5 research outputs found
Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni.
- Author
- Publication venue
- Publication date
- 02/04/2021
- Field of study
Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure-activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics
Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.
- Author
- Aamir A
- Abbas J
- Abbas N
- Abbott TEF
- Abdalla M
- Abdikadir H
- Abuhussein N
- Acquaah F
- Adamson R
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- STARSurg Collaborative Writing Committee, Data analysis, Steering committee, Advisory group, Regional leads, Collaborators and validators
- STARSurg Collaborative Writing Committee, Data analysis, Steering committee, Advisory group, Regional leads, Collaborators and validators, Nepogodiev, D
- Stechman M
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- Publication venue
- 'Wiley'
- Publication date
- 18/05/2018
- Field of study
Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability
Safety of Nonsteroidal Anti-inflammatory Drugs in Major Gastrointestinal Surgery: A Prospective, Multicenter Cohort Study
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2017
- Field of study
Background
Significant safety concerns remain surrounding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) following gastrointestinal surgery, leading to wide variation in their use. This study aimed to determine the safety profile of NSAIDs after major gastrointestinal surgery.
Methods
Consecutive patients undergoing elective or emergency abdominal surgery with a minimum one-night stay during a 3-month study period were eligible for inclusion. The administration of any NSAID within 3 days following surgery was the main independent variable. The primary outcome measure was the 30-day postoperative major complication rate, as defined by the Clavien–Dindo classification (Clavien–Dindo III–V). Propensity matching with multivariable logistic regression was used to produce odds ratios (OR) and 95 % confidence intervals.
Results
From 9264 patients, 23.9 % (n = 2212) received postoperative NSAIDs. The overall major complication rate was 11.5 % (n = 1067). Following propensity matching and adjustment, use of NSAIDs were not significantly associated with any increase in major complications (OR 0.90, 0.60–1.34, p = 0.560).
Conclusions
Early use of postoperative NSAIDs was not associated with an increase in major complications following gastrointestinal surgery
Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis
- Author
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- Goldsmith T
- Gommers J
- Gonzalez Arribas M
- Gonzalez de Chaves Pe
- Gonzalez Ruiz Aa
- Gonzalez-Argente Xf
- Gonzalez-Martinez A
- González-Crespo A
- Goodier R
- Gooiker Ga
- Gooszen Jah
- Goradia H
- Gorguner F
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- Guerra F
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- Gunaydin Y
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- Heminway R
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- Hidding E
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- Hill A
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- Hindle Fisher I
- Hirani S
- Hirst F
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- Hogendoorn W
- Holliday Rbs
- Holloway C
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- Hourston Gjm
- Howard James N
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- Hughes Ba
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- Huseynova S
- Husnoo Sb
- Hussain N
- Hussain O
- Hutchings I
- Huzmeli E
- Ibrahim A
- Ibrahim I
- Ilbak A
- Inci Et
- Ingham R
- Ingram E
- Innocenti P
- Iorga R
- Iqbal A
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- Isaac A
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- Jimenez-Gomez Lm
- Jimenez-Segovia M
- Jiménez-Morillas P
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- Karabulut E
- Karahan B
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- Kennedy Ed
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- Kerimova N
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- Khaing Ph
- Khajuria A
- Khalid H
- Khan A
- Khan I
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- Klinkert M
- Kloppenberg Fwh
- Knight Cl
- Kobal Bb
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- Kucukdiler E
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- Lakshmipathy G
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- Laterza V
- Latras-Cortés I
- Laurino A
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- Leafe O
- Ledsam A
- Lee Ahy
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- Leung W
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- Li Mm
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- Lucas de Carvalho J
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- Lujan Mompean Ja
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- Lynne S
- Lyons A
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- López-Mármol R
- López-Vendrell L
- Löwensteyn Yn
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- Mariani F
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- Martinez Rios Ce
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- Martí Fernández Rm
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- Naqib S
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- Narwani V
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- Nehikhare I
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- Neophytou C
- Nepogodiev D
- Nesargikar Pn
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- O'Neill Em
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- Ozgencil B
- Ozmen Bb
- Ozsipahi Ac
- Padilla Valverde D
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- Palanivail N
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- Palos Campos Mc
- Palyzová H
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- Pando Ruiz B
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- Paolo G
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- Petrov G
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- Pietrabissa A
- Pike G
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- Piran G
- Pistola I
- Pitts-Tucker T
- Pizzolato A
- Pla Seró S
- Player C
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- Prakash E
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- Prieto-Nieto Mi
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- Pulpito S
- Punj R
- Punjabi N
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- Radotra A
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- Raghuvir V
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- Raina V
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- Raman Kp
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- Ramsay N
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- Raut P
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- Realis Luc A
- Redgrave Na
- Redmond A
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- Reid Kg
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- Ridgway P
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- Ruiz Montesinos I
- Ruiz Em
- Russell G
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- Sabine Lm
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- Sagmeister M
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- Sahin A
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- Sakman G
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- Sanders Ja
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- Sapci I
- Saraceno F
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- Sgrò A
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- Shakweh E
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- Shanahan D
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- Shatkar V
- Shaunak R
- Sheikh Imi
- Sheldon A
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- Shoa M
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- Shumon S
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- Siddiqui Zh
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- Sitta O
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- Skalamera I
- Slade R
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- Smolák P
- Sng S
- Soldevila-Verdeguer C
- Soo Yh
- Soon Wc
- Sorah T
- Soria Aledo V
- Sotona O
- Soylemez Zobb
- Sozuer Em
- Spence O
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- Spijkerman R
- Springford Lr
- Sproule L
- Sreh A
- Srikantharajah M
- Sritharan P
- Staderini F
- Stanger Sa
- Stanley Gh
- Stanley S
- Stassen Lps
- Stather Pw
- Steccanella F
- Stechman M
- Steel M
- Stein J
- Stellingwerf Me
- Steup Wh
- Stevens S
- Stewart Ge
- Stezaker S
- Stijns Rch
- Stoddart Mt
- Stokes S
- Stone Ej
- Stott Gd
- Strange E
- Street An
- Subasi A
- Sukkari M
- Sukumar S
- Suleman Yn
- Sullivan Jal
- Sun E
- Sundar-Singh M
- Suppa A
- Suresh Rs
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- Syeed Ja
- Sykes Mc
- Szczap A
- Sánchez Estébanez E
- Sánchez-Blasco L
- Tagariello F
- Tahir M
- Tahmina A
- Tai A
- Talukdar Ss
- Tan D
- Tan Esm
- Tan Et
- Tan R
- Tan S
- Tan Y
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- Tansoker I
- Tarantino M
- Targa S
- Taskin O
- Taskin Rb
- Tavuz Ai
- Tay Ay
- Tayeh S
- Taylor F
- Taşçı Y
- Tear Ak
- Teh Jw
- Teixeira da Silva M
- Tejero Pintor Fj
- Telfer R
- Temiz C
- Teng V
- Teoh Pj
- Ter Bruggen Ffja
- Ter Horst L
- Ter Weele K
- Thacoor A
- Thakker Ce
- Thakur H
- Tharakan Rg
- Tharmachandirar T
- Theodoreson Md
- Theodoropoulou K
- Thethi R
- Thevathasan Aa
- Thirumal V
- Thomas D
- Thomas G
- Thomas-Davies M
- Thompson Jd
- Thompson Od
- Tiedt L
- Tilston Tw
- Tippins F
- Tirnaksiz Mb
- Toale C
- Tognolo L
- Toh C
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- Tongo F
- Tonkins M
- Toorenvliet Br
- Topal U
- Topalan K
- Topham C
- Torlot Ge
- Torrance Hd
- Tosun V
- Toto Of
- Trail M
- Traynor Bp
- Trecarten S
- Trimble A
- Trist Aj
- Troia A
- Trompetto M
- Truma A
- Truss A
- Tsui Ay
- Tulum H
- Tung L
- Turaga S
- Turati L
- Turkmen M
- Turley H
- Turnbull Ja
- Turner Ejh
- Turner J
- Turner L
- Turner M
- Turpan M
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- Ucar E
- Uctepe F
- Uittenbogaart M
- Ulkucu A
- Ulusahin M
- Unal Ag
- Ungcharoen N
- Uppal E
- Urquhart A
- Uzun B
- Uzun O
- Uzun S
- Uzunoglu Ec
- Vable T
- Valderrama Pérez A
- Valli A
- Vallve-Bernal M
- Van Bruggen D
- van Dalen Ashm
- van de Ven Awh
- van der Harst E
- van der Hoeven Ac
- Van der Lubbe M
- van der Pool Aem
- van der Zee C
- Van Dijck Wpm
- van Elst Tr
- van Engelenburg T
- van Geloven A
- Van Grevenstein Wmu
- Van Heumen Tm
- van Leeuwen Bl
- van Rijckevorsel Vajim
- van Steensel L
- Van Tol Rr
- van Verschuer Vmt
- van Wijnbergen Jwm
- Vanmali P
- Varley R
- Varma D
- Varma N
- Varma Rk
- Varo Muñoz A
- Vasko P
- Vasquez G
- Vaughan R
- Vazquez-Gonzalez I
- Veenker Cgh
- Vela Polanco Ff
- Vendramin E
- Venn M
- Ventre Cm
- Venturini S
- Verardi L
- Verboeket B
- Verma K
- Verma S
- Vermaas M
- Vernon Ok
- Villarejo Campos P
- Vinci A
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- Yilmaz M
- Yilmaz S
- Yilmaz T
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- Yoganathan S
- Yong Cs
- Yong N
- Yoruk I
- Yousif A
- Yow L
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- Yuksel A
- Yurdaor Ss
- Yurekli Am
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- Zimmerman D
- Ziprin P
- Zope S
- Zuhair M
- Örhalmi J
- Özkan Bb
- Šimáčková B
- Široká M
- Žebrák R
- Publication venue
- 'Wiley'
- Publication date
- 01/01/2018
- Field of study
Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien\u2013Dindo Grades III\u2013V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49\u20132.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46\u20130.75, P < 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease
Body mass index and complications following major gastrointestinal surgery: a prospective, international cohort study and meta-analysis.
- Author
- 6rhalmi J
- 6zkan Bb
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- Kleine E
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- Poelman M
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- Prabhudesai A
- Prado Perez R
- Prakash E
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- Qamar Ma
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- Rabinthiran S
- Radotra A
- Rafiq Nm
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- Raimondi P
- Raina V
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- Raji K
- Rakhimov I
- Raman Kp
- Ramana A
- Ramjeeawon N
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- Rampulla V
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- Randisi B
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- Ratnakumaran R
- Rattan G
- Ratu Sg
- Raurich-Leandro J
- Raut P
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- Redmond A
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- Reehal Rs
- Rees C
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- Reid Nb
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- Rejayee M
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- Riva M
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- Romeo F
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- Roura J
- Roy Csd
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- Ruiz Montesinos I
- Ruiz Em
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- Ryan M
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- Sandhu S
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- Secilmis E
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- Seedat M
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- Semiz A
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- Shahidi S
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- Shanahan D
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- Sheikh Imi
- Sheldon A
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- Shepherd R
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- Shoa M
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- Shuker Ba
- Shukla A
- Shumon S
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- Sng S
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- Soo Yh
- Soon Wc
- Sorah T
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- Soylemez Zobb
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- Stoddart Mt
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- Sukkari M
- Sukumar S
- Suleman Yn
- Sullivan Jal
- Sun E
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- Suppa A
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- Suresh S
- Syeed Ja
- Sykes Mc
- Szczap A
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- Tan Y
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- Tavuz Ai
- Tay Ay
- Tayeh S
- Taylor F
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- Tejero Pintor Fj
- Telfer R
- Temiz C
- Teng V
- Teoh Pj
- Ter Bruggen Ffja
- Ter Horst L
- Ter Weele K
- Thacoor A
- Thakker Ce
- Thakur H
- Tharakan Rg
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- Theodoreson Md
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- Thethi R
- Thevathasan Aa
- Thirumal V
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- Thomas G
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- Thompson Jd
- Thompson Od
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- Tirnaksiz Mb
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- Toh C
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- Tonkins M
- Toorenvliet Br
- Topal U
- Topalan K
- Topham C
- Torlot Ge
- Torrance Hd
- Tosun V
- Toto Of
- Trail M
- Traynor Bp
- Trecarten S
- Trimble A
- Trist Aj
- Troia A
- Trompetto M
- Truma A
- Truss A
- Tsui Ay
- Tulum H
- Tung L
- Turaga S
- Turati L
- Turkmen M
- Turley H
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- Turner Ejh
- Turner J
- Turner L
- Turner M
- Turpan M
- Tutam Dn
- Ucar E
- Uctepe F
- Uittenbogaart M
- Ulkucu A
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- Unal Ag
- Ungcharoen N
- Uppal E
- Urquhart A
- Uzun B
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- Uzunoglu Ec
- Vable T
- Valderrama P\ue9rez A
- Valli A
- Vallve-Bernal M
- Van Bruggen D
- van Dalen Ashm
- van de Ven Awh
- van der Harst E
- van der Hoeven Ac
- Van der Lubbe M
- van der Pool Aem
- van der Zee C
- Van Dijck Wpm
- van Elst Tr
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- van Geloven A
- Van Grevenstein Wmu
- Van Heumen Tm
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- van Steensel L
- Van Tol Rr
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- van Wijnbergen Jwm
- Vanmali P
- Varley R
- Varma D
- Varma N
- Varma Rk
- Varo Mu\uf1oz A
- Vasko P
- Vasquez G
- Vaughan R
- Vazquez-Gonzalez I
- Veenker Cgh
- Vela Polanco Ff
- Vendramin E
- Venn M
- Ventre Cm
- Venturini S
- Verardi L
- Verboeket B
- Verma K
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- Vermaas M
- Vernon Ok
- Vi\uf1as-Salas J
- Villarejo Campos P
- Vinci A
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- Wiezer R
- Wijesekera M
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- Wing Vc
- Wingfield Lr
- Winslow F
- Woin E
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- Wong V
- Wood Ad
- Woodcock N
- Woodward H
- Woon E
- Wright A
- Wright Ev
- Wye J
- Wylam D
- Wylie J
- Wynell-Mayow Wm
- Xiao C
- Xu Gx
- Xylas D
- Y\u131gman S
- Yalcin Y
- Yaman S
- Yan A
- Yang T
- Yasar C
- Yates Ja
- Yauw S
- Yavuz G
- Yazkan Z
- Yekenkurul E
- Yener A
- Yeoh Tsl
- Yetiskin E
- Yildirim N
- Yildirim R
- Yildiz S
- Yildiz Ss
- Yildiz T
- Yilmaz I
- Yilmaz M
- Yilmaz S
- Yilmaz T
- Yim N
- Yoganathan S
- Yong Cs
- Yong N
- Yoruk I
- Yousif A
- Yow L
- Yuen R
- Yuksek B
- Yuksek Ma
- Yuksel A
- Yurdaor Ss
- Yurekli Am
- Zaidi R
- Zegeye Mi
- Zengin T
- Zhang Aa
- Zhao J
- Ziff O
- Zigiotto D
- Zijlmans Jl
- Zimmerman D
- Ziprin P
- Zope S
- Zuhair M
- Publication venue
- 'Wiley'
- Publication date
- 01/01/2018
- Field of study
AIM:
Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a meta-analysis of all available prospective data.
METHODS:
This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien-Dindo Grades III-V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results.
RESULTS:
This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery for malignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49-2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46-0.75, P < 0.001) compared to normal weight patients.
CONCLUSIONS:
In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease