Rhinocerebral invasive aspergillosis

Here we present 10 cases of rhinocerebral aspergillosis. In this study we included only invasive type of cases. In 4 of these disease had extended into the brain parenchyma and in remaining cases diseases had extended intracranially but dura was not invaded. Details about the operative procedure and followup is presented. Till date only 3 of these cases are surviving.     

Jet stream related iatrogenic retinal breaks during vitreo-retinal surgery

Purpose:To evaluate the causes of jet stream injury (JSI)-related iatrogenic retinal breaks (IRBs) during vitreoretinal surgery (VRS).Methods:The precise surgical environment, which includes the indication and type of surgical procedure, retina status, details of instrumentation and fluidic parameters, and characteristics of the jet responsible for the IRB, was noted from case records. The nature of IRB and its healing and impact on anatomical and visual outcomes were analyzed.Results:Five eyes of five patients with complete documentation of both the JSI and the IRB were included. Two cases were operated for macular hole, and one each for vitreous hemorrhage, retinal detachment, and endophthalmitis. One case had infusion-fluid-related JSI, while four developed it because of injection of surgical adjuncts (drugs, PFCL, and dye). JSI developed in two cases when the vitreous cavity was filled with fluid, while it was air-filled in three cases. In four cases, the fluid migrated into subretinal space, necessitating further maneuvers following which the breaks healed, but were directly responsible for vision loss in two cases.Conclusion:JSI related IRBs are rare but may be directly responsible for vision loss if they impact the macula. The balance between jet stream velocity, its distance from the retinal surface, the intervening media (vitreous cavity), and retinal health play an important role. It can occur because of both infusion as well as injection jets. Precautions must be taken in cases vulnerable to complications with suggested modifications in the surgical technique.     

Efficacy of erenumab and factors predicting response after 3 months in treatment resistant chronic migraine: a clinical service evaluation

BackgroundCalcitonin gene-related peptide (CGRP) inhibitors have been developed as options for treatment of chronic and episodic migraine. We present our experience of the use of erenumab in a tertiary headache centre.MethodsThis was a prospective clinical audit of all patients commenced on erenumab following a locally agreed pathway and criteria over a consecutive period. Patients received monthly erenumab 140 mg for 3 months. Data were collected prospectively at baseline and 3 months follow up.ResultsOne hundred three patients were commenced on erenumab during the study period. Patients had tried a median of 7 previous prophylactics, including onabotulinum toxin A in 94%. At 3 months there was a reduction in median total (28 to 20, 29% reduction, p < 0.0001) and severe (15 to 5, 67% reduction, p < 0.0001) headache days. 39.8% of patients achieved at least a 30% reduction in total headache days; 61.8% of patients achieved at least a 50% reduction in severe headache days. Meeting either of these thresholds was considered a positive response, 68% of patients achieved this. Presence of daily headache pattern was negatively associated with response, (56% response vs. 90% without daily headache, p = 0.0003). There was no association between age, gender, presence of medication overuse or number of previously tried prophylactic treatments and response to erenumab. 43% of patients reported at least one adverse effect, most commonly constipation (26%); treatment was discontinued in 3 patients due to adverse effects.ConclusionsErenumab was an effective treatment for chronic migraine in this treatment resistant population over 3 months of follow up. Presence of daily headache predicted poorer response but there was still a significant positive response rate in this group.     

Complete and incomplete lower motor neuron facial palsy in post-COVID-19 mucormycosis

Purpose:To study facial nerve palsy (FNP) in post-COVID-19-mucormycosis patients and its ocular complications, report different presentations of FNP in such patients, and propose its etiopathogenesis based on presentation and clinico-radiologic localization.Methods:A prospective cohort study was carried out in patients of post-COVID-19-mucormycosis who presented at our tertiary center, over a period of 3 months. Motor and sensory examination of the facial nerve was done to diagnose FNP and localize the lesion clinically. Slit-lamp examination was done for grading corneal involvement. MRI brain, orbit, and paranasal sinuses (PNS) with contrast were studied to find involvement along the facial nerve. It was assessed whether this site of lesion corresponded with clinical localization. Data were analyzed using the percentage of total cases and Fisher’s test.Results:A total of 300 patients with post-COVID-19 mucormycosis were examined, of which 30 (10%) patients were found to have FNP. All were lower motor neuron (LMN) type and were associated with corneal complications. The most common site clinically was distal to the chorda tympani (66.66%) and radiologically was infratemporal (IT) fossa (63.4%). The clinical localization significantly correlated with the radiological findings (P = 0.012). Twenty percent of patients showed incomplete involvement of facial musclesConclusion:FNP was found to be of LMN type. The most common site of insult was IT fossa. There was a good clinico-radiological correspondence of lesions. Isolated lesions were also found along the peripheral nerve course, presenting as incomplete facial palsy. Recognition of FNP in post-COVID-19 mucormycosis, in all its variable forms, is important to manage corneal complications.     

Phase I and scintigraphy studies to evaluate safety,tolerability, pharmacokinetics,and lung deposition of inhaled GDC‐0214 in healthy volunteers

Several inflammatory cytokines that promote inflammation and pathogenesis in asthma signal through the Janus kinase 1 (JAK1) pathway. This phase I, randomized, placebo‐controlled trial assessed the pharmacokinetics and safety of single and multiple ascending doses up to 15 mg twice daily for 14 days of a JAK1 inhibitor, GDC‐0214, in healthy volunteers (HVs; n = 66). Doses were administered with a dry powder, capsule‐based inhaler. An accompanying open‐label gamma scintigraphy study in HVs examined the lung deposition of a single dose of inhaled Technetium‐99m (^99mTc)‐radiolabeled GDC‐0214. GDC‐0214 plasma concentrations were linear and approximately dose‐proportional after both single and multiple doses. Peak plasma concentrations occurred at 15–30 min after dosing. The mean apparent elimination half‐life ranged from 32 to 56 h across all single and multiple dose cohorts. After single and multiple doses, all adverse events were mild or moderate, and none led to treatment withdrawal. There was no clear evidence of systemic toxicity due to JAK1 inhibition, and systemic exposure was low, with plasma concentrations at least 15‐fold less than the plasma protein binding‐corrected IC50 of JAK1 at the highest dose. Scintigraphy showed that approximately 50% of the emitted dose of radiolabeled GDC‐0214 was deposited in the lungs and was distributed well to the peripheral airways. ^99mTc‐radiolabeled GDC‐0214 (1 mg) exhibited a mean plasma C_max similar to that observed in phase I at the same dose level. Overall, inhaled GDC‐0214 exhibited pharmacokinetic properties favorable for inhaled administration.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Many factors drive asthma pathogenesis, including several cytokines that signal through the Janus kinase 1 (JAK1) pathway. Inhibition of JAK1 is a possible target for asthma treatments, but previous studies show oral JAK1 inhibitors lead to increased risk of severe infections, malignancy and cardiovascular events.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study investigated the safety, pharmacokinetics, and lung deposition of GDC‐0214, an inhaled JAK1 inhibitor designed to target the lungs.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Inhaled delivery of a JAK inhibitor for 14 days exhibited low systemic exposure, leading to few adverse events and limited systemic toxicity, while demonstrating high deposition in the lungs.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Local pulmonary application of JAK inhibitors may be an effective treatment for asthma with limited systemic risks.     

Pseudo-aneurysm of mitral aortic intervalvular fibrosa: Two case reports

The fibrous body between the mitral and aortic valve, known as mitral-aortic intervalvular fibrosa (MAIVF) is prone to infection and injury resulting in pseudo-aneurysm formation. Because of its relative rarity, we are far from making any conclusion regarding the natural history and appropriate therapeutic strategy for this condition. We report two cases of this condition with two different and rare etiologies with strikingly different natural courses, providing insight into the natural course and timing of surgery in this rare entity.     

Single-shot spinal anaesthesia, combined spinal-epidural and epidural volume extension for elective caesarean section: a randomized comparison

BackgroundSingle-shot spinal and combined spinal-epidural block, with or without epidural volume extension, can be used for caesarean section. There is no trial comparing their block characteristics and adverse effects under identical conditions.Methods60 ASA I or II parturients with gestational age 37 weeks or more, scheduled for elective caesarean section under regional anaesthesia, were included in the trial. Women were randomized to three groups: group SSS: single-shot spinal; group CSE: combined spinal-epidural; group EVE: epidural volume extension of a combined spinal-epidural. Intrathecal injection was identical in the three groups (0.5% hyperbaric bupivacaine 9 mg with fentanyl 10 μg) and was injected via a 25-gauge pencil-point spinal needle, either as a single-shot spinal or through the spinal needle of the needle-through-needle CSE set. In group EVE, 5 mL of normal saline was injected through the epidural catheter. All blocks were performed with the women sitting. Haemodynamic parameters and block characteristics were assessed.ResultsThe onset of maximum sensory and motor block was significantly faster in the SSS group than in the other two. Extent and duration of sensory and motor block and the incidence of adverse effects were similar in the three groups (P > 0.05).ConclusionsIntrathecal block is similar in extent and duration whether given as a single-shot spinal or a combined spinal-epidural with or without epidural volume extension when performed for elective caesarean section using hyperbaric bupivacaine in the sitting position.     

Construction of titanium cranioplasty plate using craniectomy bone flap as template

In recent times a steady rise in cranioplasty operations has been noted because of increasing utilisation of decompressive craniectomy for trauma as well as stroke patients. A variety of techniques have been utilised for cranioplasty, with their own benefits and limitations. Titanium cranioplasty is one of the well-established and widely used techniques, with most centres utilising computer-assisted reconstruction for manufacture of titanium plates. In this paper we present a novel method for making titanium cranioplasty plates using the craniectomy bone flap as a template and the results of our experience. To date we have performed 51 cranioplasties using this method. The surgical results have been comparable to those obtained using the computer-assisted model technique. The construction cost for titanium cranioplasty plates using this method has been ￡360 cheaper per plate compared with the computer-assisted method. In addition, the CT workload and radiation exposure have been reduced.