PhPAd-DalPhos: Ligand-Enabled, Nickel-Catalyzed Cross-Coupling of (Hetero)aryl Electrophiles with Bulky Primary Alkylamines.

The base metal-catalyzed C-N cross-coupling of bulky α,α,α-trisubstituted primary alkylamines with (hetero)aryl electrophiles represents a challenging and under-developed class of transformations that is of significant potential utility, including in the synthesis of lipophilic active pharmaceutical ingredients. Herein, we report that a new, air-stable Ni(II) pre-catalyst incorporating the optimized ancillary ligand PhPAd-DalPhos enables such transformations of (hetero)aryl chloride, bromide, and tosylate electrophiles to be carried out for the first time with substrate scope rivalling that achieved using state-of-the-art Pd catalysts, including room temperature cross-couplings of (hetero)aryl chlorides that are unprecedented for any catalyst (Pd, Ni, or other).

Anaerobic fungi in the tortoise alimentary tract illuminate early stages of host-fungal symbiosis and Neocallimastigomycota evolution.

Anaerobic gut fungi (AGF, Neocallimastigomycota) reside in the alimentary tract of herbivores. While their presence in mammals is well documented, evidence for their occurrence in non-mammalian hosts is currently sparse. Culture-independent surveys of AGF in tortoises identified a unique community, with three novel deep-branching genera representing >90% of sequences in most samples. Representatives of all genera were successfully isolated under strict anaerobic conditions. Transcriptomics-enabled phylogenomic and molecular dating analyses indicated an ancient, deep-branching position in the AGF tree for these genera, with an evolutionary divergence time estimate of 104-112 million years ago (Mya). Such estimates push the establishment of animal-Neocallimastigomycota symbiosis from the late to the early Cretaceous. Further, tortoise-associated isolates (T-AGF) exhibited limited capacity for plant polysaccharides metabolism and lacked genes encoding several carbohydrate-active enzyme (CAZyme) families. Finally, we demonstrate that the observed curtailed degradation capacities and reduced CAZyme repertoire is driven by the paucity of horizontal gene transfer (HGT) in T-AGF genomes, compared to their mammalian counterparts. This reduced capacity was reflected in an altered cellulosomal production capacity in T-AGF. Our findings provide insights into the phylogenetic diversity, ecological distribution, evolutionary history, evolution of fungal-host nutritional symbiosis, and dynamics of genes acquisition in Neocallimastigomycota.

Ferric Derisomaltose Evaluation in Patients with Non-Dialysis-Dependent Chronic Kidney Disease or Peritoneal Dialysis.

Background: Iron deficiency anemia is common in patients with advanced chronic kidney disease (CKD). Ferric derisomaltose (FDI) enables iron repletion in a single dose, unlike other forms of iron for IV administration, which require multiple doses. Protocols are commonly used with other IV irons, but there are limited Canadian data for FDI, and no protocol exists. Objectives: To evaluate the efficacy and safety of FDI for patients with CKD and to ascertain information related to its use in Canadian provinces. Methods: This retrospective cohort study involved patients with non-dialysis-dependent CKD (NDD-CKD) and patients undergoing peritoneal dialysis (PD) who received FDI in a tertiary hospital in Nova Scotia between June 2020 and May 2021. Each patient was followed for a minimum of 6 months. The efficacy outcomes were the changes from baseline in hemoglobin, transferrin saturation (TSAT), and ferritin after the first dose of FDI and at 3 and 6 months. The safety outcomes were the frequency and types of adverse reactions to FDI. Electronic surveys were sent to 33 Canadian renal pharmacists to gather information about FDI use, dosing, administration, monitoring, funding, and safety in their respective organizations. Results: A total of 52 infusions were administered to 35 patients during the study period. The median times between doses 1 and 2 and between doses 2 and 3 were 19.1 and 6.6 weeks, respectively. The median change from baseline to first post-FDI follow-up blood work was significant for hemoglobin (9.0 g/L, p = 0.023), TSAT (11 percentage points, p < 0.001), and ferritin (271.4 µg/L, p < 0.001). Median darbepoetin doses decreased from baseline to 6 months (p < 0.001). Three adverse reactions occurred. At least 15 (65%) of the 23 survey respondents reported that FDI was funded by their province or was listed on their hospital drug formulary. Conclusion: This study provides evidence that FDI is an effective and safe treatment for anemia in NDD-CKD and PD patients.

Contexte: L'anémie ferriprive est fréquente chez les patients atteints d'insuffisance rénale chronique avancée (IRC). Une seule dose de dérisomaltose ferrique (FDI) permet au niveau de fer de se rétablir, contrairement à d'autres formes de fer administrées par IV qui nécessitent, elles, plusieurs doses. Des protocoles sont couramment utilisés avec d'autres fers administrés par IV, mais les données canadiennes sur le FDI sont limitées et il n'existe aucun protocole. Objectifs: Évaluer l'efficacité et l'innocuité du FDI chez les patients atteints d'IRC et vérifier les informations relatives à son utilisation dans les provinces du Canada. Méthodes: Cette étude de cohorte rétrospective comprenait des patients atteints d'IRC sans dialyse (NDD-IRC) et des patients sous dialyse péritonéale (DP) ayant reçu du FDI dans un hôpital de soins tertiaires de la Nouvelle-Écosse entre juin 2020 et mai 2021. Chaque patient a fait l'objet d'un suivi pendant au moins 6 mois. Les résultats d'efficacité étaient les changements par rapport à la base de trois mesures après la première dose de FDI et à 3 et 6 mois, soit l'hémoglobine, la saturation de la transferrine (TSAT) et la ferritine. Les résultats d'innocuité étaient la fréquence et les types de réactions indésirables au FDI. Des sondages ont été envoyés par voie électronique à 33 pharmaciens canadiens spécialisés en néphrologie afin de recueillir des renseignements sur l'utilisation, le dosage, l'administration, la surveillance, le financement et l'innocuité du FDI dans leurs organismes respectifs. Résultats: Au total, 52 perfusions ont été administrées à 35 patients au cours de la période d'étude. Les délais médians entre les doses 1 et 2, et entre les doses 2 et 3 étaient respectivement de 19,1 et 6,6 semaines. Le changement médian entre la base et le premier bilan sanguin de suivi post-FDI était important pour l'hémoglobine (9,0 g/L, p = 0,023), le TSAT (11 points de pourcentage, p < 0,001) et la ferritine (271,4 µg/L, p < 0,001). Les doses médianes de darbépoétine ont diminué par rapport à la base à 6 mois (p < 0,001). Trois effets indésirables se sont produits. Au moins 15 des 23 répondants au sondage (65 %) ont déclaré que le FDI était financé par leur province ou figurait sur les listes de médicaments des hôpitaux. Conclusion: Cette étude fournit des preuves que le FDI est un traitement efficace et sûr de l'anémie chez les patients NDD-IRC et PD.

Awake Craniotomy without Invasive Blood Pressure Monitoring.

OBJECTIVE: To assess the safety of foregoing invasive monitoring in a select group of patients undergoing awake craniotomy for supratentorial tumor resection. METHODS: Awake craniotomies were performed for tumor resection without invasive blood pressure monitoring when there was no preexisting cardiopulmonary indication as determined by the attending anesthesiologist according to institutional protocol. Noninvasive monitoring was performed every 3-5 minutes intraoperatively and then every 15 minutes in the recovery room for 4 hours before transfer to the ward. RESULTS: At a single tertiary care hospital, 74 consecutive awake surgeries were performed with noninvasive blood pressure monitoring. Among patients, 39 (52.7%) were male, 42 (83.8%) had infiltrative primary brain tumors, 2 (2.7%) had a history of coronary artery disease, 6 (8.1%) were diabetics, 10 (29.7%) were smokers, and 22 (29.7%) were on antihypertensive medications preoperatively. American Society of Anesthesiologists classification was I in 1.4% of patients, II in 36.4%, III in 60.8%, and IV in 1.4%. Intraoperative vasoactive medications were administered in 21 (28.4%) patients; 8 (38%) of these were on antihypertensive agents preoperatively. Vasodilators were administered in 13 (61.9%) patients, vasopressors were given in 6 (28.6%) patients, and both vasodilators and vasopressors were given in 2 (9.5%) patients. One patient experienced a lenticulostriate artery stroke intraoperatively, and 1 patient experienced atrial fibrillation 1 week postoperatively. There were no other perioperative anesthetic, hemorrhagic, renal, or cardiopulmonary complications. CONCLUSIONS: Intraoperative physiologic control and surgical site complication avoidance do not warrant routine invasive blood pressure monitoring during awake craniotomy for tumor resection.

How to Transect the C2 Root for C1 Lateral Mass Screw Placement: Case Series and Review of an Underappreciated Variable in Outcome.

BACKGROUND: The techniques for atlantoaxial arthrodesis have been modified over the years, and placing C1 lateral mass screws is a modern approach. C2 neuropathy is a complication of concern; however, sacrifice of the C2 nerve is an accepted and often favored adjunct. The impact of the technique for cutting the C2 nerve is not adequately addressed in the literature. The aim of this study was to evaluate the clinical outcomes from a series of roots sacrificed during C1-2 fusion with attention to the C2 transection method. METHODS: Clinical data were collected from trauma patients who underwent C1 screw fixation for atlantoaxial fusion. Chart review was performed and outcome assessed through telephone surveys to patients who were at least 6 months postoperative. Quality of life, C2 nerve function, neck pain, and head pain were assessed. RESULTS: Sixty-six roots were divided in 35 patients. There were no cases of occipital neuralgia at routine 3-month follow-up. Delayed telephone surveys were completed in 17 patients and exposed 4 cases of severe head/neck pain but none consistent with occipital neuralgia. CONCLUSIONS: C2 neuralgia is rare when sharply dividing the C2 root with the aid of bipolar electrocautery at the midportion of the ganglion where it overlies the C1-2 joint. A literature review suggests the impact of the root sacrifice method is an underappreciated modifiable factor in outcome. In future reports, description of the root transection technique is imperative and trials comparing ganglionectomy versus transection proximal to the ganglion or through the ganglion should be considered.