The influence of gut microbiome on periprosthetic joint infections: State-of-the art.

Early periprosthetic joint infection constitutes one of the most frightening complications of joint replacement. Recently, some evidence has highlighted the potential link between dysregulation of the gut microbiota and degenerative diseases of joints. It has been hypothesized that microbiome dysbiosis may increase the risk of periprosthetic joint infection by facilitating bacterial translocation from these sites to the bloodstream or by impairing local or systemic immune responses. Although the processes tying the gut microbiome to infection susceptibility are still unknown, new research suggests that the presurgical gut microbiota-a previously unconsidered component-may influence the patient's ability to resist infection. Exploring the potential impact of the microbiome on periprosthetic joint infections may therefore bring new insights into the pathogenesis and therapy of these disorders. For a successful therapy, a proper surgical procedure in conjunction with an antibacterial concept is essential. As per the surgical approach, different treatment strategies include surgical irrigation, debridement, antibiotic therapy, and implant retention with or without polyethylene exchange. Other alternatives could be one-stage or two-stage revisions surgery. Interventions that either directly target gut microbes as well as interventions that modify the composition and/or function of the commensal microbes represent an innovative and potentially successful field to be explored. In recent times, innovative therapeutic methods have arisen in the realm of microbiome restoration and the management of gut-related ailments. These progressive approaches offer fresh perspectives on tackling intricate microbial imbalances in the gastrointestinal tract. These emerging therapies signify a shift towards more precise and individualized approaches to microbiome restoration and the management of gut-related disorders. Once a more advanced knowledge of the pathways linking the gut microbiota to musculoskeletal tissues is gained, relevant microbiome-based therapies can be developed. If dysbiosis is proven to be a significant contributor, developing treatments for dysbiosis may represent a new frontier in the prevention of periprosthetic joint infections.

Orodispersible Film Based on Maltodextrin: A Convenient and Suitable Method for Iron Supplementation.

Orodispersible film (ODF) is an innovative dosage form used to administer drugs and nutrients, designed to disintegrate or dissolve in the oral cavity without needing water. One of the advantages of ODF is that it is suitable for administration in older people and children who have difficulty swallowing because of psychological or physiological deficiencies. This article describes the development of an ODF based on maltodextrin, which is easy to administer, has a pleasant taste, and is suitable for iron supplementation. An ODF containing 30 mg of iron as pyrophosphate and 400 µg of folic acid (iron ODF) was developed and manufactured on an industrial scale. The kinetic profile for serum iron and folic acid upon consumption of ODF compared with a Sucrosomial® iron capsule (known for its high bioavailability) was evaluated in a crossover clinical trial. The study was conducted in nine healthy women, and the serum iron profile (AUC0-8, Tmax, and Cmax) of both formulations was defined. Results showed that the rate and extent of elemental iron absorption with iron ODF was comparable to that obtained using the Sucrosomial® iron capsule. These data represent the first evidence of iron and folic acid absorption concerning the newly developed ODF. Iron ODF was proven to be a suitable product for oral iron supplementation.

The specialized pro-resolving lipid mediator Protectin D1 affects macrophages differentiation and activity in Adult-onset Still's disease and COVID-19, two hyperinflammatory diseases sharing similar transcriptomic profiles.

Introduction: COVID-19 and autoinflammatory diseases, such as Adult-onset Still's Disease (AOSD), are characterized by hyperinflammation, in which it is observed massive production and uncontrolled secretion of pro-inflammatory cytokines. The specialized pro-resolving lipid mediators (SPMs) family is one the most important processes counteracting hyperinflammation inducing tissue repair and homeostasis restoration. Among SPMs, Protectin D1 (PD1) is able to exert antiviral features, at least in animal models. The aim of this study was to compare the transcriptome of peripheral blood mononuclear cells (PBMCs) from patients with AOSD and COVID-19 and to evaluate the role of PD1 on those diseases, especially in modulating macrophages polarization. Methods: This study enrolled patients with AOSD, COVID-19, and healthy donors HDs, undergoing clinical assessment and blood sample collection. Next-generation deep sequencing was performed to identify differences in PBMCs transcripts profiles. Plasma levels of PD1 were assessed by commercial ELISA kits. Monocyte-derived macrophages were polarized into M1 and M2 phenotypes. We analyzed the effect of PD1 on macrophages differentiation. At 10 days, macrophages were analyzed for surface expression of subtypes markers by flow cytometry. Cytokines production was measured in supernatants by Bio-Plex Assays. Results: In the transcriptomes from AOSD patients and COVID-19 patients, genes involved in inflammation, lipid catabolism, and monocytes activation were specifically dysregulated in AOSD and COVID-19 patients when compared to HDs. Patients affected by COVID-19, hospitalized in intensive care unit (ICU), showed higher levels of PD1 when compared to not-ICU hospitalized patients and HDs (ICU COVID-19 vs not-ICU COVID-19, p= 0.02; HDs vs ICU COVID-19, p= 0.0006). PD1 levels were increased in AOSD patients with SS ≥1 compared to patients with SS=0 (p=0.028) and HDs (p=0.048). In vitro treatment with PD1 of monocytes-derived macrophages from AOSD and COVID-19 patients induced a significant increase of M2 polarization vs control (p<0.05). Furthermore, a significant release of IL-10 and MIP-1ß from M2 macrophages was observed when compared to controls (p<0.05). Discussion: PD1 is able to induce pro-resolutory programs in both AOSD and COVID-19 increasing M2 polarization and inducing their activity. In particular, PD1-treated M2 macrophages from AOSD and COVID-19 patients increased the production of IL-10 and enhanced homeostatic restoration through MIP-1ß production.

Postoperative procalcitonin is a biomarker for excluding the onset of clinically relevant pancreatic fistula after pancreaticoduodenectomy.

Background: Early detection and therapy of pancreatic fistula after pancreaticoduodenectomy is crucial to improve outcomes of this surgery. Since it is not clear if procalcitonin (PCT), can predict the onset of clinically relevant post-operative pancreatic fistula (CR-POPF), we aimed to investigate this ability. Methods: One-hundred-thirty pancreaticoduodenectomies (PD) were analyzed. Receiver Operating Characteristic curves analysis defined the optimal cut-offs for PCT and drains amylase levels (DAL). Complications were compared using chi-square for proportions test. Results: DAL ≥2,000 U/L in postoperative day (POD) 2 had 71% positive predictive value (PPV) and 91% negative predictive value (NPV) for CR-POPF (P<0.001). In POD2, PCT ≥0.5 ng/mL showed NPV 91% (P<0.045) and increased DAL PPV for CR-POPF to 81%. In POD3, POD4 and POD5, DAL (cut-offs 780, 157 and 330 U/L, respectively) showed NPV for CR-POPF >90% (P<0.0001). PCT ≥0.5 ng/mL showed NPV for CR-POPF of about 90%. In POD5, combining DAL (cut-off 330 U/L) and PCT (cut-off 0.5 ng/mL), a PPV for CR-POPF of 81% was detected. A progressive increased risk of CR-POPF from POD2 [odds ratio (OR) =3.05; P=0.0348] to POD5 (OR =4.589; P=0.0082) was observed. In POD2 and 5, PCT ≥0.5 ng/mL, alone and in combination with DAL, may be a reliable marker for identifying patients at highest risk of CR-POPF after PD. Conclusions: This association could be proposed to select high risk patients that could benefit of "intensive" postoperative management.

Associated effects of clinical characteristics, risk factors, and comorbidity on disease severity and mortality among patients with COVID-19 in Sulaimani City/ Kurdistan Region of Iraq.

The effects of clinical symptoms, laboratory indicators, and comorbidity status of SARS-CoV-2-infected patients on the severity of disease and the risk of death were investigated. Questionnaires and electronic medical records of 371 hospitalized COVID-19 patients were used for data collection (demographics, clinical manifestation, comorbidities, laboratory data). Association among categorical variables was determined using Kolmogorov-Smirnov test (P-value ≤0.05). Median age of study population (249 males, 122 females) was 65 years. Roc curves analysis found that age ≥64 years and age ≥67 years are significant cut-offs identifying patients with more severe disease and mortality at 30 days. CRP values at cut-off ≥80.7 and ≥95.8 significantly identify patients with more severe disease and mortality. Patients with more severe disease and risk of death were significantly identified with platelet value at the cut-off ≤160,000, hemoglobin value at the cut-off ≤11.7, D-Dimer values ≥1383 and ≥1270, and with values of neutrophil granulocytes (≥8.2 and ≤2) and lymphocytes (≤2 and ≤2.4). Detailed clinical investigation suggests granulocytes together with lymphopenia may be a potential indicator for diagnosis. Older age, several comorbidities (cancer, cardiovascular diseases, hypertension) and more laboratory abnormalities (CRP, D-Dimer, platelets, hemoglobin) were associated with development of more severity and mortality among COVID-19 patients.

Implications of Possible HBV-Driven Regulation of Gene Expression in Stem Cell-like Subpopulation of Huh-7 Hepatocellular Carcinoma Cell Line.

Elevated levels of STIM1, an endoplasmic reticulum Ca2+ sensor/buffering protein, appear to be correlated with poor cancer prognosis in which microRNAs are also known to play critical roles. The purpose of this study is to investigate possible HBV origins of specific microRNAs we identified in a stem cell-like subpopulation of Huh-7 hepatocellular carcinoma (HCC) cell lines with enhanced STIM1 and/or Orai1 expression that mimicked poor cancer prognosis. Computational strategies including phylogenetic analyses were performed on miRNome data we obtained from an EpCAM- and CD133-expressing Huh-7 HCC stem cell-like subpopulation with enhanced STIM1 and/or Orai1 expression originally cultured in the present work. Results revealed two putative regions in the HBV genome based on the apparent clustering pattern of stem loop sequences of microRNAs, including miR3653. Reciprocal analysis of these regions identified critical human genes, of which their transcripts are among the predicted targets of miR3653, which was increased significantly by STIM1 or Orai1 enhancement. Briefly, this study provides phylogenetic evidence for a possible HBV-driven epigenetic remodeling that alters the expression pattern of Ca2+ homeostasis-associated genes in STIM1- or Orai1 overexpressing liver cancer stem-like cells for a possible mutual survival outcome. A novel region on HBV-X protein may affect liver carcinogenesis in a genotype-dependent manner. Therefore, detection of the viral genotype would have a clinical impact on prognosis of HBV-induced liver cancers.

Validations of new cut-offs for surgical drains management and use of computerized tomography scan after pancreatoduodenectomy: The DALCUT trial.

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most fearful complication after pancreatic surgery and can lead to severe postoperative complications such as surgical site infections, sepsis and bleeding. A previous study which identified cut-offs of drains amylase levels (DALs) determined on postoperative day (POD) 1 and POD3, was able to significantly predict POPF, abdominal collections and biliary fistulas, when related to specific findings detected at the abdominal computerized tomography (CT) scan routinely performed on POD3. AIM: To validate the cut-offs of DALs in POD1 and POD3, established during the previous study, to assess the risk of clinically relevant POPF and confirm the usefulness of abdominal CT scan on POD3 in patients at increased risk of abdominal collection. METHODS: The DALCUT trial is an interventional prospective study. All patients who will undergo pancreatoduodenectomy (PD) for periampullary neoplasms will be considered eligible. All patients will receive clinical staging and, if eligible for surgery, will undergo routine preoperative evaluation. After the PD, daily DALs will be evaluated from POD1. Drains removal and possible requirement of abdominal CT scans in POD3 will be managed on the basis of the outcome of DALs in the first three postoperative days. RESULTS: This prospective study could validate the role of DALs in the management of surgical drains and in assessing the risk or relevant complications after PD. Drains could be removed in POD3 in case of POD1 DALs < 666 U/L and POD3 DALs < 207 U/L. In case of POD3 DALs ≥ 252, abdominal CT scan will be performed in POD3 to identify abdominal collections ≥ 5 cm. In this latter category of patients, drains could be maintained beyond POD3. CONCLUSION: The results of this trial will contribute to a better knowledge of POPF and management of surgical drains.

Clinical validation of full HR-HPV genotyping HPV Selfy assay according to the international guidelines for HPV test requirements for cervical cancer screening on clinician-collected and self-collected samples.

BACKGROUND: According to international guidelines, Human Papillomavirus (HPV) DNA tests represent a valid alternative to Pap Test for primary cervical cancer screening, provided that they guarantee balanced clinical sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or more (CIN2+) lesions. The study aimed to assess whether HPV Selfy (Ulisse BioMed - Trieste, Italy), a full-genotyping HPV DNA test that detects and differentiates 14 high-risk HPV (HR-HPV) types, meets the criteria for primary cervical cancer screening described in the international guidelines, on clinician-collected as well as on self-collected samples. METHODS: For each participant woman, consecutively referring to Azienda Sanitaria Universitaria Giuliano Isontina (Trieste, Italy) and CRO-National Cancer Institute (Aviano, Italy) for the cervical cancer screening program, the following samples were tested: (a) a clinician-collected cervical specimen, analyzed with the reference test (Hybrid Capture®2 test, HC2) and HPV Selfy; and (b) a self-collected vaginal sample, analyzed with HPV Selfy. Enrolled women were also asked to fulfill a questionnaire about self-sampling acceptability. As required by guidelines, a non-inferiority test was conducted to compare the clinical performance of the test under evaluation with its reference test. RESULTS: HPV Selfy clinical sensitivity and specificity resulted non-inferior to those of HC2. By analysis of a total of 889 cervical liquid-based cytology samples from a screening population, of which 98 were from women with CIN2+, HPV Selfy showed relative sensitivity and specificity for CIN2+ of 0.98 and 1.00 respectively (non-inferiority score test: P = 0.01747 and P = 0.00414, respectively); the test reached adequate intra- and inter-laboratory reproducibility. Moreover, we demonstrated that the performance of HPV Selfy on self-collected vaginal samples was non-inferior to the performance obtained on clinician-collected cervical specimen (0.92 relative sensitivity and 0.97 relative specificity). Finally, through HPV Selfy genotyping, we were able to describe HPV types prevalence in the study population. CONCLUSIONS: HPV Selfy fulfills all the requirements of the international Meijer's guidelines and has been clinically validated for primary cervical cancer screening purposes. Moreover, HPV Selfy has also been validated for self-sampling according to VALHUDES guidelines. Therefore, at date, HPV Selfy is the only full-genotyping test validated both for screening purposes and for self-sampling. Trial registration ASUGI Trieste n. 16008/2018; CRO Aviano n.17149/2018.

Utility of preoperative systemic inflammatory biomarkers in predicting postoperative complications after pancreaticoduodenectomy: Literature review and single center experience.

BACKGROUND: The role of preoperative inflammatory biomarkers (PIBs) in predicting postoperative morbidity has been assessed in colorectal and otorhinolaryngeal surgery. However, data regarding the role that preoperative inflammatory biomarkers have on morbidity after pancreaticoduodenectomiy (PD) are less consistent. AIM: To assess the utility of PIBs in predicting postoperative complications after pancreaticoduodenectomy. METHODS: A database of 317 consecutive pancreaticoduodenectomies performed from April 2003 to November 2018 has been retrospectively analyzed. Data regarding preoperative neutrophil-to-lymphocyte ratio (NLR), derived NLR and C-reactive protein (CRP), and postoperative complications of 238 cases have been evaluated. Exclusion criteria were: age < 18-years-old, previous neoadjuvant treatment, absence of data about PIBs, concomitant hematological disorders, and presence of active infections at the moment of the surgery. PIBs were compared using Mann-Whitney's test and receiver operating characteristic (ROC) analysis was performed to define the cutoffs. The positive predictive value (PPV) was computed to evaluate the probability to develop complication. P-values < 0.05 were considered statistically significant. RESULTS: According to the literature findings, only four papers have been published reporting the relation between the inflammatory biomarkers and PD postoperative morbidity. A combination of preoperative and postoperative inflammatory biomarkers in predicting complications after PD and the utility of preoperative NLR in the development of postoperative pancreatic fistula (POPF) have been reported. The combination of PIBs and postoperative day-1 drains amylase has been reported to predict the incidence of POPF. According to our results, CRP values were significantly different between patients who had/did not have postoperative complications and abdominal collections (P < 0.05). Notably, patients with preoperative CRP > 8.81 mg/dL were at higher risk of both overall complications and abdominal collections (respectively P = 0.0037, PPV = 0.95, negative predictive value [NPV] = 0.27 and P = 0.016, PPV = 0.59, NPV = 0.68). Preoperative derived neutrophil-to-lymphocyte ratio (dNLR) (cut off > 1.47) was also a predictor of abdominal collection (P = 0.021, PPV = 0.48, NPV = 0.71). Combining CRP and dNLR, PPV increased to 0.67. NLR (cut off > 1.65) was significantly associated with postoperative hemorrhage (P = 0.016, PPV = 0.17, NPV = 0.98). CONCLUSION: PIBs may predict complications after PD. During postoperative care, PIB levels could influence decisions regarding the timing of drains removal and the selection of patients who might benefit from second level diagnostic exams.

The miR-133a, TPM4 and TAp63γ Role in Myocyte Differentiation Microfilament Remodelling and Colon Cancer Progression.

MicroRNAs (miRNAs) play an essential role in the regulation of a number of physiological functions. miR-133a and other muscular miRs (myomiRs) play a key role in muscle cell growth and in some type of cancers. Here, we show that miR133a is upregulated in individuals that undertake physical exercise. We used a skeletal muscle differentiation model to dissect miR-133a's role and to identify new targets, identifying Tropomyosin-4 (TPM4). This protein is expressed during muscle differentiation, but importantly it is an essential component of microfilament cytoskeleton and stress fibres formation. The microfilament scaffold remodelling is an essential step in cell transformation and tumour progression. Using the muscle system, we obtained valuable information about the microfilament proteins, and the knowledge on these molecular players can be transferred to the cytoskeleton rearrangement observed in cancer cells. Further investigations showed a role of TPM4 in cancer physiology, specifically, we found that miR-133a downregulation leads to TPM4 upregulation in colon carcinoma (CRC), and this correlates with a lower patient survival. At molecular level, we demonstrated in myocyte differentiation that TPM4 is positively regulated by the TA isoform of the p63 transcription factor. In muscles, miR-133a generates a myogenic stimulus, reducing the differentiation by downregulating TPM4. In this system, miR-133a counteracts the differentiative TAp63 activity. Interestingly, in CRC cell lines and in patient biopsies, miR-133a is able to regulate TPM4 activity, while TAp63 is not active. The downregulation of the miR leads to TPM4 overexpression, this modifies the architecture of the cell cytoskeleton contributing to increase the invasiveness of the tumour and associating with a poor prognosis. These results add data to the interesting question about the link between physical activity, muscle physiology and protection against colorectal cancer. The two phenomena have in common the cytoskeleton remodelling, due to the TPM4 activity, that is involved in stress fibres formation.

CA19.9 Serum Level Predicts Lymph-Nodes Status in Resectable Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Center Analysis.

BACKGROUND: The choice between upfront surgery or neoadjuvant treatments (NAT) for resectable pancreatic ductal adenocarcinoma (R-PDAC) is controversial. R-PDAC with potential nodal involvement could benefit from NT. Ca (Carbohydrate antigen) 19.9 and serum albumin levels, alone or in combination, have proven their efficacy in assessing PDAC prognosis. The objective of this study was to evaluate the role of Ca 19.9 serum levels in predicting nodal status in R-PDAC. METHODS: Preoperative Ca 19.9, as well as serum albumin levels, of 165 patients selected for upfront surgery have been retrospectively collected and correlated to pathological nodal status (N), resection margins status (R) and vascular resections (VR). We further performed ROC curve analysis to identify optimal Ca 19.9 cut-off for pN+, R+ and vascular resection prediction. RESULTS: Increased Ca 19.9 levels in 114 PDAC patients were significantly associated with pN+ (p <0.001). This ability, confirmed in all the series by ROC curve analysis (Ca 19.9 ≥32 U/ml), was lost in the presence of hypoalbuminemia. Furthermore, Ca 19.9 at the cut off >418 U/ml was significantly associated with R+ (87% specificity, 36% sensitivity, p 0.014). Ca 19.9, at the cut-off >78 U/ml, indicated a significant trend to predict the need for VR (sensitivity 67%, specificity 53%; p = 0.059). CONCLUSIONS: In R-PDAC with normal serum albumin levels, Ca 19.9 predicts pN+ and R+, thus suggesting a crucial role in deciding on NAT.

Perioperative management after elective cardiac surgery: the predictive value of procalcitonin for infective and noninfective complications.

Objective: Procalcitonin (PCT) has been associated with adverse outcomes after cardiac surgery. Nevertheless, there is no consensus on thresholds and timing of PCT measurement to predict adverse outcomes. Materials & methods: A total of 960 patients undergoing elective cardiac surgery were retrospectively evaluated. PCT levels were measured from the first to the seventh postoperative day (POD). The onset of complications was recorded. Results: Complications occurred in 421 (44%) patients. PCT on the third POD was associated with the occurrence of any kind of complications (odds ratio: 1.06; p: 0.037), and noninfectious complications (odds ratio: 1.05; p: 0.035), after adjusting. PCT above the median value at the third POD (>0.33 µg/l) predicted postoperative complications (incidence rate ratio: 1.13; p = 0.035). Conclusion: PCT seems to predict postoperative complications in cardiac surgery. The determination at the third POD yields the greatest sensitivity and specificity.

Deep Learning Algorithm Trained with COVID-19 Pneumonia Also Identifies Immune Checkpoint Inhibitor Therapy-Related Pneumonitis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pneumonia and immune checkpoint inhibitor (ICI) therapy-related pneumonitis share common features. The aim of this study was to determine on chest computed tomography (CT) images whether a deep convolutional neural network algorithm is able to solve the challenge of differential diagnosis between COVID-19 pneumonia and ICI therapy-related pneumonitis. METHODS: We enrolled three groups: a pneumonia-free group (n = 30), a COVID-19 group (n = 34), and a group of patients with ICI therapy-related pneumonitis (n = 21). Computed tomography images were analyzed with an artificial intelligence (AI) algorithm based on a deep convolutional neural network structure. Statistical analysis included the Mann-Whitney U test (significance threshold at p < 0.05) and the receiver operating characteristic curve (ROC curve). RESULTS: The algorithm showed low specificity in distinguishing COVID-19 from ICI therapy-related pneumonitis (sensitivity 97.1%, specificity 14.3%, area under the curve (AUC) = 0.62). ICI therapy-related pneumonitis was identified by the AI when compared to pneumonia-free controls (sensitivity = 85.7%, specificity 100%, AUC = 0.97). CONCLUSIONS: The deep learning algorithm is not able to distinguish between COVID-19 pneumonia and ICI therapy-related pneumonitis. Awareness must be increased among clinicians about imaging similarities between COVID-19 and ICI therapy-related pneumonitis. ICI therapy-related pneumonitis can be applied as a challenge population for cross-validation to test the robustness of AI models used to analyze interstitial pneumonias of variable etiology.

The use of an implemented infection prevention bundle reduces the incidence of surgical site infections after colorectal surgery: a retrospective single center analysis.

BACKGROUND: Surgical-site infections (SSIs) represent the most common complications after colorectal surgery (CS). Role of preoperative administration of oral antibiotic prophylaxis (OAP) and mechanical bowel preparation (MBP), alone or in combination, in the prevention of SSIs after CS is debated. Aim of this study was to assess the effect of the introduction of an Implemented Infection Prevention Bundle (IIPB) in preventing SSIs in CS. METHODS: A group of 251 patients (Group 1) who underwent CS receiving only preoperative intravenous antibiotic prophylaxis (IAP) was compared to a Group of 107 patients (Group 2) who also received the IIPB. The IIPB consisted of the combination of oral administrations of three doses of Rifaximin 400 mg and MBP the day before surgery and in the administration of a cleansing enema the day of the surgical procedure. RESULTS: At the univariate analysis, Group 2 showed significant lower rates of wound infection (WI) (2.8% vs. 9.9%; p = 0.021) and anastomotic leakage (AL) (2.8% vs. 14.7%; p = 0.001) with shorter hospital stay (5 vs. 6 days; p < 0.0001). The probability of postoperative AL was lower in Group 2; patients in this Group resulted protected from AL; a statistically significant Odds ratio of 0.16 (CI 0.05-0.55 p = 0.0034) was found. In diabetic patients, that were at higher risk of WI (OR 3.53, CI 1.49-8.35 p = 0.002), despite having any impact on anastomotic dehiscence, the use of IIPB significantly reduced the rate of WI (0% vs 28.1%; p = 0.01). CONCLUSION: The use of an IIPB significantly reduces rates of SSIs and post-operative hospital stay after CS.

Laparoscopic total mesorectal excision (L-TME) for rectal cancer surgery: does elective diverting ileostomy really protect? An observational retrospective cohort study.

AIMS: Elective diverting ileostomy may reduce consequences of anastomotic leakage after laparoscopic total mesorectal excision (L-TME); however, its safety is debated because of morbidity related to stoma creation and closure. We aimed to investigate the impact of diverting ileostomy on clinical behavior of anastomotic leakage and complications related to stoma itself. MATERIAL OF THE STUDY: We retrospectively evaluated 150 L-TMEs with (Group 1, 100 patients) or without (Group 2, 50 patients) elective ileostomy for rectal cancer. RESULTS: Overall anastomotic fistula rate was 26% without significant differences between the two groups (28% in the Group 1 and 22% in the Group 2, respectively). In all the series, NAD was significantly associated with higher risk of postoperative complications (OR=2.14, p=0.02). In Group 2, NAD particularly increased the risk of anastomotic fistula (OR=6.6, p=0.014). Instead, patients of Group 1 showed higher odd of post-operative complications (OR: 3.8; CI 95%: 1.8483-8.0492; p = 0.0003) and notably 79 (79%) developed complications related to the ileostomy itself (hydroelectrolytic, metabolic and peristomal skin disorders). Moreover, thirty-two (32%) ileostomies were never reversed; among the reversed patients, 27 (39.7%) developed at least one postoperative complication and in 9 (33.3%) cases an urgent re-intervention was needed. DISCUSSION: Diverting ileostomy may mitigate clinical behavior of anastomotic leakage after L-TME. However, there is non-negligible morbidity of stoma creation and closure. CONCLUSION: Diverting ileostomy should be selectively considered in higher risk patients as those who received NAD. KEY WORDS: Anastomotic leakage, Ileostomy, Rectal cancer.

Safety and tolerability of a novel oral nutritional supplement in healthy volunteers.

BACKGROUND AND OBJECTIVE: Foods for Special Medical Purposes (FSMPs) are formulated to support the nutritional needs of subjects with impaired capacity to ingest, digest or absorb ordinary food or nutrients. Polglumyt® is a proprietary highly purified, high quality glycogen obtained from mussels. Here we report the results of a single-center, single dose, open label, single arm study carried out to investigate acceptance (i.e. gastrointestinal tolerance and palatability), metabolic profile and safety of a low osmolarity, high-density energy Polglumyt®-based drink (the investigational product, IP) as a novel FSMP. METHODS: Twelve healthy subjects received a single oral administration of the IP under fasting conditions. The study endpoints were: changes in gastrointestinal system tolerability at 3 h, 6 h and 24 h after IP intake; IP palatability evaluation; metabolic evaluation through the kinetic profile of circulating glucose, insulin and C-peptide from 0 h to 6 h after IP intake and changes from baseline in circulating triglycerides at 3 h and 6 h after IP intake. RESULTS: The IP showed a good gastrointestinal tolerability and an acceptable palatability. The IP did not affect the physiological glycemic profile and the triglycerides levels 6 h after the intake. The IP was well tolerated by study subjects, with no or minor adverse events. CONCLUSIONS: The study results encourage additional clinical investigations on the IP as a novel FSMP in patients with impaired digestion or gastrointestinal absorption, unable to assume an ordinary diet, e.g. patients undergoing invasive gastrointestinal surgery, elderly or oncological patients, even with certain metabolic disorders.

Procalcitonin in the Assessment of Ventilator Associated Pneumonia: A Systematic Review.

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most common nosocomial infection, associated with considerable mortality and morbidity in critically ill patients; however, its diagnosis and management remain challenging since clinical assessment is often poorly reliable. The aim of this systematic review was to evaluate the role of PCT in the diagnosis and management of critical ill patients affected by VAP. METHODS: We performed a systematic review of the evidence published over the last 10 years and currently available in medical literature search databases (Pubmed, Embase, Web of Knowledge, Cochrane Libraries) and searching clinical trial registries. We regarded as predefined outcomes the role of PCT in diagnosis, therapeutic monitoring, antibiotic discontinuation and prognosis. The Open Science Framework Registration number was doi.org/10.17605/OSF. IO/ZGFKQ RESULTS: 761 articles were retrieved and a total of 18 studies (n° of patients = 1774) were selected and analyzed according to inclusion criteria. In this 2020 update, the systematic review showed that currently, conflicting and inconclusive data are available about the role of PCT in the diagnosis of VAP and in the prediction (i) of the efficacy of antibiotic therapy, and (ii) of the clinical outcome. These studies, instead, seem to agree on the utility of PCT in the management of antibiotic therapy discontinuation. CONCLUSIONS: Currently there is insufficient evidence to support the role of PCT in the routine assessment of patients with VAP. The value of the results published appears to be limited by the deep methodological differences that characterize the various studies available at the present being.

Urologic surgery in a safe hospital during the COVID-19 pandemic scenario.

BACKGROUND: The COVID-19 pandemic induced a global emergency that overwhelmed most hospitals around the world. Access to hospitals has been restricted to selective oncological and urgent patients to minimize surgeries requiring Intensive Care Unit care. All other kind of non-urgent and benign surgeries have been rescheduled. The burden of oncological and urgent cases on the healthcare system has increased. METHODS: We have been asked to become the referral center for major oncological and urgent urological surgeries, increasing our surgical volume. Through meticulous hospital protocols on PPE, use of nasopharyngeal swabs, controlled hospital access and the prompt management of suspected/positive cases, we were able to perform 31% more urological surgical procedures during the COVID-19 pandemic compared to the same period in 2019. RESULTS: We observed a 72% increase in oncological surgical procedures and 150% in urgent procedures. CONCLUSIONS: Our experience shows how the management of oncological and urgent cases can be maintained during unexpected, global emergencies, such as COVID-19.