Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Bis(μ-iodo)-tetrakis(O-methyl N-phenylthiocarbamate)-tetraiodo-dibismuth

International audienceIn order to investigate the coordination chemistry of O-alkyl N-aryl thiocarbamate ligands, BiI3 was reacted with two equivalents of MeOC(=S)N(H)Ph in MeCN solution to afford the dinuclear title compound complexes [{I2Bi(μ2-I)2BiI2}{κ1-MeOC(=S)N(H)Ph}4] 1. Compound 1 was characterized by IR, UV and NMR spectroscopy, the formation of a dinuclear framework is ascertained by a single-crystal X-ray diffraction study performed at 100 K

Bis(µ-iodo)-tetrakis(O-methyl N-phenylthiocarbamate)-tetraiodo-dibismuth, the first example of a Bi(III) thiocarbamate compound

International audienceIn order to investigate the coordination chemistry of O-alkyl N-aryl thiocarbamate ligands, BiI3 was reacted with two equivalents of MeOC(=S)N(H)Ph L in MeCN solution to afford the dinuclear title compound complexes [{I2Bi(µ2-I)2BiI2} {κ1-MeOC(=S)N(H)Ph}4] C1.Compound C1 was characterized by IR, UV and NMR spectroscopy, the formation of a dinuclear framework is ascertained by a single-crystal X-ray diffraction study performed at 100 K

Bis(µ-iodo)-tetrakis(O-methyl N-phenylthiocarbamate)-tetraiodo-dibismuth, the first example of a Bi(III) thiocarbamate compound

International audienceIn order to investigate the coordination chemistry of O-alkyl N-aryl thiocarbamate ligands, BiI3 was reacted with two equivalents of MeOC(=S)N(H)Ph L in MeCN solution to afford the dinuclear title compound complexes [{I2Bi(µ2-I)2BiI2} {κ1-MeOC(=S)N(H)Ph}4] C1.Compound C1 was characterized by IR, UV and NMR spectroscopy, the formation of a dinuclear framework is ascertained by a single-crystal X-ray diffraction study performed at 100 K

Synthesis of Catena-bis(μ-bromo)-(<i>O</i>-methyl-<i>N</i>-phenylthiocarbamate)-dicopper(I) and Its Reactivity towards PAr₃ (Ar = Ph, <i>p</i>-Tol)

In order to investigate the coordination chemistry of O-alkyl N-aryl thiocarbamate ligands toward coinage metals, CuBr was reacted with one equivalent of MeOC(=S)N(H)Ph L in MeCN solution to afford the 1D-polymeric title compound [{Cu(μ2-Br)2Cu}{μ2-MeOC(=S)N(H)Ph}2]n CP1. Compound 1 was characterized by IR spectroscopy and an elemental analysis. The formation of a polymeric 1D ribbon built upon μ2-bridging bromido and thione ligands via the C=S bond was ascertained by a single-crystal X-ray diffraction study performed at 100 K. In the presence of PAr3 (Ar = Ph, p-Tol), the polymer chain was broken to yield the mononuclear complexes [(Ar3P)2Cu{MeOC(=S)N(H)Ph}Br] C1 and C2

Synthesis and crystallographic characterization of the coordination polymers [{Cu(µ2-I)2Cu}(µ2-ROC(=S)N(H)Ph)2]n (R = Me, Et)

International audienceOver the years, serval metal complexes of thiocarbamates have been reported to play a significant role in the field of organometallics, which extend their application to the medicinal and pharmaceutical fields. As a subclass, the group of Tiekink has been recently reported a new method of synthesis mononuclear complexes [(Ph3P)2Cu{ROC(=S)N(H)Ph}Cl] , which could be beneficial in the development of future pharmocological compounds. In continuation of that previous work, we were intrigued to study the reactivity of L (R= Me, L1;R= Et; L2) with CuI inMeCN solution. The characterization of both crystal of[{Cu(μ2 -I) 2 Cu}(μ2 -L)2]n CP1 and CP2 by X-ray diffraction analyses at 100 K confirmed that the formation of coordination Polymers precedes the precedes the complexation by PPh3 . The molecular structures of CP1 and CP2 show that the unidimensional ribbon of CP1 and CP2 are interconnected through acentrosymmetricrhomboid-shaped {Cu(μ2 -I)2Cu} units and through bridging L molecules

Synthesis, crystal structures and Hirshfeld analyses of phosphonothioamidates (EtO) 2 P(=O)C(=S)N(H)R (R = Cy, Bz) and their coordination on CuI and HgX 2 (X = Br, I)

International audienceThe phosphonothioamidates (EtO)2P(=O)C(=S)N(H)R (L1 R = Cy; L2 R = Bz) have been prepared by nucleophilic addition of K[(EtO)2P(=O)] to R–N = C=S and crystallographically analyzed. Both compounds are associated pairwise through strong intermolecular N–H···O bonding giving rise to 10-membered supramolecular macrocycles. This intermolecular bonding has also been studied by Hirshfeld analysis of L1 and L2. Complexation of L on CuI in MeCN solution affords the dinuclear rhomboid-shaped thione complexes [{Cu(μ2-I)2Cu}(η1-L)2] (1a,b). Crystallographic characterization of 1a reveals that L1 is ligated exclusively via the thione function to the trigonal Cu(I) centers, which are interconnected through a short Cu–Cu bond of 2.6207(4) Å. In the solid state, individual dimeric complexes are associated through intermolecular N–H···O bonding generating a supramolecular 1D ribbon. The dinuclear complexes [{XHg(μ2-X)2HgX}(η1-L)2] (2a X = Br, L = Cy; 2b X = Br, L = Bz; 2c X = I, L = Bz) were formed by stoichiometric addition of L to HgX2. The molecular structures of 2b and 2c have been elucidated by X-ray diffraction studies, which show that individual complexes are connected through intermolecular N–H···O bonding generating a supramolecular 1D ribbon. Treatment of L1 with two equivalents of HgBr2 produces the tetranuclear compound [Hg4Br8(κ1-L1)2] 3, whose unusual bromide-bridged architecture has been elucidated by X-ray crystallography

Synthesis and crystallographic characterization of the coordination polymers [{Cu(µ2-I)2Cu}(µ2-ROC(=S)N(H)Ph)2]n (R = Me, Et)

International audienceOver the years, serval metal complexes of thiocarbamates have been reported to play a significant role in the field of organometallics, which extend their application to the medicinal and pharmaceutical fields. As a subclass, the group of Tiekink has been recently reported a new method of synthesis mononuclear complexes [(Ph3P)2Cu{ROC(=S)N(H)Ph}Cl] , which could be beneficial in the development of future pharmocological compounds. In continuation of that previous work, we were intrigued to study the reactivity of L (R= Me, L1;R= Et; L2) with CuI inMeCN solution. The characterization of both crystal of[{Cu(μ2 -I) 2 Cu}(μ2 -L)2]n CP1 and CP2 by X-ray diffraction analyses at 100 K confirmed that the formation of coordination Polymers precedes the precedes the complexation by PPh3 . The molecular structures of CP1 and CP2 show that the unidimensional ribbon of CP1 and CP2 are interconnected through acentrosymmetricrhomboid-shaped {Cu(μ2 -I)2Cu} units and through bridging L molecules

Synthesis, crystal structures and biological activities of halogeno-(O-alkylphenylcarbamothioate)bis(triarylphosphine)copper(I) complexes

International audienceThe aim of this work was to synthesize and characterize a new series of copper(I) complexes with thiocarbamate ligands and to evaluate their biological activity. Treatment of CuX salts (X = Cl, Br, I) with O-alkyl N-phenylcarbamothioates in the presence of two equivalents of PAr3 (Ar = Ph, p-C6H4OMe) affords a series of mononuclear thione complexes [(Ar3P)2Cu{ROC(=S)N(H)Ph}X)] C1-C10. According to X-ray diffraction analyses, all complexes adopt a distorted tetrahedral geometry and feature intramolecular N-H···Hal bonding, giving rise to six-membered cycles. Like in the case of the literature-known chloro-compounds C1 and C2 (d(N-H···Cl) ∼ 2.29 Å), the bromo-derivatives exhibit C3-C6 strong N-H···Hal distances varying from 2.48 to 2.63 Å. This intramolecular bonding, which is weaker for the iodo complexes C7-C10 (∼ 2.75 Å), has also been studied by Hirshfeld surface analysis of C1, C3, C4 and C6. The crystal structure of two 1D-polymeric intermediates occurring during the synthesis of C7 and C9, namely [{Cu(μ2-I)2Cu}(μ2-L)2]n CP1 and CP2, has also been elucidated. The complexes display weak luminescence in solution centered on the triarylphosphine ligands. In contrast, in the solid state a high-energy band around 350-450 nm centered on the thioamidate and triarylphosphine ligands is observed, along with a second low energy band typical for MLCT/XLCT states around 450-550 nm. The screening of the biological activity of these complexes reveals the absence of any significant antibacterial capacity. However, the presence of an antioxidant activity with a maximum activity for complexes C3 and C4 has been evidenced using the colorimetric DDPH method. This has been probed in vivo on Wistar rats for the preservation of hepatocytes integrity after liver hypothermic conservation (4°C) for 24 hours in Krebs solution with normal cellular state by addition of [(Ph3P)2Cu{EtOC(=S)N(H)Ph}I] C8