Sovateltide (ILR-1620) Improves Motor Function and Reduces Hyperalgesia in a Rat Model of Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) presents a major global health challenge, with rising incidence rates and substantial disability. Although progress has been made in understanding SCI's pathophysiology and early management, there is still a lack of effective treatments to mitigate long-term consequences. This study investigates the potential of sovateltide, a selective endothelin B receptor agonist, in improving clinical outcomes in an acute SCI rat model. METHODS: Thirty male Sprague-Dawley rats underwent sham surgery (group A) or SCI and treated with vehicle (group B) or sovateltide (group C). Clinical tests, including Basso, Beattie, and Bresnahan scoring, inclined plane, and allodynia testing with von Frey hair, were performed at various time points. Statistical analyses assessed treatment effects. RESULTS: Sovateltide administration significantly improved motor function, reducing neurological deficits and enhancing locomotor recovery compared with vehicle-treated rats, starting from day 7 post injury. Additionally, the allodynic threshold improved, suggesting antinociceptive properties. Notably, the sovateltide group demonstrated sustained recovery, and even reached preinjury performance levels, whereas the vehicle group plateaued. CONCLUSIONS: This study suggests that sovateltide may offer neuroprotective effects, enhancing neurogenesis and angiogenesis. Furthermore, it may possess anti-inflammatory and antinociceptive properties. Future clinical trials are needed to validate these findings, but sovateltide shows promise as a potential therapeutic strategy to improve functional outcomes in SCI. Sovateltide, an endothelin B receptor agonist, exhibits neuroprotective properties, enhancing motor recovery and ameliorating hyperalgesia in a rat SCI model. These findings could pave the way for innovative pharmacological interventions for SCI in clinical settings.

Giant Ovarian Thecoma Associated with Meigs Syndrome: A Striking Case.

Introduction: Meigs syndrome consists of the presence of a benign ovarian tumor, ascites and pleural effusion, and the latter two subdued after surgical excision of the ovarian tumor. Elevated Ca-125 in this context is confusing and is reported only in a handful of cases. A rare but striking case with the above features is presented herein. Case Presentation: A 46-year-old woman with a giant pelvic/abdominal mass originating from her right adnexa, ascites and pleural effusion, with elevated Ca-125 (938 IU/mL) was treated with the presumptive diagnosis of stage IV ovarian cancer. Imaging modalities showed a 22 cm solid adnexal mass and the patient underwent total abdominal hysterectomy and bilateral salpigooophorectomy, omentectomy and drainage of 4L of ascetic fluid. Surprisingly, final histopathology was negative for malignancy, characterizing the primary tumor as ovarian thecoma. Ascites and pleural effusion resolved by the seventh postoperative day, setting the diagnosis of Meigs syndrome. Discussion: Meigs syndrome accounts for 1% of all ovarian tumors, however it should be considered in the differential diagnosis when clinicians come across the classic triad of the syndrome, even when Ca-125 is elevated. These patients have normal life expectancy with meticulous management, while pathophysiology of this condition remains uncertain in various points.

Surgical Antibiotic Prophylaxis: A Proposal for a Global Evidence-Based Bundle.

In the multimodal strategy context, to implement healthcare-associated infection prevention, bundles are one of the most commonly used methods to adapt guidelines in the local context and transfer best practices into routine clinical care. One of the most important measures to prevent surgical site infections is surgical antibiotic prophylaxis (SAP). This narrative review aims to present a bundle for the correct SAP administration and evaluate the evidence supporting it. Surgical site infection (SSI) prevention guidelines published by the WHO, CDC, NICE, and SHEA/IDSA/APIC/AHA, and the clinical practice guidelines for SAP by ASHP/IDSA/SIS/SHEA, were reviewed. Subsequently, comprehensive searches were also conducted using the PubMed®/MEDLINE and Google Scholar databases, in order to identify further supporting evidence-based documentation. The bundle includes five different measures that may affect proper SAP administration. The measures included may be easily implemented in all hospitals worldwide and are based on minimal drug pharmacokinetics and pharmacodynamics knowledge, which all surgeons should know. Antibiotics for SAP should be prescribed for surgical procedures at high risk for SSIs, such as clean-contaminated and contaminated surgical procedures or for clean surgical procedures where SSIs, even if unlikely, may have devastating consequences, such as in procedures with prosthetic implants. SAP should generally be administered within 60 min before the surgical incision for most antibiotics (including cefazolin). SAP redosing is indicated for surgical procedures exceeding two antibiotic half-lives or for procedures significantly associated with blood loss. In principle, SAP should be discontinued after the surgical procedure. Hospital-based antimicrobial stewardship programmes can optimise the treatment of infections and reduce adverse events associated with antibiotics. In the context of a collaborative and interdisciplinary approach, it is essential to encourage an institutional safety culture in which surgeons are persuaded, rather than compelled, to respect antibiotic prescribing practices. In that context, the proposed bundle contains a set of evidence-based interventions for SAP administration. It is easy to apply, promotes collaboration, and includes measures that can be adequately followed and evaluated in all hospitals worldwide.

Six Long-Standing Questions about Antibiotic Prophylaxis in Surgery.

Surgical site infections (SSIs) are the most common adverse event occurring in surgical patients. Optimal prevention of SSIs requires the bundled integration of a variety of measures before, during, and after surgery. Surgical antibiotic prophylaxis (SAP) is an effective measure for preventing SSIs. It aims to counteract the inevitable introduction of bacteria that colonize skin or mucosa into the surgical site during the intervention. This document aims to guide surgeons in appropriate administration of SAP by addressing six key questions. The expert panel identifies a list of principles in response to these questions that every surgeon around the world should always respect in administering SAP.

Declaration on infection prevention and management in global surgery.

Surgeons in their daily practice are at the forefront in preventing and managing infections. However, among surgeons, appropriate measures of infection prevention and management are often disregarded. The lack of awareness of infection and prevention measures has marginalized surgeons from this battle. Together, the Global Alliance for Infections in Surgery (GAIS), the World Society of Emergency Surgery (WSES), the Surgical Infection Society (SIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), the American Association for the Surgery of Trauma (AAST), and the Panamerican Trauma Society (PTS) have jointly completed an international declaration, highlighting the threat posed by antimicrobial resistance globally and the need for preventing and managing infections appropriately across the surgical pathway. The authors representing these surgical societies call all surgeons around the world to participate in this global cause by pledging support for this declaration for maintaining the effectiveness of current and future antibiotics.

The Effect of Intraoperative Transversus Abdominis Plane Blocking on Postoperative Pain After Laparoscopic Transabdominal Pre-peritoneal (TAPP) Groin Hernia Repair.

BACKGROUND: Managing postoperative pain even after laparoscopic groin hernia repair still remains an interesting challenge for clinicians especially for patients of high risk. Plenty of operative techniques and analgesic methods have been proposed in order to minimize postoperative pain after laparoscopic groin hernia repair. The aim of the present study is to compare transverse abdominis plane (TAP)-block with local analgesic infiltration at trocar entry sites in the terms of reducing postoperative pain. METHODS: Patients that underwent laparoscopic trans-abdominal pre-peritoneal (TAPP) groin hernia repair in a high-volume university hospital were included. Patients were divided in two groups depending on the analgesic method used. Pain was assessed using Visual Numerical Scale (VNS) score. RESULTS: Thirty patients were included. Intraoperative TAP-block seemed to be superior in terms of decreasing pain at the hernia area and at the trocar insertion site (p < 0.05) compared to local analgesic infiltration at the trocar insertion site at 6, 12 and 24 h after surgery (p < 0.05). In addition, pain reduction was more effective in rest rather than in motion for both analgesic methods. CONCLUSION: Intraoperative TAP-block under direct vision seems to be an effective, fast and easy technique in order to reduce postoperative pain after laparoscopic groin hernia repair, but more studies are required to validate these results in a prospective and randomized context.

WSES/GAIS/WSIS/SIS-E/AAST global clinical pathways for patients with skin and soft tissue infections.

Skin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections.Together, the World Society of Emergency Surgery, the Global Alliance for Infections in Surgery, the Surgical Infection Society-Europe, The World Surgical Infection Society, and the American Association for the Surgery of Trauma have jointly completed an international multi-society document to promote global standards of care in SSTIs guiding clinicians by describing reasonable approaches to the management of SSTIs.An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting evidence was shared by an international task force with different clinical backgrounds.

WSES/GAIS/SIS-E/WSIS/AAST global clinical pathways for patients with intra-abdominal infections.

Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The cornerstones of effective treatment of IAIs include early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using a critical care environment, combined with an optimal surgical approach. Together, the World Society of Emergency Surgery (WSES), the Global Alliance for Infections in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) have jointly completed an international multi-society document in order to facilitate clinical management of patients with IAIs worldwide building evidence-based clinical pathways for the most common IAIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting information was shared by an international task force from 46 countries with different clinical backgrounds. The aim of the document is to promote global standards of care in IAIs providing guidance to clinicians by describing reasonable approaches to the management of IAIs.

2020 update of the WSES guidelines for the management of acute colonic diverticulitis in the emergency setting.

Acute colonic diverticulitis is one of the most common clinical conditions encountered by surgeons in the acute setting. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of acute left-sided colonic diverticulitis (ALCD) according to the most recent available literature. The update includes recent changes introduced in the management of ALCD. The new update has been further integrated with advances in acute right-sided colonic diverticulitis (ARCD) that is more common than ALCD in select regions of the world.

Diet and expression of estrogen alpha and progesterone receptors in the normal mammary gland.

OBJECTIVE: It has been recently reported that expression of estrogen alpha (ER-alpha) and progesterone (PR) receptors in the normal mammary gland is inversely associated with breast cancer risk among postmenopausal women. We investigated whether dietary intakes are associated with the expression of ER-alpha and PR receptors in the apparently normal, as opposed to pathological, mammary tissue. METHODS: In a study in Greece, we examined associations of dietary intakes with ER-alpha and PR expression in the adjacent-to-pathological apparently normal mammary tissue of 562 women with either breast cancer (267 women) or BBD (299 women). Diet was assessed through an extensive food frequency questionnaire and results were analyzed using multiple logistic regression. RESULTS: Monounsaturated (p = 0.03) and, to a lesser extent, polyunsaturated lipids (p = 0.08) were positively associated with ER-alpha expression. Cereals and starchy roots were inversely associated with ER-alpha (p = 0.01), whereas milk and dairy products were inversely associated with PR expression (p = 0.02). Ethanol intake was non-significantly inversely associated with ER-alpha expression (p = 0.07). CONCLUSIONS: Our findings suggest that the weak associations of diet with breast cancer risk could be explained, to some extent, by effects of diet on receptor expression in the normal mammary gland.

Polymorphisms of the BARX1 and ADAMTS17 Locus Genes in Individuals With Gastroesophageal Reflux Disease.

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) represents a common condition having a substantial impact on the patients' quality of life, as well as the health system. According to many studies, the BARX1 and ADAMTS17 genes have been suggested as genetic risk loci for the development of GERD and its complications. The purpose of this study is to investigate the potential association between GERD and BARX1 and ADAMTS17 polymorphisms. METHODS: The present is a prospective cohort study of 160 GERD patients and 180 healthy control subjects of Greek origin, examined for BARX1 and ADAMTS17 polymorphisms (rs11789015 and rs4965272) and a potential correlation to GERD. RESULTS: The rs11789015 AG and GG genotypes were found to be significantly associated with GERD (P= 0.032; OR, 1.65; 95% CI, 1.062.57 and P= 0.033; OR, 3.00; 95% CI, 1.15-7.82, respectively), as well as the G allele (P= 0.007; OR, 1.60; 95% CI, 1.14- 2.24). Concerning the rs4965272, only the GG genotype was significantly associated with GERD (P= 0.035; OR, 3.42; 95% CI, 1.06-11.05). CONCLUSIONS: This is a study investigating the potential correlation between BARX1 and ADAMTS17 polymorphisms and the development of GERD, showing a considerable association between both polymorphisms and the disease. This finding suggests that esophageal differentiation or altered regulation on microfibrils in the cell environment could be implicated as possible mechanisms in the pathogenesis of GERD.

Risk factors for gastroesophageal reflux disease and analysis of genetic contributors.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder with an increasing prevalence. GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or complications. Several risk factors of GERD have been identified and evaluated over the years, including a considerable amount of genetic factors. Multiple mechanisms are involved in the pathogenesis of GERD including: (1) motor abnormalities, such as impaired lower esophageal sphincter (LES) resting tone, transient LES relaxations, impaired esophageal acid clearance and delayed gastric emptying; and (2) anatomical factors, such as hiatal hernia and obesity. Genetic contribution seems to play a major role in GERD and GERD- related disorders development such Barrett's esophagus and esophageal adenocarcinoma. Twin and family studies have revealed an about 31% heritability of the disease. Numerous single-nucleotide polymorphisms in various genes like FOXF1, MHC, CCND1, anti-inflammatory cytokine and DNA repair genes have been strongly associated with increased GERD risk. GERD, Barrett's esophagus and esophageal adenocarcinoma share several genetic loci. Despite GERD polygenic basis, specific genetic loci such as rs10419226 on chromosome 19, rs2687201 on chromosome 3, rs10852151 on chromosome 15 and rs520525 on the paired related homeobox 1 gene have been mentioned as potential risk factors. Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.

Knowledge, awareness, and attitude towards infection prevention and management among surgeons: identifying the surgeon champion.

Despite evidence supporting the effectiveness of best practices of infection prevention and management, many surgeons worldwide fail to implement them. Evidence-based practices tend to be underused in routine practice. Surgeons with knowledge in surgical infections should provide feedback to prescribers and integrate best practices among surgeons and implement changes within their team. Identifying a local opinion leader to serve as a champion within the surgical department may be important. The "surgeon champion" can integrate best clinical practices of infection prevention and management, drive behavior change in their colleagues, and interact with both infection control teams in promoting antimicrobial stewardship.

2018 WSES/SIS-E consensus conference: recommendations for the management of skin and soft-tissue infections.

Skin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections. SSTIs are a frequent clinical problem in surgical departments. In order to clarify key issues in the management of SSTIs, a task force of experts met in Bertinoro, Italy, on June 28, 2018, for a specialist multidisciplinary consensus conference under the auspices of the World Society of Emergency Surgery (WSES) and the Surgical Infection Society Europe (SIS-E). The multifaceted nature of these infections has led to a collaboration among general and emergency surgeons, intensivists, and infectious disease specialists, who have shared these clinical practice recommendations.

Nephrectomy versus renal repair after trauma to the kidney: preserve or sacrifice?

The objective of this retrospective study (1992-2003) is to evaluate the effect of nephrectomy in postoperative renal dysfunction. NEPHRECTOMY patients had their kidneys removed and REPAIR patients repaired or only partially resected. All patients were matched 1:1 with controls according to age, Injury Severity Score, Abdominal Abbreviated Injury Score, and mechanism of injury. Outcomes measured were renal dysfunction (serum creatinine > 2 mg/dl for > 2 consecutive days), renal dialysis, length of hospital stay, and mortality. Of 214 patients, 149 were NEPHRECTOMY and 65 REPAIR. Compared to their controls, NEPHRECTOMY and REPAIR patients had a higher rate of renal dysfunction. However, the rate was not different between NEPHRECTOMY and REPAIR. Multivariate analysis found no independent effect of the choice of operation in the development of renal dysfunction. No differences were found in the remaining outcomes measured. We conclude that although renal injury is associated with postoperative renal dysfunction, the type of operation is not. Nephrectomy can be offered when necessary without concerns about increasing the likelihood of postoperative renal failure.

Tobacco and alcohol in relation to male breast cancer: an analysis of the male breast cancer pooling project consortium.

BACKGROUND: The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. METHODS: The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) ORs and 95% confidence intervals (CI), which were then combined using fixed-effects meta-analysis. RESULTS: Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one subanalysis of very high recent alcohol consumption (>60 g/day) was tentatively associated with male breast cancer (ORunexposed referent = 1.29; 95% CI, 0.97-1.71; OR>0-<7 g/day referent = 1.36; 95% CI, 1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. CONCLUSIONS: In this analysis of the Male Breast Cancer Pooling Project, we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. IMPACT: Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer.

Alcohol and illicit drugs in traumatic deaths: prevalence and association with type and severity of injuries.

BACKGROUND: My colleagues and I studied alcohol and illicit drug intoxication in trauma fatalities and their association with the nature and severity of injuries. STUDY DESIGN: We examined the trauma registry and autopsies of all trauma fatalities at an academic Level I trauma center. Statistical analysis was performed to evaluate the association of substance use with the Injury Severity Score, body areas with severe trauma (Abbreviated Injury Score >/= 3), and spinal injuries. RESULTS: From January 2000 to May 2003, 931 trauma deaths occurred; 600 victims were tested for alcohol and illicit drugs and 256 of these (42.7%) tested positive. Male victims were significantly more likely to have a positive screen than female patients (46.1% versus 26.7%, p = 0.0003). Penetrating trauma was significantly more likely to be associated with a positive screen than blunt trauma (53.0% versus 31.0%, p < 0.001). Hispanic and African-American victims were more likely to have a positive screen than Caucasians or Asians. Half the patients in the age group 15 to 50 years had a positive screen. Victims with penetrating trauma and positive screen were significantly more likely to be dead at hospital arrival than victims with negative toxicology (68.8% versus 48.8%, p = 0.05). Pedestrians killed by automobiles who had positive screens were more likely to have severe abdominal trauma (Abbreviated Injury Score >/= 3) than victims with negative toxicology (54.2% versus 25.0%, p = 0.02). CONCLUSIONS: There is a high rate of alcohol and illicit drug use in patients who die from trauma, especially penetrating trauma in men aged 15 to 50 years, who are Hispanic or African American. Victims with penetrating trauma and positive toxicology are considerably more likely to have no vital signs on admission than victims with negative toxicology. Pedestrians killed by automobiles who had positive screens have a higher incidence of severe abdominal injuries than victims with negative screens.

Thromboprophylaxis does not protect severely injured patients against pulmonary embolism.

The existing evidence on the effectiveness of thromboprophylaxis after trauma is conflicting. Although prophylaxis with heparin and/or sequential compression devices is practiced widely, many studies failed to document a clear benefit. A recent meta-analysis suggests that prophylaxis does not reduce posttraumatic deep venous thrombosis rates compared to no prophylaxis. The objective of this prospective study is to examine if the use of thromboprophylaxis prevents posttraumatic pulmonary embolism (PE). Sixty-four critically injured patients with clinical evidence of PE were studied by computed tomographic pulmonary angiography and/or conventional pulmonary angiography. PE was diagnosed in 24 (37.5%) patients. Patients with PE were similar to patients without PE with regard to demographics, injury type and severity, operations, and mortality. Thromboprophylaxis was used with equal frequency between PE and no-PE patients (71% vs 80%, P = 0.4). The type of prophylaxis used was similar between patients with PE (17% heparin, 71% sequential compression devices, 17% combination) and patients without PE (32%, 57%, and 10%, respectively; P = 0.16, 0.28, 0.69, respectively). Current methods of posttraumatic thromboprophylaxis may be inadequate. Practices from nontrauma populations have been erroneously extrapolated to the unique trauma population. To reduce the rate of PE after trauma, new methods of thromboprophylaxis should be considered.

Pancreatic Remnant Occlusion after Whipple's Procedure: An Alternative Oncologically Safe Method.

Introduction. To present our experience regarding the use of pancreatic stump occlusion technique as an alternative management of the pancreatic remnant after pancreatoduodenectomy (PD). Methods. Between 2002 and 2009, hospital records of 93 patients who had undergone a Whipple's procedure for either pancreatic-periampullary cancer or chronic pancreatitis were retrospectively studied. In 37 patients the pancreatic duct was occluded by stapling and running suture without anastomosis of the pancreatic remnant, whereas in 56 patients a pancreaticojejunostomy was performed. Operative data, postoperative complications, oncological parameters, and survival rates were recorded. Results. 2/37 patients of the occlusion group and 9/56 patients of the anastomosis group were treated for chronic pancreatitis, whereas 35/37 and 47/56 patients for periampullary malignancies. The duration of surgery for the anastomosis group was significantly longer (mean time 220 versus 180 minutes). Mean hospitalization time was 6 days for both groups. The occlusion group had a lower morbidity rate (24% versus 32%). With regard to postoperative complications, a slightly higher incidence of pancreatic fistulas was observed in the anastomosis group. Conclusions. Pancreatic remnant occlusion is a safe, technically feasible, and reducing postoperative complications alternative approach of the pancreatic stump during Whipple's procedure.

Does nephrectomy for trauma increase the risk of renal failure?

Renal failure is a feared complication following operations for severe trauma. Injuries to the kidney may be managed by nephrectomy or nephrorrhaphy. Nephrectomy may increase the risk of renal failure in already at-risk trauma patients. Nephrectomy for trauma should be avoided to the extent possible because it is associated with renal failure. From a prospectively collected trauma database, 59 patients with nephrectomy were matched at 1:1 ratio with 59 patients with nephrorrhaphy. Matching criteria were age (+/- 5 years), Injury Severity Score (+/- 3), abdominal Abbreviated Injury Score (+/- 1), and mechanism of injury (blunt or penetrating). The rates of renal function compromise (defined as a serum creatinine level >2 mg/dl for more than 2 days) and renal replacement therapy (continuous or intermittent) were compared in the two groups. The two groups were well-matched and similar with regard to injury severity and organs injured. Between nephrectomy and nephrorrhaphy patients, there were no differences in renal function compromise (10% vs. 14%, p = 0.57), renal replacement therapy (5% vs. 0%, p = 0.12), length of hospital stay (19 +/- 26 vs. 20 +/- 21, p = 0.8), and mortality (15% vs. 12%, p = 0.59). Salvaging the injured kidney does not seem to offer an obvious clinical benefit regarding postoperative renal function. Given the increased operative complexity of nephrorrhaphy in comparison to nephrectomy and the frequent need to abbreviate the operation in patients with severe trauma, nephrectomy should not be avoided when appropriate.