The temporal effects of asymptomatic COVID-19 infection on peri-operative complications in patients receiving total joint arthroplasty.

INTRODUCTION: Recent coronavirus disease 2019 (COVID-19) infection may pose increased risk of post-operative complications after total joint arthroplasty (TJA). Current recommendations suggest waiting four-weeks before elective surgery in asymptomatic patients. The purpose of this study was to propensity-score-match patients who had positive COVID-19-test between (1) 0-2 weeks and (2) 2-4 weeks before TJA with a matching group without COVID-19 history to determine rates of complications at 90-days and 1-year post-operatively. MATERIALS AND METHODS: We queried a national-database for patients who tested positively for COVID-19 within 1-month (n = 1749) before TJA. A propensity-score-match analysis was conducted to limit influence of confounders. They were separated into mutually exclusive asymptomatic cohorts based on time of positive COVID-19-test before TJA: within 2-weeks (n = 1749) and between 2-to-4 weeks (n = 599). Asymptomatic patients were patients with positive test without symptoms of fever, shortness of breath, nausea, vomiting, diarrhea, loss of taste or smell, cough, bronchitis, pneumonia, lung infections, septic shock, and multiple-organ-dysfunction. Complications analyzed: 90-day and 1-year periprosthetic-joint infections (PJIs), surgical-site infections(SSIs), wound complications, cardiac complications, transfusions, and venous thromboembolisms. RESULTS: Asymptomatic patients who have COVID-19 demonstrated increased incidence of PJI in patients who had TJA performed within two weeks from positive test at 90-days compared to patients who did not test positive for COVID-19 (3.0 vs. 1.5%; p = 0.023). Upon totaling all 90-day post-operative complications, no significant difference was found amongst asymptomatic patients who tested positive for COVID-19 for total complications at 90-days (p = 0.936). CONCLUSIONS: Asymptomatic patients who test positive for COVID-19 don't have increased risk for post-operative complications after TJA. However, two-fold increased risk in PJI for patients who tested positive for COVID-19 in first 2-weeks cannot be ignored. These results should be taken into consideration when surgeons consider performing TJA. We recommend asymptomatic patients consider waiting two-weeks before TJA to mitigate risk of PJI. Nevertheless, there's reassurance these patients are not at increased total complication risk.

Optimization of Lipid Nanoparticles by Response Surface Methodology to Improve the Ocular Delivery of Diosmin: Characterization and In-Vitro Anti-Inflammatory Assessment.

Diosmin is a flavonoid with a great variety of biological activities including antioxidant and anti-inflammatory ones. Its cytoprotective effect in retinal pigment epithelium cells under high glucose conditions makes it a potential support in the treatment of diabetic retinopathy. Despite its benefits, poor solubility in water reduces its potential for therapeutic use, making it the biggest biopharmaceutical challenge. The design of diosmin-loaded nanocarriers for topical ophthalmic application represents a novelty that has not been yet explored. For this purpose, the response surface methodology (RSM) was used to optimize nanostructured lipid carriers (NLCs), compatible for ocular administration, to encapsulate diosmin and improve its physicochemical issues. NLCs were prepared by a simple and scalable technique: a melt emulsification method followed by ultrasonication. The experimental design was composed of four independent variables (solid lipid concentration, liquid lipid concentration, surfactant concentration and type of solid lipid). The effect of the factors was assessed on NLC size and PDI (responses) by analysis of variance (ANOVA). The optimized formulation was selected according to the desirability function (0.993). Diosmin at two different concentrations (80 and 160 µM) was encapsulated into NLCs. Drug-loaded nanocarriers (D-NLCs) were subjected to a physicochemical and technological investigation revealing a mean particle size of 83.58 ± 0.77 nm and 82.21 ± 1.12 nm, respectively for the D-NLC formulation prepared with diosmin at the concentration of 80 µM or 160 µM, and a net negative surface charge (-18.5 ± 0.60 and -18.0 ± 1.18, respectively for the two batches). The formulations were analyzed in terms of pH (6.5), viscosity, and adjusted for osmolarity, making them more compatible with the ocular environment. Subsequently, stability studies were carried out to assess D-NLC behavior under different storage conditions up to 60 days, indicating a good stability of NLC samples at room temperature. In-vitro studies on ARPE-19 cells confirmed the cytocompatibility of NLCs with retinal epithelium. The effect of D-NLCs was also evaluated in-vitro on a model of retinal inflammation, demonstrating the cytoprotective effect of D-NLCs at various concentrations. RSM was found to be a reliable model to optimize NLCs for diosmin encapsulation.

Fluorescent Nanosystems for Drug Tracking and Theranostics: Recent Applications in the Ocular Field.

The greatest challenge associated with topical drug delivery for the treatment of diseases affecting the posterior segment of the eye is to overcome the poor bioavailability of the carried molecules. Nanomedicine offers the possibility to overcome obstacles related to physiological mechanisms and ocular barriers by exploiting different ocular routes. Functionalization of nanosystems by fluorescent probes could be a useful strategy to understand the pathway taken by nanocarriers into the ocular globe and to improve the desired targeting accuracy. The application of fluorescence to decorate nanocarrier surfaces or the encapsulation of fluorophore molecules makes the nanosystems a light probe useful in the landscape of diagnostics and theranostics. In this review, a state of the art on ocular routes of administration is reported, with a focus on pathways undertaken after topical application. Numerous studies are reported in the first section, confirming that the use of fluorescent within nanoparticles is already spread for tracking and biodistribution studies. The first section presents fluorescent molecules used for tracking nanosystems' cellular internalization and permeation of ocular tissues; discussions on the classification of nanosystems according to their nature (lipid-based, polymer-based, metallic-based and protein-based) follows. The following sections are dedicated to diagnostic and theranostic uses, respectively, which represent an innovation in the ocular field obtained by combining dual goals in a single administration system. For its great potential, this application of fluorescent nanoparticles would experience a great development in the near future. Finally, a brief overview is dedicated to the use of fluorescent markers in clinical trials and the market in the ocular field.

Development, Optimization and Characterization of Eudraguard®-based Microparticles for Colon Delivery.

Development of pH-dependent systems for colon delivery of natural active ingredients is an attractive area of research in the field of nutraceutical products. This study was focused on Eudraguard® resins, that are methacrylate copolymers approved as "food grade" by European Commission and useful for the production of food supplements. In particular, Eudraguard® Biotic (EUG-B), characterized by a pH-dependent solubility and Eudraguard® Control (EUG-C), whose chemical properties support a prolonged release of the encapsulated compounds, were tested. To obtain EUG microparticles, different preparation techniques were tested, in order to optimize the preparation method and observe the effect upon drug encapsulation and specific colonic release. Unloaded microparticles were initially produced to evaluate the influence of polymer characteristics on the formulation process; subsequently microparticles loaded with quercetin (QUE) as a low solubility model drug were prepared. The characterization of microparticles in the solid-state (FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry) indicated that QUE was uniformly dispersed in a non-crystalline state in the polymeric network, without strong signs of chemical interactions. Finally, to assess the ability of EUG-C and EUG-B to control the drug release in the gastric environment, and to allow an increased release at a colonic level, suitable in vitro release tests were carried out by simulating the pH variations along the gastro-intestinal tract. Among the evaluated preparation methods, those in which an aqueous phase was not present, and in particular the emulsion-solvent evaporation method produced the best microparticle systems. The in vitro tests showed a limited drug release at a gastric level and a good specific colon release.

Vision-related quality of life and locus of control in type 1 diabetes: a multicenter observational study.

AIMS: Diabetic retinopathy remains asymptomatic until its late stages but remains a leading cause of vision impairment and blindness. We studied quality of life and the ability to deal with the discomfort deriving from the presence of a chronic disease in patients with type 1 diabetes and different stages of retinopathy. METHODS: Multicenter collaborative observational study involving nine centers screening for retinopathy in different areas of Italy. The National Eye Institute 25-item visual functioning questionnaire and the locus of control tool were administered to 449 people with type 1 diabetes between February 2016 and March 2018. Socio-demographic and clinical data were collected. RESULTS: On multivariable analysis, severe retinopathy is associated with worse scores for general vision, ocular pain, near vision activities, distance vision activities, driving, color vision, peripheral vision and lower values of internal control, independently of visual acuity. Women had a perception of worse general health, distance vision activities and driving, and lower internal control and trust in others. Worse scores for visual-specific social functioning, visual-specific mental health, visual-specific role difficulties, visual-specific dependency and peripheral vision were associated with higher HbA1c levels. Fatalism increased with rising HbA1c levels. CONCLUSIONS: These results confirm that a gap exists between patients' knowledge and expectations on retinopathy and providers' expertise and assumptions. To bridge this gap, patient-centered education and engaging approaches may be more effective than simple information given during consultations.

Endo-laparoscopic reconstruction of the abdominal wall midline with linear stapler, the THT technique. Early results of the first case series.

BACKGROUND: Midline primary hernias represent one of the most frequent abdominal wall defects in the adult population and in almost half of the cases they are associated with a rectus abdominis diastasis (RAD). Despite the high incidence of these defects there is currently no consensus in the literature on what is the preferred surgical technique for treatment. In this paper we present the first case series treated with an innovative technique that aims to repair the defects of the midline and RAD, while combining the advantages of the sublay Rives-Stoppa technique with those of the minimally-invasive surgery. METHODS: Between January 2018 and May 2018, 14 patients underwent endo-laparoscopic reconstruction of the midline. The surgery was performed under general anaesthesia through a 4 cm periumbilical incision with single port technique. The rectus abdominis sheaths were joined together and sutured lengthwise using a linear stapler. A tailor-made synthetic prosthesis was positioned in the retromuscular space. RESULTS: All cases had RAD with a mean width of 5.3 cm in the supraumbilical space. None of the surgeries needed laparotomic conversion. The average duration of the surgery was 80 min. The hospitalization was in all cases one day. The average follow-up period was 6 months. Neither recurrences, nor major or minor complications have been reported to date. CONCLUSION: Our THT is a feasible technique, easily reproducible, and effective in the repair of primary defects of the midline and RAD, which greatly reduces the operating times and hospitalization allowing a quick return to active life.

Pilonidal sinus disease: Preliminary case-control study on heat-related wound dehiscence.

BACKGROUND: Pilonidal disease is a morbid condition of the young population, that could impair quality of life with a high cost for the health care system. No consensus exists on optimal surgical treatment, even if several techniques have been proposed. In this preliminary case-control study we compared excision by knife and diathermy to investigate if wound dehiscence could be related to heat spreading during excision of the sinus. MATERIALS AND METHOD: Between January 2017 and February 2018, 29 patients underwent to sinus excision.16 patients underwent sinus excision by diathermy (named "Hot" group, case-group) while 13 patients underwent excision by the knife as the control group (named "Cold" group). The temperature data were recorded for both groups. Were considered primary and secondary outcomes. RESULTS: the cold group has worse outcomes in operative time and blood loss, but better results in post-operative pain at first day and first control, number of weekly and total dressings until healing, time for full wound recovery, days to return to work, patient feeling feedback and scar aspect. Wounds healed within 8-12 days were 84.6% in the Cold group and 18.8% in the Hot one. I° Dindo-Clavien complications were respectively 15.4% and 100.0% for the Cold and Hot group. No differences were recorded for II° Dindo-Clavien complications and in days of hospitalization. CONCLUSION: cold excision of the sinus pilonidalis has better results both in terms of precarious healing and quality of life, probably because the tissues are not subjected to diathermocoagulation damage and therefore the healing occurs more quickly. (United States National Institutes of Health, www.clinicaltrial.gov, number NCT03764657, www.researchregistry.com UIN 5003).

Characteristics of coronary microcirculatory function in patients with Takotsubo syndrome.

BACKGROUND: Takotsubo syndrome (TS) is a recently described cardiac syndrome whose pathogenesis is still unclear. We investigated the characteristics of coronary microcirculatory function in patients with TS through the analysis of the TIMI frame count (TFC) compared to normal subjects and with to subjects with microvascular angina (MA). METHODS: We enrolled 71 TS patients (F:M =69:2, mean age of 65.27±9.53 years), 70 controls (F:M =34:36, mean age of 56.63±13.5 years) and 71 patients with MA, (F:M =69:2, mean age of 65.9±9.2 years). The assessment of the microcirculation was carried out through the TFC. RESULTS: microcirculation was significantly altered in patients with TS compared with healthy controls [left anterior descending coronary artery (LAD) 25.16±6.91 vs. 17.30±3.76, P<0.001; circumflex artery (CX) 25.48±6.10 vs. 17.05±4.60, P<0.001; right coronary artery (RCA) 26.43±8.95 vs. 15.74±4.27, P<0.001, average TFC in TS 25.70±5.34 vs. 16,70±3.26, P<0.001). A TFC >20 frames was able to discriminate TS patients from controls with a specificity of 88.57% and sensitivity of 85.92% (AUC 0.927, P<0.0001). Microvascular dysfunction was diffuse in TS as well as in MA and slightly more severe in this last (mean TFC in MA 28.25±9.3 vs. 25.7±5.34 in TS, P<0.046). CONCLUSIONS: Coronary microcirculation in TS patients is diffuse and milder compared to MA patients. Cut-off values >20 frames discriminate between patients with normal microcirculation and patients with TS.

HCV clearance after direct-acting antivirals in patients with cirrhosis by stages of liver impairment: The ITAL-C network study.

BACKGROUND: Sustained virological response (SVR12) rates at 12 weeks after treatment for HCV-infected patients with decompensated cirrhosis are used when referring to those with moderate functional impairment, while few data are available for those with more severe impairment. The use of the cirrhosis staging system proposed by D'Amico might provide new insights on timing for antiviral therapy. METHODS: We investigated efficacy (SVR12), safety, and post-treatment variations in clinical and laboratory parameters in 2612 patients with advanced fibrosis (n=575) or cirrhosis (n=2037). Cirrhosis was in the compensated phase (without/with varices) or had previously been in the decompensated stage. Different direct-acting antiviral (DAA) regimens were administered in accordance with scientific guidelines. RESULTS: The SVR12 rate was 97.6% in patients with advanced fibrosis. For patients with cirrhosis, the rate was 96.5% in stage 1, 95.1% in stage 2, 100% in stage 3, 95.7% in stage 4, and 93.6% in stage 5. These rates were independent of gender, age, HCV genotype, and treatment schedule. Positive changes in biochemical parameters and CPT classes following therapy were evident in compensated and previously decompensated patients. CONCLUSION: Our findings support the use of DAAs in patients with advanced cirrhosis (stages 3-5) who are at greatest risk and have the most to gain from therapy.

Radionuclides in wastewater treatment plants: monitoring of Sicilian plants.

Three Sicilian wastewater treatment plants were monitored to assess the occurrence and the behaviour of radionuclides. Two sampling campaigns (screening and long-term) were carried out during which liquid and solid samples have been analysed. It was found that ¹³¹I mostly occurred in the samples analysed during the screening campaign (43% of the analysed samples contained ¹³¹I). High ¹³¹I specific activity was found in the mixed liquor, recycled sludge and dehydrated sludge samples. This finding was mainly due to the tendency of (131)I to be associated with solid particles. During the long-term sampling campaign an influence of the sludge retention time (SRT) on the ¹³¹I behaviour was found. Increasing the SRT and consequently decreasing the fraction of active organic biomass inside the system, the specific activity of ¹³¹I decreases.

[Medullary carcinoma of the thyroid: a clinical contribution]. / Il carcinoma midollare della tiroide: contributo clinico.

The authors report 20 cases of medullary thyroid carcinoma over the period from 1980 to 2000. Two patients turned out to be inoperable and 18 patients underwent total thyroidectomy, associated with dissection of the central lymphatic compartment in 5 patients and with dissection of the central and lateral lymphatic compartments in 10 patients with clinical or instrumental evidence of cervical lymphadenomegaly. Serum calcitonin levels proved to be a reliable marker for the diagnosis of persistence or recurrence of the disease. The follow-up, lasting from 1 to 208 months, demonstrated that in 7 cases in which serum levels of calcitonin underwent normalization there was no recurrence of disease. Among 11 cases with persistence of high calcitonin levels, 6 died and only 2 presented no evidence of metastases. On the basis of our analysis of the cases reported, total thyroidectomy associated with dissection of the central lymphatic compartment is an adequate treatment for patients in stages I and II. The authors regard routine dissection of the lateral lymphatic compartment as unadvisable.