Invasive Route Research Articles

What do women prefer? a survey on three minimally invasive surgical routes for tubal sterilization

What do women prefer? a survey on three minimally invasive surgical routes for tubal sterilization

A thousand-genome panel retraces the global spread and adaptation of a major fungal crop pathogen

Human activity impacts the evolutionary trajectories of many species worldwide. Global trade of agricultural goods contributes to the dispersal of pathogens reshaping their genetic makeup and providing opportunities for virulence gains. Understanding how pathogens surmount control strategies and cope with new climates is crucial to predicting the future impact of crop pathogens. Here, we address this by assembling a global thousand-genome panel of Zymoseptoria tritici, a major fungal pathogen of wheat reported in all production areas worldwide. We identify the global invasion routes and ongoing genetic exchange of the pathogen among wheat-growing regions. We find that the global expansion was accompanied by increased activity of transposable elements and weakened genomic defenses. Finally, we find significant standing variation for adaptation to new climates encountered during the global spread. Our work shows how large population genomic panels enable deep insights into the evolutionary trajectory of a major crop pathogen.

Temporal changes of patient characteristics over 12 years in a single-center transcatheter aortic valve implantation cohort

BackgroundBeneficial results of transcatheter aortic valve implantation (TAVI) compared to surgical aortic valve replacement (SAVR) in patients at all risk strata have led to substantial changes in guideline recommendations for valvular heart disease.AimTo examine influence of these guideline changes on a real-world TAVI cohort, we evaluated how risk profiles and outcomes of TAVI patients developed in our single-center patient cohort over a period of 12 years.MethodsBaseline, procedural and 30-day outcome parameters of TAVI patients were retrospectively compared between three time periods (period 1: 2008–2012, period 2: 2013–2017, period 3: 2018–2020).ResultsBetween 03/2008 and 12/2020, a total of 3678 patients underwent TAVI at our center. The median age was 81.1 years (25th, 75th percentile: 76.7, 84.9) with no significant change over time. The EuroSCORE II showed a continuous and significant decline from 5.3% (3.3, 8.6) in period 1 to 2.8% (1.7, 5.0) in period 3 (p < 0.001). Furthermore, rates of permanent pacemaker implantation, acute kidney injury, and paravalvular leakage ≥ moderate continuously declined over time. Accordingly, the 30-day mortality fell from 9.3% in period 1 to 4.3% in period 3 (p < 0.001).ConclusionDespite substantial guideline alterations, median patient age remained largely unchanged in our TAVI cohort over the past 12 years. Therefore, increased age still appears to be the main reason to choose TAVI over SAVR. However, risk profiles declined substantially. Significant improvements in early outcomes suggest favorable influence of less invasive access routes, improved device platforms and growing user experience.Graphical abstract

Phylogenetic Diversity of the Red Swamp Crayfish Procambarus clarkii and Its Dispersal Pattern in Northern and Central Italy

The red swamp crayfish Procambarus clarkii is one of the most threatening freshwater species in the world. The aim of this study is to provide a better understanding of the phylogeography and the invasion routes of P. clarkii populations in the Italian Peninsula through the analysis of mitochondrial phylogeny. Mitochondrial control region and cytochrome c oxidase subunit I (COI) sequences of 153 samples collected from six Italian basins were analyzed and compared to worldwide data. Except for the lakes Bolsena and Posta Fibreno, a high genetic variability was found in the other basins. The mitochondrial DNA pattern of P. clarkii from the lakes Candia and Massaciuccoli confirmed the hypothesis of double introduction events. Another entry point could be represented by Lake Trasimeno, which shows haplotypes originating from Louisiana and not shared with other Italian basins. Moreover, unique lineages were also found in the Stella River, thus enhancing the hypothesis that multiple introductions of P. clarkii occurred in northern and Central Italy and strengthening the idea that knowledge about the dispersion routes of this alien species can be useful to predict its invasiveness and elaborate control strategies to preserve biodiversity.

Role of seed infection for the near and far distance dissemination of wheat blast caused by Magnaporthe oryzae pathotype Triticum.

Magnaporthe oryzae pathotype Triticum (MoT) is a devastating fungal phytopathogen causing wheat blast disease which threatens wheat production particularly in warmer climate zones. Effective disease control is hampered by the limited knowledge on the life cycle, epidemiology, and pathogenicity of MoT. Since MoT mainly infects and colonizes the inflorescences of wheat, infection, invasion routes and colonization of MoT on wheat ears and in wheat seeds were investigated in order to assess potential seed transmission pathways. MoT was spray inoculated on two wheat cultivars (Sumai 3, susceptible and Milan, resistant) at three ear maturity stages [full ear emergence, growth stage (GS) 59; mid flowering, GS 65; and end of flowering, GS 69]. Incidence of MoT on Sumai 3 seeds was 100% and 20-25% on Milan. MoT sporulation rate on Sumai 3 contaminated seeds was more than 15 times higher than on Milan. Repeated washes of seed samples for removing paraffin fixation hampers seed microscopy. To overcome the damage of seed samples, we used hand-sectioned seed samples instead of paraffin-fixed microtome samples to facilitate microscopy. The colonization of MoT within various seed tissues was followed by light and confocal laser scanning microscopy (CLSM). Invasion of MoT in seeds predominantly occurred in the caryopsis germ region, but entry via other seed parts was also observed, confirming the potential of intense colonization of MoT in wheat grains. Fungal spread in wheat plants growing from MoT infected seeds was monitored through plating, microscopic and molecular techniques. Under greenhouse conditions, no spread of MoT from infected seeds to seedlings later than GS 21 or to ears was detected, neither in Milan nor in Sumai 3. We therefore conclude, that MoT may not systemically contaminate inflorescences and seeds in neither susceptible nor resistant wheat cultivars. However, initial blast symptoms, only found on seedlings of Sumai 3 but not Milan, resulted in the formation of new conidia, which may serve as inoculum source for plant-to-plant dissemination by airborne infection of plant stands in the field (short distance spread). Ultimately the inoculum may infect young inflorescences in the field and contaminate seeds. Our findings again stress the risk of long-distance dissemination of wheat blast across continents through MoT-contaminated seeds. This underlines the importance of mandatory use of healthy seeds in strategies to control any further spread of wheat blast.

AUGS-IUGA Joint Clinical Consensus Statement on Enhanced Recovery After Urogynecologic Surgery

AUGS-IUGA Joint Clinical Consensus Statement on Enhanced Recovery After Urogynecologic Surgery

Factors Associated With Increased Estimated Blood Loss and Factors Associated With Utilization of Type and Screen in Benign Gynecology: A Retrospective Chart Review.

There is minimal literature discussing factors associated with increased estimated blood loss (EBL) or transfusion in gynecologic surgery in tertiary academic centers. The aim of the study was to determine factors associated with transfusion and increased blood loss during gynecologic surgery. This retrospective cohort investigated patients undergoing benign gynecologic procedures at a tertiary medical center. We excluded women undergoing surgery for known or suspected malignancy, emergent surgery, obstetrical procedures, or cases with another surgical specialty. Patient age, body mass index, American Society of Anesthesiologists class, medical history, EBL, arterial line placement, preoperative laboratory studies, and transfusion receipt for up to 6 weeks postoperatively were extracted. The primary outcome was transfusion within 6 weeks of surgery; risk factors for high blood loss (EBL >500 mL) and transfusion were explored. Nine hundred seventy-five surgical procedures were included (59% vaginal, 36% laparoscopic, 4% robotic). Median EBL was 50 mL (interquartile range, 10-100 mL). Estimated blood loss increased with duration of surgery (P < 0.01). Transfusions were more likely to occur during open procedures (13%) compared with vaginal (2%), laparoscopic (2%), or robotic (3%). Arterial line placement (relative risk [RR], 11.8; 95% confidence interval [CI], 5.3-26.1) and additional intravenous placement (RR, 6.0; 95% CI, 2.6 to 13.7) were associated with transfusion. Vaginal surgery (RR, 0.13; 95% CI, 0.05 to 0.32) and urogynecologic procedures (RR, 0.1; CI, 0.01-0.7) were associated with reduced risk of needing transfusion. Most benign gynecologic surgical procedures have minimal blood loss. Patients undergoing surgery through minimally invasive routes or urogynecologic procedures are at further decreased risk of transfusion.

Synthesis and Properties of Sucrose- and Lactose-Based Aromatic Ester Surfactants as Potential Drugs Permeability Enhancers.

The delivery of therapeutics across biological membranes (e.g., mucosal barriers) by avoiding invasive routes (e.g., injection) remains a challenge in the pharmaceutical field. As such, there is the need to discover new compounds that act as drug permeability enhancers with a favorable toxicological profile. A valid alternative is represented by the class of sugar-based ester surfactants. In this study, sucrose and lactose alkyl aromatic and aromatic ester derivatives have been synthesized with the aim to characterize them in terms of their physicochemical properties, structure-property relationship, and cytotoxicity, and to test their ability as permeability enhancer agents across Calu-3 cells. All of the tested surfactants showed no remarkable cytotoxic effect on Calu-3 cells when applied both below and above their critical micelle concentration. Among the explored molecules, lactose p-biphenyl benzoate (URB1420) and sucrose p-phenyl benzoate (URB1481) cause a reversible ~30% decrease in transepithelial electrical resistance (TEER) with the respect to the basal value. The obtained result matches with the increased in vitro permeability coefficients (Papp) calculated for FTIC-dextran across Calu-3 cells in the presence of 4 mM solutions of these surfactants. Overall, this study proposes sucrose- and lactose-based alkyl aromatic and aromatic ester surfactants as novel potential and safe permeation enhancers for pharmaceutical applications.

Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats

Topical instillation of drugs targeting the posterior ocular segment is an expanding area of research. Chitosan and hyaluronic acid have remarkable mucoadhesive properties and potentially enhance pre-corneal retention time after topical instillation. Bearing this in mind, we explored the possibility of delivering epoetin beta (EPOβ) to the posterior segment of the eye in a chitosan-hyaluronic acid (CS/HA-EPOβ) nanoparticulate system using the topical route of administration. Complete ophthalmological examinations, electroretinography and microhematocrit evaluations were performed in Wistar Hannover (WH) rats, before and after topical administration of nanoparticles. The right eye received CS/HA-EPOβ and the left eye received only empty nanocarriers (control). Animals were split into 6 groups and at designated timepoints, all animals from each group (n = 3) were euthanized and both eyes enucleated. Retinal morphology and EPOβ ocular distribution were assessed, respectively, through hematoxylin and eosin (HE) and immunofluorescence staining. After topical administration, no adverse ocular signs were noted and no significant changes either in microhematocrits nor in electroretinographies were detected. During the study, intraocular pressure (IOP) was always kept within physiological range bilaterally. No histological changes were detected in any of the ocular globes. Immunofluorescence enabled the identification of EPOβ in the retina 12 h after the administration, its presence still being detectable at day 21. In conclusion, CS/HA nanoparticles could efficiently deliver EPOβ to the retina of WH rats after topical instillation, being considered biologically safe. Topical administration of this nanoformulation could be a valuable tool for retinal neuroprotection, decreasing risks associated with more invasive routes of administration, being cost effective and also increasing long-term patients’ compliance.

Solubility Enhancement and Inhalation Delivery of Cyclodextrin-Based Inclusion Complex of Delamanid for Pulmonary Tuberculosis Treatment.

Tuberculosis (TB) is a contiguous airborne disease caused by Mycobacterium tuberculosis (M.tb), primarily affecting the human lungs. The progression of drug-susceptible TB to drug-resistant strains, MDR-TB and XDR-TB, has become a global challenge toward eradicating TB. Conventional TB treatment involves frequent dosing and prolonged treatment regimens predominantly by an oral or invasive route, leading to treatment-related systemic adverse effects and patient's noncompliance. Pulmonary delivery is an attractive option as we could reduce dose, limit systemic side-effects, and achieve rapid onset of action. Delamanid (DLD), an antituberculosis drug, has poor aqueous solubility, and in this study, we aim to improve its solubility using cyclodextrin complexation. We screened different cyclodextrins and found that HP-β-CD resulted in a 54-fold increase in solubility compared to a 27-fold and 13-fold increase by SBE-β-CD and HP-ɣ-CD, respectively. The stability constant (265 ± 15M-1) and complexation efficiency (8.5 × 10-4) suggest the formation of a stable inclusion complex of DLD and HP-β-CD in a 2:1 ratio. Solid-state characterization studies (DSC, PXRD, and NMR) further confirmed successful complexation of DLD in HP-β-CD. The nebulized DLD-CD complex solution showed a mass median aerodynamic diameter of 4.42 ± 0.62μm and fine particle fraction of 82.28 ± 2.79%, suggesting deposition in the respiratory airways. In bacterial studies, minimum inhibitory concentration of DLD-CD complex was significantly reduced (four-fold) compared to free DLD in M.tb (H37Ra strain). Furthermore, accelerated stability studies confirmed that the inclusion complex was stable for 4weeks with 90%w/w drug content. In conclusion, we increased the aqueous solubility of DLD through cyclodextrin complexation and improved its efficacy in vitro.

Intranasal delivery of full-length anti-Nogo-A antibody: A potential alternative route for therapeutic antibodies to central nervous system targets

Antibody delivery to the CNS remains a huge hurdle for the clinical application of antibodies targeting a CNS antigen. The blood-brain barrier and blood-CSF barrier restrict access of therapeutic antibodies to their CNS targets in a major way. The very high amounts of therapeutic antibodies that are administered systemically in recent clinical trials to reach CNS targets are barely viable cost-wise for broad, routine applications. Though global CNS delivery of antibodies can be achieved by intrathecal application, these procedures are invasive. A non-invasive method to bring antibodies into the CNS reliably and reproducibly remains an important unmet need in neurology. In the present study, we show that intranasal application of a mouse monoclonal antibody against the neurite growth-inhibiting and plasticity-restricting membrane protein Nogo-A leads to a rapid transfer of significant amounts of antibody to the brain and spinal cord in intact adult rats. Daily intranasal application for 2 wk of anti-Nogo-A antibody enhanced growth and compensatory sprouting of corticofugal projections and functional recovery in rats after large unilateral cortical strokes. These findings are a starting point for clinical translation for a less invasive route of application of therapeutic antibodies to CNS targets for many neurological indications.

Release of ranibizumab using a porous poly(dimethylsiloxane) capsule suppressed laser-induced choroidal neovascularization via the transscleral route

The administration of anti-vascular endothelial growth factor drugs in the posterior eye segment with sustained release through less invasive methods is a challenge in the treatment of age-related macular disease. We developed a flexible capsule device using porous poly(dimethylsiloxane) (PDMS) that was able to release ranibizumab. The porous PDMS sheet was fabricated by salt-leaching of a micro-sectioned PDMS sheet containing salt microparticles. Observation with scanning electron microscopy revealed that the pore densities could be adjusted by the concentration of salt. The in vitro release study showed that the release rate of fluorescein isothiocyanate-tagged albumin could be adjusted based on the pore density of the porous PDMS sheet. Ranibizumab could be released in a sustained-release manner for 16 weeks. The device was implanted on the sclera; its efficacy in terms of the suppression of laser-induced choroidal neovascularization (CNV) in rats was compared with that of monthly intravitreal injections of ranibizumab. At 8 and 18 weeks after implantation, the CNV area was significantly reduced in rats that received the ranibizumab-releasing device compared with those that received the placebo device. However, although monthly intravitreal injections of ranibizumab reduced CNV for 8 weeks, this reduction was not sustained for 18 weeks. In conclusion, we demonstrated a novel controlled-release device using a porous PDMS sheet that could suppress CNV via a less invasive transscleral route versus intravitreal injections. This device may also reduce the occurrence of side effects associated with frequent intravitreal injections.Graphical

Ozone therapy in brazil: achievements and challenges for the future.

The practice of Ozone Therapy in Brazil began in 1975, with Doctor Heinz Konrad. In the 90’s, other professionals started to practice it in a precursory and unregulated way, with imported equipment. The work of physician Edison de Cezar Philippi stands out, who was a great disseminator and together with other physicians such as Dr. Glacus Brito, Dr. Maria Emília Serra, Dr. Ana Cristina Barreira, among others, founded the first association of Ozone Therapy in Brazil, which in 2006 became Brazilian Association of Ozone Therapy (ABOZ), with Dr. Maria Emília Gadelha Serra as its first president. In the state and regulatory scope, Ozone Therapy was an unknown technique. Numerous scientific articles were presented to the Ministry of Health, the Federal Council of&#x0D; Medicine, and ANVISA (equipment regulatory agency in Brazil). The first regulatory framework for Ozone Therapy in Brazil took place in 2015, with the publication of Resolution CFO 166/2015, which regulated Ozone Therapy in Dentistry.&#x0D; In 2018, Ozone Therapy was included as an integrative practice by the Ministry of Health of Brazil, with the publication of ORDINANCE N° 702 (21/03/2018) which included new practices in the National Policy on Integrative and Complementary Practices (PNPIC), of the Brazilian Unified Health System (SUS). From this milestone, the Professional Class Councils began to understand and regulate Ozone Therapy within the scope of each profession.&#x0D; Currently, dentistry, physiotherapy, pharmacy, nursing, veterinary medicine, and biomedicine councils have an official understanding of Ozone Therapy, each within its scope of action and with a specific definition of training. These resolutions collaborate to improve the scenario of Ozone Therapy in the country, bringing more possibilities for treatment, and health care for the entire population.&#x0D; Although there are numerous qualified studies for the practice to be regulated for medicine, the Federal Council of Medicine is still waiting for more scientific evidence, so it only authorizes activities in the experimental scope (registered clinical research).&#x0D; In the meantime, faced with the difficulties of understanding from the Federal Council of Medicine, the national congress approved a bill proposing that ozone therapy be authorized throughout the national territory. This bill is currently under review by the Senate and the next step is presidential sanction.&#x0D; Even with all the regulatory achievements in these 15 years of work, we still have many challenges to overcome. The main one is the regulation for use by doctors, so Ozone Therapy becomes an official technique. In addition, for Ozone Therapy to be carried out more ethically and scientifically, it is necessary to understand the scenario and some challenges:&#x0D; • How to establish boundaries between professional categories, since ozone has many application routes - not all professionals are prepared to perform more invasive routes.&#x0D; • The established model based on the diagnosis and treatment of the disease.&#x0D; • Banalization of the technique by unqualified professionals, leading to a false understanding and discrediting of the technique.&#x0D; • Difficulty in regulating equipment and minimum quality standards, while on the internet equipment from China enters without qualification.&#x0D; • Standardization and minimum criteria for the manufacture of Ozonized Oils, based on studies and not on empiricism.

Genomes of the cosmopolitan fruit pest Bactrocera dorsalis (Diptera: Tephritidae) reveal its global invasion history and thermal adaptation

IntroductionThe oriental fruit fly Bactrocera dorsalis is one of the most destructive agricultural pests worldwide, with highly debated species delimitation, origin, and global spread routes. ObjectivesOur study intended to (i) resolve the taxonomic uncertainties between B. dorsalis and B. carambolae, (ii) reveal the population structure and global invasion routes of B. dorsalis across Asia, Africa, and Oceania, and (iii) identify genomic regions that are responsible for the thermal adaptation of B. dorsalis. MethodsBased on a high-quality chromosome-level reference genome assembly, we explored the population relationship using a genome-scale single nucleotide polymorphism dataset generated from the resequencing data of 487 B. dorsalis genomes and 25 B. carambolae genomes. Genome-wide association studies and silencing using RNA interference were used to identify and verify the candidate genes associated with extreme thermal stress. ResultsWe showed that B. dorsalis originates from the Southern India region with three independent invasion and spread routes worldwide: (i) from Northern India to Northern Southeast Asia, then to Southern Southeast Asia; (ii) from Northern India to Northern Southeast Asian, then to China and Hawaii; and (iii) from Southern India toward the African mainland, then to Madagascar, which is mainly facilitated by human activities including trade and immigration. Twenty-seven genes were identified by a genome-wide association study to be associated with 11 temperature bioclimatic variables. The Cyp6a9 gene may enhance the thermal adaptation of B. dorsalis and thus boost its invasion, which tended to be upregulated at a hardening temperature of 38 °C. Functional verification using RNA interference silencing against Cyp6a9, led to the specific decrease in Cyp6a9 expression, reducing the survival rate of dsRNA-feeding larvae exposed to extreme thermal stress of 45 °C after heat hardening treatments in B. dorsalis. ConclusionThis study provides insights into the evolutionary history and genetic basis of temperature adaptation in B. dorsalis.

MR conditional prostate intervention systems and actuations review.

Magnetic resonance imaging (MRI) has the ability to provide high-resolution images of soft tissues without the use of radiation. So much research has been focused on the development of actuators and robotic devices that can be used in the MRI environment so "real-time" images can be obtained during surgeries. With real-time guidance from MRI, robots can perform surgical procedures with high accuracy and through less invasive routes. This technique can also significantly reduce the operation time and simplify pre-surgical procedures. Therefore, research on robot-assisted MRI-guided prostate intervention has attracted a great deal of interest, and several successful clinical trials have been published in recent years, pointing to the great potential of this technology. However, the development of MRI-guided robots is still in the primary stage, and collaboration between researchers and commercial suppliers is still needed to improve such robot systems. This review presents an overview of MRI-guided prostate intervention devices and actuators. Additionally, the expected technical challenges and future advances in this field are discussed.

Changes in nurses’ knowledge and clinical practice in managing local IV complications following an education intervention

Abstract Background Peripheral venous catheters (PVCs) are the most common invasive route for the rapid administration of medication and fluids. The care of PVC sites after cannulation can pose challenges depending on nurses’ level of knowledge and practice. Aim To transfer nurses’ knowledge into practice on preventing common local complications of intravenous (IV) therapy. Design A quasi-experimental study was undertaken. Methods: A convenience sample of nurses from surgical and medical wards of a university hospital (n=64) was used. Pre- and post-education intervention levels of nurses’ knowledge, practice and maintenance of PVCs, and the use of a visual infusion phlebitis scale to identify potential complications were assessed. Results: The effectiveness of the course was statistically significant for all three parameters (P&amp;lt;0.001). Conclusion The study highlighted the importance of ongoing education based on the latest available evidence to enable nurses to improve their knowledge and clinical practice with regard to PVC care and associated complications.

Excision of triple compartment deep infiltrating endometriosis with visceral involvement

Background: Excision of multi-compartment deep infiltrating endometriosis with visceral involvement is challenging. We illustrate an interdisciplinary approach to complete minimally invasive excision in a single surgery. Case: We present a case of deep infiltrating endometriosis with visceral involvement in the anterior, middle, and posterior compartments. A collaborative surgical approach was taken with gynecologic, colorectal, and urologic surgeons to perform a robot-assisted total laparoscopic hysterectomy, bilateral salpingectomy, ovarian cystectomy, and unilateral oophorectomy with concurrent segmental resection of rectosigmoid and excision of transmural bladder and vaginal nodules. Conclusion: Thorough preoperative evaluation and an interdisciplinary approach to surgical planning involving radiology, gynecology, colorectal surgery, and urology allowed for complete simultaneous resection of bladder, rectosigmoid, and pelvic deep infiltrating endometriosis without complications via a minimally invasive route.

Immune-awakening Saccharomyces-inspired nanocarrier for oral target delivery to lymph and tumors.

Utilization of the intestinal lymphatic pathway will allow extraordinary gains in lymph and tumors cascade-targeted delivery of oral drugs and awakening the innate/adaptive immunity of the body and the lesion microenvironment, in addition to improving oral bioavailability relative to other means of delivery of oral drugs. Here, inspired by the specific invasion route of intestinal microorganisms, we pioneered an immune-awakening Saccharomyces-inspired mesoporous silicon nanoparticle (yMSN) for the ingenious cascade-targeted delivery of therapeutic cancer vaccines and antitumor drugs to lymph and tumors via the intestinal lymphatic pathway. Encouragingly, yMSN high-loaded tumor-specific antigens (OVA, 11.9%) and anti-tumor drugs (Len, 28.6%) with high stability, namely Len/OVA/yMSN, efficiently co-delivered OVA and Len to their desired target sites. Moreover, yMSN concomitantly awakened the innate antitumor immunity of dendritic cells and macrophages, strengthening vaccine-induced adaptive immune responses and reversing macrophage-associated immunosuppression in the tumor microenvironment. Surprisingly, Len/OVA/yMSN treatment resulted in excellent synergistic antitumor efficacy and long-term antitumor memory in OVA-Hepa1-6-bearing mice. This high-performance nanocarrier provides a novel approach for lesion-targeting delivery of oral drugs accompanied with awakening of the innate/adaptive immunity of the lesion environment, and also represents a novel path for the oral delivery of diverse therapeutic agents targeting other lymph-mediated diseases.

A systematic review of subcutaneous versus intramuscular or intravenous routes of opioid administration on pain outcomes in cancer and post-surgical clinical populations - challenging current assumptions in palliative care practice.

The objective of this review is to investigate the use of the subcutaneous route of administration of analgesics, common practice within palliative medicine. Systematic review using consensus approach, direct comparison of subcutaneous route with intravenous and intramuscular routes. The limited available evidence demonstrates non-inferiority of the subcutaneous route in both cancer patients and those post-surgery. Pain management is comparable to other routes. Route-related side effects are rare and systemic side effects are comparable. Pain management is a critical role of palliative medicine. The subcutaneous route of administration offers a viable option for the delivery of parenteral analgesia within all settings, including the community. This review supports current practice, demonstrating equivalence with more invasive routes of administration.

Presence of SARS-CoV-2 on the conjunctival mucosa in patients hospitalized due to COVID-19: Pathophysiological considerations and therapeutic implications.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in a worldwide pandemic, due to its great capacity to invade the human body. Previous studies have shown that the primary route of invasion of this virus is the human respiratory tract via the co-expression of ACE2 receptor and TMPRSS2, a serine protease on the cellular surface. Interestingly, this condition is present not only on the respiratory epithelium but on the conjunctival mucosa, as well. Thus, we hypothesized that SARS-CoV-2 is present on the conjunctival mucosa. To prove that SARS-CoV-2 can be detected in the conjunctiva. Previously nasopharyngeal swab-sample based real-time polymerase chain reaction (PCR) positive COVID-19 infected patients were selected at the COVID Care Centers of Semmelweis University, Budapest, Hungary. The study was approved by the ethical committee of Semmelweis University. During their recovery, both nasopharyngeal and conjunctival swab-samples were taken and PCR method was used to detect the presence of SARS-CoV-2 RNA. Appropriate statistical analysis was performed. The study population consisted of 97 patients, 49 females (50.5%) and 48 males (49.5%), with a mean age of 67.2 ± 11.9 years. During recovery, with nasopharyngeal swabs, the PCR test was positive in 55 cases (56.70%), whereas with conjunctival swabs it was positive in 8 cases (8.25%). Both tests were positive in 5 cases (5.15%). In some patients, ocular symptoms were observed as well. The rest of the patients (29 cases) had negative nasopharyngeal PCR tests during recovery. Although only in few cases, the data of the present study provides a proof of concept that SARS-CoV-2 can be present on the conjunctival mucosa even in nasopharyngeal negative patients, a finding, which can have clinical importance. Also, on the basis of these findings one can hypothesize that - in addition to the respiratory tract - the conjunctiva can be an entrance route for SARS-CoV-2 to the human body. Thus, in high-risk conditions, in addition to covering the mouth and nose with mask, the protection of the eyes is also strongly recommended.