Ultrasonographic Assessment of Diaphragm Function to Predict Need for Mechanical Ventilation and its Liberation in Patients with Neuromuscular Disorders: An Observational Cohort Pilot Study.

BACKGROUND: Management of assisted ventilation and determining the optimal timing for discontinuation presents a significant clinical obstacle in patients affected by neuromuscular (NM) diseases. This study aimed to evaluate the efficacy of ultrasound in appraising diaphragmatic function for predicting the necessity of intubation and determining the opportune moment to discontinue mechanical ventilation (MV) in patients with NM disorders. METHODS: The study was conducted in adult patients with NM diseases requiring inpatient care in the high-dependency neurology ward and the intensive care unit. Ultrasonographic assessment of diaphragmatic excursion (DE) and diaphragmatic thickness fraction (DTF) was conducted at the patient's bedside every 48 h for ventilated patients and every 72 h for nonventilated patients until they were weaned from the ventilator or discharged home. Qualitative data are expressed as percentages or numbers, and quantitative data are represented as mean ± standard deviation. Unpaired t-tests were employed to compare continuous variables, and χ2 tests were used for categorical variables. Contingency table analysis was used to compute relative risks in comparing the baseline DE and DTF with the sequential changes in these values. RESULTS: In cases in which the baseline left DE measured less than 1 cm, the relative risk for the requirement of ventilation was 2.5 times higher, with a confidence interval of 0.62-0.99 (P = 0.19). Notably, a bilateral reduction in DE within the initial 48 h of admission was identified as predictive of need for intubation. When comparing ventilated and nonventilated patients, it was observed that the mean DE values for the left and right sides in ventilated patients (0.74 and 0.79) were significantly lower than those in nonventilated patients (1.3 and 1.66), with corresponding P values of 0.05 and 0.01, respectively. Furthermore, a decline in right DE by more than 50% within 72 h of admission presented a relative risk of 3.3 for the necessity of ventilation, with a confidence interval of 1.29-8.59 (P = 0.01). Duration of ventilation ranged from 2 to 45 days, with an average of 13.14 days, whereas the mean ventilator-free days recorded was 13.57. Notably, a sequential increase in bilateral DE correlated with an extended duration of ventilator-free days. CONCLUSIONS: The presence of a baseline left DE of less than 1 cm, a consecutive decrease in DE measurements within 48 h, and a comparative reduction in right DE of more than 50% within the initial 3 days are indicators associated with the requirement for MV in patients with NM disease. Furthermore, the upward trajectory of DE in mechanically ventilated patients is linked to an increased number of days free from ventilator support, suggesting its potential to forecast earlier weaning.

Reducing Delays in MRIs Under Sedation and General Anesthesia Using Quality Improvement Tools.

OBJECTIVE: Develop structured, quality improvement interventions to achieve a 15%-point reduction in MRIs performed under sedation or general anesthesia (GA) delayed more than 15 min within a 6-month period. METHODS: A prospective audit of MRIs under sedation or GA from January 2022 to June 2023 was conducted. A multidisciplinary team performed process mapping and root cause analysis for delays. Interventions were developed and implemented over four Plan, Do, Study, Act (PDSA) cycles, targeting workflow standardization, preadmission patient counseling, reinforcing adherence to scheduled scan times and written consent respectively. Delay times (compared with Kruskal-Wallis and Dunn's tests), delays more than 15 min and delays of 60 min or more at baseline and after each PDSA cycle were recorded. RESULTS: In all, 627 MRIs under sedation or GA were analyzed, comprising 443 at baseline and 184 postimplementation. Of the 627, 556 (88.7%) scans were performed under sedation, 22 (3.5%) under monitored anesthesia care, and 49 (7.8%) under GA. At baseline, 71.6% (317 of 443) scans were delayed over 15 min and 28.2% (125 of 443) scans by 60 min or more, with a median delay of 30 min. Postimplementation, there was a 34.7%-point reduction in scans delayed more than 15 min, a 17.5%-point reduction in scans delayed by 60 min or more, and a reduction in median delay time by 15 min (P < .001). DISCUSSION: Structured interventions significantly reduced delays in MRIs under sedation and GA, potentially improving outcomes for both patients and providers. Key factors included a diversity of perspectives in the study team, continued stakeholder engagement and structured quality improvement tools including PDSA cycles.

A Plasmodium falciparum genetic cross reveals the contributions of pfcrt and plasmepsin II/III to piperaquine drug resistance.

Piperaquine (PPQ) is widely used in combination with dihydroartemisinin as a first-line treatment against malaria. Multiple genetic drivers of PPQ resistance have been reported, including mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and increased copies of plasmepsin II/III (pm2/3). We generated a cross between a Cambodia-derived multidrug-resistant KEL1/PLA1 lineage isolate (KH004) and a drug-susceptible Malawian parasite (Mal31). Mal31 harbors a wild-type (3D7-like) pfcrt allele and a single copy of pm2/3, while KH004 has a chloroquine-resistant (Dd2-like) pfcrt allele with an additional G367C substitution and multiple copies of pm2/3. We recovered 104 unique recombinant parasites and examined a targeted set of progeny representing all possible combinations of variants at pfcrt and pm2/3. We performed a detailed analysis of competitive fitness and a range of PPQ susceptibility phenotypes with these progenies, including PPQ survival assay, area under the dose response curve, and a limited point IC50. We find that inheritance of the KH004 pfcrt allele is required for reduced PPQ sensitivity, whereas copy number variation in pm2/3 further decreases susceptibility but does not confer resistance in the absence of additional mutations in pfcrt. A deep investigation of genotype-phenotype relationships demonstrates that progeny clones from experimental crosses can be used to understand the relative contributions of pfcrt, pm2/3, and parasite genetic background to a range of PPQ-related traits. Additionally, we find that the resistance phenotype associated with parasites inheriting the G367C substitution in pfcrt is consistent with previously validated PPQ resistance mutations in this transporter.IMPORTANCEResistance to piperaquine, used in combination with dihydroartemisinin, has emerged in Cambodia and threatens to spread to other malaria-endemic regions. Understanding the causal mutations of drug resistance and their impact on parasite fitness is critical for surveillance and intervention and can also reveal new avenues to limiting the evolution and spread of drug resistance. An experimental genetic cross is a powerful tool for pinpointing the genetic determinants of key drug resistance and fitness phenotypes and has the distinct advantage of quantifying the effects of naturally evolved genetic variation. Our study was strengthened since the full range of copies of KH004 pm2/3 was inherited among the progeny clones, allowing us to directly test the role of the pm2/3 copy number on resistance-related phenotypes in the context of a unique pfcrt allele. Our multigene model suggests an important role for both loci in the evolution of this multidrug-resistant parasite lineage.

"De Novo" Hypercapnic Respiratory Failure Unmasking Neuromuscular Disorders: Experiences From a Tertiary Care Center and Review of Literature.

OBJECTIVES: Neuromuscular disorders could have respiratory involvement early or late into illness. Rarely, patients may present with a hypercapnic respiratory failure (with minimal motor signs) unmasking an underlying disease. There are hardly any studies which have addressed the spectrum and challenges involved in management of this subset, especially in the real-world scenario. METHODS: A retrospective study comprising consecutive patients hospitalized with hypercapnic respiratory failure as the sole/dominant manifestation. The clinical-electrophysiological spectrum, phrenic conductions, diaphragm thickness, and outcomes were analyzed. RESULTS: Twenty-seven patients were included, the mean age was 47.29 (SD 15.22) years, and the median duration of respiratory symptoms was 2 months (interquartile range [IQR] 1-4). Orthopnea was present in 23 patients (85.2%) and encephalopathy in 8 patients (29.6%). Phrenic nerve latencies and amplitudes were abnormal in 83.3% and 95.6%, respectively. Abnormal diaphragm thickness was noted in 78.5%. Based on a comprehensive electrophysiological strategy and paraclinical tests, an etiology was established in all. Reversible etiologies were identified in 17 patients (62.9%). These included myasthenia gravis (anti-AChR and MuSK), inflammatory myopathy, riboflavin transporter deficiency neuronopathy, Pompe disease, bilateral phrenic neuritis, and thyrotoxicosis. Respiratory onset motor neuron disease was diagnosed in 8 patients (29.6%). Despite diaphragmatic involvement, a functional respiratory recovery was noted at discharge (45%) and last follow-up (60%). Predictors for good outcomes included female sex, normal nerve conductions, and recent-onset respiratory symptoms. DISCUSSION: A good functional recovery was noted in most of the patients including respiratory onset motor neuron disease. A systematic algorithmic approach helps in proper triaging, early diagnosis, and treatment. Clinical and electrodiagnostic challenges and observations from a tertiary care referral center are discussed.