Is there a role for fibreoptic bronchoscopy in patients presenting with haemoptysis and negative CT? A systematic review and meta-analysis.

INTRODUCTION: Haemoptysis can be a feature of lung cancer and patients are typically fast-tracked for evaluation with chest radiography, contrast-enhanced CT and fibreoptic bronchoscopy (FOB). OBJECTIVE: We aim to explore whether FOB should be conducted as a component of the routine evaluation of non-massive haemoptysis, especially in the context of suspected lung cancer. METHODS: MEDLINE, EMBASE and Cochrane Library were searched for studies comparing FOB with CT in the evaluation of non-massive haemoptysis while reporting at least one of the listed primary outcomes. Primary outcomes include sensitivity of diagnostic modality with respect to lung cancer. Secondary outcomes include detection of other aetiologies such as infection. Results were synthesised using a random effects meta-analysis. Sensitivity analysis was performed for patient age group and year of study. Risk of bias assessment was carried out with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: A total of 2273 citations were screened and 11 studies were included, comprising a total sample size of 2015 patients with 226 confirmed cases of lung cancer. A total of 1816 and 1734 patients received a CT scan and FOB, respectively. The pooled sensitivities for detection of lung cancer using CT scan and bronchoscopy were 98% (95% CI 93.0% to 99.0%) and 86% (95% CI 63.0% to 95.0%), respectively. The sensitivity of CT was higher than that of FOB for both primary and secondary outcomes. CONCLUSION: This study suggests that bronchoscopy does not offer significant additional diagnostic benefit in the evaluation of patients presenting with non-massive haemoptysis and a negative CT scan.

A Comparison of Precision and Safety using Three Recognized Ultrasound-Guided Approaches to Cervical Medial Branch Blocks: A Cadaver Study.

BACKGROUND: Ultrasound (US) guidance is widely used for needle positioning for cervical medial branch blocks (CMBB) and radiofrequency ablation, however, limited research is available comparing different approaches. OBJECTIVE: We aimed to assess the accuracy and safety of 3 different US-guided approaches for CMBB. STUDY DESIGN: A cadaveric study divided into ultrasound-guided needle placement and fluoroscopy evaluation stages. SETTING: Department of Pathology, Forensic, and Insurance Medicine, Semmelweis University. METHODS: Sonographically guided third occipital nerve (TON), C3, C4, C5 and C6 medial branch injections and radiology evaluations were performed.The 3 approaches compared were:1. ES (published by Eichenberger-Siegenthaler): US probe in the coronal plane to visualize the cervical articular pillars, needle approach out of the plane, from anterior to posterior.2. Fi (published by Finlayson): US probe in the transverse plane to visualize a cervical articular pillar and its lamina, needle approach in the plane, from posterior to anterior.3. FiM (Modified Finlayson approach): Needles are placed as in Fi, but then adjusted with a coronal view of the cervical articular pillars.Fluoroscopy images were taken and later evaluated, for "crude", "high precision" and "dangerous" placement. RESULTS: One hundred and fifty-five needle placements were assessed (10 were excluded, as no anterior-posterior fluoroscopy images were saved). Interobserver agreement on position of needle placement between the 5 observers was very high; the Fleiss' Kappa was 0.921. For crude placement, no significant differences were identified between various approaches; (77.6%, 79.5%, and 75.6% for the ES, Fi, and FiM respectively). However, for placement in predefined high-precision zones, ES resulted in significantly more success (ES: 42.9%, Fi: 22.7%, and FiM: 24.4%, P = 0.032). Fi and FiM resulted in no dangerous placements, while ES led to the potential compromise of the exiting nerve root and vertebral artery on three occasions. In 10% of the placements, the levels were identified wrongly, with no difference between the various approaches. LIMITATIONS: Feedback from a live patient, may prevent some existing nerve root injections, unlike in a cadaver. Though a higher number of needles were placed in this study than in most available publications, the number is still low at each individual medial branch level. CONCLUSION: Fi proved safer than ES. Fi was equally successful in targeting the articular pillar, however, ES proved the most successful in placing the needle in the center of the articular pillar. Adding another, (coronal) US view to check needle position in FiM did not improve safety or precision. Identifying CMB levels with the US is challenging with all approaches, therefore we still recommend using fluoroscopy for level identification. While there were pros and cons with either procedure, the efficacy findings of previous papers were not replicated on elderly cadavers with arthritic necks.

Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndrome and on Dialysis: A Meta-Analysis.

This study aims to compare the safety and efficacy of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS) and undergoing dialysis. This study was conducted per the guidelines of the Preferred Reporting of Systematic Reviews and Meta-Analyses (PRISMA). A comprehensive search was performed using electronic databases, including PubMed, EMBASE, and Web of Science, to identify relevant studies comparing clopidogrel and ticagrelor in patients undergoing dialysis. To ensure the inclusion of all relevant articles, a combination of the following keywords, along with medical subject heading (MeSH) terms, was used: "clopidogrel," "ticagrelor," "acute coronary syndrome," and "dialysis." The primary endpoint of this meta-analysis was the incidence of major adverse cardiovascular events (MACE), which consisted of cardiovascular death, myocardial infarction, stroke, and revascularization. The secondary endpoint was all-cause mortality. The occurrence of any bleeding events (including major and nonmajor bleeding events) and major bleeding events was chosen as the safety endpoints. A total of four studies were included in the pooled analysis. The pooled sample size was 5,417 patients, including 892 in the ticagrelor group and 4525 in the clopidogrel group. The findings indicate that ticagrelor, compared to clopidogrel, is associated with a significantly higher risk of MACEs, all-cause death, and major bleeding events. The findings suggest that clopidogrel may be a better choice for individuals with ACS undergoing dialysis due to its lower risk of MACE, all-cause death, and major bleeding events compared to ticagrelor.

Impact of inverted internal limiting membrane-flap technique on functional outcome and structural restoration of small and medium size macular holes.

Purpose: To evaluate the impact of the inverted internal limiting membrane (ILM)-flap technique on the visual outcome and anatomical recovery for small (<250 µ), medium (<400 µ), and large (>400 µ) macular holes (MHs). Methods: Retrospective study included consecutive idiopathic MH cases operated on using the inverted ILM-flap technique. Clinical data were retrieved from electronic medical records (EMRs), surgical videos, and optical coherence tomography (OCT) machines. Eyes with axial length >25 mm, coexisting macular diseases, and follow-up <6 weeks were excluded. Data included the presence or absence of ILM flap and restoration of External Limiting Membrane (ELM), Ellipsoid Zone (EZ) lines. Mean visual improvement and structural recovery were compared between eyes showing ILM flap and those showing no flap in three MH size groups. Results: Forty eyes of 38 patients with a mean age of 62.7 ± 10.1 years and a mean MH diameter of 348 ± 152 µm were included. The mean follow-up was 527 ± 478 days with anatomical closure observed in all eyes. Mean best-corrected visual acuity (BCVA) improved significantly from 0.87 ± 0.38 to 0.35 ± 0.26. ILM flap was visible in 29 (72.5%) all MHs, 7 (53.8%) small MHs (n = 13), 8 (61.5%) medium MHs (n = 13), and 14 (100%) large MHs (n = 14). The mean BCVA change was 0.47 ± 0.34, 0.53 ± 0.48, and 0.56 ± 0.20 in large, medium, and small MHs, respectively, and the difference between eyes showing ILM flap versus no flap in each MH size group was not statistically significant (P > 0.05). However, for medium MHs, it was higher in the ILM flap (0.66 ± 0.52) group compared to the no flap (0.32 ± 0.37) group. One eye with small MH developed significant gliosis resulting in reduced BCVA. ELM was restored in all eyes with small and medium MHs. Conclusion: We observed that the ILM flap did not adversely affect anatomical and visual outcomes for MHs <400 µm. Restoration of ELM suggests minimal interference in structural recovery by an ILM flap.

Hyperekplexia: A Treatable Seizure Mimicker in Infants.

Hyperekplexia (HK) or startle disease is an uncommon, early infantile onset, potentially treatable neurogenetic disorder. It is characterized by an exaggerated startle reflex in response to tactile or acoustic or visual stimuli followed by generalized hypertonia. It is caused by genetic mutations in a number of different genes such as GLRA1, SLC6A5, GLRB, GPHN, and ARHGEF9. HK is frequently misdiagnosed as a form of epilepsy and is advised for prolonged antiseizure medications. Here, we report a two-month-old female child with HK, who was treated for epilepsy. Next-generation sequencing revealed a pathogenic homozygous missense mutation of variant c.1259C>A in exon 9 of the GLRA1 gene that was compatible with the diagnosis of hyperekplexia-1.

Multiple Evanescent White Dot Syndrome Following Adenovirus Vector-Based COVID-19 Vaccine (Covishield).

PURPOSE: To report a case of multiple evanescent white dot syndrome (MEWDS) following adenovirus vector-based Coronavirus disease 2019 (COVID-19) vaccine, Covishield and to present a summary of previously reported cases of MEWDS following COVID-19 vaccines. METHODS: Retrospective case report and review of literature. RESULTS: A 22-year-old Indian female presented with blurred vision, scotomata, and photopsias in her left eye, a day after administration of second dose of Covishield vaccine. Her clinical findings and imaging features confirmed the diagnosis of MEWDS. Her symptoms resolved spontaneously after 2 weeks. CONCLUSION: This is the first reported case of MEWDS following an adenovirus vector-based COVID-19 vaccine. Comparison with previously reported cases of MEWDS following COVID-19 vaccination showed that patients are generally healthy, young to middle-aged women, who develop symptoms after a median time of one week and recover spontaneously over a median period of 4 weeks.

Lung cancer recovery focus post pandemic: an income-deprived area paradigm.

'Stage shift' has been proposed as a marker of impact of Coronavirus 2019 (COVID-19) in lung cancer services; however, there are no data available specifically from income-deprived areas. Thus, this study evaluated the impact of the COVID-19 pandemic on lung cancer care in our area (Corby; among the most income deprived in England) and identified focus recovery areas. The study was a retrospective observational study of 668 consecutive patients with lung cancer at a district general hospital, pre-, during and after the COVID peak. Outcomes were the overall number of cases, presenting staging and treatment pathway. Overall, 32 fewer patients were diagnosed during the pandemic, with more inpatient diagnoses (p=0.01) and fewer primary care referrals (p<0.0001). There were no differences observed in treatment intent or 'stage shift'. Our results suggest that COVID-19 negatively affected the whole lung cancer pathway in our area. However, 'stage shift' might not be ideal to assess the impact of COVID-19 in income-deprived areas. Further studies will help the strategic rollout of a screening programme to identify patients with lung cancer earlier on in such areas.

A Prospective Hospital-Based Study on the Clinico-Etiological Profile of the First Episode of a Seizure in Children.

Background  This study aims to examine the clinico-etiological profile of children with the first episode of a seizure and categorize seizure types based on age groups in a tertiary care hospital. Methodology  This was a prospective observational study conducted at a tertiary care medical institute in India over two years. Children (one month to 12 years of age) with the first episode of a seizure were included in the study population. The data collected included demographic profile, history, examination, biochemical profile, electroencephalogram (EEG), and neuroimaging. Children were categorized as generalized-onset, focal-onset, and unknown-onset seizures based on the International League Against Epilepsy 2017 seizure classification. Children were also classified according to specific etiologies such as structural, metabolic, or other specific causes. All the children were followed up at the hospital's outpatient clinic or through a telephonic interview. Results  A total of 220 children were examined in this study. Among them, 64% were male and 36% were female, with a male-to-female ratio of 1.75:1. Among the 220 children, 21.8% had a family history of seizure. The most common type of seizures were generalized-onset seizures (n = 110, 50%), followed by focal-onset seizures (n = 96, 43.6%). Overall, 9% of children presented with status epilepticus as their first-episode seizure. An abnormal EEG was recorded for 122 (76%) children. While 60% of children had abnormal neuroimaging findings, the remaining had normal neuroimaging. Febrile seizures (n = 92, 41.9%) were the most common cause of the first episode of a seizure. Most of the febrile seizures occurred between the age of one and four (n = 60, 65.2%). Epilepsy syndromes were the second most common etiology, followed by central nervous system (CNS) infections, structural brain abnormalities, metabolic disorders, vascular lesions, toxins, and immune-mediated causes, in that order. In 14 (6.36%) children, the etiology was unknown at the time of the study. Conclusions First-episode seizures in children cause physical, mental, and financial stress on the parents. The collection of detailed history, examinations, and appropriate investigations can help identify the etiology of seizures. It was possible to determine the etiology of the first episode of a seizure in the majority of the patients. Generalized-onset seizures were the most common. Febrile seizures, epilepsy syndrome, CNS infections, vascular lesions, and metabolic disorders were the main etiological factors, in that order.

Ultrasonic fragmentation for removing thick organized clots during diabetic vitrectomy - A novel technique.

A 65-year-old male with proliferative diabetic retinopathy (PDR) and non-clearing vitreous hemorrhage underwent 25G pars plana vitrectomy (PPV). A large disk of thick organized blood of 5 disk diameter (DD) size was encountered in subhyaloid space. All attempts including lower cut rates to remove this disk using a 25G cutter turned futile. We used a 20G fragmatome to safely remove this hard clot from vitreous cavity in 50 s. Surgical time for removal of similar clot of 3 DD by 25G cutter in another eye was 5 min. Removal of thick clotted subhyaloid blood by ultrasonic fragmentation during diabetic vitrectomy is a safe, faster, and useful maneuver.

Outcomes from a virtual ward delivering oxygen at home for patients recovering from COVID-19: a real world observational study.

BACKGROUND: There is a lack of data on the safety of providing oxygen at home to stable patients recovering from COVID-19. METHODS: A retrospective analysis of patients discharged to a COVID-19 virtual ward (CVW) between January 2021 and March 2021 at a UK district general hospital was performed. Patients with improving clinical trajectories and oxygen requirements up to 4 L/minute were eligible. Outcomes measured were 30-day mortality and readmission rate. RESULTS: From 02 January 2021 to 16 March 2021 (74 days), 147 patients discharged to the CVW were included: 71 received continuous or ambulatory oxygen, and 76 received pulse oximetry monitoring only. Five patients were readmitted within 30 days and two patients died. There were no significant differences between readmission and mortality rates between those discharged with or without oxygen. CONCLUSION: Provision of oxygen at home for selected patients recovering from COVID-19 is safe with low risk of readmission and death.

Bilateral neovascular age-related macular degeneration: unilateral regression following endophthalmitis with persistent activity in the fellow eye.

A woman in her 70s who was being followed up for neovascular age-related macular degeneration (nAMD) in both eyes for 2 years with recalcitrant choroidal neovascularisation (CNV) and had an episode of acute endophthalmitis in one eye was identified. After treatment of postinjection culture-negative right eye (RE) endophthalmitis with intravitreal vancomycin and tazobactam, the patient had complete regression of treatment-resistant CNV in RE to date with postinfection follow-up of 2 years. In contrast, the fellow eye continued showing activity in the choroidal neovascular membrane that required antivascular endothelial growth factor injections on a pro re nata basis to date. Prolonged regression of nAMD for 3 years in the affected eye and continued activity in the fellow eye support the hypothesis that inflammation accompanying endophthalmitis or the drugs used for the treatment can have a role in the regression of nAMD.

Role of thoracic ultrasonography in pleurodesis pathways for malignant pleural effusions (SIMPLE): an open-label, randomised controlled trial.

BACKGROUND: Pleurodesis is done as an in-patient procedure to control symptomatic recurrent malignant pleural effusion (MPE) and has a success rate of 75-80%. Thoracic ultrasonography has been shown in a small study to predict pleurodesis success early by demonstrating cessation of lung sliding (a normal sign seen in healthy patients, lung sliding indicates normal movement of the lung inside the thorax). We aimed to investigate whether the use of thoracic ultrasonography in pleurodesis pathways could shorten hospital stay in patients with MPE undergoing pleurodesis. METHODS: The Efficacy of Sonographic and Biological Pleurodesis Indicators of Malignant Pleural Effusion (SIMPLE) trial was an open-label, randomised controlled trial done in ten respiratory centres in the UK and one respiratory centre in the Netherlands. Adult patients (aged ≥18 years) with confirmed MPE who required talc pleurodesis via either a chest tube or as poudrage during medical thorascopy were eligible. Patients were randomly assigned (1:1) to thoracic ultrasonography-guided care or standard care via an online platform using a minimisation algorithm. In the intervention group, daily thoracic ultrasonography examination for lung sliding in nine regions was done to derive an adherence score: present (1 point), questionable (2 points), or absent (3 points), with a lowest possible score of 9 (preserved sliding) and a highest possible score of 27 (complete absence of sliding); the chest tube was removed if the score was more than 20. In the standard care group, tube removal was based on daily output volume (per British Thoracic Society Guidelines). The primary outcome was length of hospital stay, and secondary outcomes were pleurodesis failure at 3 months, time to tube removal, all-cause mortality, symptoms and quality-of-life scores, and cost-effectiveness of thoracic ultrasonography-guided care. All outcomes were assessed in the modified intention-to-treat population (patients with missing data excluded), and a non-inferiority analysis of pleurodesis failure was done in the per-protocol population. This trial was registered with ISRCTN, ISRCTN16441661. FINDINGS: Between Dec 31, 2015, and Dec 17, 2019, 778 patients were assessed for eligibility and 313 participants (165 [53%] male) were recruited and randomly assigned to thoracic ultrasonography-guided care (n=159) or standard care (n=154). In the modified intention-to-treat population, the median length of hospital stay was significantly shorter in the intervention group (2 days [IQR 2-4]) than in the standard care group (3 days [2-5]; difference 1 day [95% CI 1-1]; p<0·0001). In the per-protocol analysis, thoracic ultrasonography-guided care was non-inferior to standard care in terms of pleurodesis failure at 3 months, which occurred in 27 (29·7%) of 91 patients in the intervention group versus 34 (31·2%) of 109 patients in the standard care group (risk difference -1·5% [95% CI -10·2% to 7·2%]; non-inferiority margin 15%). Mean time to chest tube removal in the intervention group was 2·4 days (SD 2·5) versus 3·1 days (2·0) in the standard care group (mean difference -0·72 days [95% CI -1·22 to -0·21]; p=0·0057). There were no significant between-group differences in all-cause mortality, symptom scores, or quality-of-life scores, except on the EQ-5D visual analogue scale, which was significantly lower in the standard care group at 3 months. Although costs were similar between the groups, thoracic ultrasonography-guided care was cost-effective compared with standard care. INTERPRETATION: Thoracic ultrasonography-guided care for pleurodesis in patients with MPE results in shorter hospital stay (compared with the British Thoracic Society recommendation for pleurodesis) without reducing the success rate of the procedure at 3 months. The data support consideration of standard use of thoracic ultrasonography in patients undergoing MPE-related pleurodesis. FUNDING: Marie Curie Cancer Care Committee.

Utilization of High-pressure Suction for EBUS-TBNA Sampling in Suspected Lung Cancer.

BACKGROUND: Sample adequacy for immediate molecular testing is paramount in lung cancer. To date, several endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) sampling setups have been evaluated, however, the utilization of high-pressure suction (HPS) has not yet been reported.The aim of this study was to evaluate the utilization of HPS onto the needle and its effect on sample volume and adequacy for molecular testing in patients with suspected lung cancer. METHODS: We retrospectively analyzed 128 consecutive EBUS-TBNA performed for suspected lung cancer. This was confirmed in 109 patients. Other diagnoses confirmed in 12, and 7 referred for surgery. Sixty-three patients (89 targets) had HPS (May to September 2020), and compared with 46 (72 targets) who had standard vacuum syringe suction (October 2019 to March 2020). Several parameters and outcomes evaluated, such as number of needle passes, needle strokes, needle size, target size, positron emission tomography avidity, procedure time, blood content score, sample volume, adequacy for molecular testing, as well as baseline patient characteristics and complication rate. RESULTS: There was no difference between the 2 groups in all baseline parameters and characteristics. In multivariable analysis, HPS was associated with significantly higher sample volume (11.2 vs. 9.1 mm3, P=0.036) and less additional procedures to achieve full molecular profiling (2/52 vs. 7/40, P=0.042), in necrotic targets of non-small cell lung cancer. Diagnostic yields were comparable. CONCLUSION: HPS appears to be simple, no-cost, and safe, promising higher sample volume compared with vacuum syringe suction, and also appears to be associated with higher success of full molecular testing with less additional procedures, in non-small cell lung cancer necrotic targets.

Lack of Benefit of High Flow Nasal Oxygen Therapy as Ceiling of Treatment for Severe COVID-19 Pneumonitis in Elderly Frail Patients: A Single Centre Observational Study.

Background: Severe COVID-19 pneumonitis in elderly frail patients is associated with poor outcomes, and therefore invasive mechanical ventilation is often deemed an inappropriate course of action. Some evidence suggests high-flow nasal oxygen (HFNO) may prevent the need for invasive ventilation in other groups of patients, but whether it is an appropriate ceiling of care for older frail patients is unknown. Methods: We retrospectively identified patients with severe COVID-19 pneumonitis requiring FiO2>60% who were deemed inappropriate for invasive ventilation or non-invasive continuous positive airway pressure ventilation (CPAP). Our local protocol based on national guidance suggested these patients should be considered for HFNO. We observed whether the patients received HFNO or standard oxygen therapy (SOT) and compared mortality and survival time in these groups. Results: We identified 81 patients meeting the inclusion criteria. From this group, 24 received HFNO and 57 received SOT. The HFNO group was similar in age, BMI and co-morbidities to the SOT group but less frail, as determined by the Clinical Frailty Scale (CFS). All 24 patients that received HFNO died in comparison to 46 patients (80.7%) in the SOT group. Mortality in the HFNO group was significantly higher than in the SOT group. Conclusion: Elderly frail patients with severe COVID-19 pneumonitis deemed inappropriate for invasive ventilation and did not benefit from HFNO. Further, HFNO may have been associated with harm in this group.

Virtual-reality headset mounted smartphone-based Indentation fundus videography.

To describe a simple and novel technique that overcomes the limitation of smartphone-based fundus photography and allows examiners to capture peripheral retinal images with indentation. Smartphone with video camera in flash-on mode was mounted on virtual-reality (VR) headset. This was combined with +28D lens and +20D lens and soft cotton bud to capture high-quality videos of peripheral fundus with indentation. Autofocus function of the camera and examiner's head movements to adjust the distance was used to obtain retinal video. The procedure is akin to indirect ophthalmoscopy. The feasibility of obtaining well-focused retinal images during indentation was checked. We could obtain good quality videos demonstrating indentation of the peripheral fundus in 10 eyes showing different pathologies such as laser marks, lattice degeneration, and pigmented lesions. VR headset-mounted smartphone-based indentation fundus videography is an innovative cost-effective technique to capture peripheral retinal images. The technique can be useful for documenting retinopathy of prematurity lesions and other situations where widefield photography is not possible.

Epiretinal Membrane from Uncontrolled Gliosis After Inverted ILM Flap Technique for Idiopathic Macular Hole.

We describe two cases with epiretinal membrane (ERM) from uncontrolled gliosis seen after multilayered inverted internal limiting membrane (ILM) flap technique for full thickness macular hole (FTMH). Two patients with FTMH who had undergone surgery with inverted ILM flap technique were examined by serial optical coherence tomography scans to evaluate the course of multilayered ILM flaps seen as foveal hyperreflective lesions postoperatively. We observed excessive uncontrolled gliosis over these hyperreflective ILM flaps with ERM formation, along with worsening metamorphopsia and best-corrected visual acuity. Case 1 underwent a repeat surgery for ERM. We report excessive uncontrolled gliosis as a rare complication of multilayered inverted ILM flap technique for FTMH. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:663-665.].

Outcomes of Continuous Positive Airway Pressure in the Management of Patients with Coronavirus (COVID-19) Pneumonia who are not Suitable for Invasive Ventilation.

BACKGROUND: The optimum management of respiratory failure in patients with coronavirus (COVID-19) infections has been a challenge for physicians across the globe. Many scientific societies have suggested the use of CPAP (continuous positive airway pressure) in severe cases in an effort to reduce invasive ventilation. We investigated mortality outcomes in patients who needed CPAP but were not suitable for invasive ventilation. METHODS: We retrospectively evaluated the mortality outcomes of all consecutive COVID-19 cases with severe type 1 respiratory failure requiring FiO2 >0.6 who were admitted to our hospital between 12th March and 04th May'20. British Thoracic Society guidelines were followed for identifying patients needing CPAP. Their outcomes were recorded and compared with a similar group of patients who had oxygen as a ceiling of care. Prospectively collected data between 5th May and 7th June'20 in similar but smaller groups of patients was also analyzed. RESULTS: A total of 104 COVID-19 patients with documented Do Not Attempt Resuscitation (DNAR) decision required high fraction of inspired oxygen (FiO2) >0.6(to maintain peripheral oxygen saturation (SpO2)> 92%(SpO2> 88% in COPD patients). Twenty-four patients received CPAP as the ceiling of care, with a mortality rate of 92.5%. The remaining 84 patients who were on oxygen as a ceiling of treatment had 91.7% mortality. Both population groups had a similar number of comorbidities but were less favorable in terms of age in the control group with standard O2 therapy than those who had CPAP support. Overall mortality outcomes from using CPAP therapy did not bring significant mortality benefit (p-value-0.89). CONCLUSION: CPAP did not appear to improve the survival of patients with severe respiratory failure due to COVID-19 related pneumonia and were not suitable for invasive ventilation. Further studies are warranted to adequately inform appropriate management strategies for this group of patients.

QPX7728, An Ultra-Broad-Spectrum B-Lactamase Inhibitor for Intravenous and Oral Therapy: Overview of Biochemical and Microbiological Characteristics.

QPX7728 is a novel ß-lactamase inhibitor (BLI) that belongs to a class of cyclic boronates. The first member of this class, vaborbactam, is a BLI in the recently approved Vabomere (meropenem-vaborbactam). In this paper we provide the overview of the biochemical, structural and microbiological studies that were recently conducted with QPX7728. We show that QPX7728 is an ultra-broad-spectrum ß-lactamase inhibitor with the broadest spectrum of inhibition reported to date in a single BLI molecule; in addition to potent inhibition of clinically important serine ß-lactamases, including Class A and D carbapenemases from Enterobacterales and notably, diverse Class D carbapenemases from Acinetobacter, it also inhibits many metallo ß-lactamases. Importantly, it is minimally affected by general intrinsic resistance mechanisms such as efflux and porin mutations that impede entry of drugs into gram-negative bacteria. QPX7728 combinations with several intravenous (IV) ß-lactam antibiotics shows broad coverage of Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa, including strains that are resistant to other IV ß-lactam-BLI combinations, e.g., ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam and imipenem-relebactam that were recently approved for clinical use. Based on studies with P. aeruginosa, different partner ß-lactams in combination with QPX7728 may be optimal for the coverage of susceptible organisms. This provides microbiological justification for a stand-alone BLI product for co-administration with different ß-lactams. QPX7728 can also be delivered orally; thus, its ultra-broad ß-lactamase inhibition spectrum and other features could be also applied to oral QPX7728-based combination products. Clinical development of QPX7728 has been initiated.