Global trend and epidemiological profiles of climate-related disasters from 2000 to 2021.

OBJECTIVE: The objective of this study is to analyse the epidemiological profile of global climate-related disasters in terms of morbidity and mortality, as well as to examine their temporal trends. METHOD: This cross-sectional study analysed climate-related global disasters from 2000 to 2021, utilising definitions and criteria from the United Nations Strategy for Disaster Reduction and the Centre for Research on the Epidemiology of Disasters. Data were sourced from the EM-DAT database. The study assessed trends over the entire period and compared them with previous years (1978-2000). RESULTS: A total of 7398 climate-related disasters were recorded, with hydrological disasters being the most frequent, followed by meteorological and climatological disasters. Statistically significant differences were noted in the average rates of affected individuals and injuries per million inhabitants. No significant trends were found in mortality rates, but the frequency trends for the entire period (1978-2021) and the subperiod (1978-2000) were increasing and statistically significant. However, the trend from 2000 onwards showed a non-significant decrease, potentially reflecting better disaster preparedness and response strategies under the Hyogo and Sendai Framework. CONCLUSION: The study highlights hydrological disasters as the most frequent and deadliest climate-related events, with climatological disasters affecting and injuring the most people. The lack of standardised criteria for disaster inclusion in databases presents a significant challenge in comparing results and analysing trends. Establishing uniform inclusion criteria is crucial for effective data analysis and disaster management.

The epidemiological profile of incidence and mortality from epidemics in complex humanitarian emergencies from 1990 to 2022 - A scoping review.

AIM: This study aimed to investigate the impact of communicable diseases with epidemic potential in complex emergency (CE) situations, focusing on the epidemiological profile of incidence and mortality and exploring underlying factors contributing to increased epidemic risks. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review (PRISMA-ScR) guidelines, we conducted a scoping review of articles published between 1990 and 2022. The search included terms related to complex emergencies, communicable diseases, outbreaks, and epidemics. We identified 92 epidemics related to CE occurring in 32 different countries. RESULTS: Communicable diseases like Shigellosis, Cholera, Measles, Meningococcal meningitis, Yellow Fever, and Malaria caused significant morbidity and mortality. Diarrhoeal diseases, particularly Cholera and Shigellosis, had the highest incidence rates. Shigella specifically had an incidence of 241.0 per 1000 (people at risk), with a mortality rate of 11.7 per 1000, while Cholera's incidence was 13.0 per 1000, with a mortality rate of 0.22 per 1000. Measles followed, with an incidence of 25.0 per 1000 and a mortality rate of 0.76 per 1000. Meningococcal Meningitis had an incidence rate of 1.3 per 1000 and a mortality rate of 0.13 per 1000. Despite their lower incidences, yellow fever at 0.8 per 1000 and malaria at 0.4 per 1000, their high case fatality rates of 20.1% and 0.4% remained concerning in CE. The qualitative synthesis reveals that factors such as water, sanitation, and hygiene, shelter and settlements, food and nutrition, and public health and healthcare in complex emergencies affect the risk of epidemics. CONCLUSION: Epidemics during complex emergencies could potentially lead to a public health crisis. Between 1990 and 2022, there have been no statistically significant changes in the trend of incidence, mortality, or fatality rates of epidemic diseases in CE. It is crucial to understand that all epidemics identified in CE are fundamentally preventable.

Multiplex real-time PCR FilmArray performance in the diagnosis of meningoencephalitis: lights and shadows.

PURPOSE: We aimed to evaluate the performance of the FilmArray (FA) meningitis/encephalitis (ME) panel. Secondarily, we analyzed the false positive (FP) and false negative (FN) results, as well as the predictive values of the technique, regarding the cerebrospinal fluid (CSF) characteristics. METHODS: FA is a multiplex real-time PCR detecting 14 of the most common ME pathogens in CSF. All FA performed at our hospital (2018-2022) were retrospectively reviewed. FA was compared to conventional techniques and its performance was assessed based on the final diagnosis of the episode. RESULTS: FA was performed in 313 patients with suspicion of ME. Most patients had altered mental status (65.2%) and fever (61%). Regarding CSF characteristics, 49.8% and 53.7% presented high CSF proteins and pleocytosis, respectively. There were 84 (26.8%) positive FA results, mainly for HSV-1 (10.9%), VZV (5.1%), Enterovirus (2.6%), and S. pneumoniae (1.9%). In the 136 cases where both FA and routine methods were performed, there was a 25.7% lack of agreement. We identified 6.6% FN results, but 28.6% FP, mainly due to HSV-1. This resulted in a high negative predictive value (NPV) of 93.4%, but a positive predictive value (PPV) of 73%. Remarkably, PPV as low as 36.9%, and 70.2%, were found in cases without pleocytosis, or lack of high CSF protein levels, respectively. CONCLUSION: FA was associated with high NPV, but frequent FP results and low PPV, particularly for HSV-1, and especially in patients without high CSF protein levels or pleocytosis.

Information Delay of Significant Bloodstream Isolates and Patient Mortality: A Retrospective Analysis of 6225 Adult Patients With Bloodstream Infections.

BACKGROUND: Our aim in this study was to evaluate the clinical and prognostic impact of communicating microbiological information in real time for adult patients with bloodstream infections (BSIs). METHODS: We retrospectively reviewed 6225 clinical episodes of bacteremia in a teaching hospital from January 2013 to December 2019. Bacteremia-associated mortality was compared when blood culture results were relayed to the infectious diseases specialist (IDS) in real time and periods when results were relayed the following morning. The impact of information availability using mortality at 30 days was used as the main outcome of the study. RESULTS: The initial analysis (all microorganisms included) did not show an association of mortality and information delay to the IDS (odds ratio [OR], 1.18; 95% confidence interval [CI], .99-1.42). However, information delay of BSIs caused by fast-growing microorganisms such as Enterobacterales was associated with a significant increase in the odds of death at 30 days both in the univariate (OR, 1.76; 95% CI, 1.30-2.38) and multivariate analysis (OR, 2.22; 95% CI, 1.50-3.30). Similar results were found with mortality at 14 days and 7 days in the univariate (OR, 1.54; 95% CI, 1.08-2.20 and OR, 1.56; 95% CI, 1.03-2.37, respectively) and the multivariate analysis (OR, 2.05; 95% CI, 1.27-3.32 and OR, 1.92; 95% CI, 1.09-3.40, respectively). CONCLUSIONS: Information delivered in real time has prognostic relevance and is likely to improve survival of patients with documented BSIs. Future studies should address the prognostic impact of adequate resource allocation (microbiologist/IDS with 24/7 coverage) in BSIs.

Qualitative Subgenomic RNA to Monitor the Response to Remdesivir in Hospitalized Patients With Coronavirus Disease 2019: Impact on the Length of Hospital Stay and Mortality.

BACKGROUND: There is no reliable microbiological marker to guide the indication and the response to antiviral treatment in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) in patients with COVID-19 before and after receiving treatment with remdesivir. METHODS: We included consecutive patients admitted for COVID-19 who received remdesivir according to our institutional protocol and accepted to participate in the study. A nasopharyngeal swab for quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was collected at baseline and after 3 and 5 days of treatment with remdesivir. Genomic and sgRNA were analyzed in those samples and main comorbidities and evolution were collected for the analyses. The main outcomes were early discharge (≤10 days) and 30-day mortality. RESULTS: A total of 117 patients were included in the study, of whom 24 had a negative sgRNA at baseline, with 62.5% (15/24) receiving early discharge (≤10 days) and no deaths in this group. From the 93 remaining patients, 62 had a negative sgRNA at day 5 with 37/62 (59.6%) with early discharge and a mortality rate of 4.8% (3/62). In the subgroup of 31 patients with positive sgRNA after 5 days of remdesivir, the early discharge rate was 29% (9/31) and the mortality rate was 16.1% (5/31). In multivariable analyses, the variables associated with early discharge were negative sgRNA at day 3 and not needing treatment with corticosteroids or intensive care unit admission. CONCLUSIONS: Qualitative sgRNA could help in monitoring the virological response in patients who receive remdesivir. Further studies are needed to confirm these findings.

Significant increase of CTX-M-15-ST131 and emergence of CTX-M-27-ST131 Escherichia coli high-risk clones causing healthcare-associated bacteraemia of urinary origin in Spain (ITUBRAS-2 project).

OBJECTIVES: To assess the microbiological characteristics of Escherichia coli causing healthcare-associated bacteraemia of urinary origin (HCA-BUO) in Spain (ITUBRAS-2 project), with particular focus on ESBL producers and isolates belonging to ST131 high-risk clone (HiRC). Clinical characteristics and outcomes associated with ST131 infection were investigated. METHODS: A total of 222 E. coli blood isolates were prospectively collected from patients with HCA-BUO from 12 tertiary-care hospitals in Spain (2017-19). Antimicrobial susceptibility and ESBL/carbapenemase production were determined. ST131 subtyping was performed. A subset of 115 isolates were selected for WGS to determine population structure, resistome and virulome. Clinical charts were reviewed. RESULTS: ESBL-producing E. coli prevalence was 30.6% (68/222). ST131 represented 29.7% (66/222) of E. coli isolates and accounted for the majority of ESBL producers (46/68, 67.6%). The C2/H30-Rx subclone accounted for most ST131 isolates (44/66) and was associated with CTX-M-15 (37/44) and OXA-1 enzymes (27/44). Cluster C1-M27 was identified in 4/10 isolates belonging to subclade C1/H30-R1 and associated with CTX-M-27. Additionally, ST131 isolates showed a high content of other acquired resistance genes, and clade C/ST131 isolates carried characteristic QRDR mutations. They were categorized as uropathogenic E. coli and had higher aggregate virulence scores. ST131 infection was associated with more complex patients, prior use of cephalosporins and inadequate empirical treatment but was not associated with worse clinical outcomes. CONCLUSIONS: ST131 HiRC is the main driver of ESBL-producing E. coli causing HCA-BUO in Spain, mainly associated with the expansion of subclade CTX-M-15-C2/H30-Rx and the emergence of CTX-M-27-C1/H30-R1 (Cluster C1-M27).

Pesticide residue analysis in different spice samples by automatic µSPE clean-up workflow determination using LC-MS/MS.

Spices such as paprika, curry, turmeric, dry chilli, and black pepper are grown in various geographic locations and widely used by consumers across the world. Pesticides applied during crop production practices could contaminate the produce, affecting the quality and posing a health risk for consumers. The complexity of the spice matrix and the wide range of target pesticides potentially present require special sample extraction and clean-up treatments to overcome matrix interference and ion suppression. In this study, sample extracts from spice matrices (paprika/curry/turmeric/dry chilli/black pepper) were cleaned up by an automated µSPE clean-up method for multi-residue analysis of pesticides using LC-MS/MS. The automated µSPE clean-up method involves pre-filled cartridges containing various sorbent materials suitable for numerous co-extractives and the automated clean-up process was carried out using an autosampler. The regulatory limit for pesticides in spices varies with type, with a low MRL of 0.05 mg kg-1 or higher for 99% of the analytes. At spiking concentrations of 0.05 and 0.1 mg kg-1, good recoveries between 70 and 120% with RSD values below 20% were achieved for more than 98% of the compounds. With automatic clean-up of samples that takes 5 min/sample, 20% increased output per day shows an important advantage achieved compared to manual clean-up.

Human prefoldin modulates co-transcriptional pre-mRNA splicing.

Prefoldin is a heterohexameric complex conserved from archaea to humans that plays a cochaperone role during the co-translational folding of actin and tubulin monomers. Additional functions of prefoldin have been described, including a positive contribution to transcription elongation and chromatin dynamics in yeast. Here we show that prefoldin perturbations provoked transcriptional alterations across the human genome. Severe pre-mRNA splicing defects were also detected, particularly after serum stimulation. We found impairment of co-transcriptional splicing during transcription elongation, which explains why the induction of long genes with a high number of introns was affected the most. We detected genome-wide prefoldin binding to transcribed genes and found that it correlated with the negative impact of prefoldin depletion on gene expression. Lack of prefoldin caused global decrease in Ser2 and Ser5 phosphorylation of the RNA polymerase II carboxy-terminal domain. It also reduced the recruitment of the CTD kinase CDK9 to transcribed genes, and the association of splicing factors PRP19 and U2AF65 to chromatin, which is known to depend on CTD phosphorylation. Altogether the reported results indicate that human prefoldin is able to act locally on the genome to modulate gene expression by influencing phosphorylation of elongating RNA polymerase II, and thereby regulating co-transcriptional splicing.

Impact of Anti-IL5 Therapies on Patients with Severe Uncontrolled Asthma and Possible Predictive Biomarkers of Response: A Real-Life Study.

Severe Uncontrolled Asthma (SUA) counts for more than 25% of cases of severe asthma. The main factors that impair the quality of life of these patients are high doses of oral corticosteroids, the presence of exacerbations, and reduced lung function. The objective of this study was to evaluate, in real life, the clinical improvement of patients with SUA treated with anti-interleukin 5 (IL5) therapies: mepolizumab and benralizumab, together with the search for biomarkers associated with the response. We conducted a retrospective observational cohort study that included patients with severe uncontrolled eosinophilic asthma in a tertiary hospital receiving biological therapies. Three types of response were evaluated: improvement in lung function, reduction in exacerbations, and decrease in the use of oral corticosteroids. After 12 months of treatment, significant reductions were found in the number of exacerbations, the use of oral corticosteroids, and blood eosinophil levels for both biological therapies (p < 0.001). Lung function improved, achieving a significant improvement in %FEV1 (p < 0.001), as well as asthma control, with a significant increase in asthma control test (ACT) scores in both therapies. The markers associated with the corticosteroid-saving effect were the low doses of oral corticosteroids and absence of exacerbations for mepolizumab, and higher blood eosinophilia, absence of chronic obstructive pulmonary disease (COPD), and reduction in oral corticosteroid cycles for benralizumab. The greatest improvement in lung function in both therapies was linked to lower previous FEV1 levels and absence of other respiratory diseases. The reduction in exacerbations was associated with absence of exacerbations the previous year for mepolizumab and never smokers for benralizumab. The results of this real-life study confirm the clinical benefit obtained after the introduction of an anti-IL5 biological therapy and the possible predictive biomarkers of response to treatment.

Influence of Genetics on the Response to Omalizumab in Patients with Severe Uncontrolled Asthma with an Allergic Phenotype.

Omalizumab is a monoclonal antibody indicated for the treatment of severe uncontrolled asthma with an allergic phenotype. Its effectiveness could be influenced by clinical variables and single nucleotide polymorphisms (SNPs) in one or more of the genes involved in the mechanism of action and process of response to omalizumab, and these could be used as predictive biomarkers of response. We conducted an observational retrospective cohort study that included patients with severe uncontrolled allergic asthma treated with omalizumab in a tertiary hospital. Satisfactory response after 12 months of treatment was defined as (1) Reduction ≥ 50% of exacerbations or no exacerbations, (2) Improvement of lung function ≥ 10% FEV1, and (3) Reduction ≥ 50% of OCS courses or no OCS. Polymorphisms in the FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs1054485, rs569108), C3 (rs2230199), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), IL1RL1 (rs1420101, rs17026974, rs1921622), and GATA2 (rs4857855) genes were analyzed by real-time polymerase chain reaction (PCR) using TaqMan probes. A total of 110 patients under treatment with omalizumab were recruited. After 12 months of treatment, the variables associated with a reduction in exacerbations were the absence of polyposis (odds ratio [OR] = 4.22; 95% confidence interval [CI] = 0.95-19.63), IL1RL1 rs17026974-AG (OR = 19.07; 95% CI = 1.27-547), and IL1RL1 rs17026974-GG (OR = 16.76; 95% CI = 1.22-438.76). Reduction in oral corticosteroids (OCS) was associated with age of starting omalizumab treatment (OR = 0.95; 95% CI = 0.91-0.99) and blood eosinophil levels > 300 cells/µL (OR = 2.93; 95% CI = 1.01-9.29). Improved lung function showed a relationship to the absence of chronic obstructive pulmonary disease (COPD) (OR = 12.16; 95% CI = 2.45-79.49), FCGR2B rs3219018-C (OR = 8.6; 95% CI = 1.12-117.15), GATA2 rs4857855-T (OR = 15.98; 95% CI = 1.52-519.57) and FCGR2A rs1801274-G (OR = 13.75; 95% CI = 2.14-142.68; AG vs. AA and OR = 7.46; 95% CI = 0.94-89.12; GG vs. AA). Meeting one response criterion was related to FCER1A rs2251746-TT (OR = 24; 95% CI = 0.77-804.57), meeting two to age of asthma diagnosis (OR = 0.93; 95% CI = 0.88-0.99), and meeting all three to body mass index (BMI) < 25 (OR = 14.23; 95% CI = 3.31-100.77) and C3 rs2230199-C (OR = 3; 95% CI = 1.01-9.92). The results of this study show the possible influence of the polymorphisms studied on the response to omalizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

A 12-Month Follow-Up of PROCARE+, a Transdiagnostic, Selective, Preventive Intervention for Adolescents At-Risk for Emotional Disorders.

Few studies have reported long-term follow-up data on selective preventive interventions for adolescents. No follow-up selective preventive transdiagnostic studies for adolescents at-risk for emotional disorders, such as anxiety and depression, have been reported. To fill this gap, this study aims to provide the first follow-up assessment of a randomized controlled trial (RCT) studying selective transdiagnostic prevention in at-risk adolescents. A 12-month follow-up assessment was conducted with subjects who originally received either PROCARE (Preventive transdiagnostic intervention for Adolescents at Risk for Emotional disorders), PROCARE+, which includes the PROCARE protocol along with personalized add-on modules or an active control condition (ACC) based on emotional psychoeducation, and their respective booster session for each experimental condition. 80 subjects (47.5% girls) aged between 12 and 18 years (M = 14.62; SD 1.43) who completed these treatment conditions were available for the 12-month follow-up. The results demonstrate the superior long-term efficacy of the PROCARE+ intervention in mitigating emotional symptoms and obsessive-compulsive symptomatology compared to the PROCARE and ACC conditions, with effect sizes notably exceeding those commonly observed in preventive programs. While the three treatments demonstrated beneficial impacts, the pronounced results associated with PROCARE+ at the 12-month follow-up emphasized the importance of personalized treatment modules and the sustained benefits of booster sessions in the realm of preventive psychological interventions. The findings also highlight the potential role of add-on modules in enhancing the effects of the PROCARE+ condition.

Incidence and predictors of sternal surgical wound infection in cardiac surgery: A prospective study.

Sternal surgical wound infection (SSWI) in cardiac surgery is associated with increased morbidity. We investigated the incidence of SSWI, the main germs implicated and predictors of SSWI. Prospective study including patients undergoing full median sternotomy between January 2017 and December 2019. Patients were followed-up for 3 months after hospital discharge. All sternal wound infections up to 90 days after discharge were considered SSWI. 1004 patients were included. During follow-up, 68 (6.8%) patients presented SSWI. Patients with SSWI had a higher incidence of postoperative renal failure (29.4% vs 17.1%, P = .007), a higher incidence of early postoperative reoperation for non-infectious causes (42.6% vs 9.1%, P < .001), longer ICU stay (3 [2-9] days vs 2 [2-4] days, P = .006), and longer hospital stay (24.5 [14.8-38.3] days vs 10 [7-18] days, P < .001). Gram-positive germs were presented in 49% of the cultures, and gram-negative bacteria in 35%. Early reoperation for non-infectious causes (OR 4.90, 95% CI 1.03-23.7), and a longer ICU stay (OR 1.37 95% CI 1.10-1.72) were independent predictors of SSWI. SSWI is rare but leads to more postoperative complications. The need for early reoperation because of non-infectious cause and a longer ICU stay were independently associated with SSWI.

Personalized Therapy Approach for Hospitalized Patients with Coronavirus Disease 2019.

Hospitalized patients with coronavirus disease 2019 (COVID-19) experiencing respiratory symptoms have different complications (inflammatory, co-infection, and thrombotic) that are identifiable by analytics patterns. Personalized treatment decisions decreased early mortality (odds ratio [OR] .144; 95% confidence interval [CI] .03-.686; P = .015). Increasing age (OR 1.06; P = .038) and therapeutic effort limitation (OR 9.684; P < .001) were associated with higher mortality.

Rectal colonization by resistant bacteria increases the risk of infection by the colonizing strain in critically ill patients with cirrhosis.

BACKGROUND & AIMS: It remains unclear whether rectal colonization with multidrug-resistant organisms (MDROs) is prevalent and predisposes to infections by the same pathogens in patients with cirrhosis. METHODS: Two series of critically ill patients were evaluated. In the Barcelona cohort, 486 consecutive patients were prospectively evaluated, 129 with and 357 without cirrhosis (2015-2016). Rectal swabs were performed at admission and weekly thereafter (until intensive care unit [ICU] discharge) to detect MDRO colonization. Risk factors for colonization and infection by MDROs were evaluated. A retrospective cohort from Frankfurt (421 patients with cirrhosis; 2010-2018) was investigated to evaluate MDRO rectal colonization in another epidemiological scenario. RESULTS: In the Barcelona cohort, 159 patients were colonized by MDROs (32.7%), 102 (64.2%) at admission and 57 (35.8%) during follow-up. Patients with cirrhosis showed higher rates of rectal colonization at admission than those without cirrhosis (28.7% vs. 18.2%, p = 0.01) but similar colonization rates during ICU stay. Extended-spectrum beta-lactamase-Enterobacterales were the most frequent MDROs isolated in both groups. Colonization by MDROs independently increased the risk of infection by MDROs at admission and during follow-up. Risk of new infection by the colonizing strain was also significantly increased in patients with (hazard ratio [HR] 7.41) and without (HR 5.65) cirrhosis. Rectal colonization by MDROs was also highly prevalent in Frankfurt (n = 198; 47%; 131 at admission [66.2%] and 67 [33.8%] during follow-up), with vancomycin-resistant enterococci being the most frequent colonizing organism. Rectal colonization by MDROs was also associated with an increased risk of infection by MDROs in this cohort. Infections occurring in MDR carriers were mainly caused by the colonizing strain. CONCLUSION: Rectal colonization by MDROs is extremely frequent in critically ill patients with cirrhosis. Colonization increases the risk of infection by the colonizing resistant strain. LAY SUMMARY: Rectal colonization by multidrug-resistant organisms (MDROs) is a prevalent problem in patients with cirrhosis requiring critical care. The pattern of colonizing bacteria is heterogeneous with relevant differences between centers. Colonization by MDROs is associated with increased risk of infection by the colonizing bacteria in the short term. This finding suggests that colonization data could be used to guide empirical antibiotic therapy and de-escalation policies in patients with cirrhosis.

Impact of SARS-CoV-2 viral load and duration of symptoms before hospital admission on the mortality of hospitalized COVID-19 patients.

PURPOSE: Assess the impact of viral load estimated by cycle threshold (Ct) of reverse transcription real time-polymerase chain reaction (rRT-PCR) and the days from symptoms onset on mortality in hospitalized patients with COVID19. METHODS: Retrospective observational study of 782 patients with a positive rRT-PCR from a nasopharyngeal swab was performed within the first 24 h from admission. Demographic data, clinical manifestations and laboratory parameters were collected. Uni- and multivariate analyses were performed to identify factors associated with mortality at 60 days. RESULTS: Ct was divided into three groups and the mortality rate decreased from 27.3 to 20.7% and 9.8% for Ct values of ≤ 20, 21-25 and > 25, respectively (P = 0.0001). The multivariate analysis identified as predictors of mortality, a Ct value < 20 (OR 3.13, CI 95% 1.38-7.10), between 21-25 (OR 2.47, CI 95% 1.32-4.64) with respect to a Ct value > 25. Days from symptoms onset is a variable associated with mortality as well (DSOA) ≤ 6 (OR 1.86, CI 95% 1.00-3.46), among other factors. Patients requiring hospital admission within 6 DSOA with a Ct value ≤ 25 had the highest mortality rate (28%). CONCLUSIONS: The inclusion of Ct values and DSOA in the characterization of study populations could be a useful tool to evaluate the efficacy of antivirals.

Effects of Oral Pirfenidone on Colon Anastomosis Healing and Adhesion Formation in Rats.

INTRODUCTION: Many experimental studies have examined multiple drugs or treatments to improve the healing of intestinal anastomoses. Synthetic prostacyclin analogs, immunosuppressants, erythropoietin, growth hormone, insulin-like growth factor type 1, synthetic metalloproteinases inhibitors, and hyperbaric oxygen therapy have produced promising results in low-risk models of anastomosis dehiscence. However, in high-risk models, only hyperbaric oxygen therapy has been shown to be useful. Pirfenidone (PFD), a commonly used antifibrosing drug, has not been shown to be effective for this purpose. Our objective was to evaluate the effects of PFD on anastomosis healing and adhesion genesis in a low-risk rat model of dehiscence of colonic anastomosis. METHODS: An experimental study was conducted on 40 healthy Wistar rats randomly assigned to the control group or PFD experimental group (20 rats in each group). Colon anastomosis was performed 3 cm above the peritoneal reflection using the same technique in all animals. Mechanical resistance was studied by measuring bursting pressure. Adhesions were evaluated macroscopic and histologically using common staining techniques. Animals received the first PFD dose 12 h after surgery at a dose of 500 mg/kg one a day (SID) for 5 consecutive days. On day 6, the animals were reoperated on to measure the bursting pressure in situ and to classify adhesions macroscopically, and the anastomosed colon was resected for histological analysis. RESULTS: There were no deaths, complications, or anastomosis dehiscence in either group. The mean bursting pressure was 120.8 ± 11 mm Hg and 135.5 ± 12.4 in the control and PFD groups, respectively (p < 0.001). The adhesions were less dense and had less inflammatory cell infiltration in the PFD group (p < 0.02 and 0.002, respectively). Collagen content was slightly higher in the PFD group (p = 0.04). CONCLUSIONS: Our results revealed favorable effects of PFD in this low-risk colon anastomosis model; for example, the bursting pressure was higher, and the macroscopic adhesions were soft and exhibited less inflammatory infiltration and higher collagen content in the PFD group than in the control group. The results showing that PFD treatment was associated with better healing of minor adhesions seem to be paradoxical because the therapeutic indications for this drug are directed at treating fibrosing diseases.

Dissemination of NDM-producing Klebsiella pneumoniae and Escherichia coli high-risk clones in Catalan healthcare institutions.

OBJECTIVES: To characterize the clonal spread of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli isolates between different healthcare institutions in Catalonia, Spain. METHODS: Antimicrobial susceptibility was tested by disc diffusion. MICs were determined by gradient diffusion or broth microdilution. Carbapenemase production was confirmed by lateral flow. PCR and Sanger sequencing were used to identify the allelic variants of resistance genes. Clonality studies were performed by PFGE and MLST. Plasmid typing, conjugation assays, S1-PFGE plus Southern blotting and MinION Oxford Nanopore sequencing were used to characterize resistance plasmids. RESULTS: Twenty-nine carbapenem-resistant isolates recovered from three healthcare institutions between January and November 2016 were included: 14 K. pneumoniae isolates from a tertiary hospital in the south of Catalonia (hospital A); 2 K. pneumoniae isolates from a nearby healthcare centre; and 12 K. pneumoniae isolates and 1 E. coli isolate from a tertiary hospital in Barcelona (hospital B). The majority of isolates were resistant to all antimicrobial agents, except colistin, and all were NDM producers. PFGE identified a major K. pneumoniae clone (n = 27) belonging to ST147 and co-producing NDM-1 and CTX-M-15, with a few isolates also harbouring blaOXA-48. Two sporadic isolates of K. pneumoniae ST307 and E. coli ST167 producing NDM-7 were also identified. blaNDM-1 was carried in two related IncR plasmid populations and blaNDM-7 in a conjugative 50 kb IncX3 plasmid. CONCLUSIONS: We report the inter-hospital dissemination of XDR high-risk clones of K. pneumoniae and E. coli associated with the carriage of small, transferable plasmids harbouring blaNDM genes.

Impact of remdesivir according to the pre-admission symptom duration in patients with COVID-19.

BACKGROUND: The use of remdesivir has demonstrated a significant reduction in the time to recovery in patients with COVID-19. However, the impact on mortality is still controversial. Therefore, it is necessary to evaluate whether there is a specific subgroup of patients in whom an active antiviral therapy also reduces the mortality. METHODS: Patients admitted for >48 h in our hospital for a SARS-CoV-2 confirmed or suspected infection from February 2020 to February 2021 were retrospectively analysed. The primary outcome of the study was mortality at 30 days. Univariate and multivariate analyses were performed to identify predictors of mortality. RESULTS: In total, 2607 patients (438 receiving remdesivir and 2169 not) were included with a median (IQR) age of 65 (54-77) years and 58% were male. Four hundred and seventy-six were admitted to the ICU (18.3%) and 264 required invasive mechanical ventilation (10.1%). The global 30 day mortality rate was 10.7%. Pre-admission symptom duration of 4-6 days and ≤3 days was associated with a 1.5- and 2.5-fold increase in the mortality rate, respectively, in comparison with >6 days and treatment with remdesivir was independently associated with a lower mortality rate (OR = 0.382, 95% CI = 0.218-0.671). The analysis showed that the major difference was among patients with shorter pre-admission symptom duration (<6 days). CONCLUSIONS: Patients with ≤3 days and 4-6 days from symptom onset to admission are associated with a 2.5- and 1.5-fold higher risk of death, respectively. Remdesivir was associated with 62% reduced odds of death versus standard-of-care and its survival benefit increased with shorter duration of symptoms.

Use of cryopreserved human amniotic membrane in the treatment of skin ulcers secondary to calciphylaxis.

Calciphylaxis is a rare condition characterized by skin ulceration and necrosis as a result of vascular calcification of the small and medium blood vessels of skin and subcutaneous tissues. It mainly occurs in patients with advanced chronic kidney disease and sometimes leads to complications with a fatal outcome. In this report, we describe the case of a 67-year-old male patient with end stage renal disease presenting painful skin ulcers on his lower limbs. The lesions had progressively grown and were associated to severe pain and decreased quality of life. The ulcers did not respond to conventional treatments and the patient underwent skin biopsy of these lesions obtaining anatomopathological findings compatible with calciphylaxis. In this report, we present an innovative treatment for skin ulcers secondary to calciphylaxis using cryopreserved amniotic membrane (AM) as a dressing in order to promote epithelialization of the wounds. After four applications, healing of the main ulcer and reduction in pain was achieved. In summary, applying cryopreserved AM probed to be a promising strategy to reduce pain and to enhance epithelialization and healing of chronic non-responsive ulcers in calciphylaxis.

Management of perianal fistula in inflammatory bowel disease: identification of prognostic factors associated with surgery.

PURPOSE: As one of the clinical manifestations of inflammatory bowel disease (IBD), perianal fistula disease (PFD) can potentially impact the patient quality of life. The management of PFD employs a multidisciplinary approach which includes antibiotics, biological therapies, immunomodulators, and surgery. We analyzed the outcome and prognostic factors of anal fistula surgery in IBD patients. METHODS: We conducted a retrospective study of IBD patients undergoing elective surgery for anal fistula between January 2015 and December 2018 at our University Department of Surgery. We collated demographic factors, disease activity, imaging (MRI and endoanal ultrasound), surgical interventions, and medical treatment assessing the rate of fistula closure and fecal incontinence, 2 months and 1 year after surgery. RESULTS: Thirty-five IBD patients with anal fistula underwent surgery (28 Crohn's disease, four ulcerative colitis, and three indeterminate colitis). Twenty-seven patients presented with complex fistulas and eight with simple fistulas with 10 patients undergoing single-stage surgery. In 25 patients, a two-stage surgical approach was planned and performed (draining seton plus medical treatment and then second-stage surgery with curative intent). At 1 year of follow-up, the fistula healing rate was 50% for single-stage surgery and 60% for two-stage surgery (P = 0.09). Overall, 19.2% of patients developed postoperative fecal incontinence. A time interval greater than 12 months between surgeries is a favorable prognostic factor for fistula healing with the two-stage approach (P = 0.002). CONCLUSIONS: In our retrospective study, two-stage surgery in IBD patients presenting with complex perianal fistulous disease results in a better medium-term outcome with a longer time interval between surgeries.