and 33.3% of the survivors did not recover kidney function after AKI. Risk factors for kidney injury were age, male sex, CKD and higher non-renal SOFA score. Patients with AKI had a mortality rate of 56.5%. Adjusted Cox regression analysis revealed that COVID-19-associated AKI was independently associated with in-hospital death (hazard ratio [HR] = 4.82; CI 95%, 1.36-17.08) compared to non-AKI patients. CONCLUSION: AKI was a common and harmful consequence of COVID-19. It manifested with urinary abnormalities (proteinuria, microscopic hematuria) and conferred an increased risk for death. Given the well-known short-term sequelae of AKI, prevention of kidney injury is imperative in this vulnerable cohort of patients.

Hypokalemia in Patients with COVID-19.

BACKGROUND: Patients with COVID-19 experience multiple clinical conditions that may cause electrolyte imbalances. Hypokalemia is a concerning electrolyte disorder closely associated with severe complications. This study aimed to estimate prevalence, risk factors and outcome of hypokalemia in a cohort of patients with confirmed COVID-19. METHODS: A retrospective analysis was conducted on 290 non-ICU admitted patients with COVID-19 at the tertiary teaching hospital of Modena, Italy, from February 16 to April 14, 2020. RESULTS: Hypokalemia was detected in 119 out of 290 patients (41%) during hospitalization. Mean serum potassium was 3.1 ± 0.1 meq/L. The majority of patients (90.7%) patients experienced only a mild decrease in serum potassium level (3-3.4 mEq/L). Hypokalemia was associated with hypocalcemia, which was detected in 50% of subjects. Urine potassium-to-creatinine ratio, measured in a small number of patients (n = 45; 36.1%), revealed an increase of urinary potassium excretion in most cases (95.5%). Risk factors for hypokalemia were female sex (odds ratio (OR) 2.44; 95% CI 1.36-4.37; P 0.003) and diuretic therapy (OR 1.94, 95% CI 1.08-3.48; P 0.027). Hypokalemia, adjusted for sex, age and SOFA score, was not associated with ICU transfer (OR 0.52; 95% CI 0.228-1.212; P = 0.131), in-hospital mortality (OR, 0.47; 95% CI 0.170-1.324; P = 0.154) and composite outcome of ICU transfer or in-hospital mortality (OR 0.48; 95% CI 0.222-1.047; P = 0.065) in our cohort of patients. CONCLUSIONS: Hypokalemia was a frequent disorder in subjects with COVID-19. Female sex and diuretic therapy were identified as risk factors for low serum potassium levels. Hypokalemia was unrelated to ICU transfer and death in this cohort of patients.

COVID-19 pneumonia in a kidney transplant recipient successfully treated with tocilizumab and hydroxychloroquine.

Coronavirus disease 2019 (COVID-19) pneumonia has been poorly reported in solid organ transplanted patients; prognosis is uncertain and best management unclear. We describe the case of a 61-year-old kidney transplant recipient with several comorbidities who was hospitalized and later received a diagnosis of COVID-19 pneumonia; the infection was successfully managed with the use of hydroxychloroquine and a single administration of tocilizumab, after immunosuppression reduction; the patient did not require mechanical ventilation. During the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, transplant clinicians should be readily informed about new cases of COVID-19 pneumonia in solid organ transplant recipients, with focus on therapeutic strategies employed and their outcome.

Role of Maraviroc in minimizing the risk of graft rejection in HIV-infected kidney transplant recipients.

BACKGROUND: Kidney transplantation in HIV-infected patients is characterized by a concerning high rate of allograft rejections. The etiological mechanisms leading to this increased immunoreactivity are still unknown. Maraviroc is a new antiretroviral agent that has been associated with immunomodulatory proprieties; therefore, its use may be a promising strategy to minimize the rate of rejections in HIV-infected kidney transplant (KT) recipients. METHODS: We conducted a retrospective study in our cohort of HIV-KT recipients with the aim to explore the effects of maraviroc in reducing the risk of graft rejection. RESULTS: Twenty-two HIV-infected KT recipients predominantly of Caucasian origin (86%) and with a median age of 49 (IQR, 51.9-42.2) years were evaluated. Ten HIV-infected patients were treated with maraviroc and 12 with a maraviroc-free antiretroviral regimen. After a median follow-up of 3.01 years, half of the maraviroc-treated patients (n = 5) developed seven episodes of graft rejection, most of them were T cell-mediated rejections (85.7%). Five episodes were recorded in the maraviroc-free group. The difference in the rate of graft rejections was not statistically significant (P = .23). CONCLUSIONS: The administration of maraviroc was ineffective in preventing graft rejections in our cohort of patients.

SARS-Cov-2RNA found on particulate matter of Bergamo in Northern Italy: First evidence.

BACKGROUND: The burden of COVID-19 was extremely severe in Northern Italy, an area characterized by high concentrations of particulate matter (PM), which is known to negatively affect human health. Consistently with evidence already available for other viruses, we initially hypothesized the possibility of SARS-CoV-2 presence on PM, and we performed a first experiment specifically aimed at confirming or excluding this research hyphotesys. METHODS: We have collected 34 PM10 samples in Bergamo area (the epicenter of the Italian COVID-19 epidemic) by using two air samplers over a continuous 3-weeks period. Filters were properly stored and underwent RNA extraction and amplification according to WHO protocols in two parallel blind analyses performed by two different authorized laboratories. Up to three highly specific molecular marker genes (E, N, and RdRP) were used to test the presence of SARS-CoV-2 RNA on particulate matter. RESULTS: The first test showed positive results for gene E in 15 out of 16 samples, simultaneously displaying positivity also for RdRP gene in 4 samples. The second blind test got 5 additional positive results for at least one of the three marker genes. Overall, we tested 34 RNA extractions for the E, N and RdRP genes, reporting 20 positive results for at least one of the three marker genes, with positivity separately confirmed for all the three markers. Control tests to exclude false positivities were successfully accomplished. CONCLUSION: This is the first evidence that SARS-CoV-2 RNA can be present on PM, thus suggesting a possible use as indicator of epidemic recurrence.

Influence of dialysate temperature on creatinine peritoneal clearance in peritoneal dialysis patients: a randomized trial.

BACKGROUND: Patients on continuous ambulatory peritoneal dialysis (PD) are encouraged to warm dialysate to 37 °C before peritoneal infusion; main international PD guidelines do not provide specific recommendation, and patients generally warm dialysate batches partially or do not warm them at all. Warming of dialysate is a time-consuming procedure, not free from potential risks (i.e. degradation of glucose), and should be justified by a clear clinical benefit. METHODS: We designed a single blind randomized controlled trial where 18 stable PD patients were randomized to receive a peritoneal equilibration test either with dialysate at a controlled temperature of 37 °C (intervention group) or with dialysate warmed with conventional methods (control group). Primary end-point was a higher peritoneal creatinine clearance in patients in the intervention group. RESULTS: Patients in the intervention group did not show a significantly higher peritoneal creatinine clearance when compared to the control group (6.38 ± 0.52 ml/min vs 5.65 ± 0.37 ml/min, p = 0.2682). Similar results were obtained for urea peritoneal clearance, mass transfer area coefficient of creatinine and urea. There were no significant differences in total abdominal discomfort questionnaire score, blood pressure and body temperature between the two groups. CONCLUSIONS: Using peritoneal dialysate at different temperatures without causing significant side effects to patients appears feasible. We report a lack of benefit of warming peritoneal dialysate to 37 °C on peritoneal clearances; future PD guidelines should not reinforce this recommendation. TRIAL REGISTRATION: NCT04302649, ClinicalTrials.gov ; date of registration 10/3/2020 (retrospectively registered).

Pirfenidone prevents acute kidney injury in the rat.

BACKGROUND: Pirfenidone is an orally active drug used for the treatment of idiopathic pulmonary fibrosis to slow loss of lung function; it acts mainly through an antifibrotic effect but also possesses antioxidant and anti-inflammatory properties. We assessed the effect of prophylactic administration of pirfenidone on acute kidney injury due to bilateral renal ischemia. METHODS: Eighteen rats were included and divided in: 1) sham-operated rats (S), 2) rats underwent bilateral renal ischemia for 20 min (I/R), and 3) rats treated with pirfenidone 700 mg/kg/day 24 h before surgery and subjected to bilateral renal ischemia for 20 min (I/R + PFN). All the rats were euthanized and studied 24 h after renal reperfusion. RESULTS: As was expected, the I/R group exhibited a significant reduction in creatinine clearance, urinary output and renal blood flow, as well as extensive tubular injury. These alterations were associated with a significant decrease in urinary excretion of nitrites and nitrates (UNO2/NO3V). In the I/R + PFN group, recovery of renal function and UNO2/NO3V was observed, together with lesser histological signs of tubular injury compared to the I/R group. CONCLUSIONS: This study shows that prophylactic administration of pirfenidone prevented acute kidney injury due to bilateral ischemia in the rat. Recovery of NO production appears to be one of the mechanism of pirfenidone renoprotective effect. Our findings suggest that pirfenidone is a promising drug to reduce renal injury induced by I/R.

Immunophenotypic profile and clinical outcome of monoclonal B-cell lymphocytosis in kidney transplantation.

Monoclonal B-cell lymphocytosis (MBL) is a lymphoproliferative disorder characterized by clonal expansion of a B-cell population in peripheral blood of otherwise healthy subjects. MBL is divided into CLL (chronic lymphocytic leukemia)-like, atypical CLL-like and non-CLL MBL. The aim of this study was to evaluate immunophenotypic characteristics and clinical outcomes of MBL in kidney transplant (KT) recipients. We retrospectively evaluated 593 kidney transplant (KT) recipients in follow-up at our center. Among them, 157 patients underwent peripheral blood flow cytometry for different clinical indications. A 6-color panel flow cytometry was used to diagnose MBL. This condition was detected in 5 of 157 KT recipients. Immunophenotypic characterization of MBL showed four cases of non-CLL MBL and one case of CLL-like MBL. At presentation, median age was 65 years (range 61-73). After a median follow-up of 3.1 years (95%CI; 1.1-5) from diagnosis, patients did not progress either to CLL or to lymphoma. The disorder did not increase the risk of malignancy, severe infections, graft loss and mortality among our KT recipients. Surprisingly, all cases were also affected by concomitant monoclonal gammopathy of undetermined significance, which did not progress to multiple myeloma during follow-up. In conclusion, our data suggest that MBL is an age-related disorder, with non-CLL MBL being the most common subtype among KT recipients.

Efficacy of Belimumab for active lupus nephritis in a young Hispanic woman intolerant to standard treatment: a case report.

BACKGROUND: Lupus nephritis (LN) is a frequent severe complication of Systemic Lupus Erythematosus (SLE), especially in patients of non-Caucasian ethnicity. Induction treatment for LN consists in the combination of steroids plus a second agent (cyclophosphamide or mycophenolate mofetil) or, as a second-line, calcineurin inhibitors or Rituximab. Induction treatment for LN can be complicated by a series of side effects, the most severe being serious infections. Belimumab is a fully humanized monoclonal antibody that targets soluble B lymphocyte stimulator (BLyS), approved for treatment of serologically active SLE in addition to standard of care. CASE PRESENTATION: A young Hispanic woman was diagnosed with SLE at the age of 15. After several immunosuppressive treatments for arthritic symptoms (high-dose steroids, mycophenolate mofetil, Rituximab, cyclophosphamide) leading to serious complications and scarce clinical improvement, she developed severe LN. Induction treatment with a combination of intravenous high-dose methylprednisolone and cyclophosphamide was started but, after few days, the patient developed cryptococcal meningitis. After institution of appropriate antifungal therapy, treatment with Tacrolimus was attempted but poorly tolerated by the patient and withdrawn. Eventually, Belimumab was initiated off-label as a last resource to treat LN. Belimumab was well tolerated by the patient and resulted in a rapid and marked improvement in clinical symptoms and reduction in proteinuria, serum complement levels and anti-dsDNA titer; of note, the patient developed no infectious complications. CONCLUSIONS: We report the case of a severe LN in a young Hispanic woman who did not respond to conventional and second-line induction therapies, due both to intolerance and to the development of serious infectious complications. Eventually, Belimumab was successfully added to steroids and was well tolerated by the patient, resulting in a marked improvement in clinical and biochemical parameters. We suggest that Belimumab should be considered as a potentially efficacious treatment in patients with LN who cannot tolerate conventional therapies.

Chlamydia trachomatis and HPV co-infections in HIV negative men from a multi-ethnic area of Northern Italy at high prevalence of cervical malignancies.

Chlamydia trachomatis and HPV coinfections in the male population are often a disregarded issue. We performed a study to evaluate the prevalence of such infections in heterosexual HIV negative men from a Northern Italy multi-ethnic area at high prevalence for cervical malignancies. Urethral swabs (US) or first-voided urine were evaluated retrospectively from 1317 patients attending Sexually Transmitted Infections (STI) clinic and from 3388 outpatients attending private clinics. Informations about participants' demographic characteristics and attributes of C. trachomatis, including chronic infection, and HPV genotypes testing, were collected. Exact Fisher test, bivariate, and multivariate logistic regressions were carried out. The prevalence of C. trachomatis was 1.7% in the outpatients and 16.9% in the STI group (P < 0.0001) in which the highest frequency was observed in men of age ≤25 years. Among patients with C. trachomatis, asymptomatic HPV co-infection was detected in 33% of men from the STI clinic and in 2% of the outpatients. Out of all coinfections, 56% were due to single HPV, with a prevalence of 73% in young STI men. The distribution of HPV genotypes confirmed the increased circulation of LR-HPV42, HR-HPV51, HR-HPV52 and prHR-HPV82, and the decreasing of HR-HPV16. African nationalities and leucorrhea were significantly associated risk factors, while the regular condom use offered an effective protection. This study highlights the high prevalence of C. trachomatis and HPV asymptomatic co-infection in young HIV negative men attending the STI clinic, representing a reservoir of new HPV genotypes with potential oncogenic risk.

Acute pancreatitis associated with everolimus after kidney transplantation: a case report.

BACKGROUND: Acute pancreatitis (AP) following KT is a rare and often fatal complication of the early post-transplant period. Common causative factors for AP are rare after KT; anti-rejection drugs as CyA, prednisone and MMF have been implicated, although evidence is not strong and we found no reports on possible causative role for mTOR inhibitors. CASE PRESENTATION: A 55-year-old Caucasian man with end-stage renal disease due to idiopathic membrano-prolipherative glomerulonephritis underwent single kidney transplantation (KT) from cadaveric donor. Anti-rejection protocol was based on Basiliximab induction followed by prednisone and mycophenolate mophetil (MMF) and Cyclosporine; Everolimus (Eve) was scheduled to substitute MMF at week 3. At day 1 he had an asymptomatic elevation of pancreatic enzymes, spontaneously resolved. The further course was unremarkable and on day 19 he started Eve, with following asymptomatic rise in pancreatic enzymes. At day 33 the patient presented with abdominal pain and a marked elevation in serum amylase (1383 U/l) and lipase (1015 U/l), normal liver enzymes and bilirubin, no hypercalcemia, mild elevation in triglycerids; RT-PCRs for Cytomegalovirus or Epstein-Barr virus were negative. The patient had no history of alcohol abuse; ultrasound, CT and MRI found no evidence of biliary lithiasis. CT scans showed a patchy fluid collection in the pancreatic head area, consistent with idiopathic necrotizing pancreatitis. The patient was treated medically and Eve was withdrawn 1 week after. Patient underwent guided drainage of the fluid collection, but developed bacterial sepsis; surgical intervention was required with debridement of necrotic tissue, lavage and drainage; immunosuppression was totally withdrawn. Following course was complicated with multiple systemic infection. Transplantectomy for acute rejection was performed, and patient entered hemodialysis. CONCLUSIONS: Our patient had a presentation that is consistent for a causative role of Eve. A predisposing condition (acute pancreatic insult during transplant surgery) spontaneously resolved, relapsed and evolved rapidly in AP after the initiation of treatment with Eve with a consistent time latency. None of the well-known common causative factors for AP was present. We discourage the use of Eve in patients with recent episodes of sub-clinical pancreatitis, since it may represent a precipitating factor or interfere with resolution.

Post-printing processing and aging effects on Polyjet materials intended for the fabrication of advanced surgical simulators.

Material Jetting (MJ) 3D printing technology is promising for the fabrication of highly realistic surgical simulators, however, the changes in the mechanical properties of MJ materials after post-printing treatments and over time remain quite unknown. In this study, we investigate the effect of different post-printing processes and aging on the mechanical properties of a white opaque and rigid MJ photopolymer, a white flexible MJ photopolymer and on a combination of them. Tensile and Shore hardness tests were conducted on homogeneous 3D-printed specimens: two different post-printing procedures for support removal (dry and water) and further surface treatment (with glycerol solution) were compared. The specimens were tested within 48 h from printing and after aging (30-180 days) in a controlled environment. All groups of specimens treated with different post-printing processes (dry, water, glycerol) exhibited a statistically significant difference in mechanical properties (i.e. elongation at break, elastic modulus, ultimate tensile strength). Particularly, the treatment with glycerol makes the flexible photopolymer more rigid, but then with aging the initial elongation of the material tends to be restored. For the rigid photopolymer, an increase in deformability was observed as a major effect of aging. The hardness tests on the printed specimens highlighted a significant overestimation of the Shore values declared by the manufacturer. The study findings are useful for guiding the material selection and post-printing processing techniques to manufacture realistic and durable models for surgical training.

Ultrasound Stimulation of Piezoelectric Nanocomposite Hydrogels Boosts Chondrogenic Differentiation in Vitro, in Both a Normal and Inflammatory Milieu.

The use of piezoelectric nanomaterials combined with ultrasound stimulation is emerging as a promising approach for wirelessly triggering the regeneration of different tissue types. However, it has never been explored for boosting chondrogenesis. Furthermore, the ultrasound stimulation parameters used are often not adequately controlled. In this study, we show that adipose-tissue-derived mesenchymal stromal cells embedded in a nanocomposite hydrogel containing piezoelectric barium titanate nanoparticles and graphene oxide nanoflakes and stimulated with ultrasound waves with precisely controlled parameters (1 MHz and 250 mW/cm2, for 5 min once every 2 days for 10 days) dramatically boost chondrogenic cell commitment in vitro. Moreover, fibrotic and catabolic factors are strongly down-modulated: proteomic analyses reveal that such stimulation influences biological processes involved in cytoskeleton and extracellular matrix organization, collagen fibril organization, and metabolic processes. The optimal stimulation regimen also has a considerable anti-inflammatory effect and keeps its ability to boost chondrogenesis in vitro, even in an inflammatory milieu. An analytical model to predict the voltage generated by piezoelectric nanoparticles invested by ultrasound waves is proposed, together with a computational tool that takes into consideration nanoparticle clustering within the cell vacuoles and predicts the electric field streamline distribution in the cell cytoplasm. The proposed nanocomposite hydrogel shows good injectability and adhesion to the cartilage tissue ex vivo, as well as excellent biocompatibility in vivo, according to ISO 10993. Future perspectives will involve preclinical testing of this paradigm for cartilage regeneration.

Effect of near-infrared and blue laser light on vero E6 cells SARS-CoV-2 infection model.

Photobiomodulation therapy (PBMT) employing laser light has been emerging as a safe strategy to challenge viruses. In this study the effect of blue and near-infrared (NIR) laser light was assessed in an in vitro model of SARS-CoV-2 infection. PBMT at blue wavelength inhibited viral amplification when the virus was directly irradiated and then transferred to cell culture and when cells already infected were treated. The NIR wavelength resulted less efficacious showing a minor effect on the reduction of the viral load. The cells receiving the irradiated virus or directly irradiated rescued their viability to level comparable to not treated cells. Virion integrity and antigenicity were preserved after blue and NIR irradiation, suggesting that the PBMT antiviral effect was not correlated to viral lipidic envelope disruption. Our results suggested that PBMT can be considered a valid strategy to counteract SARS-CoV-2 infection, at least in vitro.