Secondary aorto-duodenal fistula: a diagnostic challenge in a patient with fever and anemia.

A 69-year-old male, three years post-endovascular exclusion for an abdominal aortic aneurysm, presented with asthenia and fever. An abdominal CT scan showed no gastrointestinal tract communications, abscess, or contrast extravasation. Tc-99m-HMPAO-labeled leukocytes scintigraphy with SPECT/CT revealed increased uptake on the posterior surface of the aortic graft, along with air bubbles in its right iliac limb. Upper gastrointestinal endoscopy was performed, revealing a duodenal ulcer in the transition between the second and third portions. The ulcer exhibited yellow graft tissue at its center. The patient underwent in situ reconstruction, involving the replacement of the infected prosthetic graft, and the duodenal defect was addressed through segmental resection and duodenojejunal anastomosis. Secondary aorto-duodenal fistula (SADF), a rare complication of vascular surgery, may arise from factors such as local infection or graft-bowel contact. SADF, often located in the duodenum, poses a high mortality risk, necessitating early diagnosis. Clinical presentation varies from significant upper gastrointestinal bleeding to obscured bleeding.

Out-of-Hospital Cardiac Arrest Following the COVID-19 Pandemic.

Importance: Out-of-hospital cardiac arrest (OHCA) health care provision may be a good indicator of the recovery of the health care system involved in OHCA care following the COVID-19 pandemic. There is a lack of data regarding outcomes capable of verifying this recovery. Objective: To determine whether return to spontaneous circulation, overall survival, and survival with good neurological outcome increased in patients with OHCA since the COVID-19 pandemic was brought under control in 2022 compared with prepandemic and pandemic levels. Design, Setting, and Participants: This observational cohort study was conducted to examine health care response and survival with good neurological outcome at hospital discharge in patients treated following OHCA. A 3-month period, including the first wave of the pandemic (February 1 to April 30, 2020), was compared with 2 periods before (April 1, 2017, to March 31, 2018) and after (January 1 to December 31, 2022) the pandemic. Data analysis was performed in July 2023. Emergency medical services (EMS) serving a population of more than 28 million inhabitants across 10 Spanish regions participated. Patients with OHCA were included if participating EMS initiated resuscitation or continued resuscitation initiated by a first responder. Exposure: The pandemic was considered to be under control following the official declaration that infection with SARS-CoV-2 was to be considered another acute respiratory infection. Main Outcome and Measures: The main outcomes were return of spontaneous circulation, overall survival, and survival at hospital discharge with good neurological outcome, expressed as unimpaired or minimally impaired cerebral performance. Results: A total of 14 732 patients (mean [SD] age, 64.2 [17.2] years; 10 451 [71.2%] male) were included, with 6372 OHCAs occurring during the prepandemic period, 1409 OHCAs during the pandemic period, and 6951 OHCAs during the postpandemic period. There was a higher incidence of OHCAs with a resuscitation attempt in the postpandemic period compared with the pandemic period (rate ratio, 4.93; 95% CI, 4.66-5.22; P < .001), with lower incidence of futile resuscitation for OHCAs (2.1 per 100 000 person-years vs 1.3 per 100 000 person-years; rate ratio, 0.81; 95% CI, 0.71-0.92; P < .001). Recovery of spontaneous circulation at hospital admission increased from 20.5% in the pandemic period to 30.5% in the postpandemic period (relative risk [RR], 1.08; 95% CI, 1.06-1.10; P < .001). In the same way, overall survival at discharge increased from 7.6% to 11.2% (RR, 1.45; 95% CI, 1.21-1.75; P < .001), with 6.6% of patients being discharged with good neurological status (Cerebral Performance Category Scale categories 1-2) in the pandemic period compared with 9.6% of patients in the postpandemic period (RR, 1.07; 95% CI, 1.04-1.10; P < .001). Conclusions and Relevance: In this cohort study, survival with good neurological outcome at hospital discharge following OHCA increased significantly after the COVID-19 pandemic.

Standardising personalised diabetes care across European health settings: A person-centred outcome set agreed in a multinational Delphi study.

OBJECTIVE: Standardised person-reported outcomes (PRO) data can contextualise clinical outcomes enabling precision diabetes monitoring and care. Comprehensive outcome sets can guide this process, but their implementation in routine diabetes care has remained challenging and unsuccessful at international level. We aimed to address this by developing a person-centred outcome set for Type 1 and Type 2 diabetes, using a methodology with prospects for increased implementability and sustainability in international health settings. METHODS: We used a three-round questionnaire-based Delphi study to reach consensus on the outcome set. We invited key stakeholders from 19 countries via purposive snowball sampling, namely people with diabetes (N = 94), healthcare professionals (N = 65), industry (N = 22) and health authorities (N = 3), to vote on the relevance and measurement frequency of 64 previously identified clinical and person-reported outcomes. Subsequent consensus meetings concluded the study. RESULTS: The list of preliminary outcomes was shortlisted via the consensus process to 46 outcomes (27 clinical outcomes and 19 PROs). Two main collection times were recommended: (1) linked to a medical visit (e.g. diabetes-specific well-being, symptoms and psychological health) and (2) annually (e.g. clinical data, general well-being and diabetes self management-related outcomes). CONCLUSIONS: PROs are often considered in a non-standardised way in routine diabetes care. We propose a person-centred outcome set for diabetes, specifically considering psychosocial and behavioural aspects, which was agreed by four international key stakeholder groups. It guides standardised collection of meaningful outcomes at scale, supporting individual and population level healthcare decision making. It will be implemented and tested in Europe as part of the H2O project.

Revision of carpenter bees of the subgenus Neoxylocopa Michener (Hymenoptera: Apidae) from Mexico and Mesoamerica.

We present a review of the genus Xylocopa (Neoxylocopa) of Mexico and Mesoamerica in which 11 species are recognized, including: X. clarionenis, X. fimbriata, X. frontalis, X. gualanensis, X. mexicanorum, X. nautlana, X. ocellaris, X. sonorina, X. wilmattae. Additionally, two new species are described, X. griswoldi sp. nov. with distribution in the United States and Mexico, and X. maya sp. nov. present in Mexico and Belize. Three species groups within the subgenus Neoxylocopa are recognized: frontalis, mexicanorum and sonorina. Identification keys are presented for identifying species groups and species. Furthermore, images of species and morphological structures as well as information regarding distribution are provided.

Aldose reductase promotes diet-induced obesity via induction of senescence in subcutaneous adipose tissue.

OBJECTIVE: Aldose reductase (AKR1B1 in humans; Akr1b3 in mice), a key enzyme of the polyol pathway, mediates lipid accumulation in the murine heart and liver. The study objective was to explore potential roles for AKR1B1/Akr1b3 in the pathogenesis of obesity and its complications. METHODS: The study employed mice treated with an inhibitor of aldose reductase or mice devoid of Akr1b3 were used to determine their response to a high-fat diet. The study used subcutaneous adipose tissue-derived adipocytes to investigate mechanisms by which AKR1B1/Akr1b3 promotes diet-induced obesity. RESULTS: Increased expression of aldose reductase and senescence in the adipose tissue of humans and mice with obesity were demonstrated. Genetic deletion of Akr1b3 or pharmacological blockade of AKRIB3 with zopolrestat reduced high-fat-diet-induced obesity, attenuated markers of adipose tissue senescence, and increased lipolysis. CONCLUSIONS: AKR1B1/Akr1b3 modulation of senescence in subcutaneous adipose tissue contributes to aberrant metabolic responses to high-fat feeding. These data unveil new opportunities to target these pathways to combat obesity.

New Complex of Cryptic Species Discovered in Genus Biblis (Papilionoidea: Nymphalidae: Biblidinae) in Mexico.

Our research focuses on demonstrating the existence of cryptic species named under Biblis aganisa Boisduval. We used COI sequences to delimit Biblis species for Mexico using species delimitation analyses and examined phylogenetic relationships with sequences from Mexico, Costa Rica, Argentina, USA, and Guana Island using a Bayesian inference tree. We performed a discriminant analysis with quantitative traits using female and male wing and genitalia, and a tree of maximum parsimony based on 39 qualitative characters of wings, head, and male genitalia. The results were congruent in the three analyses. Three groups were formed based on DNA, ECO 01 + DHJ02, ECO 02 + DHJ01, and ECO 03. The characters that contributed over 50% separation were for wings: wing length, anal margin length, and distance from the band to the outer margin; for male genitalia, angle of the integument, uncus, and the length of the hypandrium, while for females, it was the angle of the anteapophysis and the length of the abdomen. For the analysis of qualitative characters, a tree of maximum parsimony was obtained where 20 characters were informative. We confirmed the existence of three cryptic Biblis species in Mexico, two not yet described, and one corresponding to B. aganisa (ECO 02), which is sympatric in Oaxaca and Sinaloa (ECO 03) and in the Yucatan Peninsula (ECO 01).

A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells.

It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection. Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections. Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism.

A new ant-butterfly symbiosis in the forest canopy fills an evolutionary gap.

Myrmecophilous butterflies can establish complex symbiotic relationships with ants. A caterpillar wandering among the brood of the aggressive ponerine ant Neoponera villosa was found inside the core of a nest built in the myrmecophytic bromeliad Aechmea bracteata. This is the first caterpillar found living inside a ponerine ant nest. Its DNA barcode was sequenced, and an integrative approach was used to identify it as Pseudonymphidia agave, a poorly known member of the subtribe Pachythonina in the riodinid tribe Nymphidiini. The cuticle of the tank-like caterpillar lacks projections or tubercles and is covered dorsally by specialized flat setae that form an armor of small plates. Ant-organs potentially related to caterpillar-ant signaling, such as perforated cupola organs and tentacle nectary organs, are present. These morphological traits, together with evidence of social integration (direct contact with host brood, protective morphology, slow movement, no host aggressiveness), suggest that P. agave is a symbiotic, social parasite of N. villosa, preying on its host brood. However, several knowledge gaps remain, including oviposition site, dependence on bromeliad association, steps to colony integration, and larval diet through development. Carnivory has been reported in all known members of the subtribe Pachythonina (caterpillars prey on honeydew-producing hemipterans) suggesting a shift to myrmecophagy inside the ant nests as a possible evolutionary transition.

The Nuclear Receptor ESRRA Protects from Kidney Disease by Coupling Metabolism and Differentiation.

Kidney disease is poorly understood because of the organ's cellular diversity. We used single-cell RNA sequencing not only in resolving differences in injured kidney tissue cellular composition but also in cell-type-specific gene expression in mouse models of kidney disease. This analysis highlighted major changes in cellular diversity in kidney disease, which markedly impacted whole-kidney transcriptomics outputs. Cell-type-specific differential expression analysis identified proximal tubule (PT) cells as the key vulnerable cell type. Through unbiased cell trajectory analyses, we show that PT cell differentiation is altered in kidney disease. Metabolism (fatty acid oxidation and oxidative phosphorylation) in PT cells showed the strongest and most reproducible association with PT cell differentiation and disease. Coupling of cell differentiation and the metabolism was established by nuclear receptors (estrogen-related receptor alpha [ESRRA] and peroxisomal proliferation-activated receptor alpha [PPARA]) that directly control metabolic and PT-cell-specific gene expression in mice and patient samples while protecting from kidney disease in the mouse model.

Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection.

There is a critical need for safe and effective drugs for COVID-19. Only remdesivir has received authorization for COVID-19 and has been shown to improve outcomes but not decrease mortality. However, the dose of remdesivir is limited by hepatic and kidney toxicity. ACE2 is the critical cell surface receptor for SARS-CoV-2. Here, we investigated additive effect of combination therapy using remdesivir with recombinant soluble ACE2 (high/low dose) on Vero E6 and kidney organoids, targeting two different modalities of SARS-CoV-2 life cycle: cell entry via its receptor ACE2 and intracellular viral RNA replication. This combination treatment markedly improved their therapeutic windows against SARS-CoV-2 in both models. By using single amino-acid resolution screening in haploid ES cells, we report a singular critical pathway required for remdesivir toxicity, namely, Adenylate Kinase 2. The data provided here demonstrate that combining two therapeutic modalities with different targets, common strategy in HIV treatment, exhibit strong additive effects at sub-toxic concentrations. Our data lay the groundwork for the study of combinatorial regimens in future COVID-19 clinical trials.

Impact of Intestinal Urinary Diversion on the Risk of Fracture and Loss of Bone Mass: A Systematic Review.

BACKGROUND: Patients undergoing intestinal urinary diversion (IUD) may have a higher risk of osteoporosis and risk of fractures due to metabolic acidosis and decrease of intestinal absorption surface. OBJECTIVE: We performed a systematic review of the available literature on the impact of IUD on bone demineralization. METHODS: We systematically searched PubMed®, for original articles published before April 2020. Primary end points were the risk of fracture and loss of bone density. Secondary outcomes were the metabolic changes in biochemical and urine parameters related to calcium metabolism and histological changes. RESULTS: Our electronic search identified a total of 2417 articles. After a detailed review, we selected 11 studies that addressed the impact of IUD on bone health in 10369 patients. The risk of bone fracture was studied in 3 articles, showing a higher risk in the IUD population. Of the 9 articles evaluating the relation between intestinal urinary diversion and bone density, 5 did find a positive association. One article evaluated the bone metabolism at a cellular level after IUD showing a decrease in bone turnover in this population. Three of the eight studies reporting data on serum parameters related to calcium and phosphate metabolism showed differences. Finally, a correlation between concentration of pyridolines in urine and loss of bone density was found in two of the three studies. CONCLUSIONS: Although published data on BMD are contradictory, patients undergoing IUD seem to be at higher risk of bone fractures. Our finding support the need to implement accessible strategies on osteoporosis screening and prevention in IUD patients.

Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2.

We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000-5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.

Nest Site Selection during Colony Relocation in Yucatan Peninsula Populations of the Ponerine Ants Neoponera villosa (Hymenoptera: Formicidae).

In the Yucatan Peninsula, the ponerine ant Neoponera villosa nests almost exclusively in tank bromeliads, Aechmea bracteata. In this study, we aimed to determine the factors influencing nest site selection during nest relocation which is regularly promoted by hurricanes in this area. Using ants with and without previous experience of Ae. bracteata, we tested their preference for refuges consisting of Ae. bracteata leaves over two other bromeliads, Ae. bromeliifolia and Ananas comosus. We further evaluated bromeliad-associated traits that could influence nest site selection (form and size). Workers with and without previous contact with Ae. bracteata significantly preferred this species over others, suggesting the existence of an innate attraction to this bromeliad. However, preference was not influenced by previous contact with Ae. bracteata. Workers easily discriminated between shelters of Ae. bracteata and A. comosus, but not those of the closely related Ae. bromeliifolia. In marked contrast, ants discriminated between similar sized Ae. bracteata and Ae. bromeliifolia plants, suggesting that chemical cues and plant structure play an important role. Size was also significant as they selected the largest plant when provided two dissimilar Ae. bracteata plants. Nest site selection by N. villosa workers seems to depend on innate preferences but familiarization with plant stimuli is not excluded.

Use of exochorion characters for the systematics of Hamadryas Hübner and Ectima Doubleday (Nymphalidae: Biblidinae: Ageroniini).

We studied the chorionic morphology of six species of Hamadryas, and together with previous studies, we compared our results with previously published phylogenies for the genus. Samples were obtained from 19 females collected between 2013 and 2017 whose abdomens were sectioned and preserved for later dissection. Eggs were extracted from those dissections and used for the descriptions and illustrations of the chorion. The Hamadryas egg is of the globose type; it is quasi-spheroidal and has multiple polygonal grids with differentiation in specific zones/regions, and knolls with macrocells in their summits that arise in the apical third. These characteristics are very different from those found in the majority of Biblidinae and for those reported in the literature for Batesia and Panacea, which belong to the same subtribe as Hamadryas (Ageroniina, now Ageroniini). Chorionic characters support a previously suggested division of the genus (februa, feronia and laodamia groups) and they agree with the phylogenetic proposal based on morphological characters. Our study expands previous morphological work focused on this genus and compiles all the information available to date about the exochorion of Hamadryas, which now includes data for 10 species and that of Ectima thecla thecla, the putative sister group of Hamadryas.

Porto-Sinusoidal Vascular Disease Associated to Oxaliplatin: An Entity to Think about It.

Portal sinusoidal vascular disease is a presinusoidal cause of portal hypertension (PHT) of unknown etiology, characterized by typical manifestations of PHT (esophageal varices, ascites, portosystemic collaterals), plaquetopenia and splenomegaly with a gradient of portal pressure slightly increased, according to the presinusoidal nature of the PHT. A few cases in the literature have shown a relationship between oxaliplatin and the development of presinusoidal portal hypertension, years after the chemotherapy for colorectal cancer (therefore, different to sinusoidal obstruction syndrome). There are three mechanisms through which oxaliplatin can cause sinusoidal damage: 1) damage at the level of endothelial cells and stimulates the release of free radicals and depletion of glutathione transferase, with altering the integrity of the sinusoidal cells. The damage in the endothelial sinusoidal cells allows to erythrocytes to across into the Dissé space and formation of perisinusoidal fibrosis, 2) the appearance of nodular regenerative hyperplasia is favored by the chronic hypoxia of the centrilobular areas and, finally, 3) oxaliplatin can generate an obliteration of the blood capillaries and zones of parenchymal extinction. These three facts can develop, in a minority of cases, the appearance of a presinusoidal increase of portal pressure, which typically appears years after the completion of chemotherapy and sometimes is underdiagnosed until variceal bleeding, ascites or encephalopathy appear. The knowledge of this pathology is essential to be able to perform an early diagnostic and consult to the hepatologist.

PET imaging study of brown adipose tissue (BAT) activity in mice devoid of receptor for advanced glycation end products (RAGE).

Brown adipose tissue (BAT) is responsible for adaptive thermogenesis. We previously showed that genetic deficiency of receptor for advanced glycation end products (RAGE) prevented the effects of high-fat diet (HFD). This study was to compare BAT activity in RAGE knock out (Ager-/-, RKO) and wild-type (WT) mice after treated with HFD or LFD. [18F]FDG PET-CT imaging under identical cold-stimulated conditions and mean standard uptake values (SUVmean), ratio of SUViBAT/SUVmuscle (SUVR, muscle as the reference region) and percentage ID/g were used for BAT quantification. The results showed that [18F]FDG uptake (e.g., SUVR) in WT-HFD mice was significantly reduced (three-fold) as compared to that in WT-LFD (1.40 +/- 0.07 and 4.03 +/- 0.38; P = 0.004). In contrast, BAT activity in RKO mice was not significantly affected by HFD, with SUVRRKO-LFD: 2.14 +/- 0.10 and SUVRRKO-LFD: 1.52 +/- 0.13 (P = 0.3). The uptake in WT-LFD was almost double of that in RKO-LFD (P = 0.004); however, there was no significant difference between RKO-HFD and WT-HFD mice (P = 0.3). These results, corroborating our previous findings on the measurement of mRNA transcripts for UCP1 in the BAT, suggest that RAGE may contribute to altered energy expenditure and provide a protective effect against HFD by Ager deletion (Ager -/-).

A Receptor of the Immunoglobulin Superfamily Regulates Adaptive Thermogenesis.

Exquisite regulation of energy homeostasis protects from nutrient deprivation but causes metabolic dysfunction upon nutrient excess. In human and murine adipose tissue, the accumulation of ligands of the receptor for advanced glycation end products (RAGE) accompanies obesity, implicating this receptor in energy metabolism. Here, we demonstrate that mice bearing global- or adipocyte-specific deletion of Ager, the gene encoding RAGE, display superior metabolic recovery after fasting, a cold challenge, or high-fat feeding. The RAGE-dependent mechanisms were traced to suppression of protein kinase A (PKA)-mediated phosphorylation of its key targets, hormone-sensitive lipase and p38 mitogen-activated protein kinase, upon ß-adrenergic receptor stimulation-processes that dampen the expression and activity of uncoupling protein 1 (UCP1) and thermogenic programs. This work identifies the innate role of RAGE as a key node in the immunometabolic networks that control responses to nutrient supply and cold challenges, and it unveils opportunities to harness energy expenditure in environmental and metabolic stress.

Enhanced Recovery after Radical Cystectomy.

PURPOSE OF REVIEW: Enhanced Recovery after Surgery (ERAS) programs are multimodal and interdisciplinary protocols, which aim to accelerate patient recovery and improve surgical outcomes through standardized perioperative care. In this review, we summarized the items included in most currently utilized protocols for patients undergoing radical cystectomy and we discussed the reported outcomes after the implementation. RECENT FINDINGS: Current protocols are mostly extrapolated from the colorectal surgery literature, and solid evidence in radical cystectomy is limited. Moreover, the items included in the protocols differ between countries and institutions, which make it difficult to quantify the individual contribution of each intervention to the overall effect of the ERAS program. Length of hospital stay (LOS), commonly used as a surrogate outcome of perioperative recovery, is reported to be lower for patients who benefited from an ERAS protocol. Complications and readmission rates showed no benefit to the ERAS protocols in most studies. SUMMARY: Although randomized controlled trials are needed to determinate the effect of the different items on patient recovery and the overall impact of ERAS program, available data support these protocols for patients undergoing radical cystectomy leading to a shorter LOS without increasing readmission or complication rates.

Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells.

The generation of organoids is one of the biggest scientific advances in regenerative medicine. Here, by lengthening the time that human pluripotent stem cells (hPSCs) were exposed to a three-dimensional microenvironment, and by applying defined renal inductive signals, we generated kidney organoids that transcriptomically matched second-trimester human fetal kidneys. We validated these results using ex vivo and in vitro assays that model renal development. Furthermore, we developed a transplantation method that utilizes the chick chorioallantoic membrane. This approach created a soft in vivo microenvironment that promoted the growth and differentiation of implanted kidney organoids, as well as providing a vascular component. The stiffness of the in ovo chorioallantoic membrane microenvironment was recapitulated in vitro by fabricating compliant hydrogels. These biomaterials promoted the efficient generation of renal vesicles and nephron structures, demonstrating that a soft environment accelerates the differentiation of hPSC-derived kidney organoids.