SARS-CoV-2 vaccination modelling for safe surgery to save lives : data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.Peer reviewe

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Mesenteric lengthening during pouch surgery: technique and outcomes in a tertiary centre

Anastomotic complications after ileal pouch-anal anastomosis (IPAA) are often associated with excessive tension and poor blood supply. Carrying out a tension-free IPAA might prove difficult in a proportion of cases, especially if mucosectomy and hand-sewn anastomosis are necessary. The aim of the study was to analyse the outcomes of mesenteric lengthening in patients undergoing IPAA in a tertiary centre. Consecutive patients who required mesenteric lengthening during IPAA surgery between 2000 and 2019 were retrospectively included. Short and long-term outcomes were analyzed. Chi square, Fisher’s exact test and Wilcoxon rank sum test were used as appropriate. Kaplan–Meier analysis was carried out to report the long-term rate of pouch failure. Some 131 patients (78 UC, three indeterminate colitis, 50 FAP) were included. The need for mesenteric lengthening, due to short mesentery or intraoperative complications, was unpredictable in 15 patients. The rate of surgical complications was 20.6%; eight patients required a reoperation, two of them experienced postoperative pouch ischemia. After a median follow-up time of 9.4 years, the risk of pouch failure in FAP and UC patients was 7.2% and 13% at 10 years. Despite the indication to mucosectomy has been reducing over the years, mesenteric lengthening is still required in a significant proportion of UC and FAP patients, also because of unforeseeable intraoperative conditions necessities

Study on NGF and VEGF during the Equine Perinatal Period—Part 1: Healthy Foals Born from Normal Pregnancy and Parturition

The importance of trophic factors, such as nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) during the perinatal period, is now emerging. Through their functional activities of neurogenesis and angiogenesis, they play a key role in the final maturation of the nervous and vascular systems. The present study aims to: (i) evaluate the NGF and VEGF levels obtained at parturition from the mare, foal and umbilical cord vein plasma, as well as in amniotic fluid; (ii) evaluate NGF and VEGF content in the plasma of healthy foals during the first 72 h of life (T0, T24 and T72); (iii) evaluate NGF and VEGF levels at parturition in relation to the selected mares’ and foals’ clinical parameters; (iv) evaluate the relationship between the two trophic factors and the thyroid hormone levels (TT3 and TT4) in the first 72 h of life; (v) assess mRNA expression of NGF, VEGF and BDNF and their cell surface receptors in the placenta. Fourteen Standardbred healthy foals born from mares with normal pregnancies and parturitions were included in the study. The dosage of NGF and VEGF levels was performed using commercial ELISA kits, whereas NGF, VEGF and BDNF placental gene expression was performed using semi-quantitative real-time PCR. In foal plasma, both NGF and VEGF levels decreased significantly over time, from T0 to T24 (p = 0.0066 for NGF; p p = 0.0179 for NGF; p = 0.0016 for VEGF). In foal serum, TT3 levels increased significantly over time from T0 to T24 (p = 0.0058) and from T0 to T72 (p = 0.0013), whereas TT4 levels decreased significantly over time from T0 to T24 (p = 0.0201) and from T0 to T72 (p p = 0.0115; r = 0.2862). A positive correlation was found between NGF levels in the foal plasma at T0 and lactate (p = 0.0359; r = 0.5634) as well as between VEGF levels in the foal plasma at T0 and creatine kinase (p = 0.0459; r = 0.5407). VEGF was expressed in all fetal membranes, whereas NGF and its receptors were not expressed in the amnion. The close relationship between the two trophic factors in foal plasma over time and their fine expression in placental tissues appear to be key regulators of fetal development and adaptation to extra-uterine life

Study on NGF and VEGF during the Equine Perinatal Period—Part 2: Foals Affected by Neonatal Encephalopathy

Neonatal Encephalopathy (NE) may be caused by hypoxic ischemic insults or inflammatory insults and modified by innate protective or excitatory mechanisms. Understanding the underlying pathophysiology is important in formulating a rational approach to diagnosis. The preliminary aim was to clinically characterize a population of foals spontaneously affected by NE. The study aimed to: (i) evaluate nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) levels in plasma samples obtained in the affected population at parturition from the mare’s jugular vein, umbilical cord vein and foal’s jugular vein, as well as in amniotic fluid; (ii) evaluate the NGF and VEGF content in the plasma of foals affected by NE during the first 72 h of life/hospitalization; (iii) evaluate NGF and VEGF levels at birth/admission in relation to selected mare’s and foal’s clinical parameters; (iv) evaluate the relationship between the two trophic factors and thyroid hormone levels (TT3 and TT4) in the first 72 h of life/hospitalization; and (v) assess the mRNA expression of NGF, VEGF and brain-derived neurotrophic factor (BDNF), and their cell surface receptors, in the placenta of mares that delivered foals affected by NE. Thirteen affected foals born from mares hospitalized for peripartum monitoring (group NE) and twenty affected foals hospitalized after birth (group exNE) were included in the study. Dosage of NGF and VEGF levels was performed using commercial ELISA kits, whereas NGF, VEGF, and BDNF placental gene expression was performed using a semi-quantitative real-time PCR. In group NE, NGF levels decreased significantly from T0 to T24 (p = 0.0447) and VEGF levels decreased significantly from T0 to T72 (p = 0.0234), whereas in group exNE, only NGF levels decreased significantly from T0 to T24 (p = 0.0304). Compared to healthy foals, a significant reduction of TT3 levels was observed in both NE (T24, p = 0.0066; T72 p = 0.0003) and exNE (T0, p = 0.0082; T24, p < 0.0001; T72, p < 0.0001) groups, whereas a significant reduction of TT4 levels was observed only in exNE group (T0, p = 0.0003; T24, p = 0.0010; T72, p = 0.0110). In group NE, NGF levels were positively correlated with both TT3 (p = 0.0475; r = 0.3424) and TT4 levels (p = 0.0063; r = 0.4589). In the placenta, a reduced expression of NGF in the allantois (p = 0.0033) and a reduced expression of BDNF in the amnion (p = 0.0498) were observed. The less pronounced decrease of the two trophic factors compared to healthy foals, their relationship with thyroid hormones over time, and the reduced expression of NGF and BDNF in placental tissues of mares that delivered affected foals, could be key regulators in the mechanisms of equine NE

Integrated stratigraphy of the Smirra Core (Umbria-Marche Basin, Apennines, Italy) : A new early Paleogene reference section and implications for the geologic time scale

Pelagic sections of the Umbria-Marche Basin, in the Northern Apennines (Italy), have provided key geological archives for studying critical intervals of early Paleogene time. In addition to classical sections, the Smirra Coring project provides a new record of relatively undisturbed sediments (~ 120 m from 4 overlapping holes) of the upper Scaglia Formation (Paleocene – middle Eocene). Here we present a new high-resolution integrated magneto-bio-stratigraphy of the ~ 93-m composite section drilled in Smirra Holes 1 and 2. The correlation of the magnetostratigraphy to published geomagnetic polarity timescales (GPTSs; CK95, GPTS2004, GPTS2012), as constrained by calcareous nannofossil biostratigraphy, reveals that the cores range from Chron C26r to C21n (Thanetian – Lutetian; ~ 60 to ~ 46 Ma). Sedimentation rates range from ~ 0.6 to ~ 1 cm/kyr and are comparable with those from coeval sections in the Umbria-Marche Basin. They point to significant discrepancies between existing time scales, which mainly involve the duration of Chron C23 and subchrons within C23n and C24n. Application of the average spectral misfit method on the magnetic susceptibility record reveals a strong signature of orbital forcing and allows an independent estimate of the sedimentation rates. This analysis offers additional insights into solving time scale issues, which mainly concern the duration of Chron C23n. Our results imply a significantly longer duration for C23n.2n, which would accommodate the presence of an extra third 405-kyr eccentricity related cycle in C23n. The Smirra record thus provides new constraints on the early Paleogene time scale, a key record for further cyclostratigraphic and astrochronological research, and a reference framework for paleo-climatic and -oceanographic studies

Integrated stratigraphy of the Smirra Core (Umbria-Marche Basin, Apennines, Italy): A new early Paleogene reference section and implications for the geologic time scale

Pelagic sections of the Umbria-Marche Basin, in the Northern Apennines (Italy), have provided key geological archives for studying critical intervals of early Paleogene time. In addition to classical sections, the Smirra Coring project provides a new record of relatively undisturbed sediments (~120 m from 4 overlapping holes) of the upper Scaglia Formation (Paleocene – middle Eocene). Here we present a new high-resolution integrated magneto-bio-stratigraphy of the ~93-m composite section drilled in Smirra Holes 1 and 2. The correlation of the magnetostratigraphy to published geomagnetic polarity timescales (GPTSs; CK95, GPTS2004, GPTS2012), as constrained by calcareous nannofossil biostratigraphy, reveals that the cores range from Chron C26r to C21n (Thanetian – Lutetian; ~60 to ~46 Ma). Sedimentation rates range from ~0.6 to ~1 cm/kyr and are com- parable with those from coeval sections in the Umbria-Marche Basin. They point to significant discrepancies between existing time scales, which mainly involve the duration of Chron C23 and subchrons within C23n and C24n. Application of the average spectral misfit method on the magnetic susceptibility record reveals a strong signature of orbital forcing and allows an independent estimate of the sedimentation rates. This analysis offers additional insights into solving time scale issues, which mainly concern the duration of Chron C23n. Our results imply a significantly longer duration for C23n.2n, which would accommodate the presence of an extra third 405- kyr eccentricity related cycle in C23n. The Smirra record thus provides new constraints on the early Paleogene time scale, a key record for further cyclostratigraphic and astrochronological research, and a reference frame- work for paleo-climatic and -oceanographic studies

Integrated stratigraphy of the Smirra Core (Umbria-Marche Basin, Apennines, Italy): A new early Paleogene reference section and implications for the geologic time scale

Pelagic sections of the Umbria-Marche Basin, in the Northern Apennines (Italy), have provided key geological archives for studying critical intervals of early Paleogene time. In addition to classical sections, the Smirra Coring project provides a new record of relatively undisturbed sediments (~ 120 m from 4 overlapping holes) of the upper Scaglia Formation (Paleocene – middle Eocene). Here we present a new high-resolution integrated magneto-bio-stratigraphy of the ~ 93-m composite section drilled in Smirra Holes 1 and 2. The correlation of the magnetostratigraphy to published geomagnetic polarity timescales (GPTSs; CK95, GPTS2004, GPTS2012), as constrained by calcareous nannofossil biostratigraphy, reveals that the cores range from Chron C26r to C21n (Thanetian – Lutetian; ~ 60 to ~ 46 Ma). Sedimentation rates range from ~ 0.6 to ~ 1 cm/kyr and are comparable with those from coeval sections in the Umbria-Marche Basin. They point to significant discrepancies between existing time scales, which mainly involve the duration of Chron C23 and subchrons within C23n and C24n. Application of the average spectral misfit method on the magnetic susceptibility record reveals a strong signature of orbital forcing and allows an independent estimate of the sedimentation rates. This analysis offers additional insights into solving time scale issues, which mainly concern the duration of Chron C23n. Our results imply a significantly longer duration for C23n.2n, which would accommodate the presence of an extra third 405-kyr eccentricity related cycle in C23n. The Smirra record thus provides new constraints on the early Paleogene time scale, a key record for further cyclostratigraphic and astrochronological research, and a reference framework for paleo-climatic and -oceanographic studies

A 9 million-year-long astrochronological record of the early- middle Eocene corroborated by seafloor spreading rates

The early-middle Eocene (ca. 56-41 Ma) is recorded in the pelagic Scaglia Rossa and Variegata Formations of the Umbria-Marche Basin (central Italy). Geochemical and magnetostratigraphic alignment between the Bottaccione section (Gubbio, central Italy) and the Smirra core (Cagli, central Italy) allows us to generate a continuous and wellpreserved new record that, combined with previously published data from the same area, creates a continuous high-resolution record from the Paleocene-Eocene thermal maximum (ca. 56 Ma) to the lower part of chron C21n. Comparison with carbon isotope records from Ocean Drilling Program Sites 1258 and 1263 reveals a satisfactory match, providing further evidence of the global significance of the long-term trend and superposed perturbations captured by the δ13C records. The identification of astronomically forced geochemical cycles allows us to develop a 405 k.y. tuned age model, thereby extending the astrochronology from ca. 56.0 to ca. 47.5 Ma. Marine magnetic anomaly profiles from major oceanic basins characterized by high seafloor spreading rates were used to independently test the astronomical polarity time scale associated with our tuning, as well as other polarity time scales. Our age model suggests the existence of periods of relatively constant seafloor spreading rates separated by rapid changes, while the other time scales generate more gradual variations and also include large and short-term deviations in spreading rates that occur simultaneously in different oceanic basins, implying errors in polarity reversal ages. The Umbria- Marche age model further contributes to the closure of the middle Eocene gap in the astronomical time scale

Detection and Molecular Characterization of Canine Distemper Virus in Wildlife from Northern Italy

Canine distemper virus (CDV) is a fatal, highly contagious disease found in wild and domestic carnivores. Several outbreaks have occurred in wildlife in Italy in recent years. This study aims to detect CDV in wildlife following the increasing mortality of foxes (Vulpes vulpes) in the Emilia-Romagna region (northern Italy) observed in 2021. Sixty-seven foxes and one badger (Meles meles) were subjected to necropsy followed by histological examination and were analyzed with molecular techniques to detect the presence of CDV. Of the tested animals, 16% (nine foxes and one badger) were positive for CDV. Phylogenetic analysis showed two different lineages based on complete H gene sequences. The Europe/South America-1 lineage was detected in one fox from Modena, which resembled the CDV variant associated with a previous outbreak in northern Italy in 2018, while the European Wildlife lineage was detected in animals from the Rimini province. Amino acid analysis highlighted a Y549H mutation in all sequences collected, which is commonly associated with increased virulence