High Morbidity Research Articles

Lipid A modification of colistin-resistant Klebsiella pneumoniae does not alter innate immune response in a mouse model of pneumonia.

Polymyxin resistance in carbapenem-resistant Klebsiella pneumoniae bacteria is associated with high morbidity and mortality in vulnerable populations throughout the world. Ineffective antimicrobial activity by these last resort therapeutics can occur by transfer of mcr-1, a plasmid-mediated resistance gene, causing modification of the lipid A portion of lipopolysaccharide (LPS) and disruption of the interactions between polymyxins and lipid A. Whether this modification alters the innate host immune response or carries a high fitness cost in the bacteria is not well established. To investigate this, we studied infection with K. pneumoniae (KP) ATCC 13883 harboring either the mcr-1 plasmid (pmcr-1) or the vector control (pBCSK) ATCC 13883. Bacterial fitness characteristics of mcr-1 acquisition were evaluated. Differentiated human monocytes (THP-1s) were stimulated with KP bacterial strains or purified LPS from both parent isolates and isolates harboring mcr-1. Cell culture supernatants were analyzed for cytokine production. A bacterial pneumonia model in WT C57/BL6J mice was used to monitor immune cell recruitment, cytokine induction, and bacterial clearance in the bronchoalveolar lavage fluid (BALF). Isolates harboring mcr-1 had increased colistin MIC compared to the parent isolates but did not alter bacterial fitness. Few differences in cytokines were observed with purified LPS from mcr-1 expressing bacteria in vitro. However, in a mouse pneumonia model, no bacterial clearance defect was observed between pmcr-1-harboring KP and parent isolates. Consistently, no differences in cytokine production or immune cell recruitment in the BALF were observed, suggesting that other mechanisms outweigh the effect of these lipid A mutations in LPS.

Risk of infective endocarditis and complicated infection in Staphylococcus aureus bacteremia - a retrospective cohort study on the role of bacteriuria.

S. aureus bacteremia (SAB) is a common and severe infection with high mortality and morbidity. The clinical relevance of the finding of concurrent S. aureus bacteriuria (SABU) is debated. The goal of this study was to analyze whether a concurrent SABU is associated with complicated SAB, infective endocarditis (IE) and mortality. We conducted a retrospective cohort study, reviewing medical charts of all episodes of SAB in patients > 18 years in the region of Skåne, Sweden, between 1st of January and 31st of June 2020. Episodes where a concurrent urine culture was performed were included for analysis. An episode was considered as complicated SAB if there was either attributable mortality, recurrent infection, embolic stroke, or occurrence of a complicated focus of infection. During the study period, there were 279 episodes of SAB. 154 episodes met the eligibility criteria, of whom 37 (24%) had concurrent SABU. In 78 episodes (51%), the patients had a complicated SAB. There was a significantly lower proportion of complicated SAB for episodes with concurrent SABU (32%), compared to episodes without concurrent SABU (56%), p-value 0.014. Moreover, in the cohort there were 11 episodes (7.1%) of IE and a 30 days mortality rate of 16%, with no difference between the groups with or without SABU. There is an association between concurrent SABU and a decreased risk for complicated SAB among patients with SAB. This study found no significant association between SABU and neither IE nor mortality for patients with SAB.

Protective Mechanisms of SGLTi in Ischemic Heart Disease.

Ischemic heart disease (IHD) is a common clinical cardiovascular disease with high morbidity and mortality. Sodium glucose cotransporter protein inhibitor (SGLTi) is a novel hypoglycemic drug. To date, both clinical trials and animal experiments have shown that SGLTi play a protective role in IHD, including myocardial infarction (MI) and ischemia/reperfusion (I/R). The protective effects may be involved in mechanisms of energy metabolic conversion, anti-inflammation, anti-fibrosis, ionic homeostasis improvement, immune cell development, angiogenesis and functional regulation, gut microbiota regulation, and epicardial lipids. Thus, this review summarizes the above mechanisms and aims to provide theoretical evidence for therapeutic strategies for IHD.

Sedation modality in acute respiratory distress syndrome: does method of sedation affect length of stay, outcomes, or adverse events? A systematic review

IntroductionAcute respiratory distress syndrome (ARDS) is a life-threatening, diffuse inflammatory pulmonary condition characterised by the Berlin criteria. Incidence of ARDS is estimated at 2.5–19% globally with high mortality and morbidity....

Donor Site Outcomes Following Autologous Breast Reconstruction with DIEP Flap: A Retrospective and Prospective Study in a Single Institution

Background: The deep inferior epigastric perforator artery (DIEP) free flap is the most commonly performed autologous breast reconstruction. Despite the relative reduction in donor site complications compared to nonmuscle-sparing options, there is still high morbidity associated with this surgery. The purpose of this study is to compare outcomes and complications at our institution and to discuss potential quality improvement initiatives. Methods: A retrospective cohort study was performed looking at patients who underwent delayed or immediate autologous breast reconstruction with a DIEP flap over a 6-year period (2015-2021) at our institution. Complication rates for abdominal infection, seroma, hematoma, wound dehiscence, delayed wound healing, umbilical necrosis, subjective abdominal weakness, abdominal bulge, and hernia were calculated. Additionally, a prospective cohort study was conducted using a portable ultrasound device to detect postoperative changes in the abdominal donor site, including fluid collections and postoperative edema. Results: One hundred seventeen patients underwent autologous breast reconstruction with a DIEP-free flap. Forty-one percent of patients experienced 1 or more donor site complications. Complication rates were 16.2%, 12.8%, 1.7%, 15.4%, 8.5%, 4.3%, 0%, 10.3%, and 2.6%, respectively, for the list above. There was a higher proportion of complications in patients who smoked within the past 3 months and those who had a body mass index (BMI) between 35 and 39.9, although this was not statistically significant. Bilateral reconstructions had higher rates of umbilical necrosis (24.5% vs 7.8%) and wound dehiscence (9.4% vs 0%) compared to unilateral. Twenty-one patients were included in the prospective analysis. No significant changes in abdominal wall edema were found. Twenty-four percent of the patients had detectible collections on ultrasound, and these were associated with wound dehiscence and the need for debridement. Discussion: Our institutional abdominal donor site complication rates in DIEP reconstruction patients are higher than those published in the literature. Similar complication rates were identified regardless of smoking status, BMI, and unilateral/bilateral surgery. Quality improvement initiatives could be considered and implemented to reduce future complications.

Symptom clusters and unplanned hospital readmission in Chinese patients with acute myocardial infarction on admission

BackgroudAcute myocardial infarction (AMI) has a high morbidity rate, high mortality rate, high readmission rate, high health care costs, and a high symptomatic, psychological, and economic burden on patients. Patients with AMI usually present with multiple symptoms simultaneously, which are manifested as symptom clusters. Symptom clusters have a profound impact on the quality of survival and clinical outcomes of AMI patients.ObjectiveThe purpose of this study was to analyze unplanned hospital readmissions among cluster groups within a 1-year follow-up period, as well as to identify clusters of acute symptoms and the characteristics associated with them that appeared in patients with AMI.MethodsBetween October 2021 and October 2022, 261 AMI patients in China were individually questioned for symptoms using a structured questionnaire. Mplus 8.3 software was used to conduct latent class analysis in order to find symptom clusters. Univariate analysis is used to examine characteristics associated with each cluster, and multinomial logistic regression is used to analyze a cluster membership as an independent predictor of hospital readmission after 1-year.ResultsThree unique clusters were found among the 11 acute symptoms: the typical chest symptom cluster (64.4%), the multiple symptom cluster (29.5%), and the atypical symptom cluster (6.1%). The cluster of atypical symptoms was more likely to have anemia and the worse values of Killip class compared with other clusters. The results of multiple logistic regression indicated that, in comparison to the typical chest cluster, the atypical symptom cluster substantially predicted a greater probability of 1-year hospital readmission (odd ratio 8.303, 95% confidence interval 2.550–27.031, P < 0.001).ConclusionOut of the 11 acute symptoms, we have found three clusters: the typical chest symptom, multiple symptom, and atypical symptom clusters. Compared to patients in the other two clusters, those in the atypical symptom cluster—which included anemia and a large percentage of Killip class patients—had worse clinical indicators at hospital readmission during the duration of the 1-year follow-up. Both anemia and high Killip classification suggest that the patient's clinical presentation is poor and therefore the prognosis is worse. Intensive treatment should be considered for anemia and high level of Killip class patients with atypical presentation. Clinicians should focus on patients with atypical symptom clusters, enhance early recognition of symptoms, and develop targeted symptom management strategies to alleviate their discomfort in order to improve symptomatic outcomes.

Role of extracorporeal membrane oxygenation in pediatric myocarditis

ABSTRACT Fulminant myocarditis in children is rare, but it has the potential for high morbidity and mortality. In this report, we review articles demonstrating the role of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in the fulminant myocarditis, and describe the clinical course of a healthy 11-year-old girl who rapidly deteriorated into cardiogenic shock. The patient was weaned from mechanical ventilation on day 7 and she was discharged from the ICU on day 12. VA-ECMO is considered as a life-saving therapy in patients with hemodynamic instability prior to recovery or other escalation therapy.

Role of aortic valve replacement in moderate aortic stenosis: a 10-year outcomes study

ObjectivePatients with moderate aortic stenosis (AS) exhibit high morbidity and mortality. Limited evidence exists on the role of aortic valve replacement (AVR) in this patient population. To investigate the benefit...

Cost-effectiveness analysis of procalcitonin and lung ultrasonography guided antibiotic prescriptions in primary care.

Antimicrobial resistance comes with high morbidity and mortality burden, and ultimately high impact on healthcare and social costs. Efficient strategies are needed to limit antibiotic overuse. This paper investigates the cost-effectiveness of testing patients with lower respiratory tract infection with procalcitonin, either at the point-of-care only or combined with lung ultrasonography. These diagnostic tools help detect the presence of bacterial pneumonia, guiding prescription decisions. The clinical responses of these strategies were studied in the primary care setting. Evidence is needed on their cost-effectiveness. We used data from a cluster-randomized bi-centric clinical trial conducted in Switzerland and estimated patient-level costs using data on resource use to which we applied Swiss tariffs. Combining the incremental costs of the two strategies and the reduction in the 28-days antibiotic prescription rate (APR) compared to usual care, we calculated Incremental Cost-Effectiveness Ratios (ICER). We also used the Cost-Effectiveness Acceptability Curve as an analytical decision-making tool. The robustness of the findings is ensured by Probabilistic Sensitivity Analysis and scenario analysis. In the base case scenario, the ICER compared to usual care is $2.3 per percentage point (pp) reduction in APR for the procalcitonin group, and $4.4 for procalcitonin-ultrasound combined. Furthermore, we found that for a willingness to pay per patient of more than $2 per pp reduction in the APR, procalcitonin is the strategy with the highest probability to be cost-effective. Our findings suggest that testing patients with respiratory symptoms with procalcitonin to guide antibiotic prescription in the primary care setting represents good value for money.

Serum IgG Immunoglobulin Levels are Associated with Reduced PCR Detection of Mycoplasma bovis in Naturally Infected American Bison (Bison bison).

Mycoplasma bovis is an important pathogen of North American bison (Bison bison), associated with high morbidity and mortality epizootics of respiratory and reproductive disease. Despite the significant negative impact on bison health, little is known about the kinetics of disease and the host immune response to infection. To address these questions, a cohort of bison calves was created and serially sampled 5 times, once every 2-3 mo, over a 12-mo period. At each sampling period nasal swab samples were collected and tested by PCR for the presence of M. bovis. Serum samples were also collected and assessed for M. bovis-specific antibodies using both a commercial and an in-house ELISA. Overall, 19/41 bison (46.3%) had positive PCR tests, and 31/41 (75.6%) were seropositive. Over the course of the study, the frequency of PCR-positive nasal swabs and the ELISA scores decreased, although serum samples remained positive for at least 6 mo following the final positive PCR test. Bison were grouped according to results from the in-house ELISA into high-responder (n=7), low-responder (n=5), and seronegative (n=7) groups. Mycoplasma bovis-specific IgG antibody levels were significantly elevated in the high-responder group compared to the low-responder and seronegative groups. The differences were statistically significant for 3/5 sampling periods. A trend toward increased IgG2 levels was observed in the high-responder group. High total IgG responses correlated with a decline in positive PCR tests from nasal swabs. These data provide evidence that a strong humoral response is beneficial and is probably involved in the clearance of M. bovis from bison.

Abstract A026: PIN1 isomerase promotes the initiation and progression of bladder cancer through SREBP2-mediated cholesterol biosynthesis pathway

Abstract Bladder cancer, one of the most commonly diagnosed cancers worldwide, is associated with high morbidity, mortality, and a poor prognosis. The PIN1 phospho-dependent prolyl isomerase is frequently overexpressed in many human cancer types and affects tumor initiation and progression through disrupting the balance of oncoprotein and tumor suppressor protein signaling. However, the functional pSer/Thr.Pro protein substrates of PIN1 and its effects on downstream signaling in bladder carcinogenesis remain largely unknown. Phenotypically, we discovered that ablation of Pin1 in human/mouse bladder cancer cells and organoids formed from mouse primary urothelial cells resulted in decreased cell proliferation, stemness maintenance, cell invasion, migration, urothelium clearance capacity, and reduced free/total cholesterol levels in vitro. Re-expressing Pin1 in Pin1 knockout cells reversed the defects caused by lack of Pin1. Moreover, in vivo subcutaneous xenograft and allograft transplantation mouse models combined with an orthotopic implantation model were utilized to confirm a positive role for Pin1 in controlling tumor growth and potential metastasis. Therapeutically, a combination of the sulfopin PIN1 inhibitor and the simvastatin HMGCR inhibitor was shown to suppress cell proliferation in vitro and tumor growth in vivo synergistically. Mechanistically, we observed a negative enrichment of SREBP2-driven cholesterol metabolism pathways in PIN1 knockout cells via RNA-sequencing and used a suite of diverse molecular and biochemical approaches to show that PIN1 directly binds to JNK-dependent phosphorylated SREBP2 (Ser455) and vice versa. These results indicate that active cholesterol biosynthesis pathway in bladder cancer cells is regulated by PIN1-mediated isomerization and JNK-mediated phosphorylation of its key transcriptional factor SREBP2. These findings emphasize that PIN1 can act as a regulator and potential therapeutic target in bladder cancer. Citation Format: Xue Wang, Tony Hunter. PIN1 isomerase promotes the initiation and progression of bladder cancer through SREBP2-mediated cholesterol biosynthesis pathway [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A026.

Features of cellular immunity in newborns with cytomegalovirus infection

Cytomegalovirus infection (CMVI) is gaining increasing significance in modern clinical medicine [1‐8]. As a cause of mortality in cases of monospecific disease origin or as a competing condition, CMVI ranks fourth after influenza, herpes, and adenovirusinfections. According to World Health Organization (WHO) data, in developing countries, 90‐100% of the population becomes infected with cytomegalovirus (CMV) during childhood [9]. The European regional bureau of WHO categorizes CMVI as a group of diseases that determine the future of infectious pathology. The relevance of CMVI is attributed to its widespread prevalence among pregnant women, high morbidity, and mortality among children, as well as a wide spectrum of clinical and pathological variants. The frequency of generalized forms of this disease, according to autopsy data, varies from 2.2% among children who died between 7 and 30 days of age to 63.4% among children who died in the first year of life.

Diagnostic and management dilemmas of pregnancies at the utero-tubal junction: A case series and management algorithm.

A pregnancy at the utero-tubal junction is a rare type of ectopic pregnancy and is associated with high maternal morbidity if it remains undetected. In the present study we discuss four cases of ectopic pregnancies at the utero-tubal junction which caused diagnostic and management dilemmas. Four cases of early pregnancies with the gestational sac (G-sac) implanted near the utero-tubal junction are described. In case 1 this was suspected after a failed attempt at dilatation and curettage at our hospital, cases 2 and 3 presented with amenorrhea and pain abdomen and case 4 was diagnosed on first pregnancy documentation scan after frozen embryo transfer. As initial two-dimensional (2D) transvaginal scan (TVS) failed to diagnose the exact location of the G-sac, three-dimensional (3D) TVS helped to localize the exact location of pregnancy and subsequent individualized management. Case 1 had a partial intramural ectopic pregnancy managed by laparotomy and removal of the ectopic sac. The second and third cases were eccentric uterine pregnancies. The fourth was an interstitial ectopic pregnancy managed by a laparoscopic loop and stitch technique. This case series describes the role of 3D TVS for the evaluation of pregnancies implanted at the utero-tubal junction and individual management of eccentric intrauterine, interstitial ectopic and intramural ectopic pregnancies. A diagnostic algorithm for such types of cases and management options is discussed.

Outcomes of peritoneal dialysis in cirrhosis: A systematic review and meta-analysis.

Cirrhosis and end-stage kidney disease (ESKD) are significant global health concerns, contributing to high mortality and morbidity. Haemodialysis (HD) is frequently used to treat ESKD in patients with cirrhosis. However, it often presents challenges such as haemodynamic instability during dialysis sessions, leading to less than optimal outcomes. Peritoneal dialysis (PD), while less commonly used in cirrhotic patients, raises concerns about the risks of peritonitis and mortality. Our systematic review and meta-analysis aimed to assess outcomes in PD patients with cirrhosis. We executed a comprehensive search in Ovid MEDLINE, EMBASE and Cochrane databases up to 25 September 2023. The search focused on identifying studies examining mortality and other clinical outcomes in ESKD patients with cirrhosis receiving PD or HD. In addition, we sought studies comparing PD outcomes in cirrhosis patients to those without cirrhosis. Data from each study were aggregated using a random-effects model and the inverse-variance method. Our meta-analysis included a total of 13 studies with 15,089 patients. Seven studies compared ESKD patients on PD with liver cirrhosis (2753 patients) against non-cirrhosis patients (9579 patients). The other six studies provided data on PD (824 patients) versus HD (1943 patients) in patients with cirrhosis and ESKD. The analysis revealed no significant difference in mortality between PD and HD in ESKD patients with cirrhosis (pooled odds ratio (OR) of 0.77; 95% confidence interval (CI), 0.53-1.14). In PD patients with cirrhosis, the pooled OR for peritonitis compared to non-cirrhosis patients was 1.10 (95% CI: 1.03-1.18). The pooled ORs for hernia and chronic hypotension in cirrhosis patients compared to non-cirrhosis controls were 2.48 (95% CI: 0.08-73.04) and 17.50 (95% CI: 1.90-161.11), respectively. The pooled OR for transitioning from PD to HD among cirrhotic patients was 1.71 (95% CI: 0.76-3.85). Mortality in cirrhosis patients on PD was comparable to non-cirrhosis controls, with a pooled OR of 1.05 (95% CI: 0.53-2.10). Our meta-analysis demonstrates that PD provides comparable mortality outcomes to HD in ESKD patients with cirrhosis. In addition, the presence of cirrhosis does not significantly elevate the risk of mortality among patients undergoing PD. While there is a higher incidence of chronic hypotension and a slightly increased risk of peritonitis in cirrhosis patients on PD compared to those without cirrhosis, the risks of hernia and the need to transition from PD to HD are comparable between both groups. These findings suggest PD as a viable and effective treatment option for ESKD patients with cirrhosis.

Acute viral bronchiolitis in infants: A narrative literature review

Severe acute bronchiolitis is mostly caused by the respiratory syncytial virus (RSV) and is the main cause of hospitalization in children under one year old. Although it has a low mortality rate, it has a high morbidity rate, requiring early diagnosis through a detailed clinical history and physical examination. A narrative review of fourteen articles found in the PubMED/MEDLINE, SciELO and BVS electronic databases was therefore carried out, with the aim of reviewing the most up-to-date literature on the subject. Currently, the monoclonal antibody Palivizumab is the main agent used to prevent bronchiolitis and is available for patients at high risk of developing the serious disease. In addition, the Abryso vaccine was recently approved by the National Health Surveillance Agency (Anvisa) and will be administered to pregnant women in the last trimester of pregnancy, with the aim of preventing the disease in newborns. Finally, it was found that the appropriate management of acute viral bronchiolitis consists of supportive measures such as hydration, nutritional support and oxygenation when necessary, while the use of corticosteroids and bronchodilators has not been shown to reduce the length of hospital stay or the natural course of the disease.

Patterns of Palliative Care Consultation in Neurosurgical Patients.

Numerous neurosurgical (NSG) conditions entail high morbidity, mortality, and prolonged ICU stays. Palliative care (PC) serves to alleviate suffering, align treatment with patient preferences, and is linked to enhanced patient and family outcomes as well as reduced care costs. Notably, no studies have addressed demographic and clinical factors associated with PC receipt in NSG patients. Our aim is to identify characteristics and outcomes, particularly end of life outcomes, of hospitalized NSG patients associated with a PC consult compared with usual NSG care. A retrospective chart review was performed of patients admitted to the NSG service from January 1, 2017 to December 31, 2018 at the University of Iowa Hospitals & Clinics. Data regarding demographics, clinical outcomes, and GOC and ACP documentation were collected. The most common reasons for a PC consult were goals of care, end of life issues, and comfort care. Of 121 total decedent patients, 97 (80.2%) had PC referrals. Patients with a PC referral had longer hospital stays (10.3days vs 4days) and had the majority of care in the ICU (90.7% vs 83.3%). However, fewer PC patients died in the ICU (42.3% vs 75%) and more had PCA/NCA use (51.5% vs 8.3%), code status changes to DNR (90.7% vs 62.5%), GOC documented (78.4% vs 0%) and ACP documentation (35.1% vs 16.7%). In conclusion, in NSG patients, the integration of PC may contribute to improved end-of-life care.

CHANGES IN LEFT ATRIAL VOLUME DURING ECHOSTRESS IN PATIENTS UNDERGOING MITRAL VALVE PLASTIC CARDIAC SURGERY

Abstract Mitral Regurgitation (MR) is characterized by a high morbidity and mortality that often finds a solution only in the reparative surgical treatment, in particular in presence of myxomatous degeneration that cause the prolapse of one or both leaflets. This results in an increase in diastolic pressure that leads to a progressive dilation of the left atrium. The increase in Left Atrium Volume Index (LAVI) during stress test represents a negative prognostic factor in the clinical evolution of many pathologies, such as ischemic heart disease, hypertrophic cardiomyopathy, heart failure. An increase in peak/rest LAVI >6.8 ml/m2 correlates with a higher incidence of heart failure decompensation, reduced left ventricular contractile reserve (LVCR), pulmonary congestion. We evaluate the effect of MR reparative surgery on the changes of LAVI during stress–echo. We enrolled 19 patients, 11 females and 8 males, affected by MR candidate to cardiac surgery. We performed a physical stress–echo test by using the ABCDE protocol suggested by the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI), before and after 12 weeks from surgery. During each test, the changes in LAVI (ΔLAVI) expressed as peak/rest difference in ml/m2 was measured. In addition, the prognostic score deriving from the sum of the ABCDE criteria was calculated, such as the LVCR (C parameter of the score) that represents a parameter of the force deriving from the hemodynamic changes during the test. In all patients we observed a significant reduction in ΔLAVI (8.4+0.5 mL/m2 vs 9.7+0.7 mL/m2; p<0.0001). In addition, there was a significant reduction in the ABCDE prognostic score (from 4.19+0.43 to 3.48+0.37; p=0.002), secondary to the increase in the LVCR observed approximately 3 months after surgery (from 1.77 mmHg/ml to 2.44 mmHg/ml, p<0.0001), as well as a significant reduction in pulmonary congestion during stress (B parameter). There were no significant changes in ejection fraction, wall motion score index–WMSI (A parameter), coronary reserve (D parameter) and heart rate reserve (E parameter). These data demonstrate for the first time that mitral valve plastic surgery is able to reduce the ΔLAVI during stress echocardiography in patients with severe MR. The surgical procedure also resulted in both an improvement in the LVCR and a reduction in the degree of pulmonary congestion, that ultimately led to an improvement in the ABCDE prognostic score.

Frailty Assessment for Risk Stratification in Pancreatic Surgery – Results of a Single-Center Cohort Study

Abstract Background Large cohort studies found an increase in frailty with age. Age is a known risk factor for pancreatic cancer. Seventy percent of new diagnoses are made in patients aged more than 65 years. Pancreatic resections represent the only hope for cure but are associated with high morbidity. The definition “fit for pancreatic surgery”, currently mainly based on age and comorbidities, is continuously challenged. Aims The aim of this study is to analyze the impact of frailty on postoperative outcomes after pancreatic resections. Methods Data of consecutive patients undergoing pancreatic resections between January 2015 and July 2022 were retrospectively analyzed. Postoperative complications were graded by the Clavien-Dindo Classification, Comprehensive Complication Index (CCI) and complications specific to pancreatic resections as recommended and published by the International Study Group of Pancreatic Surgery. The modified frailty index (mFI) was defined by 11 variables. An mFI score above 0.27 was set to define frailty. Results A pancreatic resection was performed in 159 patients, of which 23 (15%) were classified as frail. Pancreatoduodenectomies were similarly distributed in both groups. Frail patients were older (median of 74 vs. 69 years). Male gender was associated with frailty (83%, p=0.001)., Moreover, frailty was associated with an increased rate of preoperative biliary drainage. Although intensive care stay was increased in the frail group (median 3 vs. 0 days; p=0.01), total length of hospital stay was not affected. Frailty was associated with severe complications as defined by a comprehensive complication index >50 (35% vs. 10%; p=0.003), an increased rate of severe type C pancreatic fistula (13% vs. 2%, p=0.04), and a higher 90-day mortality (13% vs. 2%, p=0.04). Conclusion Assessment of frailty should be used for preoperative risk stratification since frailty is associated with a higher morbidity and mortality after pancreatic resections.

Characterization of Colon Anastomosis Healing in Obese Mice

Abstract Background Colon anastomosis leak is the most feared complication in colorectal surgery, with high morbidity and mortality. Despite the identification of correctible risk factors, its incidence has remained stable for the past 50 years. One of the risk factors is obesity, a systemic disease whose prevalence is continuously increasing worldwide. To understand the implicated mechanisms, and to develop therapeutic strategies, characterization of colon anastomosis healing in obese subjects is mandatory. Aims We aimed to describe the colon anastomotic healing process in obese mice, with a secondary aim to identify potential targets to decrease post-operative leaks. Methods Three groups of mice were fed different diets for 16 weeks: normal diet only (ND), high-fat diet reverted to normal diet on day of surgery (HF-ND), or high-fat diet only (HF-HF). Surgery consisted of left colon hemi-transection on the anti-mesenteric wall, and subsequent anastomosis with separate stitches. N=5 mice from each group were sacrificed at days 3, 5, 7, 10 and 14 after surgery. Results HF-HF mice had diarrhea and lost weight up to day 10 after surgery, compared to day 1 for ND mice. Overall, abscess rate was 4% in ND and HF-ND, and 8% in HF-HF mice. Free leak rate was 0% in ND and HF-ND, and 16% in HF-HF mice (p=0.03). Angiogenesis was decreased in HF-HF mice at day 5 compared to ND mice (p=0.02). Conclusion Obese mice undergoing continued high-fat diet (HF-HF) globally demonstrated worst outcomes after colon anastomosis with increased leak rates, and decreased angiogenesis. Despite having similarly low angiogenesis, these results seem to be mitigated in high-fat diet fed mice reverting to normal diet on day of surgery (HF-ND), hinting towards an involvement of gut microbiota. Further analysis of gut microbiota and angiogenesis pathways are warranted in order to determine therapeutic strategies.

Pathological Complete Response after Radio Chemotherapy and Esophagectomy – false Sense of Security?

Abstract Background Esophageal cancer (EC) is associated with a high morbidity and mortality, even in a curative treatment approach. The current standard of care for curative treatment of EC consists of neoadjuvant radio chemotherapy (RCT) followed by resection. Pathological response in the resected tissue is a well-known predictor of disease-free (DFS) and overall survival (OS). Yet, even in a pathological complete response (pCR), cancer recurrence is not infrequent. Aims To analyze DFS and OS in patients with pCR after trimodal therapy and identify risk factors for recurrence. Methods We retrospectively analyzed all patients with pathological complete response after RCT and esophagectomy treated for EC between 01/2014 and 12/2021. Clinical data such as demographic data, tumor characteristics at staging and restaging and postoperative follow-up, were extracted from electronic medical records. Results Of 28 patients, 10 (35.7%) developed cancer recurrence. There were no statistically significant differences in patient or tumor characteristics between patients with or without recurrence. Recurrence occurred after a median 21 months (IQR 30). Median OS was 40.5 months (IQR 40) in patients with and 48.5 months (IQR 32) in patients without recurrence (p=0.121). Recurrence was mostly distant (n = 9, 90%). 4 (of 10, 40%) patients were then addressed in curative, 6 (60%) in palliative intention. Predictive factors for cancer recurrence were persistent tumor in endosonography and/or computed tomography during restaging. Conclusion Even in patients with pCR after RCT and esophagectomy, around one third develops cancer recurrence. A tight follow-up with special attention to distant rather than local recurrence seems beneficial. Patients with an aspect of only partial response at restaging are at higher risk for recurrence and should be monitored even closer.