18F-FDG PET/CT in left ventricular assist device infections: In-depth characterization and clinical implications.

BACKGROUND: Previous retrospective studies suggest a good diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/computed tomography (CT) in left ventricular assist device (LVAD) infections. Our aim was to prospectively evaluate the role of PET/CT in the characterization and impact on clinical management of LVAD infections. METHODS: A total of 40 patients (aged 58 [53-62] years) with suspected LVAD infection and 5 controls (aged 69 [64-71] years) underwent 18F-FDG-PET/CT. Four LVAD components were evaluated: exit site and subcutaneous driveline (peripheral), pump pocket, and outflow graft. The location with maximal uptake was considered the presumed site of infection. Infection was confirmed by positive culture (exit site or blood) and/or surgical findings. RESULTS: Visual uptake was present in 40 patients (100%) in the infection group vs 4 (80%) control subjects. For each individual component, the presence of uptake was more frequent in the infection than in the control group. The location of maximal uptake was most frequently the pump pocket (48%) in the infection group and the peripheral components (75%) in the control group. Maximum standard uptake values (SUVmax) were higher in the infection than in the control group: SUVmax (average all components): 6.9 (5.1-8.5) vs 3.8 (3.7-4.3), p = 0.002; SUVmax (location of maximal uptake): 10.6 ± 4.0 vs 5.4 ± 1.9, p = 0.01. Pump pocket infections were more frequent in patients with bacteremia than without bacteremia (79% vs 31%, p = 0.011). Pseudomonas (32%) and methicillin-susceptible Staphylococcus aureus (29%) were the most frequent pathogens and were associated with pump pocket infections, while Staphylococcus epidermis (11%) was associated with peripheral infections. PET/CT affected the clinical management of 83% of patients with infection, resulting in surgical debridement (8%), pump exchange (13%), and upgrade in the transplant listing status (10%), leading to 8% of urgent transplants. CONCLUSIONS: 18F-FDG-PET/CT enables the diagnosis and characterization of the extent of LVAD infections, which can significantly affect the clinical management of these patients.

Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act.

BACKGROUND: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D - , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D - , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS: Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.

Potentiation of cholinergic and corticofugal inputs to the lateral amygdala in threat learning.

The amygdala, cholinergic basal forebrain, and higher-order auditory cortex (HO-AC) regulate brain-wide plasticity underlying auditory threat learning. Here, we perform multi-regional extracellular recordings and optical measurements of acetylcholine (ACh) release to characterize the development of discriminative plasticity within and between these brain regions as mice acquire and recall auditory threat memories. Spiking responses are potentiated for sounds paired with shock (CS+) in the lateral amygdala (LA) and optogenetically identified corticoamygdalar projection neurons, although not in neighboring HO-AC units. Spike- or optogenetically triggered local field potentials reveal enhanced corticofugal-but not corticopetal-functional coupling between HO-AC and LA during threat memory recall that is correlated with pupil-indexed memory strength. We also note robust sound-evoked ACh release that rapidly potentiates for the CS+ in LA but habituates across sessions in HO-AC. These findings highlight a distributed and cooperative plasticity in LA inputs as mice learn to reappraise neutral stimuli as possible threats.

A Study of Cytomorphological Spectrum of Head and Neck Lesions in Pediatric Age Group.

Introduction: Fine Needle Aspiration Cytology (FNAC) is a well-established early diagnostic technique for evaluating mass lesions in adult patients. Now, FNAC in children is gaining acceptance and is used as a first-line investigation in diagnosis of pediatric lesions. Aims: To analyze the cytomorphologic spectrum of head and neck lesions in pediatric age group with histopathological correlation wherever possible and to study the utility of FNAC in pediatric head and neck lesions. Materials and Methods: A prospective study was carried out on all FNACs of head and neck lesions in pediatric age group (0-18 years), detected clinically or under radiological guidance for a period of 3 years from August 2018 to July 2021. Results: The study included 238 cases. Most of the cases were seen in the age group of 13-18 years and with male to female ratio of 1.35:1. Most common site of FNAC was lymph nodes (70.2%) and the commonest lesion encountered was reactive lymphadenitis (50.8%). Second most common site was thyroid (15.9%). Soft tissue/bone, salivary gland, miscellaneous/skin lesions were also encountered. Among the 43 neoplastic lesions, benign (31 cases) were more common than the malignant (12 cases). The malignant cases included non-Hodgkins lymphoma, Hodgkins lymphoma, metastasis to lymph node, low-grade sarcoma, papillary thyroid carcinoma, and Langerhans cell histiocytosis of bone. Histopathological correlation was done in 32 cases (13.4%). Statistical analysis showed a sensitivity of 85.29% and specificity of 97.74%. Overall diagnostic accuracy was 96.3%. Conclusion: This study highlighted various cytomorphological patterns in head and neck lesions with high diagnostic accuracy in children. FNAC helps in proper planning of treatment modalities in head and neck masses in pediatric age group.

Highly sensitive technique for detection of adulterants in centella herbal samples using surface enhanced Raman spectroscopy (SERS).

The trace level detection of adulterants in food, nutritional supplements and medicinal herbs is highly challenging in the field of food processing and herbal industries. In addition, laborious sample processing procedures and well trained personnel are required to analyse the samples using conventional analytical equipments. In this study, a highly sensitive technique with minimal sampling processes and human intervention is proposed for the trace amount detection of pesticidal residues in centella powder. Herein, graphene oxide gold (GO-Au) nanocomposite coated parafilm is developed as substrate by simple dropcasting technique to facilitate dual surface enhanced Raman signal. The dual SERS enhancement involving chemical enhancement from graphene and electromagnetic signal enhancement from gold nanoparticles is utilized for detection of chlorpyrifos in the ppm level concentration. The flexible polymeric surfaces could be the better choice for SERS substrates due to their inherent properties such as flexibility, transparency, roughness and hydrophobicity. Among the various types of flexible substrates explored, GO-Au nanocomposites coated parafilm substrates showed better Raman signal enhancement. Parafilm coated with GO-Au nanocomposites is successful in achieving detection limits down to 0.1 ppm of chlorpyrifos in centella herbal powder sample. Thus, the fabricated parafilm based GO-Au SERS substrates could be used as a screening tool at quality control of herbal product manufacturing sectors for trace level detection of adulterants in herbal samples from their unique chemical and structural information.

Efficacy of ceftazidime-avibactam in solid organ transplant recipients with bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae.

We aimed to compare the efficacy of ceftazidime-avibactam (CAZ-AVI) versus the best available therapy (BAT) in solid organ transplant (SOT) recipients with bloodstream infection caused by carbapenemase-producing Klebsiella pneumoniae (CPKP-BSI). A retrospective (2016-2021) observational cohort study was performed in 14 INCREMENT-SOT centers (ClinicalTrials.gov identifier: NCT02852902; Impact of Specific Antimicrobials and MIC Values on the Outcome of Bloodstream Infections Due to ESBL- or Carbapenemase-producing Enterobacterales in Solid Organ Transplantation: an Observational Multinational Study). Outcomes were 14-day and 30-day clinical success (complete resolution of attributable manifestations, adequate source control, and negative follow-up blood cultures) and 30-day all-cause mortality. Multivariable logistic and Cox regression analyses adjusted for the propensity score to receive CAZ-AVI were constructed. Among 210 SOT recipients with CPKP-BSI, 149 received active primary therapy with CAZ-AVI (66/149) or BAT (83/149). Patients treated with CAZ-AVI had higher 14-day (80.7% vs 60.6%, P = .011) and 30-day (83.1% vs 60.6%, P = .004) clinical success and lower 30-day mortality (13.25% vs 27.3%, P = .053) than those receiving BAT. In the adjusted analysis, CAZ-AVI increased the probability of 14-day (adjusted odds ratio [aOR], 2.65; 95% confidence interval [CI], 1.03-6.84; P = .044) and 30-day clinical success (aOR, 3.14; 95% CI, 1.17-8.40; P = .023). In contrast, CAZ-AVI therapy was not independently associated with 30-day mortality. In the CAZ-AVI group, combination therapy was not associated with better outcomes. In conclusion, CAZ-AVI may be considered a first-line treatment in SOT recipients with CPKP-BSI.

New revelations from the zone of uncertainty.

In this issue of Neuron, Schroeder et al.1 provide the first functional account of inhibitory signaling from the zona incerta to neocortex in behaving animals. Incertocortical afferents exhibit bidirectional plasticity during threat learning, highlighting a distinct top-down signaling regime.

Potentiated cholinergic and corticofugal inputs support reorganized sensory processing in the basolateral amygdala during auditory threat acquisition and retrieval.

Reappraising neutral stimuli as environmental threats reflects rapid and discriminative changes in sensory processing within the basolateral amygdala (BLA). To understand how BLA inputs are also reorganized during discriminative threat learning, we performed multi-regional measurements of acetylcholine (ACh) release, single unit spiking, and functional coupling in the mouse BLA and higher-order auditory cortex (HO-AC). During threat memory recall, sounds paired with shock (CS+) elicited relatively higher firing rates in BLA units and optogenetically targeted corticoamygdalar (CAmy) units, though not in neighboring HO-AC units. Functional coupling was potentiated for descending CAmy projections prior to and during CS+ threat memory recall but ascending amygdalocortical coupling was unchanged. During threat acquisition, sound-evoked ACh release was selectively enhanced for the CS+ in BLA but not HO-AC. These findings suggest that phasic cholinergic inputs facilitate discriminative plasticity in the BLA during threat acquisition that is subsequently reinforced through potentiated auditory corticofugal inputs during memory recall.

Fabrication of sandwich structures of Ag/analyte/MoO3sea urchins for SERS detection of methylene blue dye molecules.

A substrate for surface-enhanced Raman spectroscopy (SERS) in a sandwich configuration, noble metal/analyte/defect-rich metal oxide, is demonstrated for the detection of methylene blue(MB). The sandwich structure (Ag/MB/SUMoO3) is fabricated by physical vapour deposition of Ag nanoparticles over the MB analytes that are adsorbed on sea urchin MoO3(SUMoO3). SUMoO3are grown on a glass substrate by chemical bath deposition. The morphology of the fabricated sandwich structures shows serrated spikes of MoO3from the core region decorated with strings of silver nanoparticles. The silver-decoration and the oxygen defects of SUMoO3promote absorption in the visible region and facilitate charge transfer between MB and SUMoO3, which are beneficial for achieving superior SERS properties in this configuration compared to the contribution from individual components alone. The sandwich structure is able to detect the MB molecule up to 100 nM with an enhancement factor of 8.1 × 106. The relative standard deviation of SERS intensity for the 1618 cm-1peak of MB across the substrate is 29.2%. The configuration offers stability to SERS substrate under ambient conditions. The combined effect of charge transfer, surface plasmon resonance, and MB resonance results in the improved SERS detection of MB molecules with the Ag/MB/SUMoO3sandwich structure.

An unusual cause of pyrexia of unknown origin with sepsis: A diagnostic challenge.

Sphingobacterium species are ubiquitous and are abundant in nature and rarely involved in causing human infections. A 62-year-old man presented with recurrent episodes of high fever up to 40 â€‹°C accompanied by rigors, sweating, and malaise for the past 4 weeks. After a thorough workup, only elevated C-reactive protein with a leucocytosis was evident. Blood culture showed growth of Gram-negative bacilli which was identified as spingobacterium spiritivorum. Although S. spiritivorum is rare, with limited cases reported in the literature, it must be considered as a causative organism in patients with persistent fevers with sepsis.

The effect of induction immunosuppression for kidney transplant on the latent HIV reservoir.

The HIV latent viral reservoir (LVR) remains a major challenge in the effort to find a cure for HIV. There is interest in lymphocyte-depleting agents, used in solid organ and bone marrow transplantation to reduce the LVR. This study evaluated the LVR and T cell receptor repertoire in HIV-infected kidney transplant recipients using intact proviral DNA assay and T cell receptor sequencing in patients receiving lymphocyte-depleting or lymphocyte-nondepleting immunosuppression induction therapy. CD4+ T cells and intact and defective provirus frequencies decreased following lymphocyte-depleting induction therapy but rebounded to near baseline levels within 1 year after induction. In contrast, these biomarkers were relatively stable over time in the lymphocyte-nondepleting group. The lymphocyte-depleting group had early TCRß repertoire turnover and newly detected and expanded clones compared with the lymphocyte-nondepleting group. No differences were observed in TCRß clonality and repertoire richness between groups. These findings suggest that, even with significant decreases in the overall size of the circulating LVR, the reservoir can be reconstituted in a relatively short period of time. These results, while from a relatively unique population, suggest that curative strategies aimed at depleting the HIV LVR will need to achieve specific and durable levels of HIV-infected T cell depletion.

HOPE in action: A prospective multicenter pilot study of liver transplantation from donors with HIV to recipients with HIV.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States.

BACKGROUND: Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety. METHODS: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors. RESULTS: Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history. CONCLUSION: The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety.

Incidence of Sino-Nasal Symptoms in COVID-19 Patients.

Corona virus disease was first reported in December 2019 in Wuhan, China and is spreading across the world in an alarming fashion. To contain the spread, it is very important to identify the subtle/not readily apparent symptoms of COVID-19 at the earliest. The aim of the study is to determine the incidence duration progress of sino-nasal symptoms in COV 2 positive patients using SNAQ scoring. Patients who tested positive for SARS-COV 2 by RT-PCR and admitted in our hospital under category A (n = 382) were included in the study. A detailed history was collected from all the patients and sino-nasal assessment questionnaire (SNAQ) was provided to the patient with complaints of sinonasal symptoms and they were asked to fill the forms on day 3, 7 and 14. To identify the characteristics of sinonasal symptoms in COVID-19 patients with a history of smoking, smoking history was also collected in detail and patients were classified based on Brinkman's index into mild, moderate and severe smokers. In this study, the incidence of sinonasal symptoms was 24%. Average SNAQ scoring on day 3 was 30.09 and on day 7 was 12.9 and day 14 is 3.8. There was a decline in score on day 7 compared to day 3 indicating symptoms decrease by day7. Average SNAQ scoring in non-smokers and mild and moderate smokers was 20.18, 34.11, 57.5 respectively. The SNAQ scoring in smokers was more than that of non-smokers and was also persistent for a longer duration compared to non-smokers. Sino-nasal symptoms catch our eye because it is an important route for transmission. Viral shedding from sinonasal tract may be an important source for transmission. History and degree of smoking should also be considered while dividing COVID-19 patients into categories.

Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients.

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Behavioral Approaches to Study Top-Down Influences on Active Listening.

The massive network of descending corticofugal projections has been long-recognized by anatomists, but their functional contributions to sound processing and auditory-guided behaviors remain a mystery. Most efforts to characterize the auditory corticofugal system have been inductive; wherein function is inferred from a few studies employing a wide range of methods to manipulate varying limbs of the descending system in a variety of species and preparations. An alternative approach, which we focus on here, is to first establish auditory-guided behaviors that reflect the contribution of top-down influences on auditory perception. To this end, we postulate that auditory corticofugal systems may contribute to active listening behaviors in which the timing of bottom-up sound cues can be predicted from top-down signals arising from cross-modal cues, temporal integration, or self-initiated movements. Here, we describe a behavioral framework for investigating how auditory perceptual performance is enhanced when subjects can anticipate the timing of upcoming target sounds. Our first paradigm, studied both in human subjects and mice, reports species-specific differences in visually cued expectation of sound onset in a signal-in-noise detection task. A second paradigm performed in mice reveals the benefits of temporal regularity as a perceptual grouping cue when detecting repeating target tones in complex background noise. A final behavioral approach demonstrates significant improvements in frequency discrimination threshold and perceptual sensitivity when auditory targets are presented at a predictable temporal interval following motor self-initiation of the trial. Collectively, these three behavioral approaches identify paradigms to study top-down influences on sound perception that are amenable to head-fixed preparations in genetically tractable animals, where it is possible to monitor and manipulate particular nodes of the descending auditory pathway with unparalleled precision.

Advancing organ transplantation through HIV-to-HIV transplantation.

PURPOSE OF REVIEW: Persons living with HIV (PLWH) have a life expectancy that is nearly equivalent to the general population, and thus are facing health conditions associated with normal aging as well as long-term HIV infection. End-organ disease is associated with significant morbidity and mortality and solid organ transplantation (SOT) may be a viable option for many PLWH. We review the history and recent updates in SOT in PLWH, specifically focusing on HIV-to-HIV transplantation. RECENT FINDINGS: Following promising data out of South Africa and to expand the donor pool, the United States passed the HIV Organ Procurement Equity (HOPE) Act, allowing for HIV-to-HIV SOT. Preliminary data to date, especially in HIV-to-HIV kidney transplantation, suggest overall excellent patient and graft survival outcomes with no HIV breakthrough infection. SUMMARY: Preliminary HIV D+R+ SOT data to date suggest promising patient outcomes and no significant adverse events to recipients or living donors. This is an important step in expanding the donor pool and increasing opportunity for SOT in PLWH.

Inverted central auditory hierarchies for encoding local intervals and global temporal patterns.

In sensory systems, representational features of increasing complexity emerge at successive stages of processing. In the mammalian auditory pathway, the clearest change from brainstem to cortex is defined by what is lost, not by what is gained, in that high-fidelity temporal coding becomes increasingly restricted to slower acoustic modulation rates.1,2 Here, we explore the idea that sluggish temporal processing is more than just an inability for fast processing, but instead reflects an emergent specialization for encoding sound features that unfold on very slow timescales.3,4 We performed simultaneous single unit ensemble recordings from three hierarchical stages of auditory processing in awake mice - the inferior colliculus (IC), medial geniculate body of the thalamus (MGB) and primary auditory cortex (A1). As expected, temporal coding of brief local intervals (0.001 - 0.1 s) separating consecutive noise bursts was robust in the IC and declined across MGB and A1. By contrast, slowly developing (∼1 s period) global rhythmic patterns of inter-burst interval sequences strongly modulated A1 spiking, were weakly captured by MGB neurons, and not at all by IC neurons. Shifts in stimulus regularity were not represented by changes in A1 spike rates, but rather in how the spikes were arranged in time. These findings show that low-level auditory neurons with fast timescales encode isolated sound features but not the longer gestalt, while the extended timescales in higher-level areas can facilitate sensitivity to slower contextual changes in the sensory environment.

Ethical rationing of healthcare resources during COVID-19 outbreak: Review.

While rationing of healthcare resources is inevitable even in the most developed economies, particularly on the wake of a pandemic, ethical basis of its implementation needs to be reviewed. With sudden and huge demand for drugs and medical supplies and equipments, the need for rationing arises and thus the concept becomes unavoidable. Thus, we aimed to review and analyse on the key ethical issues in the concept of healthcare rationing. Our search in various PubMed databases resulted articles explaining on the concept of strategizing the priorities based on universal ethical principles of justice, benevolence and ensuring equality rather than wealth, power, geographical location or other personal biases. Concrete and pragmatic regulations and guidelines for systematic rationing have to be framed and followed. In addition, physicians being sensitive and empowered on deciding bedside rationing in coordination with the recommendations of ethicists and healthcare officials, will ensure fair practice.

Coronavirus Disease 2019 in Solid Organ Transplant: A Multicenter Cohort Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described. METHODS: We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. RESULTS: Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7-5.5, P < .001], congestive heart failure [aOR 3.2, 95% CI 1.4-7.0, P = .004], chronic lung disease [aOR 2.5, 95% CI 1.2-5.2, P = .018], obesity [aOR 1.9, 95% CI 1.0-3.4, P = .039]) and presenting findings (lymphopenia [aOR 1.9, 95% CI 1.1-3.5, P = .033], abnormal chest imaging [aOR 2.9, 95% CI 1.1-7.5, P = .027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality. CONCLUSIONS: Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.