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More than 140 different mutations have been reported in the Cu/Zn superoxide dismutase-1 ( SOD1) gene in patients with amyotrophic lateral sclerosis (ALS), some occurring as founder mutations. Occasionally, specific mutations are associated with a particular phenotype. We evaluated a possible genotype-phenotype correlation and looked for a founder effect in nine patients from six unrelated families with ALS, all carrying the G41S mutation, originating from north-west Tuscany in central Italy. Mutational analysis of the SOD1 gene was carried out by direct sequencing. A haplotype study was carried out using eight polymorphic markers flanking the SOD1 gene. The clinical pattern of the nine familial ALS (FALS) patients was characterized by spinal onset with early upper and lower motor neuron involvement, appearance of bulbar signs within one year, and death a few months later. Mean age at onset was 49.3 years and mean duration of disease was 0.9 years. Genotyping revealed a common haplotype for the G41S allele. We provide the first evidence that the G41S mutation in Italy originates from a common founder. In addition, our findings strengthen the data reported previously and indicate that the G41S mutation is consistently associated with a uniform and dramatic, fast-progressing phenotype. [ABSTRACT FROM AUTHOR]

Amyotrophic Lateral Sclerosis (ALS), the most common form among motoneuron diseases, is characterized by a progressive neurodegenerative process involving motor neurons in the motor cortex, brain stem and spinal cord. Sporadic (SALS) accounts for the majority of patients but in about 10% of ALS cases the disease is inherited (FALS), usually as an autosomal dominant trait. In the present study we show the results of a referred based multicenter study on the distribution of SOD1 gene mutations in the largest cohort of Italian ALS patients described so far. Two hundred and sixty–four patients (39 FALS and 225 SALS) of Italian origin were studied. In 7 out of 39 FALS patients we found the following SOD1 gene mutations: i) a new G12R missense mutation in exon 1, found in a patient with a slowly progressive disease course; ii) the G41S mutation, in four unrelated patients with rapidly progressive course complicated with cognitive decline in two of them; iii) the L114F mutation, in a patient with a slowly progressive phenotype; iv) the D90A mutation, in a heterozygous patient with atypical phenotype. In addition, in one SALS patient a previously reported synonymous variant S59S was identified. In 17 (3 FALS and 14 SALS) out of 264 patients (6.4 %) the polymorphism A→C at position 34 of intron 3 (IVS3: + 34 A→C) was found, and in one FALS patient a novel variant IVS3 + 62 T→C was identified. The frequency of SOD1 gene mutations (17.9 %) in FALS cases was comparable with that found in other surveys with a similar sample size of ALS cases. No SOD1 gene mutations have been identified in SALS cases. Within FALS cases, The most frequent mutation was the G41S identified in four FALS. [ABSTRACT FROM AUTHOR]

The endangered Greater Caribbean manatee (Trichechus manatus manatus), one of the largest aquatic herbivores in the Caribbean, plays a crucial role in nutrient recycling within the ecosystem, and the study of its feeding ecology is important for its conservation. Despite several studies determining the items consumed by manatees, there remains limited understanding of their nutritional significance for the species in the Western Caribbean. This study, aimed to analyze the bromatological composition of the food components in the manatee’s diet in the Mexican Caribbean across three distinct environments. We manually collected aquatic and semi-aquatic primary producers potentially part of the manatee diet in marine, brackish and riverine areas of the southern region of Quintana Roo, Mexico. Then, we analyzed them for moisture, crude protein, crude fiber, ash, ether extract, digestible nutrients, and digestible energy. We present the initial data on nutrient values in the manatee diet in the Caribbean, establishing a foundation for exploring the factors that influence spatial, temporal, and species-specific variations in nutrient content at a regional level. Our bromatological analysis demonstrated that the most nutritionally important plants for manatees, based mainly on protein content and freshwater contribution, include the seagrasses Halodule wrightii, Syringodium filiforme, Thalassia testudinum, the water lily Pontederia crassipes, and Vallisneria sp. Effective habitat management for manatees is crucial for their survival, ensuring that feeding resources are maintained in both enough quantity and high quality. Given its nutritional significance for manatees, we recommend that seagrasses in the region should be prioritized as conservation targets. [ABSTRACT FROM AUTHOR]

The herpetofauna of the insular systems of Mexico is composed of 226 species, of which 14 are anurans, two are salamanders, and 210 are reptiles, comprised of two crocodilians, 195 squamates, and 13 turtles. Although the surface of the Mexican islands is only 0.26% of the Mexican territorial extension, these 226 species constitute 16.1% of Mexico's documented herpetofauna of 1405 species. We classified the Mexican islands into five physiographic regions: the islands of Pacific Baja California; the islands of the Gulf of California; the islands of the Tropical Pacific; the islands of the Gulf of Mexico; and the islands of the Mexican Caribbean. The highest species richness among these regions is in the Gulf of California, with 108 species, and the lowest richness is 40 for the islands of the Pacific Baja California and 46 for those of the Gulf of Mexico. We identified introduced species, risk of wildfires, climate change, and urban/tourist development as the main environmental threats impinging on these species. In addition, we assessed the conservation status of the native species by comparing the SEMARNAT (NOM-059), IUCN Red List, and the Environmental Vulnerability Score (EVS) systems. The comparison of these systems showed that the NOM-059 and the IUCN systems seriously underestimate the degree of threat for insular endemics, being particularly concerning for those insular species that are known only from their respective type localities. The EVS system proved to be practical and indicated that 94 species have a high vulnerability status, 62 a medium status, and 56 a low status. The Relative Herpetofaunal Priority system, which contrasts the number of endemic and threatened species among different physiographic areas, indicates that the regions with the highest priority are the Islands of the Gulf of California, followed by the islands of the Tropical Pacific. Finally, we discussed the completeness of the Mexican Natural Protected Areas on the insular systems of the country; the result is outstanding since Mexico is already close to achieving the goal of having all their islands under some degree of federal protection. [ABSTRACT FROM AUTHOR]

How social contact is perceived as rewarding and subsequently modifies interactions is unclear. Dopamine (DA) from the ventral tegmental area (VTA) regulates sociality, but the ongoing, unstructured nature of free behavior makes it difficult to ascertain how. Here, we tracked the emergence of a repetitive stereotyped parental retrieval behavior and conclude that VTA DA neurons incrementally refine it by reinforcement learning (RL). Trial-by-trial performance was correlated with the history of DA neuron activity, but DA signals were inconsistent with VTA directly influencing the current trial. We manipulated the subject's expectation of imminent pup contact and show that DA signals convey reward prediction error, a fundamental component of RL. Finally, closed-loop optogenetic inactivation of DA neurons at the onset of pup contact dramatically slowed emergence of parental care. We conclude that this component of maternal behavior is shaped by an RL mechanism in which social contact itself is the primary reward. • VTA DA neuron activity during maternal care inversely correlates with performance • Performance of pup retrieval is influenced by the history of DA neuron activity • VTA DA neurons signal reward prediction error for pup contact • Silencing VTA DA neurons affects future performance but not the current trial The mechanism by which social contact is perceived as rewarding and shapes future interactions is poorly understood. Xie et al. find that midbrain dopamine neurons signal a social reward prediction error, instructing the emergence of maternal behavior by reinforcement learning and affecting future, but not current, trials. [ABSTRACT FROM AUTHOR]

The article focuses on understanding the mechanisms underlying both the rewarding and aversive effects of opioids in the brain, particularly investigating the role of the dorsal peduncular nucleus (DPn) in regulating these responses. It mentions through whole-brain mapping and optogenetic techniques in mice injected with oxycodone, the study reveals that DPn neurons, which project to the parabrachial nucleus (PBn).

Background: Survival after cardiac arrest depends on adequate cardiopulmonary resuscitation (CPR). Manual or mechanical external chest compression may be ineffective to restore circulation: structures subjected to external chest compression may differ in forces transfer to intrathoracic structures due to anatomic characteristics and physiological changes. This clinical study aims to assess the association of trans-oesophageal findings during CPR and successful resuscitation.Methods: Retrospective cohort study. Trans-oesophageal assessment of right ventricular fractional area change, right ventricular outflow tract fractional shortening, left ventricular volumes, ejection fraction, and aortic diameters were performed in refractory out-of-hospital cardiac arrest patients admitted to emergency department for extracorporeal CPR.Results: 19 patients were analyzed. 15 of 19 patients (79%) received venous-arterial extracorporeal membrane oxygenation support. Resuscitation was successful with return of spontaneous circulation or electromechanical activity in 7 patients (group-SUXX) and failed in 12 patients (group-FAIL). 6 patients (32%) were alive at 24 h from the cardiac arrest, one patient (5%) survived to hospital discharge. Left ventricular outflow tract (LVOT) was open during CPR in all patients in group-SUXX and in 1 patient in group-FAIL (p 0.0002). None of the patients with closed LVOT had successful resuscitation. Patients in group-SUXX had a higher ejection fraction (p 0.03), ascending aortic diameter (p 0.04), and survival rate than those in group-FAIL (p 0.015). In a multiple variable Cox's proportional model LVOT opening was the only variable associated with successful resuscitation.Conclusions: Trans-oesophageal echocardiography can be useful in the emergency setting of cardiopulmonary arrest for discriminating between successful and failing resuscitation. [ABSTRACT FROM AUTHOR]

Introduction: Early noninvasive respiratory support (NIRS) is correlated with a success rate of 60-75% in patients experiencing SARS-CoV-2 ARDS. We conducted a prospective case-control study to assess differences in outcomes between Helmet c-PAP (H-c-PAP) and noninvasive positive pressure ventilation (NIPPV). Methods: All patients with SARS-CoV-2 ARDS, treated with H-c-PAP or NIPPV between October 2021 and April 2022 were sampled. We recorded: demographics, comorbidities, clinical, respiratory, sepsis, NIRS parameters, and outcomes. A "NIRS team" followed the patients in respiratory support supplying them with early and timely intensive physiotherapy i-PKT as well. The Cox's proportional hazard model was applied for multivariate analyses. Results: 368 patients were admitted to our hospital medical ward. 85 patients were treated with H-c-PAP and 145 underwent NIPPV. 138 patients needing oxygen supplementation alone were excluded. The two groups were homogeneously distributed and ICU admission rates were lower in the H-c-PAP one (9.4 vs 11% P  = .001) while mortality was higher in the NIPPV group (22.7 vs 9.4%, P  = .001). The two multivariate models, that had overall mortality as primary outcome, identified age, H-c-PAP daily, i-PKT and ICU admission as independent variables impacting on the outcome. Age was no longer a significant independent predictor after the inclusion of elderly patients (age >80). The third model showed daily i-PKT could prevent ICU admission whereas the length of NIRS was inversely proportional to outcome. Conclusions: A "NIRS multidisciplinary team" made it possible to adopt an early and timely combination of NIRS and i-PKT resulting in the saving of both patient lives and ICU resources., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Continuous renal replacement therapies (CRRTs) and sequential extracorporeal blood purification (EBP) therapies can be used in patients with severe COVID-19 disease to support kidney failure and restore immune homeostasis. EBP prescription should be based on the patient's clinical needs and frequently re-evaluated during the intensive care unit (ICU) stay. Personalization of treatment at the bedside plays a fundamental role for patient recovery. This aim can be simplified by using both clinical and molecular data collected from a patient-individualized web registry. In this case report, we describe how we apply a sequential approach to EBP therapies following the rapid evolution of a critically ill COVID-19 patient with acute kidney injury. We show patient strategies and outcomes using bedside data from a registry-based method for the routine use of EBP. We explain the choice of specific hemofilter prescription, also focusing on dose and anticoagulation strategies. We describe the difficulties, uncertainties, and mistakes made during EBP prescription. Furthermore, we discuss the causes and workable solutions that can be adopted by the ICU physician for a better EBP prescription, considering the current lack of well-recognized indications. Trial Registration: ClinicalTrials.gov identifier: NCT03807414., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Clemente Santorsola et al.)

Background: Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam., Methods: We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least ≥24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality., Results: The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index ≥ 3, dialysis, concomitant COVID-19, and INCREMENT score ≥ 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48 hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy., Conclusions: Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy., Competing Interests: Potential conflicts of interest. No reported conflicts of interest, (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Effective response to a mass-casualty incident (MCI) entails the activation of hospital MCI plans. Unfortunately, there are no tools available in the literature to support hospital responders in predicting the proper level of MCI plan activation. This manuscript describes the scientific-based approach used to develop, test, and validate the PEMAAF score (Proximity, Event, Multitude, Overcrowding, Temporary Ward Reduction Capacity, Time Shift Slot [Prossimità, Evento, Moltitudine, Affollamento, Accorpamento, Fascia Oraria], a tool able to predict the required level of hospital MCI plan activation and to facilitate a coordinated activation of a multi-hospital network., Methods: Three study phases were performed within the Metropolitan City of Milan, Italy: (1) retrospective analysis of past MCI after action reports (AARs); (2) PEMAAF score development; and (3) PEMAAF score validation. The validation phase entailed a multi-step process including two retrospective analyses of past MCIs using the score, a focus group discussion (FGD), and a prospective simulation-based study. Sensitivity and specificity of the score were analyzed using a regression model, Spearman's Rho test, and receiver operating characteristic/ROC analysis curves., Results: Results of the retrospective analysis and FGD were used to refine the PEMAAF score, which included six items-Proximity, Event, Multitude, Emergency Department (ED) Overcrowding, Temporary Ward Reduction Capacity, and Time Shift Slot-allowing for the identification of three priority levels (score of 5-6: green alert; score of 7-9: yellow alert; and score of 10-12: red alert). When prospectively analyzed, the PEMAAF score determined most frequent hospital MCI plan activation (>10) during night and holiday shifts, with a score of 11 being associated with a higher sensitivity system and a score of 12 with higher specificity., Conclusions: The PEMAAF score allowed for a balanced and adequately distributed response in case of MCI, prompting hospital MCI plan activation according to real needs, taking into consideration the whole hospital response network.

Introduction: Not enough data exist to inform the optimal duration and type of antimicrobial therapy against GN infections in critically ill patients., Methods: Narrative review based on a literature search through PubMed and Cochrane using the following keywords: "multi-drug resistant (MDR)", "extensively drug resistant (XDR)", "pan-drug-resistant (PDR)", "difficult-to-treat (DTR) Gram-negative infection," "antibiotic duration therapy", "antibiotic combination therapy" "antibiotic monotherapy" "Gram-negative bacteremia", "Gram-negative pneumonia", and "Gram-negative intra-abdominal infection"., Results: Current literature data suggest adopting longer (≥10-14 days) courses of synergistic combination therapy due to the high global prevalence of ESBL-producing (45-50%), MDR (35%), XDR (15-20%), PDR (5.9-6.2%), and carbapenemases (CP)/metallo-β-lactamases (MBL)-producing (12.5-20%) Gram-negative (GN) microorganisms (i.e., Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii ). On the other hand, shorter courses (≤5-7 days) of monotherapy should be limited to treating infections caused by GN with higher (≥3 antibiotic classes) antibiotic susceptibility. A general approach should be based on (i) third or further generation cephalosporins ± quinolones/aminoglycosides in the case of MDR-GN; (ii) carbapenems ± fosfomycin/aminoglycosides for extended-spectrum β-lactamases (ESBLs); and (iii) the association of old drugs with new expanded-spectrum β-lactamase inhibitors for XDR, PDR, and CP microorganisms. Therapeutic drug monitoring (TDM) in combination with minimum inhibitory concentration (MIC), bactericidal vs. bacteriostatic antibiotics, and the presence of resistance risk predictors (linked to patient, antibiotic, and microorganism) should represent variables affecting the antimicrobial strategies for treating GN infections., Conclusions: Despite the strategies of therapy described in the results, clinicians must remember that all treatment decisions are dynamic, requiring frequent reassessments depending on both the clinical and microbiological responses of the patient.

Social sensitivity to other individuals in distress is crucial for survival. The anterior cingulate cortex (ACC) is a structure involved in making behavioral choices and is influenced by observed pain or distress. Nevertheless, our understanding of the neural circuitry underlying this sensitivity is incomplete. Here, we reveal unexpected sex-dependent activation of ACC when parental mice respond to distressed pups by returning them to the nest ("pup retrieval"). We observe sex differences in the interactions between excitatory and inhibitory ACC neurons during parental care, and inactivation of ACC excitatory neurons increased pup neglect. Locus coeruleus (LC) releases noradrenaline in ACC during pup retrieval, and inactivation of the LC-ACC pathway disrupts parental care. We conclude that ACC maintains sex-dependent sensitivity to pup distress under LC modulation. We propose that ACC's involvement in parenting presents an opportunity to identify neural circuits that support sensitivity to the emotional distress of others., Competing Interests: Declaration of interests P.O. has a financial interest in Certerra, a company that offers whole-brain imaging services., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The proper posology of antibiotics in the critically ill in CRRT is difficult to assess. We therefore performed a prospective observational cohort study to make clear hints in this topic. Our results reveal a high Sieving Coefficient for all antibiotics, equal to or higher than those described in previous papers. CVVH clearance in relation to total body clearance was significant, (i.e., >than 25% for all classes). A strong correlation between the antibiotic concentrations obtained in plasma and ultrafiltrate was found both at the peak and in the valley, with the determination of two equations that allow a new method for calculating the amount of antibiotic lost in CVVH both for trough levels and peak. Based on the results of our study and considering the limitations we believe that we can extrapolate the following final considerations: (1) it is likely to carry out a loading dose for the main antibiotics (2) subsequent administrations must take into account the daily loss identified by the linear regression equation. This angular coefficient gives the idea that the average daily loss of given antibiotic is about 25%; this implies that on the basis of the linear regression equation that correlates ultrafiltered/plasma antibiotic concentration, the dosage should be increased by 25% every day, while still ensuring a daily plasma TDM of the drug.

The outcome for critically ill patients is burdened by a double mortality rate and a longer hospital stay in the case of sepsis or septic shock. The adequate use of antibiotics may impact on the outcome since they may affect the pharmacokinetics (Pk) and pharmacodynamics (Pd) of antibiotics in such patients. Acute renal failure (ARF) occurs in about 50% of septic patients, and the consequent need for continuous renal replacement therapy (CRRT) makes the renal elimination rate of most antibiotics highly variable. Antibiotics doses should be reduced in patients experiencing ARF, in accordance with the glomerular filtration rate (GFR), whereas posology should be increased in the case of CRRT. Since different settings of CRRT may be used, identifying a standard dosage of antibiotics is very difficult, because there is a risk of both oversimplification and failing the therapeutic efficacy. Indeed, it has been seen that, in over 25% of cases, the antibiotic therapy does not reach the necessary concentration target mainly due to lack of the proper minimal inhibitory concentration (MIC) achievement. The aim of this narrative review is to clarify whether shared algorithms exist, allowing them to inform the daily practice in the proper antibiotics posology for critically ill patients undergoing CRRT.

Obesity is a global pandemic that is causally linked to many life-threatening diseases. Apart from some rare genetic conditions, the biological drivers of overeating and reduced activity are unclear. Here, we show that neurotensin-expressing neurons in the mouse interstitial nucleus of the posterior limb of the anterior commissure (IPAC), a nucleus of the central extended amygdala, encode dietary preference for unhealthy energy-dense foods. Optogenetic activation of IPAC Nts neurons promotes obesogenic behaviors, such as hedonic eating, and modulates food preference. Conversely, acute inhibition of IPAC Nts neurons reduces feeding and decreases hedonic eating. Chronic inactivation of IPAC Nts neurons recapitulates these effects, reduces preference for sweet, non-caloric tastants and, furthermore, enhances locomotion and energy expenditure; as a result, mice display long-term weight loss and improved metabolic health and are protected from obesity. Thus, the activity of a single neuronal population bidirectionally regulates energy homeostasis. Our findings could lead to new therapeutic strategies to prevent and treat obesity., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Patients in intensive care units (ICU) are at high risk to experience potential drug-drug interactions (pDDIs) because of the complexity of their drug regimens. Such pDDIs may be driven by pharmacokinetic or pharmacodynamic mechanisms with clinically relevant consequences in terms of treatment failure or development of drug-related adverse events. The aim of this paper is to review the pharmacokinetic-driven pDDIs involving antibiotics in ICU adult patients. A MEDLINE Pubmed search for articles published from January 2000 to June 2022 was completed matching the terms "drug-drug interactions" with "pharmacokinetics", "antibiotics", and "ICU" or "critically-ill patients". Moreover, additional studies were identified from the reference list of retrieved articles. Some important pharmacokinetic pDDIs involving antibiotics as victims or perpetrators have been identified, although not specifically in the ICU settings. Remarkably, most of them relate to the older antibiotics whereas novel molecules seem to be associated with a low potential for pDDIs with the exceptions of oritavancin as potential perpetrator, and eravacicline that may be a victim of strong CYP3A inducers. Personalized therapeutic drug regimens by means of available web-based pDDI checkers, eventually combined with therapeutic drug monitoring, when available, have the potential to improve the response of ICU patients to antibiotic therapies.

Background: Mesentery thickening and enlarged lymphnodes are typical findings of Crohn's disease (CD), but their role is unknown. Aim of the present study was to evaluate their prevalence and significance on postoperative complications and long-term surgical recurrence after CD surgery., Methods: 1272 consecutive, unselected patients were retrospectively reviewed, divided into 4 groups based on the presence or absence of a thickened mesentery and enlarged lymphnodes, and stratified for primary or recurrent surgical procedure. In all patients but those treated with strictureplasty the mesentery and lymphnodes were removed. Patients' characteristics, peri-operative findings, and long-term recurrence were compared by univariate and multivariate analysis., Results: Thickened mesentery and enlarged lymphnodes were not present in all cases, were typical of ileal location and penetrating behaviour, had a constant decrease over recurrences, were independent of either pre-operative medical therapy or surgical approach, did not increase the duration of surgery and complications, presented similar 20-years recurrence rate to normal mesentery and lymphnodes. Lymphopathy was associated to a worst nutritional status during disease recurrences. At multivariate analysis, age, location, and behaviour, but not mesenteric characteristics, were related to an increased risk of surgical recurrence., Conclusions: This study provides new information on mesentery and lymphnodes in CD patients. Further studies are needed to clarify the appropriate surgical approach., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: To investigate the prevalence, incidence and characteristics of bacterial infections and their impact on outcome in critically ill patients infected with COVID-19., Methods: We conducted a prospective observational study in eight Italian ICUs from February to May 2020; data were collected through an interactive electronic database. Kaplan-Meier analysis (limit product method) was used to identify the occurrence of infections and risk of acquisition., Results: During the study period 248 patients were recruited in the eight participating ICUs. Ninety (36.3%) patients developed at least one episode of secondary infection. An ICU length of stay between 7 and 14 days was characterized by a higher occurrence of infectious complications, with ventilator-associated pneumonia being the most frequent. At least one course of antibiotic therapy was given to 161 (64.9%) patients. Overall ICU and hospital mortality were 33.9% and 42.9%, respectively. Patients developing bacteremia had a higher risk of ICU mortality [45.9% vs. 31.6%, odds ratio 1.8 (95% CI 0.9-3.7), p = 0.069] and hospital mortality [56.8% vs. 40.3%, odds ratio 1.9 (95% CI 1.1-3.9), p = 0.04]., Conclusion: In critically ill patients infected with COVID-19 the incidence of bacterial infections is high and associated with worse outcomes. Regular microbiological surveillance and strict infection control measures are mandated., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: The authors declare no conflict of interest.

Background & Aims: There is uncertainty regarding the optimal duration of treatment with azathioprine (AZA) in ulcerative colitis (UC) and Crohn's disease (CD). We analyzed the clinical course and predictors of relapse after AZA withdrawal in patients in sustained deep remission., Methods: A prospective study was performed on patients who stopped their treatment with AZA while being in steroid-free, extended deep remission (normal clinical, endoscopic, and histologic indexes, C-reactive protein, and fecal calprotectin [FC]). Standard biochemical tests and FC were measured at 3 and 6 months, then every 6 months. Bowel ultrasounds and ileocolonoscopy were performed every 6 and 12 months, respectively. Multivariate analysis for predictors of relapse was performed using a Cox proportional hazards model and hazard ratios were calculated. Spearman nonparametric correlation test was also used. The accuracy of significant predictors was calculated., Results: Fifty-seven patients with inflammatory bowel disease stopped AZA after median 7 years (range, 5-19) and were followed up for median 50 months (range, 25-85). Twenty-six patients (18/31 UC, 8/26 CD; P = .003) relapsed, within a median 15 months (range, 2-37). FC was the only variable significantly correlated with later relapse of both diseases (UC: hazard ratio, 3.3; 95% confidence interval, 1.2-10; CD: hazard ratio, 4.5; 95% confidence interval, 1.4-12.5). The sensitivity, specificity, and positive and negative predictive values of FC were 50%, 100%, 100%, and 59% in UC and 50%, 94%, 80%, and 81% in CD., Conclusions: More than half patients with UC and one-third of patients with CD relapse after AZA withdrawal despite previous deep remission. FC positivity is associated with high risk of relapse, allowing early correction of the therapeutic strategy., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary tract infections, as well as hospital-acquired pneumonia, and for gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against Klebsiella pneumoniae carbapenemase (KPC) enzyme producers, but clinical trial data on its efficacy in this setting are lacking., Methods: We retrospectively reviewed 138 cases of infections caused by KPC-producing K. pneumoniae (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic., Results: The 138 patients started CAZ-AVI salvage therapy after a first-line treatment (median, 7 days) with other antimicrobials. CAZ-AVI was administered with at least 1 other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs 55.8%, P = .005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index ≥3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival., Conclusions: CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.