Nanotechnological approaches to address photosensitizers' limitations: towards improved clinical applicability of photodynamic therapy

Photodynamic therapy (PDT) uses a combination of molecular oxygen, light and a photosensitizer (PS) to generate singlet oxygen or reactive oxygen species (ROS), which can eradicate tumoral cells. All currently approved PSs for cancer treatment are molecular PSs. To date, no nanoparticlebased PSs are used clinically although it has widely been shown that nanotechnology may help to improve the properties of molecular PSs; for instance, molecular PSs suffer from some intrinsic limitations that undermine their therapeutic efficacy. In the present minireview, the most critical weaknesses exhibited by molecular PSs are described, and the potential use of nanoparticles (NPs) to address them and to reach the clinics is discussed

DICER1 Syndrome: A Multicenter Surgical Experience and Systematic Review

DICER1 syndrome is a rare genetic disorder that predisposes patients to the development of malignant and non-malignant diseases. Presently, DICER1 syndrome diagnosis still occurs late, usually following surgical operations, affecting patients' outcomes, especially for further neoplasms, which are entailed in this syndrome. For this reason, herein we present a multicenter report of DICER1 syndrome, with the prospective aim of enhancing post-surgical surveillance. A cohort of seven patients was collected among the surgical registries of Pediatric Surgery at the University of Pisa with the General and Oncologic Surgery of Federico II, University of Naples, and the Pediatric Surgery, Regina Margherita Hospital, University of Turin. In each case, the following data were analyzed: sex, age at diagnosis, age at first surgery, clinical features, familial, genetic investigations, and follow-up. A comprehensive literature review of DICER1 cases, including case reports and multicenter studies published from 1996 to June 2022, was performed. Eventually, the retrieved data from the literature were compared with the data emerging from our cohort of patients

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

PROHEXADIONE-CA: MODES OF ACTION OF A MULTIFUNCTIONAL PLANT BIOREGULATOR FOR FRUIT TREES

Prohexadione-Ca is a plant bioregulator that is primarily used to inhibit excessive vegetative growth in fruit trees and other crop plants. Additionally, effects on the incidence of bacterial and fungal diseases and on insect pests are often observed. Further, the compound may reduce abortion of fruitlets thereby increasing fruit set. Prohexadione-Ca is relatively short-lived and possesses very favorable toxicological and ecotoxicological features. The compound acts as a structural mimic of 2-oxoglutaric acid. Therefore, distinct dioxygenases involved in gibberellin biosynthesis, which require this compound as a co-substrate, are blocked (e.g. GA20 3ß-hydroxylase). As a result, less growth-active gibberellins are formed and treated plants remain compact. 2-Oxoglutaric acid-dependent dioxygenases are also involved in flavonoid metabolism. In shoots of apples and pears, prohexadione-Ca causes considerable changes in the formation of flavonoids and their phenolic precursors by inhibiting flavanone 3-hydroxylase. Prohexadione-Ca triggers pathogen resistance by inducing the formation of 3-deoxyflavonoids, in particular luteoforol, with phytoalexin-like properties. A similar mechanism may explain the lowered incidence of insect pests. Finally, treatments with prohexadione-Ca lead to reduced ethylene formation. This is due to structural similarities with ascorbic acid, the co-substrate of aminocyclopropanecarboxylic acid oxidase, another dioxygenase, which is involved in ethylene biosynthesis. Lowered ethylene levels explain increases in fruit se

Prohexadione-Ca: Modes of Action of a Multifunctional Plant Bioregulator for Fruit Trees

Prohexadione-Ca is a plant bioregulator that is primarily used to inhibit excessive vegetative growth in fruit trees and other crop plants. Additionally, effects on the incidence of bacterial and fungal diseases and on insect pests are often observed. Further, the compound may reduce abortion of fruitlets thereby increasing fruit set. Prohexadione-Ca is relatively short-lived and possesses very favorable toxicological and ecotoxicological features. The compound acts as a structural mimic of 2-oxoglutaric acid. Therefore, distinct dioxygenases involved in gibberellin biosynthesis, which require this compound as a co-substrate, are blocked (e.g. GA20 3ß-hydroxylase). As a result, less growth-active gibberellins are formed and treated plants remain compact. 2-Oxoglutaric acid-dependent dioxygenases are also involved in flavonoid metabolism. In shoots of apples and pears, prohexadione-Ca causes considerable changes in the formation of flavonoids and their phenolic precursors by inhibiting flavanone 3-hydroxylase. Prohexadione-Ca triggers pathogen resistance by inducing the formation of 3-deoxyflavonoids, in particular luteoforol, with phytoalexin-like properties. A similar mechanism may explain the lowered incidence of insect pests. Finally, treatments with prohexadione-Ca lead to reduced ethylene formation. This is due to structural similarities with ascorbic acid, the co-substrate of aminocyclopropanecarboxylic acid oxidase, another dioxygenase, which is involved in ethylene biosynthesis. Lowered ethylene levels explain increases in fruit se

Reduction of scab incidence (Venturia inaequalis) in apple with prohexadione-Ca and trinexapac-ethyl, two growth regulating acylcyclohexanediones

Prohexadione-calcium and trinexapac-ethyl, inhibitors of 2-oxoglutaric acid-dependent dioxygenases, were tested for their efficacy in controlling scab infection on apple (cv. Golden Delicious) scions under greenhouse and field conditions. Their effectiveness was compared with other types of growth inhibitors (chlormequat chloride and paclobutrazol). Furthermore, to determine the time required to build-up plant resistance against scab, the compounds were applied at different concentrations and timings prior the inoculation with Venturia inaequalis. Prohexadione-calcium and trinexapac-ethyl significantly reduced scab incidence starting approximately 10 and lasting for approximately 25 days after application. In field conditions, the practical application of these compounds mayresult valuable both to control the vegetative/ reproductive balance of the trees and to effectively reduce the amount of fungicides used to control scab

Influence of stigmatic morphology on flower colonization by Erwinia amylovora and Pantoea agglomerans

The morphology of apple and pear stigma was investigated with confocal laser scanning microscopy and scanning electron microscopy. The floral colonization process by Erwinia amylovora was studied with gfplabelled bacteria and confocal laser scanning microscopy to allow the in vivo observation of the pathogen colonization on intact, viable plant tissues without any kind of staining of the specimens. The interaction on the stigma between Erwinia amylovora and Pantoea agglomerans, both labelled with genes encoding for fluorescent proteins (DsRed-GFP), was also investigated. A stylar groove, covered by papillae and dwelling from the stigma along the style, was visualized. In laboratory conditions, this groove was shown to be an important way for E. amylovora migration towards the nectarthodes. Due to its anatomical structure the groove can sustain bacterial multiplication and thus may play an important role on the interactions between the pathogen and the bacterial antagonist P. agglomerans