EASIER trial (Erector-spinAe analgeSia for hepatopancreaticobiliary pain In the Emergency Room): a single-centre open-label cohort-based randomised controlled trial analysing the efficacy of the ultrasound-guided erector-spinae plane block compared with intravenous morphine in the treatment of acute hepatopancreaticobiliary pain in the emergency department.

BACKGROUND: Ultrasound-guided (USG) erector-spinae plane block (ESPB) may be better than intravenous opioids in treating acute hepatopancreaticobiliary (HPB) pain in the ED. METHODS: This open-label randomised controlled trial was conducted in the ED of a tertiary-care hospital between March and August 2023. All adult patients with severe HPB pain were recruited during times that a primary investigator was present. Unconsenting patients, numeric rating scale (NRS) ≤6, age ≤18 and ≥80 years, pregnant, unstable or with allergies to local anaesthetics or opioids were excluded. Patients in the intervention arm received bilateral USG ESPB with 0.2% ropivacaine at T7 level, by a trained ED consultant, and those in the control arm received 0.1 mg/kg intravenous morphine. Pain on a 10-point NRS was assessed by the investigators at presentation and at 1, 3, 5 and 10 hours after intervention by the treatment team, along with rescue analgesia requirements and patient satisfaction. Difference in NRS was analysed using analysis of co-variance (ANCOVA) and t-tests. RESULTS: 70 participants were enrolled, 35 in each arm. Mean age was 40.4±13.2 years, mean NRS at presentation in the intervention arm was 8.0±0.9 and 7.6±0.6 in the control arm. NRS at 1 hour was significantly lower in the ESPB group (ANCOVA p<0.001). At 1, 3, 5 and 10 hours, reduction of NRS in the intervention arm (7±1.6, 6.7±1.9, 6.6±1.8, 6.1±1.9) was significantly greater than the control arm (4.4±2, 4.6±1.8, 3.7±2.2, 3.8±1.8) (t-test, p<0.001). Fewer patients receiving ESPB required rescue analgesia at 5 (t-test, p=0.031) and 10 hours (t-test, p=0.04). More patients were 'very satisfied' with ESPB compared with receiving only morphine at each time period (p<0.001). CONCLUSION: ESPB is a promising alternative to morphine in those with HPB pain. TRIAL REGISTRATION NUMBER: CTRI/2023/03/050595.

Kif1a and intact microtubules maintain synaptic-vesicle populations at ribbon synapses in zebrafish hair cells.

Sensory hair cells of the inner ear utilize specialized ribbon synapses to transmit sensory stimuli to the central nervous system. This sensory transmission necessitates rapid and sustained neurotransmitter release, which relies on a large pool of synaptic vesicles at the hair-cell presynapse. Work in neurons has shown that kinesin motor proteins traffic synaptic material along microtubules to the presynapse, but how new synaptic material reaches the presynapse in hair cells is not known. We show that the kinesin motor protein Kif1a and an intact microtubule network are necessary to enrich synaptic vesicles at the presynapse in hair cells. We use genetics and pharmacology to disrupt Kif1a function and impair microtubule networks in hair cells of the zebrafish lateral-line system. We find that these manipulations decrease synaptic-vesicle populations at the presynapse in hair cells. Using electron microscopy, along with in vivo calcium imaging and electrophysiology, we show that a diminished supply of synaptic vesicles adversely affects ribbon-synapse function. Kif1a mutants exhibit dramatic reductions in spontaneous vesicle release and evoked postsynaptic calcium responses. Additionally, we find that kif1a mutants exhibit impaired rheotaxis, a behavior reliant on the ability of hair cells in the lateral line to respond to sustained flow stimuli. Overall, our results demonstrate that Kif1a-based microtubule transport is critical to enrich synaptic vesicles at the active zone in hair cells, a process that is vital for proper ribbon-synapse function.

Presynaptic Nrxn3 is essential for ribbon-synapse assembly in hair cells.

Hair cells of the inner ear rely on specialized ribbon synapses to transmit sensory information to the central nervous system. The molecules required to assemble these synapses are not fully understood. We show that Nrxn3, a presynaptic adhesion molecule, is critical for ribbon-synapse assembly in hair cells. In both mouse and zebrafish models, loss of Nrxn3 results in significantly fewer intact ribbon synapses. In zebrafish we demonstrate that a 60% loss of synapses in nrxn3 mutants dramatically reduces both presynaptic responses in hair cells and postsynaptic responses in afferent neurons. Despite a reduction in synapse function in this model, we find no deficits in the acoustic startle response, a behavior reliant on these synapses. Overall, this work demonstrates that Nrxn3 is a critical and conserved molecule required to assemble ribbon synapses. Understanding how ribbon synapses assemble is a key step towards generating novel therapies to treat forms of age-related and noise-induced hearing loss that occur due to loss of ribbon synapses.

Acute management of COVID-19 in the emergency department: An evidence-based review.

Coronavirus disease (COVID-19) has been relentlessly battering the world wave after wave in different countries at different rates and times. Emergency departments (EDs) around the globe have had to constantly adapt to this ever-changing influx of information and recommendations by various national and international health agencies. This review compiles the available evidence on the guidelines for triaging, evaluation, and management of critically ill patients with COVID-19 presenting to the ED and in need of emergency resuscitation. The quintessential components of resuscitation focus on airway, breathing, and circulation with good supportive care as the cornerstone of acute management of critically ill COVID-19 patients. Irrational investigations and therapeutics must be avoided during these times of medical uncertainty and antibiotic stewardship should be diligently followed.

What is the minimum effective anesthetic volume (MEAV90) of 0.2% ropivacaine required for ultrasound-guided popliteal-sciatic nerve block?

BACKGROUND AND AIMS: Popliteal-Sciatic nerve block under Ultrasound Guidance (USG) using a local anesthetic agent like Ropivacaine is an established technique for providing analgesia and muscle relaxation for lower limb surgeries with minimal untoward events. Establishing the minimal volume of 0.2% ropivacaine required to provide intraoperative and postoperative analgesia will further reduce the drug requirements and adverse effects toward the patient. MATERIAL AND METHODS: This randomized prospective observational blinded study was done in a tertiary care referral hospital in South India over 9 months from August 2017 till April 2018. The block was performed on all recruited patients under ultrasound guidance with a starting volume of 16 ml 0.2% ropivacaine. Duration of time for loss of pin-prick sensation around the sole of the foot (tibial nerve) and the lateral malleolus (common peroneal nerve) was noted. If successful, the volume of the drug for subsequent patients was randomized by lottery method to either be kept the same or reduced. If the block failed, the subsequent patient recruited would have an increased volume of drug injected. RESULTS: By Probit regression analysis using the biased coin up-and-down method we found that 9.3 ml (MEAV90) of 0.2% ropivacaine was sufficient for providing adequate analgesia. Factors such as patient age or weight had no role in efficacy of the block. There were no adverse effects such as allergy to the drug or systemic toxicity noted in the studied patients. CONCLUSION: 9.3 ml of 0.2% ropivacaine is sufficient to provide analgesia (assessed by pin-prick) in 90% of patients undergoing popliteal-sciatic block for lower limb surgeries.

Acute Undifferentiated Febrile Illness in Patients Presenting to a Tertiary Care Hospital in South India: Clinical Spectrum and Outcome.

BACKGROUND: Acute undifferentiated febrile illness (AUFI) may have similar clinical presentation, and the etiology is varied and region specific. MATERIALS AND METHODS: This prospective observational study was conducted in a tertiary hospital in South India. All adult patients presenting with AUFI of 3-14 days duration were evaluated for etiology, and the differences in presentation and outcome were analyzed. RESULTS: The study cohort included 1258 patients. A microbiological cause was identified in 82.5% of our patients. Scrub typhus was the most common cause of AUFI (35.9%) followed by dengue (30.6%), malaria (10.4%), enteric fever (3.7%), and leptospirosis (0.6%). Both scrub typhus and dengue fever peaked during the monsoon season and the cooler months, whereas no seasonality was observed with enteric fever and malaria. The mean time to presentation was longer in enteric fever (9.9 [4.7] days) and scrub typhus (8.2 [3.2] days). Bleeding manifestations were seen in 7.7% of patients, mostly associated with dengue (14%), scrub typhus (4.2%), and malaria (4.6%). The requirement of supplemental oxygen, invasive ventilation, and inotropes was higher in scrub typhus, leptospirosis, and malaria. The overall mortality rate was 3.3% and was highest with scrub typhus (4.6%) followed by dengue fever (2.3%). Significant clinical predictors of scrub typhus were breathlessness (odds ratio [OR]: 4.96; 95% confidence interval [CI]: 3.38-7.3), total whole blood cell count >10,000 cells/mm3 (OR: 2.31; 95% CI: 1.64-3.24), serum albumin <3.5 g % (OR: 2.32; 95% CI: 1.68-3.2). Overt bleeding manifestations (OR: 2.98; 95% CI: 1.84-4.84), and a platelet count of <150,000 cells/mm3 (OR: 2.09; 95% CI: 1.47-2.98) were independent predictors of dengue fever. CONCLUSION: The similarity in clinical presentation and diversity of etiological agents demonstrates the complexity of diagnosis and treatment of AUFI in South India. The etiological profile will be of use in the development of rational guidelines for control and treatment of AUFI.