Implementing a new HCV model of care for people who use drugs.

Background & Aims: An estimated 50 million individuals have chronic hepatitis C virus (HCV) infection worldwide and people who use drugs (PWUD) are disproportionately affected. Persistent stigma and discrimination make it challenging for PWUD to access healthcare, potentially hindering HCV elimination progress in this population. To mitigate healthcare access barriers in PWUD, an HCV care model that simplified screening and linkage to care pathways was developed and rolled out in the Balearic Islands, Spain. Methods: The prospective multicentre community model of care was implemented in 21 centres serving PWUD. This model involved: (1) participant recruitment and HCV antibody screening onsite via a point-of-care anti-HCV test, phlebotomy, or laboratory records; (2) HCV RNA, HBsAg and anti-HIV testing via a dried blood spot or phlebotomy; (3) linkage to specialist care and treatment prescription via telemedicine, when required; and (4) onsite monitoring of: (a) sustained virologic response (SVR) 4 and ≥12 weeks after treatment completion and; (b) potential new HCV infection or reinfection ∼1 year after phase 1 or SVR ≥12 monitoring. Care model acceptability was assessed. Results: Between April 2021 and April 2023, 1,423 participants were recruited, of whom 464 (33%) were anti-HCV+ and 170 (12%) had detectable HCV RNA. Of the latter, 147 (86%) initiated therapy, of whom 124 (84%) completed it. SVR ≥12 monitoring was performed in 95 (77%) of these, of whom 88 (93%) had undetectable HCV RNA. Upon re-screening, four HCV reinfections were detected. Over 90% accepted study participation and screening and treatment decentralisation. Conclusions: This adapted care model, which decentralised screening, diagnosis, and treatment, effectively increased healthcare access among PWUD, improving progress towards HCV elimination in this population in Spain. Impact and implications: People who use drugs (PWUD) are among the most affected by chronic hepatitis C virus (HCV) infection globally. A simplified model of care was implemented in 21 centres serving this population across the Balearic Islands, Spain, to offer HCV care to 1,423 PWUD in 2021-2023. This decentralised screening, diagnosis, and treatment model resulted in an HCV cure rate of 93% of those who both completed therapy and were monitored post treatment completion. The Hepatitis C Free Balears model can guide the HCV elimination efforts of regional health authorities and other stakeholders in the rest of Spain and other parts of the world.

Impact of primary aldosteronism on kidney function: results from the SPAIN-ALDO registry.

AIM: To evaluate the impact of aldosterone excess on renal function in individuals with primary aldosteronism and to compare its evolution after surgery or mineralocorticoid receptor antagonist (MRA) treatment. METHODS: A multicentre, retrospective cohort study of primary aldosteronism patients in follow-up in 36 Spanish tertiary hospitals, who underwent specific treatment for primary aldosteronism (MRA or adrenalectomy). RESULTS: A total of 789 patients with primary aldosteronism were included, with a median age of 57.5 years and 41.8% being women. At primary aldosteronism diagnosis, the prevalence of chronic kidney disease (CKD) was 10.7% ( n  = 84), with 75% of cases classified as state 3a ( n  = 63). Primary aldosteronism patients with CKD had a longer duration of hypertension, a higher prevalence of type 2 diabetes, dyslipidaemia, cardiovascular events, hypokalaemia, and albuminuria. Unilateral adrenalectomy was performed in 41.8% of cases ( n  = 330), and 459 patients were treated with MRA. After a median follow-up of 30.7 months (range 13.3-68.4), there was a significant decline in the estimated glomerular filtration rate (eGFR) in operated patients and those receiving MRA. During follow-up, 24.4% of patients with CKD at the time of primary aldosteronism diagnosis had normalized renal function, and 39% of those with albuminuria had albuminuria remission. There were no differences in renal function or albuminuria regression between the two therapy groups. However, development of albuminuria was less common in operated than in medically treated patients (0 vs. 6.0%, P  = 0.009). CONCLUSION: CKD affects around 10% of the patients with primary aldosteronism, with a higher risk in individuals with long-term hypertension, type 2 diabetes, dyslipidaemia, cardiovascular events, hypokalaemia, and albuminuria. At short-term, both MRA and surgical treatment lead to a reduction of renal function, but adrenalectomy led to higher renal protection.

Tuning the Inorganic Core of a reduced Ni2Ge2 Cluster.

Tetranuclear cores (M-E)2 of transition metals (M) and tetrylenes (EII=Si, Ge, Sn) are key motifs in homogeneous and heterogeneous catalysis. They exhibit a continuum of M-M and E-E bonding within the inorganic core that leads to a variety of structures for which there are no specific synthetic methods. Herein, we report a series of highly reduced [Ni0GeII]2 squares solely stabilized by bulky terphenyl (C6H3-2,6-Ar2) ligands, for which we provide complementary and high-yielding syntheses. Reactivity studies with common Lewis bases (carbene and CO) evince that the structure of the (M-E)2 core can be transformed. We have investigated this core modification by computational means, offering a rationale to better understand the continuum of bonding across these clusters.

Nitrous oxide activation by picoline-derived Ni-CNP hydrides.

Oxygen atom transfer (OAT) from N2O to the Ni-H bond of proton-responsive picoline-derived CNP nickel complexes has been investigated both experimentally and theoretically. These Ni-CNP complexes efficiently catalyse the reduction of N2O with pinacolborane (HBpin) under mild conditions.

Broad-Scope Amination of Aryl Sulfamates Catalyzed by a Palladium Phosphine Complex.

Among phenol-derived electrophiles, aryl sulfamates are attractive substrates since they can be employed as directing groups for C-H functionalization prior to catalysis. However, their use in C-N coupling is limited only to Ni catalysis. Here, we describe a Pd-based catalyst with a broad scope for the amination of aryl sulfamates. We show that the N-methyl-2-aminobiphenyl palladacycle supported by the PCyp2ArXyl2 ligand (Cyp = cyclopentyl; ArXyl2 = 2,6-bis(2,6-dimethylphenyl)phenyl) efficiently catalyzes the C-N coupling of aryl sulfamates with a variety of nitrogen nucleophiles, including anilines, primary and secondary alkyl amines, heteroaryl amines, N-heterocycles, and primary amides. DFT calculations support that the oxidative addition of the aryl sulfamate is the rate-determining step. The C-N coupling takes place through a cationic pathway in the polar protic medium.

Autonomous cortisol secretion in patients with primary aldosteronism: prevalence and implications on cardiometabolic profile and on surgical outcomes.

Purpose: The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes. Methods: This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 µg/dL (confirmed ACS if >5 µg/dL and possible ACS if 1.8-5 µg/dL) in the absence of specific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels. Results: The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS-PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS-PA and PA-only patients was similar, except for older age and larger tumor size of the adrenal lesion in the ACS-PA group. When comparing the ACS-PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64-22.32)) and cardiovascular events (OR 5.0 (2.29-11.07)) was higher in ACS-PA patients than in ACS patients. The coexistence of ACS in patients with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS-PA and PA-only groups. Conclusion: Co-secretion of cortisol and aldosterone affects almost one-third of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS-PA and PA-only are similar.

A genuine germylene PGeP pincer ligand for formic acid dehydrogenation with iridium.

We report an iridium system constructed around a long-tethered PGeP ligand that facilitates access to the less common germylene form, so far unreported for an 'NHC-type' Ge ligand. Its bonding is substantiated by computational studies and we have demonstrated its use for the catalytic dehydrogenation of formic acid, highlighting the potential of this underdeveloped type of ligand.

Catalytic Nitrous Oxide Reduction with H2 Mediated by Pincer Ir Complexes.

Reduction of nitrous oxide (N2O) with H2 to N2 and water is an attractive process for the decomposition of this greenhouse gas to environmentally benign species. Herein, a series of iridium complexes based on proton-responsive pincer ligands (1-4) are shown to catalyze the hydrogenation of N2O under mild conditions (2 bar H2/N2O (1:1), 30 °C). Among the tested catalysts, the Ir complex 4, based on a lutidine-derived CNP pincer ligand having nonequivalent phosphine and N-heterocyclic carbene (NHC) side donors, gave rise to the highest catalytic activity (turnover frequency (TOF) = 11.9 h-1 at 30 °C, and 16.4 h-1 at 55 °C). Insights into the reaction mechanism with 4 have been obtained through NMR spectroscopy. Thus, reaction of 4 with N2O in tetrahydrofuran-d8 (THF-d8) initially produces deprotonated (at the NHC arm) species 5NHC, which readily reacts with H2 to regenerate the trihydride complex 4. However, prolonged exposure of 4 to N2O for 6 h yields the dinitrogen Ir(I) complex 7P, having a deprotonated (at the P-arm) pincer ligand. Complex 7P is a poor catalytic precursor in the N2O hydrogenation, pointing out to the formation of 7P as a catalyst deactivation pathway. Moreover, when the reaction of 4 with N2O is carried out in wet THF-d8, formation of a new species, which has been assigned to the hydroxo species 8, is observed. Finally, taking into account the experimental results, density functional theory (DFT) calculations were performed to get information on the catalytic cycle steps. Calculations are in agreement with 4 as the TOF-determining intermediate (TDI) and the transfer of an apical hydrido ligand to the terminal nitrogen atom of N2O as the TOF-determining transition state (TDTS), with very similar reaction rates for the mechanisms involving either the NHC- or the P-CH2 pincer methylene linkers.

Electrophilic activation of alkynes promoted by a cationic alkylidene complex of Pt(II).

Pt(II) alkylidene 1a has been reacted with terminal alkynes to afford ylide complexes 3a-d, resulting from electrophilic activation of the CC bond and its insertion into the platinacyclic fragment of 1a that contains the carbene functionality. DFT calculations indicate that the observed regioselectivity is determined by the nucleophilic attack of the alkyne to the alkylidene carbon.

Smoking in hospitalized patients. A great opportunity. / Tabaquismo en pacientes hospitalizados. Una gran oportunidad.

The objective of this study is to describe the characteristics of smokers admitted to different medical and surgical services in a university hospital and the perception of patients regarding the need for a specialized intervention. The sample comprises a total of 307 patients (mean age of 59.4 years), being 40% (n = 123) non-smokers, 42.7% (n = 131) ex-smokers, and 17.3% (n = 53) smokers. The average consumption of smokers was 22.2 cigarettes / day and the severity of nicotine dependence evaluated with the Fagerström test exceeded 5 points in more than half of the sample. On the other hand, 77.7% had made at least one previous attempt to quit tobacco use. Almost the entire sample (89.9%) of smokers and ex-smokers considered it necessary to develop tobacco treatment programs during hospitalization. Finally, the importance of the hospital context is argued as an opportunity to address the cessation of smoking. The data obtained in this study will allow focusing more appropriately on the management of these patients and optimizing resources.

El objetivo de este estudio es conocer las características de los fumadores ingresados en diferentes servicios médicos y quirúrgicos en un hospital universitario y la percepción de los pacientes respecto a la necesidad de una intervención especializada. La muestra comprende un total de 307 pacientes (edad media de 59,4 años), siendo un 40% (n = 123) no fumadores, 42,7% (n = 131) exfumadores, y un 17,3% (n = 53) fumadores. El consumo medio de los fumadores era de 22,2 cigarrillos/día y la gravedad de la dependencia a la nicotina evaluado con el test de Fagerström sobrepasaba los 5 puntos en más de la mitad de la muestra. Por otra parte, el 77,7% había realizado al menos un intento previo de abandono del consumo de tabaco. Casi la totalidad de la muestra (89,9%) de los fumadores y ex fumadores consideraba necesario desarrollar programas de tratamiento del tabaquismo en la hospitalización. Finalmente se argumenta la importancia del contexto hospitalario como oportunidad para abordar la cesación del hábito tabáquico. Los datos obtenidos en el presente estudio permitirán enfocar más adecuadamente el manejo de estos pacientes y optimizar los recursos.

Ammonia-Borane Dehydrogenation Catalyzed by Dual-Mode Proton-Responsive Ir-CNNH Complexes.

Metal complexes incorporating proton-responsive ligands have been proved to be superior catalysts in reactions involving the H2 molecule. In this contribution, a series of IrIII complexes based on lutidine-derived CNNH pincers containing N-heterocyclic carbene and secondary amino NHR [R = Ph (4a), tBu (4b), benzyl (4c)] donors as flanking groups have been synthesized and tested in the dehydrogenation of ammonia-borane (NH3BH3, AB) in the presence of substoichiometric amounts (2.5 equiv) of tBuOK. These preactivated derivatives are efficient catalysts in AB dehydrogenation in THF at room temperature, albeit significantly different reaction rates were observed. Thus, by using 0.4 mol % of 4a, 1.0 equiv of H2 per mole of AB was released in 8.5 min (turnover frequency (TOF50%) = 1875 h-1), while complexes 4b and 4c (0.8 mol %) exhibited lower catalytic activities (TOF50% = 55-60 h-1). 4a is currently the best performing IrIII homogeneous catalyst for AB dehydrogenation. Kinetic rate measurements show a zero-order dependence with respect to AB, and first order with the catalyst in the dehydrogenation with 4a (-d[AB]/dt = k[4a]). Conversely, the reaction with 4b is second order in AB and first order in the catalyst (-d[AB]/dt = k[4b][AB]2). Moreover, the reactions of the derivatives 4a and 4b with an excess of tBuOK (2.5 equiv) have been analyzed through NMR spectroscopy. For the former precursor, formation of the iridate 5 was observed as a result of a double deprotonation at the amine and the NHC pincer arm. In marked contrast, in the case of 4b, a monodeprotonated (at the pincer NHC-arm) species 6 is observed upon reaction with tBuOK. Complex 6 is capable of activating H2 reversibly to yield the trihydride derivative 7. Finally, DFT calculations of the first AB dehydrogenation step catalyzed by 5 has been performed at the DFT//MN15 level of theory in order to get information on the predominant metal-ligand cooperation mode.

Dehydrogenative Double C-H Bond Activation in a Germylene-Rhodium Complex*.

Transition metal tetrylene complexes offer great opportunities for molecular cooperation due to the ambiphilic character of the group 14 element. Here we focus on the coordination of germylene [(ArMes2 )2 Ge :] (ArMes =C6 H3 -2,6-(C6 H2 -2,4,6-Me3 )2 ) to [RhCl(COD)]2 (COD=1,5-cyclooctadiene), which yields a neutral germyl complex in which the rhodium center exhibits both η6 - and η2 -coordination to two mesityl rings in an unusual pincer-type structure. Chloride abstraction from this species triggers a singular dehydrogenative double C-H bond activation across the Ge/Rh motif. We have isolated and fully characterized three rhodium-germyl species associated to three C-H cleavage events along this process. The reaction mechanism has been further investigated by computational means, supporting the key cooperative action of rhodium and germanium centers.

Sphincter damage during fistulotomy for perianal fistulae and its relationship with faecal incontinence.

BACKGROUND: The length of sphincter which can be divided during fistulotomy for perianal fistula is unclear. The aim was to quantify sphincter damage during fistulotomy and determine the relationship between such damage with symptoms and severity of faecal incontinence and long-term quality of life (QOL). METHODS: A prospective cohort study was performed over a 2-year period. Patients with intersphincteric and mid to low transsphincteric perianal fistulas without risk factors for faecal incontinence were scheduled for fistulotomy. All patients underwent 3D endoanal ultrasound (3D-EAUS) pre-operatively and 8 weeks postoperatively. Measurements were taken of pre- and postoperative anal sphincter involvement and division. Anal continence was assessed using the Jorge-Wexner scale and QOL scores pre, 6 and 12 months postoperatively. RESULTS: Forty-nine patients were selected. A strong correlation between pre- and postoperative measurements was found p < 0.001. A median length of 41% of the external anal sphincter and 32% of the internal anal sphincter was divided during fistulotomy. Significant differences in mild symptoms of anal continence were found with increasing length of external anal sphincter division. But there was no significant deterioration in continence, soiling, or quality of life scores at the 1-year follow-up. Division of over two-thirds of the external anal sphincter was associated with the highest incontinence rates. CONCLUSIONS: 3D-EAUS is a valuable tool for quantifying the extent of sphincter involvement pre- and postoperatively. Post-fistulotomy faecal incontinence is mild and increases with increasing length of sphincter division but does not affect long-term quality of life.

Efficacy and safety of preoperative preparation with Lugol's iodine solution in euthyroid patients with Graves' disease (LIGRADIS Trial): Study protocol for a multicenter randomized trial.

BACKGROUND: Currently, both the American Thyroid Association and the European Thyroid Association recommend preoperative preparation with Lugol's Solution (LS) for patients undergoing thyroidectomy for Graves' Disease (GD), but their recommendations are based on low-quality evidence. The LIGRADIS trial aims to provide evidence either to support or refute the systematic use of LS in euthyroid patients undergoing thyroidectomy for GD. METHODS: A multicenter randomized controlled trial will be performed. Patients ≥18 years of age, diagnosed with GD, treated with antithyroid drugs, euthyroid and proposed for total thyroidectomy will be eligible for inclusion. Exclusion criteria will be prior thyroid or parathyroid surgery, hyperparathyroidism that requires associated parathyroidectomy, thyroid cancer that requires adding a lymph node dissection, iodine allergy, consumption of lithium or amiodarone, medically unfit patients (ASA-IV), breastfeeding women, preoperative vocal cord palsy and planned endoscopic, video-assisted or remote access surgery.Between January 2020 and January 2022, 270 patients will be randomized for either receiving or not preoperative preparation with LS. Researchers will be blinded to treatment assignment. The primary outcome will be the rate of postoperative complications: hypoparathyroidism, recurrent laryngeal nerve injury, hematoma, surgical site infection or death. Secondary outcomes will be intraoperative events (Thyroidectomy Difficulty Scale score, blood loss, recurrent laryngeal nerve neuromonitoring signal loss), operative time, postoperative length of stay, hospital readmissions, permanent complications and adverse events associated to LS. CONCLUSIONS: There is no conclusive evidence supporting the benefits of preoperative treatment with LS in this setting. This trial aims to provide new insights into future Clinical Practice Guidelines recommendations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03980132.

Intraoperative Scintigraphy With Portable Gamma Camera for the Localization of Interaortocaval Paraganglioma.

ABSTRACT: A 15-year-old adolescent girl diagnosed of interaortocaval paraganglioma with a positive 123I-MIGB SPECT/CT and 1 unsuccessful prior surgery was operated on with the assistance of a handheld gamma camera. Once the lesion was located and removed, 2 images were taken, one of the surgical field (without 123I-MIGB uptake) and another of the tumor ex vivo (with high 123I-MIGB uptake), confirming that the lesion had been satisfactorily excised. This case highlights the use of a portable gamma camera as a useful tool to locate this rare tumor, with a SPECT/CT positive for 123I-MIGB and a difficult anatomical location suspected.