Efficacy and safety of direct-acting antiviral agents for HCV in mild-to-moderate chronic kidney disease

Background and aimsThe advent of direct-acting antiviral agents promises to change the management of hepatitis C virus infection (HCV) in patients with chronic kidney disease (CKD), a patient group in which the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a ‘real-world’ cohort of patients with CKD.MethodsWe performed an observational single-arm multi-centre study in a large (n = 198) cohort of patients with stage 1–3 CKD who underwent antiviral therapy with DAAs for the treatment of HCV. The primary end-point was sustained virologic response (serum HCV RNA <15 IU/mL, 12 weeks after treatment ended) (SVR12). We collected data on on-treatment adverse events (AEs), severe AEs, and laboratory abnormalities.ResultsThe average baseline eGFR (CKD-EPI equation) was 70.06 ± 20.1 mL/min/1.72 m²; the most common genotype was HCV 1b (n = 93, 51%). Advanced liver scarring was found in 58 (46%) patients by transient elastography. Five regimens were adopted: elbasvir/grazoprevir (n = 5), glecaprevir/pibrentasvir (n = 4), ritonavir-boosted paritaprevir/ombitasvir/dasabuvir (PrOD) regimen (n = 40), simeprevir ± daclatasvir (n = 2), and sofosbuvir-based combinations (n = 147). The SVR12 rate was 95.4% (95% CI, 93.8%; 96.8%). There were nine virological failures – eight being relapsers. Adverse events occurred in 30% (51/168) of patients, and were managed clinically without discontinuation of therapy or hospitalization. One of the most common AEs was anaemia (n = 12), which required discontinuation or dose reduction of ribavirin in some cases (n = 6); deterioration of kidney function occurred in three (1.7%).ConclusionsAll-oral, interferon-free therapy with DAAs for chronic HCV in mild-to-moderate CKD was effective and well-tolerated in a ‘real–world’ clinical setting. Studies are in progress to address whether sustained viral response translates into better survival in this population.     

In vitro sensitivity of Plasmodium falciparum to conventional and novel antimalarial drugs in Papua New Guinea

Objective Recent clinical studies have shown high rates of malaria treatment failure in endemic areas of Papua New Guinea (PNG), necessitating a change of treatment from chloroquine (CQ) or amodiaquine (AQ) plus sulphadoxine‐pyrimethamine to the artemisinin combination therapy (ACT) artemether plus lumefantrine (LM). To facilitate the monitoring of antimalarial drug resistance in this setting, we assessed the in vitro sensitivity of Plasmodium falciparum isolates from Madang Province. Methods A validated colorimetric lactate dehydrogenase assay was used to assess growth inhibition of 64 P. falciparum isolates in the presence of nine conventional or novel antimalarial drugs [CQ, AQ, monodesethyl‐amodiaquine (DAQ), piperaquine (PQ), naphthoquine (NQ), mefloquine (MQ), LM, dihydroartemisinin and azithromycin (AZ)]. Results The geometric mean (95% confidence interval) concentration required to inhibit parasite growth by 50% (IC₅₀) was 167 (141–197) nm for CQ, and 82% of strains were resistant (threshold 100 nm ), consistent with near‐fixation of the CQ resistance‐associated pfcrt allele in PNG. Except for AZ [8.351 (5.418–12.871) nm ], the geometric mean IC₅₀ for the other drugs was <20 nm . There were strong associations between the IC₅₀s of 4‐aminoquinoline (CQ, AQ, DAQ and NQ), bisquinoline (PQ) and aryl aminoalcohol (MQ) compounds suggesting cross‐resistance, but LM IC₅₀ only correlated with that of MQ. Conclusions Most PNG isolates are resistant to CQ in vitro but not to other ACT partner drugs. The non‐isotopic semi‐automated high‐throughput nature of the Plasmodium lactate dehydrogenase assay facilitates the convenient serial assessment of local parasite sensitivity, so that emerging resistance can be identified with relative confidence at an early stage.     

Would rational use of antibiotics be compromised in the era of test‐based management of malaria?

Editorial: L’utilisation rationnelle des antibiotiques sera‐t‐elle compromise dans l’ère de la prise en charge de la malaria basée sur les tests? L’OMS a publié des directives révisées sur le traitement de la malaria qui recommandent la confirmation parasitologique avant le début du traitement des patients fébriles, y compris les enfants de moins de cinq ans. Le respect des nouvelles directives conduirait à un grand nombre de maladies fébriles confirmées comme étant non‐malariques. Sans les compétences et la capacité de distinguer les causes de fièvre non malarique dans les régions à pauvres ressources, la tendance serait pour les cliniciens à recourir à l’utilisation présomptueuse d’antibiotiques dans tous les cas à test négatif. Une augmentation significative de l’utilisation inappropriée des antibiotiques en Afrique subsaharienne va accroître le problème mondial de la résistance aux antibiotiques. Des interventions ciblées sont nécessaires pour améliorer l’utilisation rationnelle des antibiotiques dans l’ère de la prise en charge de la malaria basée sur les tests. Cela comprend des modifications appropriées dans les directives actuelles de la PCIME, l’équipement et la reformation du personnel dans les services de soins primaires, l’établissement de systèmes de surveillance sentinelle pour déterminer l’étiologie de la maladie fébrile non‐malarique et les profils de sensibilité aux antibiotiques, ainsi qu’un mécanisme efficace pour la diffusion des données de surveillance afin d’améliorer le diagnostic et la prise en charge des maladies fébriles chez les enfants.     

Bloqueio do nervo supraclavicular e do tronco superior para tratamento cirúrgico de fratura de clavícula em paciente portador de doença de Steinert – Relato de caso

Background and objectives

Ultrasound‐guided upper limb blocks may provide great benefits to patients with serious diseases. Patients with Steinert's disease have muscle weakness and risk of triggering myotony or malignant hyperthermia due to the use of anesthetic agents and surgical stress. The objective of this report was to demonstrate a viable alternative for clavicle fracture surgery with upper trunk and supraclavicular nerve block, thus reducing the spread of local anesthetic to the phrenic nerve in a patient with muscular dystrophy.

Lung Function,Radiological Findings and Biomarkers of Fibrogenesis in a Cohort of COVID-19 Patients Six Months After Hospital Discharge

IntroductionImpairment in pulmonary function tests and radiological abnormalities are a major concern in COVID-19 survivors. Our aim is to evaluate functional respiratory parameters, changes in chest CT, and correlation with peripheral blood biomarkers involved in lung fibrosis at two and six months after SARS-CoV-2 pneumonia.MethodsCOVID-FIBROTIC (clinicaltrials.gov NCT04409275) is a multicenter prospective observational cohort study aimed to evaluate discharged patients. Pulmonary function tests, circulating serum biomarkers, chest radiography and chest CT were performed at outpatient visits.ResultsIn total, 313, aged 61.12 ± 12.26 years, out of 481 included patients were available. The proportion of patients with DLCO < 80% was 54.6% and 47% at 60 and 180 days. Associated factors with diffusion impairment at 6 months were female sex (OR: 2.97, 95%CI 1.74–5.06, p = 0.001), age (OR: 1.03, 95% CI: 1.01–1.05, p = 0.005), and peak RALE score (OR: 1.22, 95% CI 1.06–1.40, p = 0.005). Patients with altered lung diffusion showed higher levels of MMP-7 (11.54 ± 8.96 vs 6.71 ± 4.25, p = 0.001), and periostin (1.11 ± 0.07 vs 0.84 ± 0.40, p = 0.001). 226 patients underwent CT scan, of whom 149 (66%) had radiological sequelae of COVID-19. In severe patients, 68.35% had ground glass opacities and 38.46% had parenchymal bands. Early fibrotic changes were associated with higher levels of MMP7 (13.20 ± 9.20 vs 7.92 ± 6.32, p = 0.001), MMP1 (10.40 ± 8.21 vs 6.97 ± 8.89, p = 0.023), and periostin (1.36 ± 0.93 vs 0.87 ± 0.39, p = 0.001).ConclusionAlmost half of patients with moderate or severe COVID-19 pneumonia had impaired pulmonary diffusion six months after discharge. Severe patients showed fibrotic lesions in CT scan and elevated serum biomarkers involved in pulmonary fibrosis.     

Posición operatoria en cirugía colorrectal. La importancia de lo básico

Intra-operative positioning in colorectal surgery is very important from three points of view: the proper surgical approach and exposure, adequate anaesthetic requirements with maintenance of the airway, and the potential complications related to the position. In the present study, we analyse the indications, positioning, advantages and disadvantages of each operative position, their potential complications and how to avoid them. These complications can be of a diverse nature, the most common being injuries related to stretching or compression of peripheral nerves, followed by thromboembolic, haemodynamic, and ischaemic or compartmental syndromes related to ischaemia-reperfusion after a long time in the Trendelenburg position. Anaesthetists and surgeons should coordinate and take responsibility for the position of surgical patients.     

Severe hypokalemia and rebound hyperkalemia during barbiturate coma in patients with severe traumatic brain injury

ObjectivesTo evaluate the incidence of severe potassium disturbances during barbiturate coma therapy in patients with severe traumatic brain injury (TBI), and the characteristics of these patients.MethodsThe study comprised 37 patients with severe TBI who were treated for barbiturate coma between 2015 and 2017 in level 3 intensive care units of two hospitals.ResultsNo potassium disturbance occurred in 14 patients. Seventeen patients developed mild-moderate hypokalemia (2.6–3.5 mEq/L), and 6 patients developed severe hypokalemia (<2.5 mEq/L) following the induction of barbiturate therapy. The incidence of mild-to-severe barbiturate-induced hypokalemia was 62.2% and the rate of severe hypokalemia was 16.2%. The mean potassium supply per day during thiopentone therapy was statistically significantly different between patients with mild-to-moderate hypokalemic and those with severe hypokalemic (p < 0.001). Four of 6 patients with severe hypokalemia developed rebound hyperkalemia exceeding 6 mEq/L following the cessation of barbiturate infusion. The nadir potassium concentration was 1.5 mEq/L and the highest value was 6.8 mEq/L. The mean time to reach nadir potassium concentrations was 2.8 days. The mortality rate of the 6 patients was 66.7%. Of the 2 survivors of severe hypokalemia, the Glasgow Outcome Scale (GOS) on discharge and the extended GOS one year after the trauma were 5 and 8 respectively.ConclusionsSevere hypokalemia refractory to medical treatment and rebound hyperkalemia is a serious adverse effect of thiopentone coma therapy in patients with severe TBI. Excessive and aggressive potassium replacement during the barbiturate-induced hypokalemia period must be avoided. Weaning barbiturate treatment over time may be advantageous in the management of severe serum potassium disturbances.     

Single shot spinal anaesthesia with hypobaric bupivacaine for hip fracture repair surgery in the elderly. Randomized,double blinded comparison of 3.75 mg vs. 7.5 mg

BackgroundArterial hypotension is the most frequent adverse effect of subarachnoid anaesthesia in the elderly sustaining a femoral proximal fracture. Decreasing the local anaesthetic dose reduces the incidence of hypotension but shortens sensory block duration that could be insufficient in some surgical procedures. Sensory block duration could be prolonged using hypobaric local anaesthetics. We evaluated whether low hypobaric bupivacaine doses were adequate for this type of surgery while maintaining the haemodynamic stability.MethodsA prospective, randomized, double blinded study was designed. Patients over 65 years old, sustaining traumatic hip fracture, were assigned to one of two groups: B0.5 group, hypobaric bupivacaine 7.5 mg 5 mg/ml (control group), and B0.25 group, hypobaric bupivacaine 3.75 mg 2.5 mg/ml (study group). After subarachnoid injection, sensory level and motor blockade degree were registered, as were blood pressure, and heart rate at basal time and at 2, 5, 10, 15, 20 and 30 min after injection. The doses of vasopressor needed were registered as well. Surgical conditions and the duration of the surgical procedure—whether rescue analgesia or anaesthesia was needed—and sensory level regression to T12, were registered as well.ResultsSixty four patients was the calculated sample size. The study was stopped in an interim analysis because an elevated number of patients in the B0.25 group needed iv rescue anaesthesia. In the analyzed cases, blood pressure was significantly lower in the B0.5 group at the 15 and 30 min measurements. Vasopressor drugs needs were similar between groups [ephedrine accumulated mean (SD) doses 11.4 (5.2) mg vs. 9.1 (2.7) mg, p = 0.045)]. Sensory block regression to T12 was faster in the B0.25 group, [(mean (SD) 68.2 (29.0) min vs. 112.8 (17.3) min in the B0.5 group, p < 0.05]. Five out of 19 patients in the B0.25 group needed intravenous anaesthesia rescue before surgery started.ConclusionLowering hypobaric bupivacaine dose to 3.75 mg in subarachnoid anaesthesia for hip fracture repair surgery in elderly patients decrease intraoperative blood pressure, but in an important number of patients intravenous anaesthesia rescue was needed and preclude recommendation.