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PhD in Veterinary Sciences for Animal Health and Food Safety

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Logo di PhD in Veterinary Sciences for Animal Health and Food Safety

Anna Cerullo

Contacts

Supervisor

Marco Gandini

Curriculum vitae

Curriculum Vitae

Phd thesis

Title

Evaluation of the efficiency of the honey-based devices in preventing and treating surgical site infections and in promoting the healing of incisional hernias in rat models.

Background
Surgical Site Infections(SSIs) are among the most common postoperative complications in both human 1,2 and veterinary medicine, 3,4 and can be associated with severe complications such as wound dehiscence or abdominal hernia following laparotomic wound infections. 5,6 Conventional treatments can be ineffective and expensive due to the presence of multidrug-resistant (MDR) bacteria.7-9 The use of medical honey has been reconsidered in recent years, primarily because no resistance has been reported. 10,11 However, the practicality of using liquid honey is often a concern. For this reason, the use of Pectin-Honey Hydrogels (PHHs) has been previously proposed. 12 PHHs could help reduce the use of antimicrobials during and after surgery, and, as a result, lower the risk of antibiotic resistance.


2. Specific aims of the project, Methods, Results
2.1 Part 1


The primary aim of the PhD project was to produce PHHs and evaluate their antimicrobial activity against a polymicrobial broth created using rat caecal content. In the 1 st year of my PhD project, I prepared the caecal slurry (CS), following previously described methods. 13-14 The antimicrobial activity of PHH against CS bacteria was then assessed, as previously reported. Briefly, the CS was divided into three aliquots (1ml each) and a buffer solution (14ml) was added to each aliquot. In the 1 st aliquot(A), PHH was added, while the 2 nd aliquot(B) without PHHs was used as a negative control. The 3 rd aliquot(C), included gentamicin sulfate and served as a positive control. The antibacterial effect (R) of PHH was determined after 24h by comparing CFU/ml in A and in B as R=100×(B-A)/B. When PHH was used, bacterial growth was reduced by 99.9%.


2.2 Part 2
The 2 nd aim of the PhD project was to assess the efficacy of PHHs in preventing the onset of SSIs in rats. During the 1 st semester of the 2 nd year, a total of 28 adult male Sprague-Dawley rats were randomly allocated to either the “treated”(T) or “control”(C) group. Under general anesthesia, a midline laparotomy was performed, and following closure of the linea alba, I contaminated the wounds with 100 μL of CS in both groups. A PHH was applied on the linea alba before the skin closure in Group T only. After euthanizing the rats 14 days after surgery, a blind assessment of the laparotomic wounds was conducted to check for the presence of SSI. Additionally, I obtained a sterile swab of the linea alba for bacterial culture, and a comparison was made using a X 2 test. The abdominal wall was harvested, fixed in 10% formalin, and assessed blindly at histopathology. A scoring system ranging from 1 to 3 was used to evaluate wound healing, and the results were compared using a Mann-Whitney test. Notably, no signs of SSI were detected in either group. Furthermore, there were no differences between the 2 groups in terms of microbiological (p=0.25) and histological evaluations (p>0.05).

2.3 Part 3


The third aim was to evaluate whether the use of PHH before skin closure improves the healing of abdominal hernias repaired with a polypropylene(PP) mesh in a contaminated field. The hypothesis was that the combination of PHH with PP mesh would reduce the incidence of
abdominal adhesions and SSI. In the 2 nd semester of the 2 nd year, a hernia model 15 was created in 20 rats, and these rats were randomly divided into the “treated”(T) and “control”(C) group. During hernia repair, a mixed bacterial culture (10 5 bacteria/ml) was applied to the wounds in both groups. Only in group T, a PHH was placed on PP mesh before skin closure. Macroscopic, microbiological, histological, and immunohistochemistry against COX-2 evaluations were conducted 15-17 and compared using a Mann-Whitney test. Adhesions were more severe(p=0.001) and extensive(p=0.002) in group C. No differences were observed in the bacteriological evaluation. Both groups displayed moderate to severe values for reparative and inflammatory reactions at histopathological levels. The use of PHH in conjunction with PP mesh reduced adhesion formation, extension, and severity compared to PP mesh alone.

3. Future development
Part 4
In the 3 rd year, horses undergoing clean-contaminated abdominal surgery will be included. At surgery, horses will be randomly assigned to the “treated”(T) or “control”(C) group. In Group T, PHH will be applied to the linea alba before skin closure. SSI in horses will be scored according to Biedrzycki et al. 18 It is expected that incidence and SSI score will be reduced in group T.

References:
1. Behera HS, Chayani N, Bal M, et al. Identification of population of bacteria from culture negative surgical site infection patients using molecular tool. BMC Surg. 2021;21(1):28. Published 2021 Jan 7. doi:10.1186/s12893-020-01016-y


2. Alkaaki A, Al-Radi OO, Khoja A, Alnawawi A, Alnawawi A, Maghrabi A, Altaf A, Aljiffry M. Surgical site infection following abdominal surgery: a prospective cohort study. Can J Surg. 2019 Apr 1;62(2):111-117. doi: 10.1503/cjs.004818. PMID: 30907567; PMCID: PMC6440888.


3. Follette CM, Giuffrida MA, Balsa IM, et al. A systematic review of criteria used to report complications in soft tissue and oncologic surgical clinical research studies in dogs and cats. Vet Surg. 2020;49(1):61-69. doi:10.1111/vsu.13279


4. Gandini M, Cerullo A, Giusto G. Scoping review: occurrence and definitions of postoperative complications in equine colic surgery [published online ahead of print, 2022 Oct 5]. Equine Vet J. 2022;10.1111/evj.13881. doi:10.1111/evj.13881


5. Walming S, Angenete E, Block M, Bock D, Gessler B, Haglind E. Retrospective review of risk factors for surgical wound dehiscence and incisional hernia. BMC Surg. 2017;17(1):19. Published 2017 Feb 22. doi:10.1186/s12893-017-0207-0


6. Mair TS, Smith LJ. Survival and complication rates in 300 horses undergoing surgical treatment of colic. Part 3: Long-term complications and survival. Equine Vet J. 2005;37(4):310-314. 


7. Dziubinski N, Mählmann K, Lübke-Becker A, Lischer C. Retrospective Identification of Bacterial Isolates From Emergency Laparotomy Surgical Site Infections in Horses. J Equine Vet Sci. 2020;87:102927. doi:10.1016/j.jevs.2020.102927


8. Foschi D, Yakushkina A, Cammarata F, et al. Surgical site infections caused by multi-drug resistant organisms: a case-control study in general surgery. Updates Surg. 2022;74(5):1763-1771. doi:10.1007/s13304-022-01243-3


9. Corsini, C. M. M; Silva, V. O; Carvalho, O. V; Sepúlveda, R. V; Valente, F. L; Reis, E. C. C; Moreira, M. A. S; Silva Júnior, A; Borges, A. P. B. Emergence of multidrug-resistant bacteria isolated from surgical site infection in dogs and cats. Arq. bras. med. vet. zootec;2020.72(4): 1213-1220.


10. Combarros-Fuertes P, Fresno JM, Estevinho MM, Sousa-Pimenta M, Tornadijo ME, Estevinho LM. Honey: Another Alternative in the Fight against Antibiotic-Resistant Bacteria?. Antibiotics (Basel). 2020;9(11):774.


11. Tramuta C, Nebbia P, Robino P, et al. Antibacterial activities of Manuka and Honeydew honey-based membranes against bacteria that cause wound infections in animals. Antibakterielle Aktivität von Membranen aus Manuka- und Honigtauhonig gegen Wundkeime
bei Tieren. Schweiz Arch Tierheilkd. 2017;159(2):117-121. 

12. Giusto G, Beretta G, Vercelli C, et al. Pectin-honey hydrogel: Characterization, antimicrobial activity and biocompatibility. Biomed Mater Eng. 2018;29(3):347-356. doi:10.3233/BME- 181730


13. Gupta V, Tyagi A. A rat model of polymicrobial infection in full-thickness excision wounds. J Tissue Viability. 2021;30(4):537-543.


14. Starr ME, Steele AM, Saito M, Hacker BJ, Evers BM, Saito H. A new cecal slurry preparation protocol with improved long-term reproducibility for animal models of sepsis. PLoS One. 2014;9(12):e115705. Published 2014 Dec 22. doi:10.1371/journal.pone.0115705


15. Anastasio, A.T.; Van Eps, J.L.; Fernandez-Moure, J.S. Surgical Technique for Development of a Clinically-Representative Ventral Hernia Repair Infection Rat Model. MethodsX 2020, 7,
100887.


16. Vercelli C, Re G, Iussich S, et al. In Vivo Evaluation of a Pectin-Honey Hydrogel Coating on
Polypropylene Mesh in a Rat Model of Acute Hernia. Gels. 2021;7(3):132. Published 2021 Aug
31. doi:10.3390/gels7030132


17. Pereira-Lucena, C.G.; Neto, R.A.; De Rezende, D.T.; Lopes-Filho, G.D.J.; Matos, D.; Linhares, M.M. Early and late postoperative inflammatory and collagen deposition responses in three different meshes: An experimental study in rats. Hernia 2013, 18, 563–570.


18. Biedrzycki AH, Brounts SH. Case series evaluating the use of absorbable staples compared with metallic staples in equine ventral midline incisions. Equine Vet Educ. 2016;28(2):83 -88.

Research activities

Publications

 

  1. Spadari A, Gialletti R, Gandini M, Valle E, Cerullo A, Cavallini D, Bertoletti A, Rinnovati R, Forni G, Scilimati N, Giusto G*. Short-Term Survival and Postoperative Complications Rates in Horses Undergoing Colic Surgery: A Multicentre Study. Animals (Basel). 2023 Mar 20;13(6):1107. doi: 10.3390/ani13061107. PMID: 36978647; PMCID: PMC10044551.

 

  1. Gandini M*, Cerullo A, Gallo L, Iussich S, Minoli L, Giusto G. Ex vivo evaluation of a technique for equine jejunocecal anastomosis using radiofrequency thermofusion and a Cushing oversew. Vet Surg. 2023 May;52(4):545-553. doi: 10.1111/vsu.13946. Epub 2023 Mar 15. PMID: 36922367.

 

  1. Cerullo A, Gandini M*, Giusto G. Occurrence and Definitions of Intra and Postoperative Complications Related to Laparoscopy in Equids: A Scoping Review. Vet Sci. 2022 Oct 17;9(10):577. doi: 10.3390/vetsci9100577. PMID: 36288190; PMCID: PMC9609183.

 

  1. Gandini M, Cerullo A, Franci P, Giusto G*. Changes in Perioperative Antimicrobial and Anti-Inflammatory Drugs Regimens for Colic Surgery in Horses: A Single Center Report. Vet Sci. 2022 Oct 4;9(10):546. doi: 10.3390/vetsci9100546. PMID: 36288159; PMCID: PMC9607452.

 

  1. Gandini M*, Cerullo A, Giusto G. Scoping review: Occurrence and definitions of postoperative complications in equine colic surgery. Equine Vet J. 2023 Jul;55(4):563-572. doi: 10.1111/evj.13881. Epub 2022 Oct 19. PMID: 36199160.

 

  1. Giusto G*, Cerullo A, Gandini M. Transillumination Techniques for Vessel Identification During Small Colon Resection in Six Horses. J Equine Vet Sci. 2022 Nov;118:104113. doi: 10.1016/j.jevs.2022.104113. Epub 2022 Aug 27. PMID: 36031032.

 

  1. Gialletti R, Nannarone S, Gandini M*, Cerullo A, Bertoletti A, Scilimati N, Giusto G. Comparison of Mesh and Barbed Suture for Laparoscopic Nephrosplenic Space Ablation in Horses. Animals (Basel). 2021 Apr 12;11(4):1096. doi: 10.3390/ani11041096. PMID: 33921312; PMCID: PMC8069580.

 

  1. Giusto G, Cerullo A, Labate F, Gandini M*. Incomplete Ileocecal Bypass for Ileal Pathology in Horses: 21 Cases (2012-2019). Animals (Basel). 2021 Feb 5;11(2):403. doi: 10.3390/ani11020403. PMID: 33562529; PMCID: PMC7915807.

 

  1. Giusto G, Cerullo A*, Gandini M. Gastric and Large Colon Impactions Combined With Aggressive Enteral Fluid Therapy May Predispose to Large Colon Volvulus: 4 Cases. J Equine Vet Sci. 2021 Jul;102:103617. doi: 10.1016/j.jevs.2021.103617. Epub 2021 Apr 18. PMID: 34119200.

 

  1. Giusto G*, Cerullo A, Gandini M. Surgical colic caused by fibrous bands and adhesions in absence of previous abdominal surgery: 9 cases (2012–2019). Equine Vet Educ. 2021 Jun;35(7):e293-e298. doi: 10.1111/eve.13487.

 

 

Conferences and Seminars

 

76° Convegno SISVET

[ Bari, 21/06/2023 – 23/06/2023 ]

 

  • Oral Presentation (Prof. G. Giusto)

Abdominal surgery under epidural anaesthesia in calves.

  1. Giusto*, C. Bellino, A. Cerullo, A. Ceppa, M. Gandini

 

  • Oral Presentation (Dr. M. Serpieri)

Injectable anesthetia with Ketamine, Medetomidine, and Butorphanol in rats.

  1. Serpieri*, A. Cerullo, G. Bonaffini, G. Quaranta, M. Mauthe von Degerfeld

 

28th SIVE International Congress

[ Venice, 03/02/2023 – 04/02/2023 ]

 

  • Poster

Incidenza e definizioni di complicazioni intra e postoperatorie associate alla laparoscopia negli equidi.

  1. Cerullo*, M. Gandini, G. Giusto.

 

  • Poster

Effects of low postoperative total plasma protein on outcome and short-term complications in horses undergoing surgery for small intestinal lesions.

  1. Dal Cero*, M. Gandini, A. Cerullo, G. Giusto.

 

  • Poster

Management of hyperlipemia in ponies after colic surgery in according to energy balance.

  1. Bordin*, G. Giusto, M. Gandini, A. Cerullo, E. Valle

 

27th SIVE International Congress - FEEVA

[ Rome, 28/10/2022 – 29/10/2022 ]

 

  • Oral Presentation

Sopravvivenza e complicazioni post-operatorie a breve termine in cavalli sottoposti a chirurgia di colica: studio multicentrico.

  1. Giusto, R. Gialletti, E. Valle, A. Cerullo*, R. Rinnovati, G. Forni, Cavallini, A. Bertoletti, N. Scilimati, M. Gandini, A. Spadari.

 

  • Oral presentation (Prof. Gandini)

Volvolo nodoso del piccolo intestino: differenze nel quadro clinico e nella patogenesi tra puledri e cavalli adulti (5 casi).

  1. Gandini*, A. Cerullo, G. Giusto

 

26th SIVE International Congress

[ Bologna, 28/01/2022 – 29/01/2022 ]

 

  • Oral presentation

Verifica dell’associazione tra il sovrappeso ed il rischio di infezioni incisionali in seguito a chirurgia di colica nel cavallo. G. Giusto, E. Valle, A. Cerullo*, Gandini

 

  • Poster

Valutazione del rapporto tra lunghezza della sutura e lunghezza della ferita come fattore di rischio per l'infezione del sito chirurgico in seguito a laparotomia nei cavalli.

  1. Gandini, A. Cerullo*, G. Giusto

 

  • Poster

Confronto clinico tra sutura continua di lembert e graffe metalliche per le anastomosi termino-terminale digiuno-digiunale nei cavalli.

  1. Gandini, A. Cerullo, G. Giusto*

 

  • Poster

Infezione incisionale in seguito a laparotomia d’urgenza nel cavallo.

  1. Gandini, G. Giusto, A. Cerullo, N. Scilimati*, A. Bertoletti, R. Gialletti.

 

13th International Equine Colic Research Symposium

[ Birmingham, 04/09/2021 – 07/09/2021 ]

 

  • Poster

Tick-borne diseases as a cause of post-operative fever after colic surgery in northern Italy.

  1. A. Cerullo*, G. Giusto, S. Zanet, E. Battisti, E. Ferroglio, M. Gandini

 

  • Poster

Surgical colic caused by adhesions in absence of previous abdominal surgery: 9 cases (2012-2019).

  1. Giusto, A. Cerullo*, M. Gandini

 

  • Poster

Incomplete ileocecal bypass for ileal pathologyin horses: 21 cases (2012–2019).

  1. Giusto*, A. Cerullo, M. Gandini

 

 

Professional Training: 

  1. Elementi base per l'approccio dei ricercatori all'utilizzo degli animali ai fini scientifici. Istituto zooprofilattico sperimentale della Lombardia e dell'Emilia Romagna - Portale formazione. Online Course
  2. 5th International Colic Surgery Conference and Laboratory, 29/11/22 - 06/12/22 University of Florida, Professional and Workforce Development. Online Course
  3. Corso di formazione in modalità e-learning: How to make the most out of your scientific paper (2020), 15-08-2023.
  4. Corso di formazione in modalità e-learning: How to write a scientific paper (2020), 15-08-2023. 
  5. Corso di formazione in modalità e-learning: Lavorare in gruppo nelle organizzazioni, 15-08-2023.
  6. Corso di formazione in modalità e-learning: Prepararsi alla selezione: dal CV al colloquio di lavoro, 17-08-2023

Publications

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Last update: 27/10/2023 11:46

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