A Novel Marking Technique for Accurate Minimal Invasive Approaches in Spine Tumor Surgeries With Activated Carbon Marking.

BACKGROUND AND OBJECTIVES: To describe a novel, practical, reproducible, and effective preoperative marking technique for accurate localization of the spinal level in a series of patients with tumor lesions. METHODS: We retrospectively analyzed patients undergoing minimally invasive (MIS) surgery for spine tumors from 2016 to 2021, in which this marking technique was used. Twenty-one patients, with tumor lesions involving difficult radioscopic visualization (cervicothoracic junction or upper dorsal spine, C6-T8), were included. Tumor lesion level was previously determined with enhanced MRI in all cases. Twenty-four to forty-eight hours before surgery, computed tomography image-guided carbon marking was performed by administration of aqueous suspension of carbon with a 21-gauge needle placed resembling the MIS approach planned trajectory. During surgery, activated carbon marking was followed until reaching the final target on the bone. Next, sequential dilators and an MIS retractor were placed. Then, bone resection and tumor exeresis were performed according to the case. RESULTS: Average age was 60.6 years (26-76 years). Fifteen (71%) patients were women. In most cases (76%), tumor pathology involved intradural lesions (meningiomas and schwannomas). In all cases, the marking described allowed to accurately guide the MIS approach to tumor site. Neither intraoperative fluoroscopy nor approach enlargement was required in any procedure. Postoperative complications were reported in only 4 patients, none related with the marking. CONCLUSION: Computed tomography image-guided activated carbon marking allows to accurately lead MIS approaches in a practical, reproducible, and effective way in cases of tumors localized in regions of the spine of difficult radioscopic visualization.

Eleven New Species of the Genus Tarzetta (Tarzettaceae, Pezizales) from Mexico.

The genus Tarzetta is distributed mainly in temperate forests and establishes ectomycorrhizal associations with angiosperms and gymnosperms. Studies on this genus are scarce in México. A visual, morphological, and molecular (ITS-LSU) description of T. americupularis, T. cupressicola, T. davidii, T. durangensis, T. mesophila, T. mexicana, T. miquihuanensis, T. poblana, T. pseudobronca, T. texcocana, and T. victoriana was carried out in this work, associated with Abies, Quercus, and Pinus. The results of SEM showed an ornamented ascospores formation by Mexican Taxa; furthermore, the results showed that T. catinus and T. cupularis are only distributed in Europe and are not associated with any American host.

Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study.

BACKGROUND: In the preplanned interim analysis of the TOPAZ-1 study, durvalumab plus gemcitabine-cisplatin significantly improved overall survival versus placebo plus gemcitabine-cisplatin in participants with advanced biliary tract cancer. We aimed to report updated overall survival and safety data from TOPAZ-1 with additional follow-up and data maturity beyond the interim analysis. METHODS: TOPAZ-1 was a phase 3, randomised, double-masked, placebo-controlled, global study done at 105 sites in 17 countries. Participants aged 18 years or older with unresectable, locally advanced, or metastatic biliary tract cancer were randomly assigned (1:1) to durvalumab plus gemcitabine-cisplatin or placebo plus gemcitabine-cisplatin using a computer-generated randomisation scheme, stratified by disease status and primary tumour location. Participants received durvalumab (1500 mg) or placebo on day 1 of each cycle every 3 weeks for up to eight cycles, plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) intravenously on days 1 and 8 of each cycle every 3 weeks for up to eight cycles, followed by durvalumab (1500 mg) or placebo monotherapy every 4 weeks until disease progression or other discontinuation criteria were met. Investigators and participants were masked to study treatment. The primary endpoint was overall survival. TOPAZ-1 met its primary endpoint at the preplanned interim analysis, and the study is active but no longer recruiting participants. Updated overall survival and safety data from TOPAZ-1, with additional follow-up (data cutoff Feb 25, 2022) and data maturity beyond the interim analysis, are reported here. Efficacy was assessed in the full analysis set (all randomly assigned participants). Safety was assessed in the safety analysis set (all participants who received at least one dose of study treatment). The TOPAZ-1 study is registered with ClinicalTrials.gov, NCT03875235. FINDINGS: From April 16, 2019, to Dec 11, 2020, 914 participants were enrolled, 685 of whom were randomly assigned (341 to the durvalumab plus gemcitabine-cisplatin group and 344 to the placebo plus gemcitabine-cisplatin group). 345 (50%) participants were male and 340 (50%) were female. Median follow-up at the updated data cutoff was 23·4 months (95% CI 20·6-25·2) in the durvalumab plus gemcitabine-cisplatin group and 22·4 months (21·4-23·8) in the placebo plus gemcitabine-cisplatin group. At the updated data cutoff, 248 (73%) participants in the durvalumab plus gemcitabine-cisplatin group and 279 (81%) participants in the placebo plus gemcitabine-cisplatin group had died (median overall survival 12·9 months [95% CI 11·6-14·1] vs 11·3 months [10·1-12·5]; hazard ratio 0·76 [95% CI 0·64-0·91]). Kaplan-Meier-estimated 24-month overall survival rates were 23·6% (95% CI 18·7-28·9) in the durvalumab plus gemcitabine-cisplatin group and 11·5% (7·6-16·2) in the placebo plus gemcitabine-cisplatin group. Maximum grade 3 or 4 adverse events occurred in 250 (74%) of 338 participants in the durvalumab plus gemcitabine-cisplatin group and 257 (75%) of 342 in the placebo plus gemcitabine-cisplatin group. The most common maximum grade 3 or 4 treatment-related adverse events were decreased neutrophil count (70 [21%] vs 86 [25%]), anaemia (64 [19%] vs 64 [19%]), and neutropenia (63 [19%] vs 68 [20%]). INTERPRETATION: Durvalumab plus gemcitabine-cisplatin showed robust and sustained overall survival benefit with no new safety signals. Findings continue to support the regimen as a standard of care for people with untreated, advanced biliary tract cancer. FUNDING: AstraZeneca.

[Percutaneous radiofrequency ablation of osteoid osteoma: results from 9 years of experience in a third-level center.] / Ablación percutánea por radiofrecuencia de osteoma osteoide: resultados en 9 años de experiencia en un centro de tercer nivel.

Introduction: Osteoid osteoma is a benign bone tumor that accounts for roughly 2-3% of primary bone tumors and up to 10-12% of benigns bone neoplasms. It is most commonly seen in young adults, and shows male predominance. Over the last years, minimally invasive thermal ablation techniques such as radiofrequency ablation have gained popularity over classical surgery. In this study we evaluate results and complications of CT guided osteoid osteoma radiofrequency ablation. Materials and methods: In this retrospective cohort study all patients that were diagnosed with osteoid osteoma and treated using radiofrequency ablation between January 2014 and December 2022 were included. Pain was assessed using Visual Analog Scale (VAS) pre and post procedure. Technical success was established as positioning of the radiofrequency electrode in the nidus. Primary clinical success was defined as absence of pain after one radiofrequency session. All patients that required a second radiofrequency ablation were included in the overall clinical success group. Results: During the studied period, 61 osteoid osteoma radiofrequency ablations were performed. Fiftyseven of them were included in this study, 32 were men and 25 female. Pre procedure median pain was 9 according to VAS score. Only 23 patients were treated as outpatient, the rest stayed in hospital for 24 hours. Median follow up time was 21,7 months (SD 8,3). Biopsy was performed in 52 patients. Technical success was accomplished in 57 patients (100%). Primary clinical success was 80,7% (46 patients). Those who continued with pain or had recurrence after a symptoms free period (11 patients), were treated with a second radiofrequency ablation, achieving an overall success rate of 94,7%. Only one patient suffered a minor complication (1,7%). Conclusion: CT guided osteoid osteoma radiofrequency ablation is a safe, effective and low complication rate procedure, that can be performed on an outpatient basis. We believe it should be considered as a first line treatment option for osteoid osteoma.

Introducción: El osteoma osteoide es un tumor óseo benigno, que representa el 2-3% de las neoplasias óseas primarias y hasta el 10-12% de los tumores óseos benignos. Tiene mayor incidencia en adultos jóvenes, con predominancia masculina. En los últimos años las técnicas de termoablación mínimamente invasivas han sido utilizadas para el tratamiento del osteoma osteoide, como alternativa a la cirugía clásica. En este estudio evaluaremos los resultados y complicaciones de ablación por radiofrecuencia de osteoma osteoide. Materiales y métodos: Se analizó una cohorte de pacientes en forma retrospectiva con diagnóstico de osteoma osteoide tratados con radiofrecuencia en el Hospital Italiano de Buenos Aires desde Enero del año 2014 hasta Diciembre del año 2022. Todos los pacientes fueron evaluados con la Escala Visual Analógica del dolor (EVA) pre y post procedimiento. El éxito técnico del procedimiento fue considerado como el correcto posicionamiento del electrodo de radiofrecuencia en el nido de la lesión, y el éxito clínico primario como ausencia de dolor post procedimiento. Mientras que los pacientes que requirieron de una segunda sesión de radiofrecuencia para controlar los síntomas serán incluidos como éxito clínico secundario. Resultados: Durante el período mencionado se realizaron 61 ablaciones percutáneas de osteoma osteoide. Se incluyeron en el análisis 57 pacientes, 32 fueron hombres y 25 mujeres. La media de dolor medido por EVA pre procedimiento fue 9. Del total de los pacientes, 23 fueron tratados de manera ambulatoria, el resto permanecieron internados durante 24hs. El tiempo medio de seguimiento fue de 21,7 meses (DS8,3). Se realizó biopsia de la lesión durante el procedimiento en 52 pacientes. Se logró el éxito técnico en 57 pacientes (100%), de ellos el éxito clínico primario se logró en 46 pacientes (80,7%). Los 11 pacientes que continuaron con dolor o presentaron recurrencia de los síntomas luego de un período asintomáticos fueron tratados con una segunda sesión de radiofrecuencia, logrando un éxito clínico secundario 94,7%. Un solo paciente presentó complicaciones post procedimiento (1,7%), correspondiente a hematoma en la planta del pie. Conclusión: Podemos concluir que la ablación percutánea por radiofrecuencia de OO guiada por tomografía en manos de expertos, es un procedimiento seguro, de alta efectividad y baja tasa de complicaciones que puede realizarse de manera ambulatoria. Por lo que consideramos que debe ser tenida en cuenta como primera elección para el tratamiento de esta patología.

[Retroperitoneal schwannoma mimicking colorectal cancer metastases: a false positive result report.] / Schwannoma retroperitoneal simulando metástasis de cáncer colorrectal: reporte de un resultado falso positivo.

Introduction: schwannomas are benign and common soft tissue tumors. They are usually asymptomatic and are discovered for other reasons. Materials: we present the case of an 82-year-old male patient with a recent diagnosis of moderately differentiated adenocarcinoma of the colon and a hypermetabolic periaortic nodule as an incidental finding. Results: percutaneous biopsy of the periaortic nodule confirmed the diagnosis of schwannoma. At one year of follow-up, growth of the schwannoma has been demonstrated. There are no signs of progression of his oncological disease. Conclusions: schwannomas are benign tumors, rarely found in the retroperitoneum and can be sources of false-positive positron emission tomography results.

Introducción: los schwannomas son tumores benignos y frecuentes de las partes blandas. Habitualmente son asintomáticos y son descubiertos por otros motivos. Materiales y métodos: presentamos el caso de un paciente masculino de 82 años con diagnóstico reciente de adenocarcinoma de colon moderadamente diferenciado y con un nódulo periaórtico hipermetabólico como hallazgo incidental. Resultados: la biopsia percutánea del nódulo periaórtico confirmó el diagnóstico de schwannoma. Al año de seguimiento, se ha demostrado crecimiento del schwannoma. No hay signos de progresión de su enfermedad oncológica. Conclusión: los schwannomas son tumores benignos, infrecuentes en el retroperitoneo y pueden ser fuentes de resultados falsos positivos en tomografía por emisión de positrones.

Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease.

BACKGROUND: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy. METHODS: Patients with a diagnosis of pCCA between 1997-2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS. RESULTS: Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55-1.07). CONCLUSIONS: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.

Synthesis, derivatization, and conformational scanning of peptides containing N-Aminoglycine.

N-alkylated glycine residues are the main constituent of peptoids and peptoid-peptide hybrids that are employed across the biomedical and materials sciences. While the impact of backbone N-alkylation on peptide conformation has been extensively studied, less is known about the effect of N-amination on the secondary structure propensity of glycine. Here, we describe a convenient protocol for the incorporation of N-aminoglycine into host peptides on solid support. Amide-to-hydrazide substitution also affords a nucleophilic handle for further derivatization of the backbone. To demonstrate the utility of late-stage hydrazide modification, we synthesized and evaluated the stability of polyproline II helix and ß-hairpin model systems harboring N-aminoglycine derivatives. The described procedures provide facile entry into peptidomimetic libraries for conformational scanning.

Plain language summary of the FOENIX-CCA2 study: futibatinib for people with advanced bile duct cancer.

WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from a phase 2 study called FOENIXCCA2. The study evaluated treatment with futibatinib in people with a rare form of advanced bile duct cancer called intrahepatic cholangiocarcinoma (or iCCA), where the tumors have changes in the structure of a gene called FGFR2. These changes include FGFR2 gene fusions. Bile duct cancer often returns after surgery or cannot be treated by surgery because the tumor has spread, so it requires treatment with chemotherapy. People live for a median of 1 year after their first chemotherapy treatment and 6 months after their second treatment. This study included people whose cancer had grown/spread after one or more chemotherapy treatments. The aims of the study were to see if futibatinib could shrink the size of tumors and stop the cancer from growing/spreading and to see how long people lived when treated with futibatinib. Clinicians also looked at side effects from taking futibatinib and at how it affected people's quality of life. WHAT WERE THE RESULTS?: Futibatinib treatment shrank tumors in over 80% of people who received treatment. Tumors shrank by at least 30% in 42% of people. Futibatinib stopped tumors from growing/spreading for a median of 9.7 months. People who took the medicine lived for a median of 21.7 months, and 72% of people were still alive after 1 year. Side effects from taking futibatinib were like those reported for similar medicines, and clinicians considered the side effects to be manageable by adjusting the dose of futibatinib or treating the side effects. Most people reported that their quality of life stayed the same or improved during the first 9 months of taking futibatinib. WHAT DO THE RESULTS MEAN?: The results support the use of futibatinib for treating people with advanced bile duct cancer. Based on the results of this study, futibatinib is now approved in the US, Europe, and Japan. Futibatinib is approved for treating adults with advanced bile duct cancer who have received previous treatment for their cancer, and whose tumors have a gene fusion or other change in the FGFR2 gene.Clinical Trial Registration: NCT02052778 (FOENIX-CCA2).

Beyond N-Alkylation: Synthesis, Structure, and Function of N-Amino Peptides.

The growing list of physiologically important protein-protein interactions (PPIs) has amplified the need for compounds to target topologically complex biomolecular surfaces. In contrast to small molecules, peptide and protein mimics can exhibit three-dimensional shape complementarity across a large area and thus have the potential to significantly expand the "druggable" proteome. Strategies to stabilize canonical protein secondary structures without sacrificing side-chain content are particularly useful in the design of peptide-based chemical probes and therapeutics.Substitution of the backbone amide in peptides represents a subtle chemical modification with profound effects on conformation and stability. Studies focused on N-alkylation have already led to broad-ranging applications in peptidomimetic design. Inspired by nonribosomal peptide natural products harboring amide N-oxidations, we envisioned that main-chain hydrazide and hydroxamate bonds would impose distinct conformational preferences and offer unique opportunities for backbone diversification. This Account describes our exploration of peptide N-amination as a strategy for stabilizing canonical protein folds and for the structure-based design of soluble amyloid mimics.We developed a general synthetic protocol to access N-amino peptides (NAPs) on solid support. In an effort to stabilize ß-strand conformation, we designed stitched peptidomimetics featuring covalent tethering of the backbone N-amino substituent to the preceding residue side chain. Using a combination of NMR, X-ray crystallography, and molecular dynamics simulations, we discovered that backbone N-amination alone could significantly stabilize ß-hairpin conformation in multiple models of folding. Our studies revealed that the amide NH2 substituent in NAPs participates in cooperative noncovalent interactions that promote ß-sheet secondary structure. In contrast to Cα-substituted α-hydrazino acids, we found that N-aminoglycine and its N'-alkylated derivatives instead stabilize polyproline II (PPII) conformation. The reactivity of hydrazides also allows for late-stage peptide macrocyclization, affording novel covalent surrogates of side-chain-backbone H-bonds.The pronounced ß-sheet propensity of Cα-substituted α-hydrazino acids prompted us to target amyloidogenic proteins using NAP-based ß-strand mimics. Backbone N-amination was found to render aggregation-prone lead sequences soluble and resistant to proteolysis. Inhibitors of Aß and tau identified through N-amino scanning blocked protein aggregation and the formation of mature fibrils in vitro. We further identified NAP-based single-strand and cross-ß tau mimics capable of inhibiting the prion-like cellular seeding activity of recombinant and patient-derived tau fibrils.Our studies establish backbone N-amination as a valuable addition to the peptido- and proteomimetic tool kit. α-Hydrazino acids show particular promise as minimalist ß-strand mimics that retain side-chain information. Late-stage derivatization of hydrazides also provides facile entry into libraries of backbone-edited peptides. We anticipate that NAPs will thus find applications in the development of optimally constrained folds and modulators of PPIs.

Pemigatinib for patients with previously treated, locally advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements: A joint analysis of the French PEMI-BIL and Italian PEMI-REAL cohort studies.

BACKGROUND: Pemigatinib is approved for patients with pretreated, locally advanced or metastatic CCA harboring FGFR2 rearrangements or fusions. We aim to assess the effectiveness and safety of pemigatinib in real-world setting. MATERIAL AND METHODS: A joint analysis of two multicentre observational retrospective cohort studies independently conducted in France and Italy was performed. All consecutive FGFR2-positive patients affected by CCA and treated with pemigatinib as second- or further line of systemic treatment in clinical practice, within or outside the European Expanded Access Program, were included. RESULTS: Between July 2020 and September 2022, 72 patients were treated with pemigatinib in 14 Italian and 25 French Centres. Patients had a median age of 57 years, 76% were female, 81% had ECOG-PS 0-1, 99% had intrahepatic CCA, 74% had ≥ 2 metastatic sites, 67% had metastatic disease at diagnosis, while 38.8% received ≥ 2 previous lines of systemic treatment. At data cut-off analysis (April 2023), ORR and DCR were 45.8% and 84.7%, respectively. Median DoR was 7 months (IQR: 5.8-9.3). Over a median follow-up time of 19.5 months, median PFS and 1-year PFS rate were 8.7 months and 32.8%. Median OS and 1-year OS rate were 17.1 months and 60.6%. Fatigue (69.4%), ocular toxicity (68%), nail toxicities (61.1%), dermatologic toxicity (41.6%) hyperphosphataemia (55.6%), stomatitis (48.6%), and diarrhea (36.1%) were the most frequent, mainly G1-G2 AEs. Overall incidence of G3 AEs was 22.2%, while no patient experienced G4 AE. Dose reduction and temporary discontinuation were needed in 33.3% and 40.3% of cases, with 1 permanent discontinuation due to AEs. CONCLUSIONS: These results confirm the effectiveness and safety of pemigatinib in a real-world setting.

Somatostatin Receptor Imaging with [18F]FET-ßAG-TOCA PET/CT and [68Ga]Ga-DOTA-Peptide PET/CT in Patients with Neuroendocrine Tumors: A Prospective, Phase 2 Comparative Study.

There is a clinical need for 18F-labeled somatostatin analogs for the imaging of neuroendocrine tumors (NET), given the limitations of using [68Ga]Ga-DOTA-peptides, particularly with regard to widespread accessibility. We have shown that [18F]fluoroethyl-triazole-[Tyr3]-octreotate ([18F]FET-ßAG-TOCA) has favorable dosimetry and biodistribution. As a step toward clinical implementation, we conducted a prospective, noninferiority study of [18F]FET-ßAG-TOCA PET/CT compared with [68Ga]Ga-DOTA- peptide PET/CT in patients with NET. Methods: Forty-five patients with histologically confirmed NET, grades 1 and 2, underwent PET/CT imaging with both [18F]FET-ßAG-TOCA and [68Ga]Ga-peptide performed within a 6-mo window (median, 77 d; range, 6-180 d). Whole-body PET/CT was conducted 50 min after injection of 165 MBq of [18F]FET-ßAG-TOCA. Tracer uptake was evaluated by comparing SUVmax and tumor-to-background ratios at both lesion and regional levels by 2 unblinded, experienced readers. A randomized, blinded reading of both scans was also then undertaken by 3 experienced readers, and consensus was assessed at a regional level. The ability of both tracers to visualize liver metastases was also assessed. Results: A total of 285 lesions were detected on both imaging modalities. An additional 13 tumor deposits were seen in 8 patients on [18F]FET-ßAG-TOCA PET/CT, and [68Ga]Ga-DOTA-peptide PET/CT detected an additional 7 lesions in 5 patients. Excellent correlation in SUVmax was observed between both tracers (r = 0.91; P < 0.001). No difference was observed between median SUVmax across regions, except in the liver, where the median tumor-to-background ratio of [18F]FET-ßAG-TOCA was significantly lower than that of [68Ga]Ga-DOTA-peptide (2.5 ± 1.9 vs. 3.5 ± 2.3; P < 0.001). Conclusion: [18F]FET-ßAG-TOCA was not inferior to [68Ga]Ga-DOTA-peptide in visualizing NET and may be considered in routine clinical practice given the longer half-life and availability of the cyclotron-produced fluorine radioisotope.

Risk factors for COVID-19 in-hospital mortality in Argentina: A competing risk survival analysis.

COVID-19 poses dire threats for low and middle-income countries (LMICs). Yet, there remains limited rigorous evidence describing the characteristics and outcomes of hospitalized patients for LMICs, and often the evidence was based on small samples and/or unicentric. The objective of this study was to examine risk factors of COVID-19 mortality in Argentina, a hard-hit middle-income Latin American country. We analyze data on 5,146 COVID-19 patients from 11 centers across 10 cities in Argentina, making this one of the largest multi-centric retrospective observational descriptive studies in the LMICs. Information on demographics and co-morbidities was extracted from medical records. Outcomes of relevance consisted of whether the patient was discharged or deceased (as established in medical records), along with date of each event. We use survival models that account for competing risks. Median age was 60 years (IQR: 48-72), there were fewer women (40.8%) hospitalized than men (59.2%), and the most prevalent comorbidities were hypertension (40.9%), diabetes (20.0%) and obesity (19.1%). Patients were hospitalized for a median duration of 8 days (IQR: 5-13), and in-hospital mortality was 18.1%, though it varied substantially across health centers (95%CI: 17.1%-19.2%). Baseline characteristics most associated with in-hospital mortality were respiratory rate (adjusted HR = 3.6, 95%CI: 2.5-5.4 for ≥ 26 breathes/min), older age (adjusted HR = 2.5, 95%CI: 2.0-3.3 for the 80+ age group), and chronic kidney disease (adjusted HR = 2.2, 95%CI: 1.8-2.8). Associations were attenuated when survival models did not account for the competing risk of being discharged. We document lower mortality rates than those in prior studies, likely due to a lower prevalence of comorbidities amongst patients in our sample. Compared with standard Cox models, we find that, when using competing risk models, risk factors have a larger role in explaining COVID-19 mortality. Overall, we provide rigorous evidence describing the characteristics and outcomes of hospitalized patients for LMICs. Thus, our findings are useful to conduct a more accurate in-hospital monitoring of patient subgroups who may be at greater risk. They also provide valuable guidance for public health and policy efforts in Argentina and other developing countries.

CT-Guided Trans-osseous Biopsy: Experience in 24 Patients.

PURPOSE: The objective of this study is to assess the effectiveness of computed tomography-guided trans-osseous biopsies in deep-seated lesions and report encountered complications. MATERIALS AND METHODS: A retrospective cohort study was performed which included twenty-four patients with pathologic medical history and lesions non-accessible by common approaches. Exclusion criteria include patients who could be biopsied without trans-osseous access, as for example procedures aided with hydro- or pneumo-dissection. The population studied included 13 females (54.2%) and the overall average age was 64.5 (IIQ 43-69). The procedures were carried out through the following bones: sternum (n = 6), vertebral (n = 5), iliac (n = 5), scapula (n = 3), rib (n = 2), sacral (n = 2), and pubis (n = 1). RESULTS: The efficiency for these procedures was 87.5%, while 8.33% of them were non-diagnostic and 4.17% were inconclusive due to vital risk during the procedure. CONCLUSION: Computed tomography-guided trans-osseous biopsy resulted in a safe and effective technique for those lesions blocked by vital structures or apparently directly inaccessible.

Chemotherapy with or without selective internal radiation therapy for intrahepatic cholangiocarcinoma: Data from clinical trials.

BACKGOUND AND AIMS: In advanced, liver-only intrahepatic cholangiocarcinoma (iCCA), selective internal radiation therapy (SIRT) has been suggested as promising in nonrandomized studies. We aimed to compare data from patients with advanced, liver-only iCCA treated in the first line in clinical trials with either chemotherapy alone or the combination with SIRT. APPROACH AND RESULTS: We collected individual patients' data from the ABC-01, ABC-02, ABC-03, BINGO, AMEBICA, and MISPHEC prospective trials. Data from patients with liver-only iCCA treated in chemotherapy-only arms of the first 5 trials were compared with data from patients treated with SIRT and chemotherapy in MISPHEC. Emulated target trial paradigm and Inverse Probability of Treatment Weighting (IPTW methods) using the propensity score were used to minimize biases. We compared 41 patients treated with the combination with 73 patients treated with chemotherapy alone, the main analysis being in 43 patients treated with cisplatin-gemcitabine or gemcitabine-oxaliplatin. After weighting, overall survival was significantly higher in patients treated with SIRT: median 21.7 months (95% CI: 14.1; not reached) versus 15.9 months(95% CI: 9.8; 18.9), HR = 0.59 (95% CI: 0.34; 0.99), p = 0.049. Progression-free survival was significantly improved: median 14.3 months (95% CI: 7.8; not reached) versus 8.4 months (95% CI: 5.9; 12.1), HR = 0.52 (95% CI: 0.31; 0.89), p < 0.001. Results were confirmed in most sensitivity analyses. CONCLUSIONS: This analysis derived from prospective clinical trials suggests that SIRT combined with chemotherapy might improve outcomes over chemotherapy alone in patients with advanced, liver-only iCCA. Randomized controlled evidence is needed to confirm these findings.

Stabilizing Pseudouridimycin: Synthesis, RNA Polymerase Inhibitory Activity, and Antibacterial Activity of Dipeptide-Modified Analogues.

Pseudouridimycin (PUM) is a microbially produced C-nucleoside dipeptide that selectively targets the nucleotide addition site of bacterial RNA polymerase (RNAP) and that has a lower rate of spontaneous resistance emergence relative to current drugs that target RNAP. Despite its promising biological profile, PUM undergoes relatively rapid decomposition in buffered aqueous solutions. Here, we describe the synthesis, RNAP-inhibitory activity, and antibacterial activity of chemically stabilized analogues of PUM. These analogues feature targeted modifications that mitigate guanidine-mediated hydroxamate bond scission. A subset of analogues in which the central hydroxamate is replaced with amide or hydrazide isosteres retain the antibacterial activity of the natural product.

Broadening the Knowledge of Mexican Boletes: Addition of a New Genus, Seven New Species, and Three New Combinations.

Boletes are one of the most common groups of fungi in temperate, subtropical, and tropical ecosystems. In Mexico, the northern region has mainly been explored in terms of bolete diversity. This study describes a new genus and seven new species based on macromorphological, micromorphological, molecular, phylogenetic, and ecological data. Garcileccinum gen. nov. is typified with G. salmonicolor based on multigene phylogenetic analysis of nrLSU, RPB2, and TEF1, and it is closely related to Leccinum and Leccinellum. Garcileccinum viscosum and G. violaceotinctum are new combinations. Boletellus minimatenebris (ITS, nrLSU, and RPB2), Cacaoporus mexicanus (RPB2 and ATP6), Leccinum oaxacanum, Leccinum juarenzense (nrLSU, RPB2, and TEF1), Tylopilus pseudoleucomycelinus (nrLSU and RPB2), and Xerocomus hygrophanus (ITS, nrLSU, and RPB2) are described as new species. Boletus neoregius is reclassified as Pulchroboletus neoregius comb. nov. based on morphological and multigene phylogenetic analysis (ITS and nrLSU), and its geographic distribution is extended to Central Mexico, since the species was only known from Costa Rica. Furthermore, T. leucomycelinus is a new record from Mexico. This study contributes to increasing our knowledge of boletes and expands the diversity found in Mexican forests.