γδ+ T-Cells Is a Useful Biomarker for the Differential Diagnosis between Celiac Disease and Non-Celiac Gluten Sensitivity in Patients under Gluten Free Diet.

BACKGROUND: The differential diagnosis between patients with celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is difficult when a gluten-free diet (GFD) has been initiated before the diagnostic work-up. Isolated increases in TCRγδ+ and celiac lymphogram (increased TCRγδ+ plus decreased CD3-) may enable differential diagnosis in this challenging clinical setting. This study evaluated: (1) the accuracy of %TCRγδ+ and celiac lymphogram for diagnosing CD before and after GFD and for differentiation with NCGS; (2) TCRγδ+ kinetics at baseline and after starting GFD in both CD and NCGS. METHODS: The inclusion criteria were patients with CD (n = 104), NCGS (n = 37), and healthy volunteers (n = 18). An intestinal biopsy for intraepithelial lymphogram by flow cytometry was performed at baseline and after GFD. The optimal cutoff for CD diagnostic accuracy was established by maximizing the Youden index and via logistic regression. RESULTS: %TCRγδ+ showed better diagnostic accuracy than celiac lymphogram for identifying CD before and after GFD initiation. With a cutoff > 13.31, the accuracy for diagnosing CD in patients under GFD was 0.88 [0.80-0.93], whereas the accuracy for diagnosing NCGS (%TCRγδ+ ≤ 13.31) was 0.84 [0.76-0.89]. The percentage of TCRγδ+ cells showed differential kinetics between CD (baseline 22.7% [IQR, 16.4-33.6] vs. after GFD 26.4% [IQR, 17.8-36.8]; p = 0.026) and NCGS (baseline 9.4% [IQR, 4.1-14.6] vs. after GFD 6.4% [IQR, 3.2-11]; p = 0.022). CONCLUSION: TCRγδ+ T cell assessment accurately diagnoses CD before and after a GFD. Increased TCRγδ+ was maintained in the long term after GFD in CD but not in NCGS. Altogether, this suggests the potential usefulness of this marker for the differential diagnosis of these two entities in patients on a GFD.

Clinical sub-phenotypes of Staphylococcus aureus bacteraemia.

BACKGROUND: Staphylococcus aureus bacteraemia (SAB) is a clinically heterogeneous disease. The ability to identify sub-groups of patients with shared traits (sub-phenotypes) is an unmet need that could allow patient stratification for clinical management and research. We aimed to test the hypothesis that clinically-relevant sub-phenotypes can be reproducibly identified amongst patients with SAB. METHODS: We studied three cohorts of hospitalised adults with monomicrobial SAB: a UK retrospective observational study (Edinburgh cohort, n=458), the UK ARREST randomised trial (n=758), and the Spanish SAFO randomised trial (n=214). Latent class analysis was used to identify sub-phenotypes using routinely-collected clinical data, without considering outcomes. Mortality and microbiologic outcomes were then compared between sub-phenotypes. RESULTS: Included patients had predominantly methicillin-susceptible SAB (1366/1430,95.5%). We identified five distinct, reproducible clinical sub-phenotypes: (A) SAB associated with older age and comorbidity, (B) nosocomial intravenous catheter-associated SAB in younger people without comorbidity, (C) community-acquired metastatic SAB, (D) SAB associated with chronic kidney disease, and (E) SAB associated with injection drug use. Survival and microbiologic outcomes differed between the sub-phenotypes. 84-day mortality was highest in sub-phenotype A, and lowest in B and E. Microbiologic outcomes were worse in sub-phenotype C. In a secondary analysis of the ARREST trial, adjunctive rifampicin was associated with increased 84-day mortality in sub-phenotype B and improved microbiologic outcomes in sub-phenotype C. CONCLUSIONS: We have identified reproducible and clinically-relevant sub-phenotypes within SAB, and provide proof-of-principle of differential treatment effects. Through clinical trial enrichment and patient stratification, these sub-phenotypes could contribute to a personalised medicine approach to SAB.

Prognostic Relevance of Preoperative Immune, Inflammatory, and Nutritional Biomarkers in Patients Undergoing Gastrectomy for Resectable Gastric Adenocarcinoma: An Observational Multicentre Study.

Background: The aim of this study was to evaluate different preoperative immune, inflammatory, and nutritional scores and their best cut-off values as predictors of poorer overall survival (OS) and disease-free survival (DFS) in patients who underwent curative gastric cancer resection. Methods: This was a retrospective observational multicentre study based on data of the Spanish EURECCA Esophagogastric Cancer Registry. Time-dependent Youden index and log-rank test were used to obtain the best cut-offs of 18 preoperative biomarkers for OS and DFS. An adjusted Cox model with variables selected by bootstrapping was used to identify the best preoperative biomarkers, which were also analysed for every TNM stage. Results: High neutrophil-to-lymphocyte ratio (NLR), high monocyte systemic inflammation index (moSII), and low prognostic nutritional index (PNI) were identified as independent predictors of poor outcome: NLR > 5.91 (HR:1.73; 95%CI [1.23-2.43]), moSII >2027.12 (HR:2.26; 95%CI [1.36-3.78]), and PNI >40.31 (HR:0.75; 95%CI [0.58-0.96]) for 5-year OS and NLR > 6.81 (HR:1.75; 95%CI [1.24-2.45]), moSII > 2027.12 (HR:2.46; 95%CI [1.49-4.04]), and PNI > 40.31 (HR:0.77; 95%CI [0.60,0.97]) for 5-year DFS. These outcomes were maintained in the whole cohort for NLR and moSII (p < 0.05) but not in stage II and for PNI in all tumoral stages. The associations of NLR-PNI and moSII-PNI were also a relevant prognostic factor for OS. Conclusions: High NLR, high moSII (for stages I and III), and low PNI (regardless of tumour stage) were the most promising preoperative biomarkers to predict poor OS and DFS in gastric cancer patients treated with curative intent.

Increasing Gram-Negative Catheter-Related Bloodstream Infection in Cancer Patients.

Background: We aimed to assess the incidence, etiology and outcomes of catheter-related bloodstream infection (CRBSI) in onco-hematological patients, to assess the differences between patients with hematological malignancies (HMs) and solid tumors (STs) and to identify the risk factors for Gram-negative (GN) CRBSI. Methods: All consecutive episodes of BSI in adult cancer patients were prospectively collected (2006-2020). The etiology of CRBSI was analyzed in three different 5-year periods. Risk factors for GN CRBSI were assessed in the whole cohort and separately in patients with HMs and STs. Results: Among 467 episodes of monomicrobial CRBSI, 407 were Gram-positive (GP) (87.1%), 49 GN (10.5%) and 11 fungal (2.4%). Hematological patients (369 episodes) were more frequently neutropenic and were more likely to carry central venous catheters and develop GP CRBSI. Patients with STs (98 episodes) had more comorbidities, more frequently carried port reservoirs and commonly presented more GN CRBSI. GN CRBSI significantly increased over the study period, from 5.2% to 23% (p < 0.001), whereas GP CRBSI decreased from 93.4% to 73.3% (p < 0.001). CRBSI episodes involving port reservoirs and peripherally-inserted central catheters were significantly increased (p < 0.001). The most frequent GPs were coagulase-negative staphylococci (CoNS) (57.8%) and Pseudomonas aeruginosa was the most common GN (3%). Multidrug-resistant (MDR) GN represented 32.7% of all GN CRBSIs and increased over time (p = 0.008). The independent risk factors for GN CRBSI in the whole cohort were solid tumor, chronic kidney disease and carrying a port reservoir. Carrying a port reservoir was also a risk factor in patients with STs. Health-care acquisition was identified as a risk factor for GN CRBSI in the whole cohort, as well as in patients with STs and HMs. Inadequate empirical antibiotic treatment (IEAT) occurred regardless of the etiology: 49% for GNs and 48.6% for GPs (p = 0.96). In GP CRBSI, IEAT was mainly due to inadequate coverage against CoNS (87%), whereas in GN CRBSI, IEAT was associated with multidrug resistance (54.2%). Early (48 h and 7-day) and 30-day case-fatality rates were similar when analyzed according to the type of underlying disease and etiology, except for the 30-day case-fatality rate, which was higher in the group of patients with STs compared to those with HMs (21.5% vs. 12.5%, p = 0.027). The 48 h case-fatality rate was significantly higher in patients in whom the catheter had not been removed (5.6% vs. 1%; p = 0.011), and it remained significant for GP CRBSI (6% vs. 1.3%, p = 0.023). Conclusions: GNs are an increasing cause of CRBSI in cancer patients, particularly in solid tumor patients carrying port reservoirs. Multidrug resistance among GNs is also increasing and is associated with higher rates of IEAT. Decreased 48 h survival was associated with the non-removal of the catheter. These findings should be considered when deciding on early therapeutic management for cancer patients with suspected CRBSI.

Persistent COVID-19 symptoms 1 year after hospital discharge: A prospective multicenter study.

OBJECTIVE: To determine the health status and exercise capacity of COVID-19 survivors one year after hospital discharge. METHODS: This multicenter prospective study included COVID-19 survivors 12 months after hospital discharge. Participants were randomly selected from a large cohort of COVID-19 patients who had been hospitalized until 15th April 2020. They were interviewed about persistent symptoms, underwent a physical examination, chest X-ray, and a 6-minute walk test (6MWT). A multivariate analysis was performed to determine the risk factors for persistent dyspnea. RESULTS: Of the 150 patients included, 58% were male and the median age was 63 (IQR 54-72) years. About 82% reported ≥1 symptoms and 45% had not recovered their physical health. The multivariate regression analysis revealed that the female sex, chronic obstructive pulmonary disease, and smoking were independent risk factors for persistent dyspnea. Approximately 50% completed less than 80% of the theoretical distance on the 6MWT. Only 14% had an abnormal X-ray, showing mainly interstitial infiltrates. A third of them had been followed up in outpatient clinics and 6% had undergone physical rehabilitation. CONCLUSION: Despite the high rate of survivors of the first wave of the COVID-19 pandemic with persistent symptomatology at 12 months, the follow-up and rehabilitation of these patients has been really poor. Studies focusing on the role of smoking in the persistence of COVID-19 symptoms are lacking.

Use of failure-to-rescue after emergency surgery as a dynamic indicator of hospital resilience during the COVID-19 pandemic. A multicenter retrospective propensity score-matched cohort study.

BACKGROUND: Surgical failure-to-rescue (FTR, death rate following complications) is a reliable cross-sectional quality of care marker, but has not been evaluated dynamically. We aimed to study changes in FTR following emergency surgery during the COVID-19 pandemic. MATERIAL AND METHODS: Matched cohort study including all COVID-19-non-infected adult patients undergoing emergency general surgery in 25 Spanish hospitals during COVID-19 pandemic peak (March-April 2020), non-peak (May-June 2020), and 2019 control periods. A propensity score-matched comparative analysis was conducted using a logistic regression model, in which period was regressed on observed baseline characteristics. Subsequently, a mixed effects logistic regression model was constructed for each variable of interest. Main variable was FTR. Secondary variables were post-operative complications, readmissions, reinterventions, and length of stay. RESULTS: 5003 patients were included (948, 1108, and 2947 in the pandemic peak, non-peak, and control periods), with comparable clinical characteristics, prognostic scores, complications, reintervention, rehospitalization rates, and length of stay across periods. FTR was greater during the pandemic peak than during non-peak and pre-pandemic periods (22.5% vs. 17.2% and 12.7%), being this difference confirmed in adjusted analysis (odds ratio [OR] 2.13, 95% confidence interval [95% CI] 1.27-3.66). There was sensible inter-hospital variability in FTR changes during the pandemic peak (median FTR change +8.77%, IQR 0-29.17%) not observed during the pandemic non-peak period (median FTR change 0%, IQR -6.01-6.72%). Greater FTR increase was associated with higher COVID-19 incidence (OR 2.31, 95% CI 1.31-4.16) and some hospital characteristics, including tertiary level (OR 3.07, 95% CI 1.27-8.00), medium-volume (OR 2.79, 95% CI 1.14-7.34), and high basal-adjusted complication risk (OR 2.21, 95% CI 1.07-4.72). CONCLUSION: FTR following emergency surgery experienced a heterogeneous increase during different periods of the COVID-19 pandemic, suggesting it to behave as an indicator of hospital resilience. FTR monitoring could facilitate identification of centres in special needs during ongoing health care challenges.

Real-Life Use of Ceftolozane/Tazobactam for the Treatment of Bloodstream Infection Due to Pseudomonas aeruginosa in Neutropenic Hematologic Patients: a Matched Control Study (ZENITH Study).

We sought to assess the characteristics and outcomes of neutropenic hematologic patients with Pseudomonas aeruginosa (PA) bloodstream infection (BSI) treated with ceftolozane-tazobactam (C/T). We conducted a multicenter, international, matched-cohort study of PA BSI episodes in neutropenic hematologic patients who received C/T. Controls were patients with PA BSI treated with other antibiotics. Risk factors for overall 7-day and 30-day case fatality rates were analyzed. We compared 44 cases with 88 controls. Overall, 91% of episodes were caused by multidrug-resistant (MDR) strains. An endogenous source was the most frequent BSI origin (35.6%), followed by pneumonia (25.8%). There were no significant differences in patient characteristics between groups. C/T was given empirically in 11 patients and as definitive therapy in 41 patients. Treatment with C/T was associated with less need for mechanical ventilation (13.6% versus 33.3%; P = 0.021) and reduced 7-day (6.8% versus 34.1%; P = 0.001) and 30-day (22.7% versus 48.9%; P = 0.005) mortality. In the multivariate analysis, pneumonia, profound neutropenia, and persistent BSI were independent risk factors for 30-day mortality, whereas lower mortality was found among patients treated with C/T (adjusted OR [aOR] of 0.19; confidence interval [CI] 95% of 0.07 to 0.55; P = 0.002). Therapy with C/T was associated with less need for mechanical ventilation and reduced 7-day and 30-day case fatality rates compared to alternative agents in neutropenic hematologic patients with PA BSI. IMPORTANCE Ceftolozane-tazobactam (C/T) has been shown to be a safe and effective alternative for the treatment of difficult to treat infections due to Pseudomonas aeruginosa (PA) in the general nonimmunocompromised population. However, the experience of this agent in immunosuppressed neutropenic patients is very limited. Our study is unique because it is focused on extremely immunosuppressed hematological patients with neutropenia and bloodstream infection (BSI) due to PA (mainly multidrug resistant [MDR]), a scenario which is often associated with very high mortality rates. In our study, we found that the use of C/T for the treatment of MDR PA BSI in hematological neutropenic patients was significantly associated with improved outcomes, and, in addition, it was found to be an independent risk factor associated with increased survival. To date, this is the largest series involving neutropenic hematologic patients with PA BSI treated with C/T.

Effect of Combination Antibiotic Empirical Therapy on Mortality in Neutropenic Cancer Patients with Pseudomonas aeruginosa Pneumonia.

To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006−2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy [IEAT] on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain [38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001]. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 [95%CI 1.01−2.03]; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 [95%CI 0.27−0.78]; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 [95%CI 0.76−2.05]; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.

Assessing dynamic change in muscle during treatment of patients with cancer: Precision testing standards.

BACKGROUND: Computed tomography images acquired during routine cancer care provide an opportunity to determine body composition with accuracy and precision. Quantification of skeletal muscle is of interest owing to its association with clinical outcomes. However, the standards of precision testing considered mandatory in other areas of radiology are lacking from the literature in this area. We aim to describe the change in skeletal muscle over time at different anatomical levels using the precision error. METHODS: Thirty-eight male patients with squamous cell carcinoma of the head and neck were evaluated at two time points encompassing their treatment plan. Precision testing consisted of analyzing the cross-sectional area (CSA) of the skeletal muscle and total adipose tissue of 76 CT studies (38 images at baseline repeated twice and 38 follow-up images repeated twice) measured by a skilled observer. The % coefficient of variation (%CV), the root-mean-square standard deviation (RMS SD) and the corresponding 95% least significant change (LSC) were calculated for four anatomical levels: upper arm, thigh, chest and abdomen. RESULTS: The median time between scans was 223.6 (SD 31.2) days. Precision error (% CV) for total skeletal muscle cross sectional area was 0.86% for upper arm, 0.26% for thigh, 0.39% for chest and 0.63% for abdomen. The corresponding LSC values in upper arm, thigh, chest and abdomen were 2.4%, 0.7%, 1.1% and 1.8%, respectively. Based on the LSC for RMS SD, patients were classified in two categories according to muscle cross-sectional area: stable (i.e within LSC value) or gained and loss. To compare the four anatomical levels, the proportion of patients with muscle loss exceeding the LSC value was 74.3% for arm, 86.2% for thigh, 82.9% for chest and 76.3% for abdomen. For these same anatomic regions, the mean muscle loss for those patients classified below the LSC was 14.6% (SD 9.3), 13.4% (SD 7.8), 11.9% (SD 6.5) and 11.6% (SD 5.5), respectively. Only the loss of muscle area was significantly higher in thigh (p = 0.023), using L3 as the reference level. CONCLUSIONS: We recommend the uniform use of a standard precision test when reporting muscle change over time. LSC values vary from 0.7 to 2.4% depending on anatomic site; with the lowest precision error to detect change in the thigh. Based on this analysis, muscle wasting appears to be systemic and while present in limbs and trunk is significantly higher in the thigh than in the chest, abdomen or upper arm.

Transanal Total Mesorectal Excision Versus Anterior Total Mesorectal Excision for Rectal Cancer: A Propensity Score Matched, Population-Based Study in Catalonia, Spain.

BACKGROUND: The clinical value of transanal total mesorectal excision is debated. OBJECTIVE: This study aimed to compare short- and medium-term effects of transanal versus anterior total mesorectal excision for rectal cancer. DESIGN: This was a multicenter retrospective cohort study. SETTING: The study included all Catalonian public hospitals. PATIENTS: All patients receiving transanal or anterior total mesorectal excision (open or laparoscopic) for nonmetastatic primary rectal cancer in 2015 to 2016 were included. MAIN OUTCOME MEASURES: Data on vital status were collected to March 2019. Between-group differences were minimized by applying propensity score matching to baseline patient characteristics. Competing risk models were used to assess systemic and local recurrence along with death at 2 years, and multivariable Cox regression was used to assess 2-year disease-free survival. Results are expressed with their 95% CIs. RESULTS: The final subsample was 537 patients receiving total mesorectal excision (transanal approach: n = 145; anterior approach: n = 392). Median follow-up was 39.2 months (interquartile range, 33.0-45.8). Accounting for death as a competing event, there was no association between transanal total mesorectal excision and local recurrence (matched subhazard ratio 1.28, 95% CI 0.55-2.96). There were no statistical differences in the comparative rate of local recurrence (transanal: 1.77 per 100 person-years, 95% CI 0.76-3.34; anterior: 1.37 per 100 person-years, 95% CI 0.8-2.15) or mortality (transanal: 3.98 per 100 person-years, 95% CI 2.36-6.16; anterior: 2.99 per 100 person-years, 95% CI 2.1-4.07). Groups presented similar 2-year cumulative incidence of local recurrence (4.83% versus 3.57%) and disease-free survival (HR, 1.33; 95% CI 0.92-1.92). LIMITATIONS: We used data only from the public system, the study is retrospective, and data on individual surgeons are not reported. CONCLUSION: These population-based results support the use of either the transanal, open, or laparoscopic approach for rectal cancer in Catalonia. See Video Abstract at http://links.lww.com/DCR/B744.ESCISIÓN MESORRECTAL TOTAL TRANSANAL VERSUS ESCISIÓN MESORRECTAL TOTAL ANTERIOR PARA EL CÁNCER DE RECTO: UN ESTUDIO POBLACIONAL CON EMPAREJAMIENTO DE PUNTAJE DE PROPENSIÓN EN CATALUÑA, ESPAÑA. ANTECEDENTES: Se debate el valor clínico de la escisión mesorrectal total transanal. OBJETIVO: Comparar los efectos a corto y mediano plazo de la escisión mesorrectal total transanal versus anterior para el cáncer de recto. DISEO: Este fue un estudio de cohorte retrospectivo multicéntrico. AJUSTE: El estudio incluyó a todos los hospitales públicos de Cataluña. PACIENTES: Todos los pacientes no metastásicos que recibieron escisión mesorrectal total anterior o transanal (abierta o laparoscópica) por cáncer de recto primario en 2015-16. PRINCIPALES MEDIDAS DE VALORACION: Los datos sobre el estado vital se recopilaron hasta marzo de 2019. Las diferencias entre los grupos se minimizaron aplicando el emparejamiento de puntajes de propensión a las características iniciales del paciente. Se utilizaron modelos de riesgo competitivo para evaluar la recurrencia sistémica y local junto con la muerte a los dos años, y la regresión de Cox multivariable para evaluar la supervivencia libre de enfermedad a dos años. Los resultados se expresan con sus intervalos de confianza del 95%. RESULTADOS: La submuestra final fue de 537 pacientes que recibieron escisión mesorrectal total (abordaje transanal: n = 145; abordaje anterior: n = 392). La mediana de seguimiento fue de 39,2 meses (rango intercuartílico 33,0-45,8). Teniendo en cuenta la muerte como un evento competitivo, no hubo asociación entre la escisión mesorrectal total transanal y la recurrencia local (cociente de subriesgo apareado 1,28, 0,55-2,96). No hubo diferencias estadísticas en la tasa comparativa de recurrencia local (transanal: 1,77 por 100 personas-año, 0,76-3,34; anterior: 1,37 por 100 personas-año, 0,8-2,15) o mortalidad (transanal: 3,98 por 100 personas-año, 2,36-6,16; anterior: 2,99 por 100 personas-año, 2,1-4,07). Los grupos presentaron una incidencia acumulada de dos años similar de recidiva local (4,83% frente a 3,57%, respectivamente) y supervivencia libre de enfermedad (índice de riesgo 1,33, 0,92-1,92). LIMITACIONES: Utilizamos datos solo del sistema público, el estudio es retrospectivo y no se informan datos sobre cirujanos individuales. CONCLUSIONES: Estos resultados poblacionales apoyan el uso del abordaje transanal, abierto o laparoscópico para el cáncer de recto en Cataluña. Consulte. Video Resumen en http://links.lww.com/DCR/B744. (Traducción- Dr. Francisco M. Abarca-Rendon).

P-POSSUM as mortality predictor in COVID-19-infected patients submitted to emergency digestive surgery. A retrospective cohort study.

BACKGROUND: COVID-19 infection is associated with a higher mortality rate in surgical patients, but surgical risk scores have not been validated in the emergency setting. We aimed to study the capacity for postoperative mortality prediction of the P-POSSUM score in COVID-19-positive patients submitted to emergency general and digestive surgery. MATERIAL AND METHODS: Consecutive patients undergoing emergency general and digestive surgery from March to June 2020, and from March to June 2019 in 25 Spanish hospitals were included in a retrospective cohort study. MAIN OUTCOME: 30-day mortality. P-POSSUM discrimination was quantified by the area under the curve (AUC) of ROC curves; calibration was assessed by linear regression slope (ß estimator); and sensitivity and specificity were expressed as percentage and 95% confidence interval (CI). RESULTS: 4988 patients were included: 177 COVID-19-positive; 2011 intra-pandemic COVID-19-negative; and 2800 pre-pandemic. COVID-19-positive patients were older, with higher surgical risk, more advanced pathologies, and higher P-POSSUM values (1.79% vs. 1.09%, p < 0.001, in both the COVID-19-negative and control cohort). 30-day mortality in the COVID-19-positive, intra-pandemic COVID-19-negative and pre-pandemic cohorts were: 12.9%, 4.6%, and 3.2%. The P-POSSUM predictive values in the three cohorts were, respectively: AUC 0.88 (95% CI 0.81-0.95), 0.89 (95% CI 0.87-0.92), and 0.91 (95% CI 0.88-0.93); ß value 0.97 (95% CI 0.74-1.2), 0.99 (95% CI 0.82-1.16), and 0.78 (95% CI 0.74-0.82); sensitivity 83% (95% CI 61-95), 91% (95% CI 84-96), and 89% (95% CI 80-94); and specificity 81% (95% CI 74-87), 76% (95% CI 74-78), and 80% (95% CI 79-82). CONCLUSION: The P-POSSUM score showed a good predictive capacity for postoperative mortality in COVID-19-positive patients submitted to emergency general and digestive surgery.

Predictive Value of Skeletal Muscle Mass in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Patients Treated With Immune Checkpoint Inhibitors.

BACKGROUND: Reduced muscle mass has been associated with increased treatment complications in several tumor types. We evaluated the impact of skeletal muscle index (SMI) on prognosis and immune-related adverse events (IrAEs) in a cohort of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoints inhibitors (ICI). METHODS: A single-institutional, retrospective study was performed including 61 consecutive patients of R/M HNSCC diagnosed between July 2015 and December 2018. SMI was quantified using a CT scan at L3 to evaluate body composition. Median baseline SMI was used to dichotomize patients in low and high SMI. Kaplan-Meier estimations were used to detect overall survival (OS) and progression-free survival (PFS). Toxicity was recorded using Common Terminology Criteria for Adverse Event v4.3. RESULTS: Patients were 52 men (85.2%) with mean of age 57.7 years (SD 9.62), mainly oral cavity (n = 21; 34.4%). Low SMI was an independent factor for OS in the univariate (HR, 2.06; 95% CI, 1.14-3.73, p = 0.017) and multivariate Cox analyses (HR, 2.99; 95% CI, 1.29-6.94; p = 0.011). PFS was also reduced in patients with low SMI (PFS HR, 1.84; 95% CI, 1.08-3.12; p = 0.025). IrAEs occurred in 29 (47.5%) patients. There was no association between low SMI and IrAEs at any grade (OR, 0.56; 95% CI, 0.20-1.54; p = 0.261). However, grades 3 to 4 IrAEs were developed in seven patients of whom three had low SMI. CONCLUSIONS: Low SMI before ICI treatment in R/M HNSCC patients had a negative impact on OS and PFS. Further prospective research is needed to confirm the role of body composition as a predictive biomarker in ICI treatment.

Adequacy of nutritional support using computed tomography (CT) in patients with head and neck cancer (HNC) during chemo-radiotherapy (CRT).

We assessed forty HNC patients receiving treatment with curative intent. Specific quantitative muscle and fat changes were evaluated using CT. Nutrition support was provided according to ESPEN guidelines, with adjusted body weight (ABW) in overweight/obese patients used to define their nutritional targets. Linear regression models were used to evaluate clinical predictors of tissue loss. Mean overall losses were body weight (-10.5%), and CT-defined muscle (-8.4%) and fat mass (-24.8%), p < 0.001. A subset of 20 patients had high muscle loss (-14.7%) with concurrent negative energy balance as reflected by considerable fat loss (-29.7%); those tended to have higher baseline body mass index (26.2 vs. 23.3 kg/m2, p = 0.063). In multivariate regression, only ABW independently predicted muscle loss (p < 0.001) and fat loss (p = 0.002). Nutrition support according to guidelines was appropriate for a subset of patients. ABW use to set nutrition targets in overweight/obese patients would appear to be insufficient, based on large tissue losses.

Endoscopic biliary drainage in unresectable biliary obstruction: the role of endoscopic ultrasound-guidance in a cohort study.

BACKGROUND AND STUDY AIMS: the use of endoscopic ultrasound-guided biliary drainage (EUS-BD) has increased in cases of failed endoscopic retrograde cholangiopancreatography (ERCP) and there are some concerns. The main aim of the study was to determine the role of EUS-BD in a palliative case cohort. The secondary aim was to compare the efficacy, safety and survival of EUS-BD and ERCP procedures. PATIENTS AND METHODS: this was an observational study at a single tertiary institution, with a consecutive inclusion from January 2015 to December 2016. The inclusion criteria were unresectable tumors of the biliopancreatic region with an indication of BD. Statistical comparison analysis was performed between the ERCP and EUS-BD groups. The incidence between groups was compared using the Chi-square and Fisher exact tests. The log rank test was used to compare the risk of death. RESULTS: fifty-two cases with an indication of palliative BD were included in the study. Transpapillary drainage via ERCP was possible in 44 procedures and EUS-BD was required in eight cases; 15.4% of the cohort and seven using lumen apposing metal stent (LAMS). The technical and clinical success of global endoscopic BD was 100% and 88.5% (ERCP: 84.6% and 78.9%; EUS-BD: 100% and 62.5%, respectively). Pancreatitis was the most frequent adverse event (AE) in the ERCP group (9.62%) and bleeding in the EUS-BD (25%). There were fatal AEs in ERCP (1.9%) and EUS-BD (25%) cases. Patient survival was higher with ERCP transpapillary stents compared to EUS-guided stents, which was statistically significant (p = 0.007). CONCLUSIONS: the requirement of EUS-BD in palliative biliopancreatic pathology is not marginal. EUS-BD is associated with a lower survival rate and a higher rate of fatal AE, which argues against its use as a first choice procedure.

Concentrations of trace elements and KRAS mutations in pancreatic ductal adenocarcinoma.

Trace elements are a possible risk factor for pancreatic ductal adenocarcinoma (PDAC). However, their role in the occurrence and persistence of KRAS mutations remains unstudied. There appear to be no studies analyzing biomarkers of trace elements and KRAS mutations in any human cancer. We aimed to determine whether patients with KRAS mutated and nonmutated tumors exhibit differences in concentrations of trace elements. Incident cases of PDAC were prospectively identified in five hospitals in Spain. KRAS mutational status was determined through polymerase chain reaction from tumor tissue. Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Concentrations of trace elements were compared in 78 PDAC cases and 416 hospital-based controls (case-control analyses), and between 17 KRAS wild-type tumors and 61 KRAS mutated tumors (case-case analyses). Higher levels of iron, arsenic, and vanadium were associated with a statistically nonsignificant increased risk of a KRAS wild-type PDAC (OR for higher tertile of arsenic = 3.37, 95% CI 0.98-11.57). Lower levels of nickel and manganese were associated with a statistically significant higher risk of a KRAS mutated PDAC (OR for manganese = 0.34, 95% CI 0.14-0.80). Higher levels of selenium appeared protective for both mutated and KRAS wild-type PDAC. Higher levels of cadmium and lead were clear risk factors for both KRAS mutated and wild-type cases. This is the first study analyzing biomarkers of trace elements and KRAS mutations in any human cancer. Concentrations of trace elements differed markedly between PDAC cases with and without mutations in codon 12 of the KRAS oncogene, thus suggesting a role for trace elements in pancreatic and perhaps other cancers with such mutations. Environ. Mol. Mutagen., 60:693-703, 2019. © 2019 Wiley Periodicals, Inc.

Safety of lumen-apposing stent with or without coaxial plastic stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a retrospective study.

BACKGROUND: The aim of this study was to evaluate whether the placement of a coaxial double-pigtail plastic stent (DPS) within a lumen-apposing metal stent (LAMS) may improve the safety of endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs). METHODS: This was a retrospective cohort study including patients with PFCs and an indication for transmural drainage. Two strategies (LAMS alone or LAMS plus DPS) were used at the endoscopist's discretion. RESULTS: A total of 41 patients were treated (21 LAMS alone; 20 LAMS plus DPS). The characteristics of the PFCs, and the technical and clinical success rates did not differ between groups. The LAMS alone group had a significantly higher rate of adverse events than the LAMS plus DPS group (42.9 % vs. 10.0 %; P = 0.04). Bleeding was the most frequent adverse event observed. CONCLUSIONS: The addition of a coaxial DPS to LAMS was associated with a lower rate of adverse events in EUS-guided drainage of PFCs.