Dr Cino Bendinelli

Background: Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. A further therapeutic option may be open abdomen (OA) management with negative peritoneal pressure therapy (NPPT) to remove inflammatory ascites and attenuate the systemic damage from SCIAS, although there are definite risks of leaving the abdomen open whenever it might possibly be closed. This potential therapeutic paradigm is the rationale being assessed in the Closed Or Open after Laparotomy (COOL trial) (https://clinicaltrials.gov/ct2/show/NCT03163095). Initially, the COOL trial received Industry sponsorship; however, this funding mandated the use of a specific trademarked and expensive NPPT device in half of the patients allocated to the intervention (open) arm. In August 2022, the 3¿M/Acelity Corporation without consultation but within the terms of the contract canceled the financial support of the trial. Although creating financial difficulty, there is now no restriction on specific NPPT devices and removing a cost-prohibitive intervention creates an opportunity to expand the COOL trial to a truly global basis. This document describes the evolution of the COOL trial, with a focus on future opportunities for global growth of the study. Methods: The COOL trial is the largest prospective randomized controlled trial examining the random allocation of SCIAS patients intra-operatively to either formal closure of the fascia or the use of the OA with an application of an NPPT dressing. Patients are eligible if they have free uncontained intraperitoneal contamination and physiologic derangements exemplified by septic shock OR severely adverse predicted clinical outcomes. The primary outcome is intended to definitively inform global practice by conclusively evaluating 90-day survival. Initial recruitment has been lower than hoped but satisfactory, and the COOL steering committee and trial investigators intend with increased global support to continue enrollment until recruitment ensures a definitive answer. Discussion: OA is mandated in many cases of SCIAS such as the risk of abdominal compartment syndrome associated with closure, or a planned second look as for example part of "damage control"; however, improved source control (locally and systemically) is the most uncertain indication for an OA. The COOL trial seeks to expand potential sites and proceed with the evaluation of NPPT agnostic to device, to properly examine the hypothesis that this treatment attenuates systemic damage and improves survival. This approach will not affect internal validity and should improve the external validity of any observed results of the intervention. Trial registration: National Institutes of Health (https://clinicaltrials.gov/ct2/show/NCT03163095).

Sigmoid volvulus is a common surgical emergency, especially in elderly patients. Patients can present with a wide range of clinical states: from asymptomatic, to frank peritonitis secondary to colonic perforation. These patients generally need urgent treatment, be it endoscopic decompression of the colon or an upfront colectomy. The World Society of Emergency Surgery united a worldwide group of international experts to review the current evidence and propose a consensus guidelines on the management of sigmoid volvulus.

Intra-abdominal infections (IAI) are among the most common global healthcare challenges and they are usually precipitated by disruption to the gastrointestinal (GI) tract. Their successful management typically requires intensive resource utilization, and despite the best therapies, morbidity and mortality remain high. One of the main issues required to appropriately treat IAI that differs from the other etiologies of sepsis is the frequent requirement to provide physical source control. Fortunately, dramatic advances have been made in this aspect of treatment. Historically, source control was left to surgeons only. With new technologies non-surgical less invasive interventional procedures have been introduced. Alternatively, in addition to formal surgery open abdomen techniques have long been proposed as aiding source control in severe intra-abdominal sepsis. It is ironic that while a lack or even delay regarding source control clearly associates with death, it is a concept that remains poorly described. For example, no conclusive definition of source control technique or even adequacy has been universally accepted. Practically, source control involves a complex definition encompassing several factors including the causative event, source of infection bacteria, local bacterial flora, patient condition, and his/her eventual comorbidities. With greater understanding of the systemic pathobiology of sepsis and the profound implications of the human microbiome, adequate source control is no longer only a surgical issue but one that requires a multidisciplinary, multimodality approach. Thus, while any breach in the GI tract must be controlled, source control should also attempt to control the generation and propagation of the systemic biomediators and dysbiotic influences on the microbiome that perpetuate multi-system organ failure and death. Given these increased complexities, the present paper represents the current opinions and recommendations for future research of the World Society of Emergency Surgery, of the Global Alliance for Infections in Surgery of Surgical Infection Society Europe and Surgical Infection Society America regarding the concepts and operational adequacy of source control in intra-abdominal infections.

Background: Diaphragmatic hernia (DH) presenting acutely can be a potentially life-threatening condition. Its management continues to be debatable. Methods: A bibliographic search using major databases was performed using the terms "emergency surgery" "diaphragmatic hernia," "traumatic diaphragmatic rupture" and "congenital diaphragmatic hernia." GRADE methodology was used to evaluate the evidence and give recommendations. Results: CT scan of the chest and abdomen is the diagnostic gold standard to evaluate complicated DH. Appropriate preoperative assessment and prompt surgical intervention are important for a clinical success. Complicated DH repair is best performed via the use of biological and bioabsorbable meshes which have proven to reduce recurrence. The laparoscopic approach is the preferred technique in hemodynamically stable patients without significant comorbidities because it facilitates early diagnosis of small diaphragmatic injuries from traumatic wounds in the thoraco-abdominal area and reduces postoperative complications. Open surgery should be reserved for situations when skills and equipment for laparoscopy are not available, where exploratory laparotomy is needed, or if the patient is hemodynamically unstable. Damage Control Surgery is an option in the management of critical and unstable patients. Conclusions: Complicated diaphragmatic hernia is a rare life-threatening condition. CT scan of the chest and abdomen is the gold standard for diagnosing the diaphragmatic hernia. Laparoscopic repair is the best treatment option for stable patients with complicated diaphragmatic hernias. Open repair is considered necessary in majority of unstable patients in whom Damage Control Surgery can be life-saving.

Multidisciplinary team (MDT) meetings are the mainstay of the decision-making process for patients presenting with complex clinical problems such as papillary thyroid carcinoma (PTC). Adherence to guidelines by MDTs has been extensively investigated; however, scarce evidence exists on MDT performance and variability where guidelines are less prescriptive. We evaluated the consistency of MDT management recommendations for T1 and T2 PTC patients and explored key variables that may influence therapeutic decision making. A retrospective review of the prospective database of all T1 and T2 PTC patients discussed by the MDT was conducted between January 2016 and May 2021. Univariate analysis (with Bonferroni correction significance calculated at p < 0.006) was performed to establish clinical variables linked to completion thyroidectomy and Radioactive iodine (RAI) recommendations. Of 468 patients presented at thyroid MDT, 144 pT1 PTC and 118 pT2 PTC met the selection criteria. Only 18% (n = 12) of pT1 PTC patients initially managed with hemithyroidectomy were recommended completion thyroidectomy. Mean tumour diameter was the only variable differing between groups (p = 0.003). pT2 patients were recommended completion thyroidectomy in 66% (n = 16) of instances. No measured variable explained the difference in recommendation. pT1 patients initially managed with total thyroidectomy were not recommended RAI in 71% (n = 55) of cases with T1a status (p = 0.001) and diameter (p = 0.001) as statistically different variables. For pT2 patients, 60% (n = 41) were recommended RAI post-total thyroidectomy, with no differences observed among groups. The majority of MDT recommendations were concordant for patients with similar measurable characteristics. Discordant recommendations for a small group of patients were not explained by measured variables and may have been accounted for by individual patient factors. Further research into the MDT decision-making process is warranted.

Purpose: Prehospital guidelines stratify and manage patients with Glasgow Coma Scale (GCS) less than nine and any sign of head injury as affected by severe traumatic brain injury (STBI). We hypothesized that this group of patients is so inhomogeneous that uniform treatment guidelines cannot be advocated. Methods: Patients (2005¿2012) with prehospital GCS below nine and abbreviated injury scale head and neck above two were identified from trauma registry. Patients with acute lethal injuries, isolated neck injuries, extubated within 24¿h or transferred interhospitally were excluded. Patients were dichotomized based on the worst prehospital GCS (recorded before sedatives) into two groups: GCS 3¿5 and GCS 6¿8. These were statistically compared using univariate analysis. Results: The GCS 3¿5 group (99 patients) when compared with the GCS 6¿8 group (49 patients) had shorter prehospital times (63 vs. 79¿min; p < 0.05), more frequent episodes of both hypoxia (30.3% vs. 7.7%; p < 0.05) and hypotension (26.7% vs. 6.4%; p < 0.05), more often required craniectomy (15.1% vs. 4.0%; p = 0.05) and higher mortality (33.3% vs. 2%; p < 0.05). In the GCS 3¿5 group, prehospital endotracheal intubation was attempted more often (57.5% vs. 28.6%, p < 0.05) and was more often successful (39.3% vs. 10.2%; p = 0.05). Length of stay in ICU did not differ. Conclusions: STBI patients are fundamentally different based on whether their initial GCS falls into 3¿5 or 6¿8 category. Recommendations from trials investigating trauma patients with GCS less than nine as one group should be translated with caution to clinical practice.

Objective: Post-thyroidectomy hypocalcaemia is a significant cause of morbidity and prolonged hospitalization, usually due to transient parathyroid gland damage, treated with calcium and vitamin D supplementation. We present a randomized, double-blinded placebo-controlled trial of preoperative loading with high-dose cholecalciferol (300¿000 IU) to reduce post-thyroidectomy hypocalcaemia. Patients and Measurements: Patients (n¿=¿160) presenting for thyroidectomy at tertiary hospitals were randomized 1:1 to cholecalciferol (300¿000¿IU) or placebo 7¿days prior to thyroidectomy. Ten patients withdrew prior to surgery. The primary outcome was post-operative hypocalcaemia (corrected calcium <2.1¿mmol/L in first 180¿days). Results: The study included 150 patients undergoing thyroidectomy for Graves' disease (31%), malignancy (20%) and goitre (49%). Mean pre-enrolment vitamin D was 72¿±¿26¿nmol/L. Postoperative hypocalcaemia occurred in 21/72 (29%) assigned to cholecalciferol and 30/78 (38%) participants assigned to placebo (P¿=¿0.23). There were no differences in secondary end-points between groups. In pre-specified stratification, baseline vitamin D status did not predict hypocalcaemia, although most individuals were vitamin D replete at baseline. Post-hoc stratification by day 1 parathyroid hormone (PTH) (<10¿pg/mL, low vs =10¿pg/mL, normal) was explored due to highly divergent rates of hypocalcaemia in these groups. Using a Cox regression model, the hazard ratio for hypocalcaemia in the cholecalciferol group was 0.56 (95%CI 0.32-0.98, P¿=¿0.04) after stratification for Day 1 PTH. Further clinical benefits were observed in these subgroups. Conclusions: Pre-thyroidectomy treatment with high-dose cholecalciferol did not reduce the overall rate of hypocalcaemia following thyroidectomy. In subgroups stratified by day 1 PTH status, improved clinical outcomes were noted.

BACKGROUND: Lower GI hemorrhage is a common source of morbidity and mortality. Tranexamic acid is an antifibrinolytic that has been shown to reduce blood loss in a variety of clinical conditions. Information regarding the use of tranexamic acid in treating lower GI hemorrhage is lacking. OBJECTIVE: The aim of this trial was to determine the clinical efficacy of tranexamic acid when used for lower GI hemorrhage. DESIGN: This was a prospective, double-blind, placebo-controlled, randomized clinical trial. SETTINGS: The study was conducted at a tertiary referral university hospital in Australia. PATIENTS: Consecutive patients aged >18 years with lower GI hemorrhage requiring hospital admission from November 2011 to January 2014 were screened for trial eligibility (N = 265). INTERVENTIONS: A total of 100 patients were recruited after exclusions and were randomly assigned 1:1 to either tranexamic acid or placebo. MAIN OUTCOME MEASURES: The primary outcome was blood loss as determined by reduction in hemoglobin levels. The secondary outcomes were transfusion rates, transfusion volume, intervention rates for bleeding, length of hospital stay, readmission, and complication rates. RESULTS: There was no difference between groups with respect to hemoglobin drop (11 g/L of tranexamic acid vs 13 g/L of placebo; p = 0.9445). There was no difference with respect to transfusion rates (14/49 tranexamic acid vs 16/47 placebo; p = 0.661), mean transfusion volume (1.27 vs 1.93 units; p = 0.355), intervention rates (7/49 vs 13/47; p = 0.134), length of hospital stay (4.67 vs 4.74 d; p = 0.934), readmission, or complication rates. No complications occurred as a direct result of tranexamic acid use. LIMITATIONS: A larger multicenter trial may be required to determine whether there are more subtle advantages with tranexamic acid use in some of the secondary outcomes. CONCLUSIONS: Tranexamic acid does not appear to decrease blood loss or improve clinical outcomes in patients presenting with lower GI hemorrhage in the context of this trial. see Video Abstract at http://links.lww.com/DCR/A453.

Recent advances in the arena of theranostics have necessitated a re-examining of previously established fields. The existing paradigm of therapeutic thyroid-stimulating hormone receptor (TSHR) targeting in the post-surgical management of differentiated thyroid cancer using levothyroxine and recombinant human thyroid-stimulating hormone (TSH) is well understood. However, in an era of personalized medicine, and with an increasing awareness of the risk profile of longstanding pharmacological hyperthyroidism, it is imperative clinicians understand the molecular basis and magnitude of benefit for individual patients. Furthermore, TSHR has been recently re-conceived as a selective target for residual metastatic thyroid cancer, with pilot data demonstrating effective targeting of nanoparticles to thyroid cancers using this receptor as a target. This review examines the evidence for TSHR signaling as an oncogenic pathway and assesses the evidence for ongoing TSHR expression in thyroid cancer metastases. Priorities for further research are highlighted.

Background: In patients with severe traumatic brain injury (TBI), early CT perfusion (CTP) provides additional information beyond the non-contrast CT (NCCT) and may alter clinical management. We hypothesized that this information may prognosticate functional outcome. Methods: Five-year prospective observational study was performed in a level-1 trauma centre on consecutive severe TBI patients. CTP (obtained in conjunction with first routine NCCT) was interpreted as: abnormal, area of altered perfusion more extensive than on NCCT, and the presence of ischaemia. Six months Glasgow Outcome Scale-Extended of four or less was considered an unfavourable outcome. Logistic regression analysis of CTP findings and core variables [preintubation Glasgow Coma Scale (GCS), Rotterdam score, base deficit, age] was conducted using Bayesian model averaging to identify the best predicting model for unfavourable outcome. Results: Fifty patients were investigated with CTP (one excluded for the absence of TBI) [male: 80%, median age: 35 (23¿55), prehospital intubation: 7 (14.2%); median GCS: 5 (3¿7); median injury severity score: 29 (20¿36); median head and neck abbreviated injury scale: 4 (4¿5); median days in ICU: 10 (5¿15)]. Thirty (50.8%) patients had an unfavourable outcome. GCS was a moderate predictor of unfavourable outcome (AUC¿=¿0.74), while CTP variables showed greater predictive ability (AUC for abnormal CTP¿=¿0.92; AUC for area of altered perfusion more extensive than NCCT¿=¿0.83; AUC for the presence of ischaemia¿=¿0.81). Conclusion: Following severe TBI, CTP performed at the time of the first follow-up NCCT, is a non-invasive and extremely valuable tool for early outcome prediction. The potential impact on management and its cost effectiveness deserves to be evaluated in large-scale studies. Level of evidence III: Prospective study.

The CIAOW study (Complicated intra-abdominal infections worldwide observational study) is a multicenter observational study underwent in 68 medical institutions worldwide during a six-month study period (October 2012-March 2013). The study included patients older than 18 years undergoing surgery or interventional drainage to address complicated intra-abdominal infections (IAIs).1898 patients with a mean age of 51.6 years (range 18-99) were enrolled in the study. 777 patients (41%) were women and 1,121 (59%) were men. Among these patients, 1,645 (86.7%) were affected by community-acquired IAIs while the remaining 253 (13.3%) suffered from healthcare-associated infections. Intraperitoneal specimens were collected from 1,190 (62.7%) of the enrolled patients.827 patients (43.6%) were affected by generalized peritonitis while 1071 (56.4%) suffered from localized peritonitis or abscesses.The overall mortality rate was 10.5% (199/1898).According to stepwise multivariate analysis (PR = 0.005 and PE = 0.001), several criteria were found to be independent variables predictive of mortality, including patient age (OR = 1.1; 95%CI = 1.0-1.1; p < 0.0001), the presence of small bowel perforation (OR = 2.8; 95%CI = 1.5-5.3; p < 0.0001), a delayed initial intervention (a delay exceeding 24 hours) (OR = 1.8; 95%CI = 1.5-3.7; p < 0.0001), ICU admission (OR = 5.9; 95%CI = 3.6-9.5; p < 0.0001) and patient immunosuppression (OR = 3.8; 95%CI = 2.1-6.7; p < 0.0001). © 2014 Sartelli et al.; licensee BioMed Central Ltd.

Background: Damage control surgery is a management sequence initiated to reduce the risk of death in severely injured patients presenting with physiological derangement. Damage control principles have emerged as an approach in non-trauma abdominal emergencies in order to reduce mortality compared with primary definitive surgery. Methods: A PubMed/MEDLINE literature review was conducted of data available over the past decade (up to August 2013) to gain information on current understanding of damage control surgery for abdominal surgical emergencies. Future directions for research are discussed. Results: Damage control surgery facilitates a strategy for life-saving intervention for critically ill patients by abbreviated laparotomy with subsequent reoperation for delayed definitive repair after physiological resuscitation. The six-phase strategy (including damage control resuscitation in phase 0) is similar to that for severely injured patients, although non-trauma indications include shock from uncontrolled haemorrhage or sepsis. Minimal evidence exists to validate the benefit of damage control surgery in general surgical abdominal emergencies. The collective published experience over the past decade is limited to 16 studies including a total of 455 (range 3-99) patients, of which the majority are retrospective case series. However, the concept has widespread acceptance by emergency surgeons, and appears a logical extension from pathophysiological principles in trauma to haemorrhage and sepsis. The benefits of this strategy depend on careful patient selection. Damage control surgery has been performed for a wide range of indications, but most frequently for uncontrolled bleeding during elective surgery, haemorrhage from complicated gastroduodenal ulcer disease, generalized peritonitis, acute mesenteric ischaemia and other sources of intra-abdominal sepsis. Conclusion: Damage control surgery is employed in a wide range of abdominal emergencies and is an increasingly recognized life-saving tactic in emergency surgery performed on physiologically deranged patients. © 2013 BJS Society Ltd.