Long-term outcomes of the global tuberculosis and COVID-19 co-infection cohort

Background: Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19. Methods: We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both. Results: Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53). Conclusions: In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

First Sagittarius A* Event Horizon Telescope Results. VIII. Physical Interpretation of the Polarized Ring

In a companion paper, we present the first spatially resolved polarized image of Sagittarius A* on event horizon scales, captured using the Event Horizon Telescope, a global very long baseline interferometric array operating at a wavelength of 1.3 mm. Here we interpret this image using both simple analytic models and numerical general relativistic magnetohydrodynamic (GRMHD) simulations. The large spatially resolved linear polarization fraction (24%–28%, peaking at ∼40%) is the most stringent constraint on parameter space, disfavoring models that are too Faraday depolarized. Similar to our studies of M87*, polarimetric constraints reinforce a preference for GRMHD models with dynamically important magnetic fields. Although the spiral morphology of the polarization pattern is known to constrain the spin and inclination angle, the time-variable rotation measure (RM) of Sgr A* (equivalent to ≈46° ± 12° rotation at 228 GHz) limits its present utility as a constraint. If we attribute the RM to internal Faraday rotation, then the motion of accreting material is inferred to be counterclockwise, contrary to inferences based on historical polarized flares, and no model satisfies all polarimetric and total intensity constraints. On the other hand, if we attribute the mean RM to an external Faraday screen, then the motion of accreting material is inferred to be clockwise, and one model passes all applied total intensity and polarimetric constraints: a model with strong magnetic fields, a spin parameter of 0.94, and an inclination of 150°. We discuss how future 345 GHz and dynamical imaging will mitigate our present uncertainties and provide additional constraints on the black hole and its accretion flow

Use of 2‑Bromophenylboronic Esters as Benzyne Precursors in the Pd-Catalyzed Synthesis of Triphenylenes

<i>ortho</i>-Substituted aryl boronates are introduced as aryne precursors for transition-metal-catalyzed transformations. On treatment with ^<i>t</i>BuOK and Pd(0), metal-bound aryne intermediates are formed that undergo effective trimerization to form useful triphenylene compounds. For <i>meta</i>-substituted arynes, the 3:1 product ratio in favor of non-C₃ symmetric material is indicative of a benzyne mechanism

Synthesis of Hindered Biaryls via Aryne Addition and <i>in Situ</i> Dimerization

Benzynes generated under Knochel conditions from 2-iodophenylsulfonates and ^<i>i</i>PrMgCl smoothly add to thiol, selenol, and amine nucleophiles. Treatment of the resulting aryl Grignard intermediate with a copper salt and an organic oxidant then affords symmetrical biaryls in good yield. 3-Substituted arynes undergo regioselective addition, enabling synthesis of atropisomeric biaryls with chelating S, Se, or N groups in the 2,2′ positions

Insertion Reactions on Carbopalladated Benzyne: From Eight- to Nine- and Ten-Membered Palladacycles. Applications to the Synthesis of N‑Heterocycles

The ortho-metalated complexes [Pd­{<i>C</i>,<i>N</i>-C₆H₂CH₂CH₂NH₂-2,(OMe)₂-4,5}­(μ-Br)]₂ (<b>A</b>) and [Pd­{<i>C</i>,<i>N</i>-C₆H₄CH₂CMe₂NH₂-2}­(μ-Cl)]₂ (<b>B</b>), derived from homoveratrylamine and phentermine, respectively, react with benzyne generated in situ, to afford the previously reported eight-membered palladacycles <b>1a</b> and <b>1b</b>, respectively, arising from the insertion of one molecule of the aryne into the Pd–C_aryl bond. Complexes <b>1</b> react with isocyanides RNC (R = Xy, ^tBu) in 1:4 molar ratio to give the nine-membered iminoacyl palladacycles [Pd­(<i>C</i>,<i>N</i>-C­(NR)-C₆H₄{C₆H₂CH₂CH₂NH₂-2­(OMe)₂-4,5)-2′})­Br­(CNR)] (R = Xy (<b>2a)</b>, R = ^tBu (<b>3a</b>)) and [Pd­(<i>C</i>,<i>N</i>-C­(NXy)-C₆H₄{C₆H₄CH₂CMe₂NH₂-2)-2′})­Cl­(CNR)] (R = Xy (<b>2b</b>), R = ^tBu (<b>3b</b>)). Complex <b>2a</b> decomposes in refluxing toluene to afford palladium(0) and 7,8-dihydro-10,11-dimethoxy-5-[(2,6-dimethylphenyl)­imino]­dibenzo­[<i>c</i>,<i>e</i>]­azocinium triflate (<b>4a</b>). When <b>1b</b> reacts with TlOTf and XyNC (molar ratio 1:2:2), 7,8-dihydro-5-[(2,6-dimethylphenyl)­imino]-7,7-dimethyl­dibenzo­[<i>c</i>,<i>e</i>]­azocinium triflate (<b>4b</b>) is obtained, resulting from an isocyanide insertion/C–N reductive coupling sequence. The amidinium triflates <b>4a</b> and <b>4b</b> present <i>E</i>/<i>Z</i> isomerism in CHCl₃ solution. The stoichiometric carbonylation of dinuclear complexes <b>1</b> renders, after depalladation, the lactams 7,8-dihydro-10,11-dimethoxy­dibenzo­[<i>c</i>,<i>e</i>]­azocin-5­(6<i>H</i>)-one (<b>5a</b>) and 7,8-dihydro-7,7-dimethyl­dibenzo­[<i>c</i>,<i>e</i>]­azocin-5­(6<i>H</i>)-one (<b>5b</b>) or the previously reported ester derivative [2′-MeO₂CC₆H₄C₆H₂­CH₂CH₂NH₃-2-(OMe)₂-4,5]Br (<b>6a</b>) or [2′-MeO₂CC₆H₄C₆H₄­CH₂CMe₂NH₃-2]Cl (<b>6b</b>), depending on the reaction conditions. The eight-membered palladacycles <b>1</b> react with alkenes to afford complexes [PdCl₂(biarylamine)₂] (<b>7a</b>, <b>7b</b>, <b>8b</b>), containing the Heck-type functionalized phenethylamines. The reaction of <b>1b</b> with ^tBuOK in toluene at 95 °C, under a N₂ atmosphere, affords 6,7-dihydro-6,6-dimethyl-5<i>H</i>-dibenz­[<i>b</i>,<i>d</i>]­azepine (<b>9b</b>), resulting from a C–N reductive coupling process. The crystal structures of compounds [Pd­(<i>C</i>,<i>N</i>-C­(NXy)-C₆H₄­{C₆H₂CH₂CH₂NH₂-2­(OMe)₂-4,5)-2′})­Br­(CNXy)]·CH₂Cl₂·1/2H₂O (<b>2a</b>·CH₂Cl₂·1/2H₂O), [Pd­(<i>C</i>,<i>N</i>-C­(NXy)-C₆H₄­{C₆H₄CH₂CMe₂NH₂-2)-2′})­Cl­(CNXy)]·0.72Et₂O·0.28CHCl₃ (<b>2b</b>·0.72Et₂O·0.28CHCl₃), and 7,8-dihydro-10,11-dimethoxy­dibenzo­[<i>c</i>,<i>e</i>]­azocin-5­(6<i>H</i>)-one (<b>5a</b>) have been determined by X-ray diffraction studies

Reactivity toward Neutral N- and P‑Donor Ligands of Eight-Membered Palladacycles Arising from Monoinsertion of Alkynes into the Pd–C Bond of Orthopalladated Homoveratrylamine and Phentermine. A New Example of the Transphobia Effect

Eight-membered palladacycles arising from the insertion of one molecule of alkyne into the Pd–C bond of the palladacycles derived from homoveratrylamine and phentermine react with neutral N- and P-donor ligands to give mononuclear or unusual dinuclear complexes, containing a vinylarylethylamino bridge, depending on the size of the ligand and the substituents of the palladacycle. Diffusion-ordered nuclear magnetic resonance spectroscopy experiments are used to measure the diffusion coefficients and propose the nuclearity of these complexes in solution. Density functional theory calculations show that steric and electronic (transphobia) effects are responsible for the unprecedented observed reactivity differences. A mechanism for the formation of the unusual dinuclear complexes is proposed

Reactivity toward CO of Eight-Membered Palladacycles Derived from the Insertion of Alkenes into the Pd–C Bond of Cyclopalladated Primary Arylalkylamines of Pharmaceutical Interest. Synthesis of Tetrahydrobenzazocinones, Ortho-Functionalized Phenethylamines, Ureas, and an Isocyanate

The ortho-metalated complex [Pd­{<i>C,N</i>-C₆H₂CH₂CH₂NH₂-2,(OMe)₂-4,5}­(μ-Br)]₂ (<b>1a</b>) derived from homoveratrylamine reacts with ethyl acrylate, methyl vinyl ketone, or 2-norbornene to give the dimeric complex arising from the insertion of the alkene into the Pd–C bond, [Pd­{<i>C,N</i>-CH­(R)­CH₂C₆H₂CH₂CH₂NH₂-2,(OMe)₂-4,5}­(μ-Br)]₂ (R = CO₂Et (<b>2a1</b>), C­(O)­Me (<b>2a2</b>)) or [Pd­{<i>C,N</i>-CH­(C₅H₈)­CHC₆H₂CH₂CH₂NH₂-2,(OMe)₂-4,5}­(μ-Br)]₂ (<b>2a3</b>). Complexes <b>2a</b> and the phentermine homologues <b>2b</b> react with CO to afford Pd(0) and (1) tetrahydrobenzazocinones, the heterocycles resulting from CO insertion into the Pd–C bond and C–N coupling, (2) unnatural amino acid derivatives, resulting from CO insertion and the reaction of the obtained acyl complex with the solvent (MeOH), or the product of protonolysis of the Pd–C bond, depending on the nature of the initial cyclopalladated compound, or (3) ureas, alone or mixed with an isocyanate, in the presence of a base. Phentermine derivatives <b>2b</b> react with HCl to give a dinuclear palladium complex [PdCl­(μ-Cl)­(L)], where L is the amine arising from the protonolysis of the Pd–C bond or the alkyl group resulting from Pd–N bond protonolysis, depending on the nature of the inserted alkene. The crystal structures of some palladium complexes and organic compounds have been determined by X-ray diffraction studies