Organ recovery from deceased donors with prior COVID-19: A case series.

Although guidance documents have been published regarding organ donation from individuals with a prior history of COVID-19 infection, no data exist regarding successful recovery and transplantation from deceased donors with a history of or positive testing suggesting a prior SARS-CoV-2 infection. Here, we report a case series of six deceased donors with a history of COVID-19 from whom 13 organs were recovered and transplanted through several of the nation's organ procurement organizations (OPOs). In addition, at least two potential donors were authorized for donation but with no organs were successfully allocated and did not proceed to recovery. No transmission of SARS-CoV-2 was reported from the six donors to recipients, procurement teams, or hospital personnel. Although more studies are needed, organ donation from deceased donors who have recovered from COVID-19 should be considered.

There are no best practices in a pandemic: Organ donation within the COVID-19 epicenter.

LiveOnNY, the organ procurement organization (OPO) for the greater New York metropolitan area, suspended several best practices to manage the rising referrals of deaths from hospitals during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. On April 2, 2020 hospitals in the donor service area were notified that coronavirus disease 2019 (COVID-19) referrals should be deferred. Still, only 2% of referred patients to the OPO in April 2020 were on ventilators and considered possible organ donors, versus a baseline of 11% in 2019. Few of these deaths were unrelated to COVID-19. Accordingly, organ donors declined to 10 in April (from 26 in March). Despite the exclusion of marginal donors and organs, the implementation of COVID-19 donor testing, and the availability of local procurement surgeons, only 1 organ (a liver) was accepted by a transplant center outside of New York State and 8 organs (5 livers, 4 kidneys) were transplanted in state; 11 organs (1 liver, 10 kidneys) were discarded. Allocation was unsuccessful for 11 additional organs (1 liver, 4 kidneys, 4 hearts, 2 lungs). Despite the obstacles, organ donation remained an important model of collaboration and satisfaction for the health care community in the pandemic's US epicenter. Declining COVID-19 deaths led to the resumption of the comprehensive referral policy on May 6, 2020, with improvement to 18 donors in May.

Human Lymph Nodes Maintain TCF-1hi Memory T Cells with High Functional Potential and Clonal Diversity throughout Life.

Translating studies on T cell function and modulation from mouse models to humans requires extrapolating in vivo results on mouse T cell responses in lymphoid organs (spleen and lymph nodes [LN]) to human peripheral blood T cells. However, our understanding of T cell responses in human lymphoid sites and their relation to peripheral blood remains sparse. In this study, we used a unique human tissue resource to study human T cells in different anatomical compartments within individual donors and identify a subset of memory CD8+ T cells in LN, which maintain a distinct differentiation and functional profile compared with memory CD8+ T cells in blood, spleen, bone marrow, and lungs. Whole-transcriptome and high-dimensional cytometry by time-of-flight profiling reveals that LN memory CD8+ T cells express signatures of quiescence and self-renewal compared with corresponding populations in blood, spleen, bone marrow, and lung. LN memory T cells exhibit a distinct transcriptional signature, including expression of stem cell-associated transcription factors TCF-1 and LEF-1, T follicular helper cell markers CXCR5 and CXCR4, and reduced expression of effector molecules. LN memory T cells display high homology to a subset of mouse CD8+ T cells identified in chronic infection models that respond to checkpoint blockade immunotherapy. Functionally, human LN memory T cells exhibit increased proliferation to TCR-mediated stimulation and maintain higher TCR clonal diversity compared with memory T cells from blood and other sites. These findings establish human LN as reservoirs for memory T cells with high capacities for expansion and diverse recognition and important targets for immunotherapies.

Isolation of antibiotic-resistant gram-negative organisms from donor respiratory culture does not impact non-lung solid organ recipient management.

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) gram-negative bacteria may be transmitted from organ donors to solid organ transplant recipients and are associated with poor outcomes post-transplant. METHODS: We reported the prevalence of MDR/XDR gram-negative respiratory colonization among 702 deceased organ donors in the New York City area from 2011 to 2014 and performed chart reviews for a subset of recipients to determine whether donor respiratory culture results were predictive of subsequent recipient infection or used to guide post-transplant antimicrobial therapy. RESULTS: Fifty donors (7% of the cohort) had MDR or XDR gram-negative bacteria isolated from endotracheal aspirate or bronchoalveolar lavage culture. Organs from these 50 donors were transplanted into 120 recipients; chart review was performed for 89 of these recipients (38 kidney, 32 liver, 11 heart, 6 kidney/pancreas, 1 liver/kidney, 1 lung). None of the 89 recipients of organs from donors with MDR/XDR gram-negative respiratory colonization were reported to have a donor-derived infection post-transplant, and chart review for the 88 non-lung recipients indicated that peri-transplant antibiotics were not adjusted specifically for donor respiratory culture results. CONCLUSION: These results suggest that donor respiratory culture results are not predictive of post-transplant infection in non-lung recipients and are unlikely to impact post-transplant management.

Cautious renal transplantation for the elderly is realistic.

Excellent results of transplantation in elderly recipients, together with regulatory requirements encourage continued consideration of this modality. The organ shortage compels the use of deceased-donor kidneys and may be a suboptimal therapy. However, the elderly patient may not tolerate the prolonged wait for an optimal organ. While individual comorbidities can be evaluated, patient selection requires the transplantation team to render a judgment based on the candidate's overall condition, which is best correlated with the ability to accomplish activities of daily living and to perform moderate exercise. Psychosocial considerations are complex in the elderly patient because of frequent dementia, absence of a sufficient support mechanism and the need for more resources than those required by younger patients. After transplantation, appropriate management of immunosuppression typically entails lower doses in elderly patients, a logical consequence of immunosenescence. Transplantation should not be considered an acceptable exercise in futility when the ability to offer this life-saving therapy to other patients will be adversely affected by doing so.

Spontaneous Production Rates in Music and Speech.

Individuals typically produce auditory sequences, such as speech or music, at a consistent spontaneous rate or tempo. We addressed whether spontaneous rates would show patterns of convergence across the domains of music and language production when the same participants spoke sentences and performed melodic phrases on a piano. Although timing plays a critical role in both domains, different communicative and motor constraints apply in each case and so it is not clear whether music and speech would display similar timing mechanisms. We report the results of two experiments in which adult participants produced sequences from memory at a comfortable spontaneous (uncued) rate. In Experiment 1, monolingual pianists in Buffalo, New York engaged in three production tasks: speaking sentences from memory, performing short melodies from memory, and tapping isochronously. In Experiment 2, English-French bilingual pianists in Montréal, Canada produced melodies on a piano as in Experiment 1, and spoke short rhythmically-structured phrases repeatedly. Both experiments led to the same pattern of results. Participants exhibited consistent spontaneous rates within each task. People who produced one spoken phrase rapidly were likely to produce another spoken phrase rapidly. This consistency across stimuli was also found for performance of different musical melodies. In general, spontaneous rates across speech and music tasks were not correlated, whereas rates of tapping and music were correlated. Speech rates (for syllables) were faster than music rates (for tones) and speech showed a smaller range of spontaneous rates across individuals than did music or tapping rates. Taken together, these results suggest that spontaneous rate reflects cumulative influences of endogenous rhythms (in consistent self-generated rates within domain), peripheral motor constraints (in finger movements across tapping and music), and communicative goals based on the cultural transmission of auditory information (slower rates for to-be-synchronized music than for speech).

Reassessing marketing of kidneys from the 2008 perspective.

Progressive improvements in all aspects of the kidney transplant regimen establish this form of renal replacement therapy as superior to peritoneal or hemodialysis in terms of extent of rehabilitation and long-term recipient survival. Continuous growth in the number of patients with kidney failure sustained by dialytic therapy has not been associated with substantially increased deceased donor kidney contributions, causing intensified stressful waiting periods for potential recipients lacking a live kidney donor. Neither public relation campaigns nor local government efforts have substantially increased kidney donation. Buying a donor kidney is illegal and condemned as fostering exploitation of poor people by the wealthy. Widely publicized examples of coercion of unwilling donors create a negative image of harmful, inhumane conduct deployed to obtain kidneys sold and transplanted under unsavory circumstances. Yet efforts to establish and test governmental programs to supervise and sustain acceptable standards for the sale and implantation of kidneys from fully informed, medically evaluated and protected, fairly compensated donors have been resisted and frustrated by those who consider such compensation loathsome. Accordingly, while selling kidneys is prohibited by law, pressure from those wanting to quench the number of deaths of wait-listed dialysis patients continues forcing reexamination of an issue that, like prohibition of the possession and sale of alcohol in the United States in 1920, places the will of a people in opposition to unreasonably restrictive laws. The debate continues.

Effects of adolescent Δ9-tetrahydrocannabinol exposure on the behavioral effects of cocaine in adult Sprague-Dawley rats.

Cannabis is the most popular, illegal drug used by adolescents in the United States. Exposure to cannabis and its main psychoactive ingredient, Δ9-tetrahydrocannabinol (THC), during adolescence may have long-lasting effects on the development of behavioral and neurobiological processes. This study investigated the effects of chronic adolescent exposure to THC on sensitization to the psychomotor-stimulating effects of cocaine and on the reinforcing effects of cocaine in adult male Sprague-Dawley rats. During adolescence (P28-P45), rats were given once-daily intraperitoneal injections of either vehicle or 1 mg/kg THC. On P90, the acute locomotor-stimulating effects of cocaine and sensitization to cocaine were evaluated. Also, cocaine-maintained behavior was evaluated by determining within-session cocaine dose-effect curves, acquisition of behavior maintained by a small cocaine dose (0.1 mg/kg/infusion), and breakpoints on a progressive ratio schedule of reinforcement. In general, there was no effect of adolescent THC exposure on the locomotor-stimulating effects of cocaine following acute or repeated administration. However, the reinforcing effects of cocaine were potentiated in rats treated with THC during adolescence, but this effect was only observed with small doses of cocaine. Rats exposed to THC during adolescence also more rapidly acquired self-administration behavior when a small cocaine dose was available. Together, these results demonstrate that exposure to THC during adolescence may enhance sensitivity to cocaine and/or enhance the reinforcing effects of cocaine even into adulthood under certain conditions. In conclusion, frequent exposure to THC during adolescence may produce long-lasting changes in behavior, possibly increasing susceptibility to addiction. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Patient access to transplantation with an Internet-identified live kidney donor: a survey of U.S. centers.

BACKGROUND: To investigate legitimate transplantation in the United States with an Internet-identified live donor organ, from the patient's perspective, kidney centers were contacted by a researcher posing as an ideal patient and recipient pair seeking to find a center to perform their transplant. METHODS: Responses were obtained with fewer than three phone calls and within less than 2 wk from 100 of 206 UNOS listed centers; 42 pediatric or inactive centers were excluded. RESULTS: A total of 37% (76 of 100) indicated a willingness to consider such a transplant. Eight centers acknowledged having previously performed one, with 100% (8/8) of these indicating that they would still consider future participation. CONCLUSION: Large numbers of Internet-facilitated transplants are not yet being performed in the United States. Because it was possible to elicit a definite answer with 3 or fewer calls at only 49% of centers, we conclude that a significant proportion of centers are not providing easy access to potential donors and recipients. Agreeable centers were clustered geographically, suggesting that multiple factors may be influencing opinions. 100% of agreeable centers required their own standard evaluation of the donor and recipient and indicated that financial exchange between the pair was illegal. We conclude that Internet-based live donor kidney transplants are occurring and have received cautious acceptance at a significant number of legitimate centers. The utility of asking "How did the recipient-donor pair present to our institution" may no longer be relevant. We suggest that every pair seeking access to legitimate transplantation should undergo standardized evaluation with open acknowledgment of the relationship as a modifier.

Medication errors in the outpatient setting: classification and root cause analysis.

OBJECTIVES: To understand and classify causal factors linked to medication errors and to define opportunities for systematic changes to improve the safety of prescription medication use. DESIGN, SETTING, AND PARTICIPANTS: All recipients of liver, kidney, and/or pancreas allografts followed up by an academic medical center and encountered in the acute care facility, outpatient clinic, or by telephone during 12 months (April 1, 2004, through March 31, 2005). Errors were sought by specific review of the expected and actual medication lists. Main Outcome Measure Proportion of medication errors in each of 5 classifications developed through iterative revision. Definitions included failure to provide a correct prescription (prescription error); deliver a prescribed medication to the patient (delivery error); possess enough medication for a 24-hour or greater supply (availability error); accurately use an available, prescribed medication (patient error); and identify the type, dosage, or frequency of a medication (reporting error). RESULTS: We identified 149 errors in 93 patients who were prescribed a mean of 10.9 medications each. Adverse events were associated with 48 errors (32%), including hospitalization (17 patients) or outpatient invasive procedure (3 patients) in 13%. Nine episodes of rejection and 6 failed allografts were identified. The most common error type was patient error in 83 errors (56%) with prescription errors in 20 errors (13%), delivery errors in 20 errors (13%), availability errors in 15 errors (10%), and reporting errors in 12 errors (8%). Root cause analysis identified the patient as the cause in 101 errors (68%) while pharmacies and other sectors of the health care team caused 41 errors (27%). Finances were linked to 7 errors (5%). Error frequency was estimated during 4 weeks of outpatient visits at 15 of 219 visits. CONCLUSIONS: Outpatient medication errors are abundant, often occult, and associated with significant adverse events in a complex transplant population. The health care system is associated with nearly one third of errors.

Brain network dysfunction in youth with obsessive-compulsive disorder induced by simple uni-manual behavior: The role of the dorsal anterior cingulate cortex.

In an effort to elucidate differences in functioning brain networks between youth with obsessive-compulsive disorder and controls, we used fMRI signals to analyze brain network interactions of the dorsal anterior cingulate cortex (dACC) during visually coordinated motor responses. Subjects made a uni-manual response to briefly presented probes, at periodic (allowing participants to maintain a "motor set") or random intervals (demanding reactive responses). Network interactions were assessed using psycho-physiological interaction (PPI), a basic model of functional connectivity evaluating modulatory effects of the dACC in the context of each task condition. Across conditions, OCD were characterized by hyper-modulation by the dACC, with loci alternatively observed as both condition-general and condition-specific. Thus, dynamically driven task demands during simple uni-manual motor control induce compensatory network interactions in cortical-thalamic regions in OCD. These findings support previous research in OCD showing compensatory network interactions during complex memory tasks, but establish that these network effects are observed during basic sensorimotor processing. Thus, these patterns of network dysfunction may in fact be independent of the complexity of tasks used to induce brain network activity. Hypothesis-driven approaches coupled with sophisticated network analyses are a highly valuable approach in using fMRI to uncover mechanisms in disorders like OCD.

Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites.

Tissue-resident memory T cells (TRMs) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRMs remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells constitute a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69+ subset of memory CD4+ and CD8+ T cells in lung and spleen that is distinct from that of CD69- TEM cells in tissues and circulation and defines human TRMs based on homology to the transcriptional profile of mouse CD8+ TRMs. Human TRMs in diverse sites exhibit increased expression of adhesion and inhibitory molecules, produce both pro-inflammatory and regulatory cytokines, and have reduced turnover compared with circulating TEM, suggesting unique adaptations for in situ immunity. Together, our results provide a unifying signature for human TRM and a blueprint for designing tissue-targeted immunotherapies.

An atlas of B-cell clonal distribution in the human body.

B-cell responses result in clonal expansion, and can occur in a variety of tissues. To define how B-cell clones are distributed in the body, we sequenced 933,427 B-cell clonal lineages and mapped them to eight different anatomic compartments in six human organ donors. We show that large B-cell clones partition into two broad networks-one spans the blood, bone marrow, spleen and lung, while the other is restricted to tissues within the gastrointestinal (GI) tract (jejunum, ileum and colon). Notably, GI tract clones display extensive sharing of sequence variants among different portions of the tract and have higher frequencies of somatic hypermutation, suggesting extensive and serial rounds of clonal expansion and selection. Our findings provide an anatomic atlas of B-cell clonal lineages, their properties and tissue connections. This resource serves as a foundation for studies of tissue-based immunity, including vaccine responses, infections, autoimmunity and cancer.

Live and deceased donor kidney transplantation in patients aged 75 years and older in the United States.

OBJECTIVE: To examine the outcomes of geriatric ESRD patients selected for kidney transplantation. DESIGN: Data were extracted from the USRDS Standard Analysis Files (SAF). All persons ages 75 and over who received a kidney transplant from 1994 to 2000 were compared with those remaining on dialysis or on a transplant waiting list. Data on mortality or removal from the waiting list were obtained from the United Network for Organ Sharing (UNOS). The main outcome measure was patient and kidney transplant survival. RESULTS: Superior five year survival after kidney transplantation was attained by the geriatric cohort given a live donor transplant (59.9%), compared with recipients of deceased donor kidneys (40.3%), dialysis patients waiting for transplant (29.7%), and those who were not selected for kidney transplantation and remained on dialysis (12.5%). The likelihood of being removed from the waiting list for any reason was higher in this group (over 75) (30.3%) than in the 66-75 age group (26.8%). Their average annual mortality rate on the waiting list was 7.9, compared to 6.6% for those 66-75. CONCLUSION: Even after the age of 75 years, kidney transplantation provides substantial life prolongation and excellent graft survival.

Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement.

Management of the surgical patient with end-stage renal disease.

For health providers guiding the end-stage renal disease patient's care, conventional surgical and anesthetic principles may demand substantial modifications to optimize both the immediate outcome and long-term survival. Elective operation is conducted in the setting of optimized acid/base balance, volume status and potassium management with pre-operative dialysis completed within 24 hours of the procedure (either hemodialysis or peritoneal dialysis). When peripheral intravenous access is inadequate, central venous access is obtained preferentially through the internal jugular veins because of the catastrophic consequences of catheter-induced subclavian stenosis. Infectious prophylaxis incorporates antibiotic selection considering the lack of native renal drug clearance, the potential for drug loss across dialysis membranes and potential interactions with immunosuppressive medications. Judicious intraoperative blood and fluid replacement should not be so restricted as to permit inadequate end organ perfusion, even if post-operative dialysis is necessitated. Hemostasis may be facilitated by the use of desmopressin to correct uremic platelet dysfunction. Wound closure techniques should accommodate the delayed healing associated with kidney failure and/or iatrogenic immunosuppression.