Changing operating room practices: the effect on postoperative endophthalmitis rates following cataract surgery

PurposeTo determine whether four new operating room (OR) protocols instituted because of COVID-19 reduced the cataract surgical postoperative endophthalmitis rate (POE).DesignRetrospective, sequential, clinical registry study.Methods85 552 sequential patients undergoing cataract surgery at the Aravind Eye Hospitals between 1 January 2020 and 25 March 2020 (56 551 in group 1) and 3 May 2020 and 31 August 2020 (29 011 in group 2). In group 1, patients were not gowned, surgical gloves were disinfected but not changed between cases, OR floors were not cleaned between every case, and multiple patients underwent preparation and surgery in the same OR. In group 2, each patient was gowned, surgical gloves were changed between each case, OR floors and counters were cleaned between patients, and only one patient at a time underwent preparation and surgery in the OR.ResultsGroup 1 was older, had slightly more females, and better preoperative vision. More eyes in group 2 underwent phacoemulsification (p=0.18). Three eyes (0.005%) in group 1 and 2 eyes (0.006%) in group 2 developed POE (p=0.77). Only one eye that underwent phacoemulsification developed POE; this was in group 1. There was no difference in posterior capsule rupture rate between the two groups.ConclusionsAdopting a set of four temporary OR protocols that are often mandatory in the Western world did not reduce the POE rate. Along with previously published studies, these results challenge the necessity of these common practices which may be needlessly costly and wasteful, arguing for the reevaluation of empiric and potentially unnecessary guidelines that govern ophthalmic surgeries.

The Multi Split Ventilator System: Performance Testing of Respiratory Support Shared by Multiple Patients

Ventilator sharing has been proposed as a method of increasing ventilator capacity during instances of critical shortage. We sought to assess the ability of a regulated, shared ventilator system (Multi Split Ventilator System, MSVS) to individualize support to multiple simulated patients using one ventilator. We employed simulated patients of varying size, compliance, minute ventilation requirement, and PEEP requirement. Performance tests were performed to assess the ability of the QSVS, versus control, to achieve individualized respiratory goals to clinically disparate patients sharing a single ventilator following ARDSNet guidelines. Resilience tests measured the effects of simulated adverse events occurring to one patient on another patient sharing a single ventilator. The QSVS met individual oxygenation and ventilation requirements for multiple simulated patients with a tolerance similar to a single ventilator. Abrupt endotracheal tube occlusion or extubation occurring to one patient resulted in modest, clinically tolerable changes in ventilation parameters for the remaining patients. The QSVS is a regulated, shared ventilator system capable of individualizing ventilatory support to clinically dissimilar simulated patients. It is also resilient to common adverse events. The QSVS represents a feasible option to ventilate multiple patients during a severe ventilator shortage.

Constitutively active SARM1 variants that induce neuropathy are enriched in ALS patients

Background In response to injury, neurons activate a program of organized axon self-destruction initiated by the NAD+ hydrolase, SARM1. In healthy neurons SARM1 is autoinhibited, but single amino acid changes can abolish autoinhibition leading to constitutively active SARM1 enzymes that promote degeneration when expressed in cultured neurons. Methods To investigate whether naturally occurring human variants might disrupt SARM1 autoinhibition and potentially contribute to risk for neurodegenerative disease, we assayed the enzymatic activity of all 42 rare SARM1 alleles identified among 8507 amyotrophic lateral sclerosis (ALS) patients and 9671 controls. We then intrathecally injected mice with virus expressing SARM1 constructs to test the capacity of an ALS-associated constitutively active SARM1 variant to promote neurodegeneration in vivo. Results Twelve out of 42 SARM1 missense variants or small in-frame deletions assayed exhibit constitutive NADase activity, including more than half of those that are unique to the ALS patients or that occur in multiple patients. There is a > 5-fold enrichment of constitutively active variants among patients compared to controls. Expression of constitutively active ALS-associated SARM1 alleles in cultured dorsal root ganglion (DRG) neurons is pro-degenerative and cytotoxic. Intrathecal injection of an AAV expressing the common SARM1 reference allele is innocuous to mice, but a construct harboring SARM1V184G, the constitutively active variant found most frequently among the ALS patients, causes axon loss, motor dysfunction, and sustained neuroinflammation. Conclusions These results implicate rare hypermorphic SARM1 alleles as candidate genetic risk factors for ALS and other neurodegenerative conditions.

Molnupiravir Extends COVID-19 Viral Phase, Evidenced by the High Frequency of Rare and Dangerous Mutations in SARS-COV-2

This paper analyzes SARS-COV-2 mutations data from Merck’s Molnupiravir trials, in the larger context. •5-day treatment with Molnupiravir caused the appearance and selection (to a frequency >5%) of two of the most dangerous spike mutations – E484K and P681H – in multiple patients of a very small group (2/202 and 4/202, respectively).•Molnupiravir disproportionately increases the frequency of dangerous and unusual mutations•Molnupiravir worsens COVID-19 in patients, especially those who start treatment within 3 days of symptom onset. Some theoretically possible mechanisms causing this include acute bone marrow disorder and/or the generation of immune-evasive or even immunosuppressive viral genomes. •These mechanisms are likely to extend the virus shedding period in a substantial number of patients. The virus shed by these patients would be highly mutated and likely selected toward virulence.•Molnupiravir allows for virus diversification in the treated minority and purification in the untreated, a luxury rarely experienced by any virus in the nature. •Merck failed to collect enough data about Molnupiravir driven mutations. •For each important safety event, the collected data represents a few realizations of a random variable with unknown heavy tailed statistical distribution. Merck incorrectly treated this data as worst-case scenarios.

Evaluation of Pre-operative Dermoscopy in Early Diagnosis of Non-melanocytic Skin Cancer

BACKGROUND: Dermatoscopy is an integral part of every clinical examination of skin tumors. Dermoscopy has markedly enhances the early diagnosis of non-melanocytic skin cancer (NMSC) compared to naked-eye inspection. Besides its value in the noninvasive diagnosis tool of skin cancer, dermoscopy has also gained increased interest in the response assessment and management of NMSC including basal cell carcinoma, Bowen’s disease, squamous cell carcinoma and merkel cell carcinoma. NMSCs are usually considered a curable disease, however they currently present a growing global healthcare problem due to the increasing incidence, hence this is the reason for my work. AIM: The main aim of the study is to prove the value of dermoscopy in the precision of pre-operative diagnosis of NMSC confirmed by postoperative histopathology (PH) findings. Additional goals are to declare dermoscopy subtypes of NMSC in according to the age, sex, localization, UV radiation, anatomical region, and phototype of skin. METHODS: We used two types of dermoscopy, non-polarized, and polarized dermoscopy. Non-polarized dermoscopy uses magnifying lenses and LED illumination light. This method requires contact with pre-liquid (gel, oil, and alcohol) skin to reduce reflection. Non-polarized dermoscopy allows visualization of structures located in the epidermis and dermoepidermal junction, but not below it. Polarized dermoscopy in addition to the magnifying and light lenses, it uses two polarizing filters to enable cross-polarization. This type of method does not require liquid medium on the skin surface and does not require skin contact. Polarized dermoscopy allows visualization of structures located deeper and below the dermoepidermal junction and the superficial dermis. RESULTS: This paper provides an update on NMSC with special emphasis of dermoscopy in the precision of preoperative diagnosis of NMSC confirmed by postoperative histopathology findings. CONCLUSION: Our first experiences with pre-operative dermoscopy in 11 patients indicate its value in the diagnosis of NMCS. Our further studies in multiple patients should determine its accuracy in pre-operative diagnosis confirmed by post-operative PH findings.

Ambulatory Voice Biofeedback: Acquisition and Retention of Modified Daily Voice Use in Patients With Phonotraumatic Vocal Hyperfunction

Purpose: Voice ambulatory biofeedback (VAB) has potential to improve carryover of therapeutic voice use into daily life. Previous work in vocally healthy participants demonstrated that motor learning inspired variations to VAB produced expected differences in acquisition and retention of modified daily voice use. This proof-of-concept study was designed to evaluate whether these VAB variations have the same desired effects on acquisition and retention in patients with phonotraumatic vocal hyperfunction (PVH). Method: Seventeen female patients with PVH wore an ambulatory voice monitor for 6 days: three baseline days, one biofeedback day, one short-term retention day, and one long-term retention day. Short- and long-term retention were 1- and 7-days postbiofeedback, respectively. Patients were block-randomized to receive one of three types of VAB: 100%, 25%, and Summary. Performance was measured in terms of adherence time below a subject-specific vocal intensity threshold. Results: All three types of VAB produced a biofeedback effect with 13 out of 17 patients displaying an increase in adherence time compared to baseline days. Additionally, multiple patients from each VAB group increased their adherence time during short- and/or long-term retention monitoring compared to baseline. Conclusions: These findings show that VAB can be associated with acquisition and retention of desired voice use in patients with PVH. Specifically, all three feedback types improved multiple patients' performance and retention for up to 1 week after biofeedback removal. Future work can investigate the impact of incorporating VAB into voice therapy.

Case Report: Oral Cimetidine Administration Causes Drug-Induced Immune Hemolytic Anemia by Eliciting the Production of Cimetidine-Dependent Antibodies and Drug-Independent Non-specific Antibodies

Previously, it was reported that multiple patients had hemolytic anemia associated with cimetidine administration, while only one patient who had received intravenous cimetidine was serologically diagnosed with drug-induced immune hemolytic anemia (DIIHA) caused by cimetidine-dependent antibodies. However, the ability of oral cimetidine intake to induce the production of antibodies has not been examined. In this study, we report a 44-year-old male patient in whom oral cimetidine administration resulted in cimetidine-dependent antibodies and drug-independent non-specific antibodies, leading to the development of DIIHA. Serological tests showed that the results of direct antiglobulin test (DAT) for anti-IgG (3+) and anti-C3d (1+) were positive. The IgM and IgG cimetidine-dependent antibodies (the highest total titer reached 4,096) were detected in the plasma incubated with O-type RBCs and 1 mg/mL cimetidine or the plasma incubated with cimetidine-coated RBCs. IgG-type drug-independent non-specific antibodies were detected in blood samples collected at days 13, 34, 41, and 82 post-drug intake. This is the first study to report that oral administration of cimetidine can elicit the production of cimetidine-dependent antibodies, leading to DIIHA, and the production of drug-independent non-specific antibodies, resulting in hemolytic anemia independent of cimetidine. Presence of pathogenic antibodies were detectable longer than 41 days. This suggests that patients with DIIHA caused by cimetidine need to be given necessary medical monitoring within 41 days after cimetidine intake.

The clinical spectrum and immunopathological mechanisms underlying ZIKV-induced neurological manifestations

Since the 2015 to 2016 outbreak in America, Zika virus (ZIKV) infected almost 900,000 patients. This international public health emergency was mainly associated with a significant increase in the number of newborns with congenital microcephaly and abnormal neurologic development, known as congenital Zika syndrome (CZS). Furthermore, Guillain–Barré syndrome (GBS), a neuroimmune disorder of adults, has also been associated with ZIKV infection. Currently, the number of ZIKV-infected patients has decreased, and most of the cases recently reported present as a mild and self-limiting febrile illness. However, based on its natural history of a typical example of reemerging pathogen and the lack of specific therapeutic options against ZIKV infection, new outbreaks can occur worldwide, demanding the attention of researchers and government authorities. Here, we discuss the clinical spectrum and immunopathological mechanisms underlying ZIKV-induced neurological manifestations. Several studies have confirmed the tropism of ZIKV for neural progenitor stem cells by demonstrating the presence of ZIKV in the central nervous system (CNS) during fetal development, eliciting a deleterious inflammatory response that compromises neurogenesis and brain formation. Of note, while the neuropathology of CZS can be due to a direct viral neuropathic effect, adults may develop neuroimmune manifestations such as GBS due to poorly understood mechanisms. Antiganglioside autoantibodies have been detected in multiple patients with ZIKV infection–associated GBS, suggesting a molecular mimicry. However, further additional immunopathological mechanisms remain to be uncovered, paving the way for new therapeutic strategies.

Pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular SARS-CoV-2 testing

Background As SARS-CoV-2 testing expands, particularly to widespread asymptomatic testing, high sensitivity point-of-care PCR platforms may optimise potential benefits from pooling multiple patients’ samples. Method We tested patients and asymptomatic citizens for SARS-CoV-2, exploring the efficiency and utility of CovidNudge (i) for detection in individuals’ sputum (compared to nasopharyngeal swabs), (ii) for detection in pooled sputum samples, and (iii) by modelling roll out scenarios for pooled sputum testing. Results Across 295 paired samples, we find no difference (p = 0.1236) in signal strength for sputum (mean amplified replicates (MAR) 25.2, standard deviation (SD) 14.2, range 0–60) compared to nasopharyngeal swabs (MAR 27.8, SD 12.4, range 6–56). At 10-sample pool size we find some drop in absolute strength of signal (individual sputum MAR 42.1, SD 11.8, range 13–60 vs. pooled sputum MAR 25.3, SD 14.6, range 1–54; p < 0.0001), but only marginal drop in sensitivity (51/53,96%). We determine a limit of detection of 250 copies/ml for an individual test, rising only four-fold to 1000copies/ml for a 10-sample pool. We find optimal pooled testing efficiency to be a 12–3-1-sample model, yet as prevalence increases, pool size should decrease; at 5% prevalence to maintain a 75% probability of negative first test, 5-sample pools are optimal. Conclusion We describe for the first time the use of sequentially dipped sputum samples for rapid pooled point of care SARS-CoV-2 PCR testing. The potential to screen asymptomatic cohorts rapidly, at the point-of-care, with PCR, offers the potential to quickly identify and isolate positive individuals within a population “bubble”.