Neurocognitive screening in patients following SARS-CoV-2 infection: tools for triage.

BACKGROUND: Cognitive complaints are common in patients recovering from Coronavirus Disease 2019 (COVID-19), yet their etiology is often unclear. We assess factors that contribute to cognitive impairment in ambulatory versus hospitalized patients during the sub-acute stage of recovery. METHODS: In this cross-sectional study, participants were prospectively recruited from a hospital-wide registry. All patients tested positive for SARS-CoV-2 infection using a real-time reverse transcriptase polymerase-chain-reaction assay. Patients ≤ 18 years-of-age and those with a pre-existing major neurocognitive disorder were excluded. Participants completed an extensive neuropsychological questionnaire and a computerized cognitive screen via remote telemedicine platform. Rates of subjective and objective neuropsychological impairment were compared between the ambulatory and hospitalized groups. Factors associated with impairment were explored separately within each group. RESULTS: A total of 102 patients (76 ambulatory, 26 hospitalized) completed the symptom inventory and neurocognitive tests 24 ± 22 days following laboratory confirmation of SARS-CoV-2 infection. Hospitalized and ambulatory patients self-reported high rates of cognitive impairment (27-40%), without differences between the groups. However, hospitalized patients showed higher rates of objective impairment in visual memory (30% vs. 4%; p = 0.001) and psychomotor speed (41% vs. 15%; p = 0.008). Objective cognitive test performance was associated with anxiety, depression, fatigue, and pain in the ambulatory but not the hospitalized group. CONCLUSIONS: Focal cognitive deficits are more common in hospitalized than ambulatory patients. Cognitive performance is associated with neuropsychiatric symptoms in ambulatory but not hospitalized patients. Objective neurocognitive measures can provide essential information to inform neurologic triage and should be included as endpoints in clinical trials.

Histologic acute graft pyelonephritis after kidney transplantation: Incidence, clinical characteristics, risk factors, and association with graft loss.

BACKGROUND: Histologic acute graft pyelonephritis (HAGPN) after kidney transplantation (KT) has been assessed less frequently than urinary tract infections (UTIs) or clinical acute graft pyelonephritis. Risk factors for HAGPN, its association with graft loss, and measures that might prevent it are not known. METHODS: We performed a retrospective review of HAGPN cases identified from KT occurring between January 2008 and December 2017 at our institution. We compared the HAGPN cases to a randomly selected control group of KTs to identify risk factors using univariate and multivariate Cox regression models. The association between HAGPN and graft loss was also assessed, similarly. RESULTS: HAGPN was identified in 46 of 1391 patients (cumulative incidence, 5% [95% CI, 3%-7%]) undergoing KT at a single center from January 2008 through December 2017 (median time to diagnosis, 241 days after KT; interquartile range, 122-755 days). Indications for biopsy were follow-up of treated rejection (n = 20 [43%]), KT protocol biopsy (n = 19 [41%]), and acute kidney injury (n = 7 [15%]). Histologic rejection, UTI, and asymptomatic bacteriuria (ASB) were present in 23 (50%), 9 (20%), and 16 (35%). Multivariate Cox proportional hazards models comparing KT recipients with or without HAGPN (n = 46 and n = 138, respectively) showed that HAGPN was associated with urologic complication by day 30, delayed graft function, previous UTI or ASB, and a history of rejection. In the univariate and multivariate analyses, HAGPN was associated with an increased risk of graft loss. CONCLUSION: HAGPN is an infrequent, unanticipated, and clinically significant complication of KT.

Antibiotic stewardship: Early discontinuation of antibiotics based on procalcitonin level in COVID-19 pneumonia.

WHAT IS KNOWN AND OBJECTIVE: Procalcitonin (PCT) levels rise in systemic inflammation, especially if bacterial in origin. COVID-19, caused by the novel coronavirus SARS-CoV-2, presents with acute respiratory distress syndrome. Elevated procalcitonin in COVID-19 is considered as a marker for severity of disease. There is no study available that indicates whether elevated PCT in COVID-19 is associated with inflammation or superimposed bacterial infection. The objective of this study is to evaluate the association between PCT levels and superadded bacterial infection, and the effect of discontinuation of antibiotic in the low PCT (<0.25 ng/ml) group on patients' outcomes. METHODS: A retrospective chart review of patients admitted with COVID-19 pneumonia at a single tertiary care centre. We collected information on demographics, co-morbidities, PCT level, antibiotic use, culture results for bacterial infection, hospital length of stay (LOS) and mortality. STATISTICAL ANALYSIS: Continuous variables were summarized with the sample median, interquartile range, mean and range. Categorical variables were summarized with number and percentage of patients. RESULTS AND DISCUSSION: We studied a total of 147 patients with COVID-19 pneumonia. 101 (69%) patients had a low PCT level (< 0.25 ng/ml). Bacterial culture results were negative for all patients, except 1 who had a markedly elevated PCT level (141.ng/ml). In patients with low PCT, 42% received no antibiotics, 59% received antibiotics initially, 32 (57%) patients antibiotic discontinued early (within 24 hours) and their culture remained negative for bacterial infections during hospitalizations. LOS was shorter (6 days in low PCT group compared to 9 days) in high PCT group. LOS was 1 day shorter (5 days vs 6 days) in no antibiotic group compared to antibiotic group. Our study examines the association between PCT level and superadded bacterial infection in COVID-19 pneumonia. Our results demonstrate that most patients admitted with COVID-19 have a low PCT (<0.25 ng/ml), which suggests no superadded bacterial infection and supports the previously published literature regarding low PCT in viral pneumonia. WHAT IS NEW AND CONCLUSION: Procalcitonin level remains low in the absence of bacterial infection. Early de-escalation/discontinuation of antibiotics is safe without adverse outcomes in COVID-19 pneumonia. Early de-escalation/discontinuation of antibiotics is associated with lower LOS.

Bordetella bronchiseptica bloodstream infection in a renal transplant patient.

Bordetella bronchiseptica is a gram-negative coccobacillus that infects animals, but rarely affects humans. B. bronchiseptica has been reported to cause disease in immunocompromised hosts. We present a case of a 61-year-old man with a renal transplant who developed B. bronchiseptica bacteremia likely as a result of close contact between dogs and his skin cancer biopsy sites. The patient was successfully treated with 2 weeks of oral levofloxacin. This case alerts physicians to B. bronchiseptica as a cause of bacteremia in solid organ transplant patients with exposure to animals.

Disseminated mycobacterial infections after tumor necrosis factor inhibitor use, revealing inborn errors of immunity.

Tumor necrosis factor-a inhibitors can be associated with increased risk of infections, particularly reactivation of latent tuberculosis or nontuberculous mycobacterium (NTM). However, because disseminated NTM is rare, inborn errors of immunity should be considered. We present three patients with disseminated NTM after tumor necrosis factor-a inhibitor use who were found to have inborn errors of immunity.

Severe Mpox Proctitis Complicated by Bowel Obstruction.

Mpox is a rare infection caused by the zoonotic orthopoxvirus. We present the case of a 44-year-old man with HIV and a history of kidney transplant who presented with mpox and developed proctitis-associated bowel obstruction, urinary retention, and eosinophilia. Our case highlights potential gastrointestinal manifestations of severe mpox infection.

Neurophenotypes of COVID-19: risk factors and recovery outcomes.

Coronavirus disease 2019 (COVID-19) infection is associated with risk of persistent neurocognitive and neuropsychiatric complications, termed "long COVID". It is unclear whether the neuropsychological manifestations of COVID-19 present as a uniform syndrome or as distinct neurophenotypes with differing risk factors and recovery outcomes. We examined post-acute neuropsychological profiles following SARS-CoV-2 infection in 205 patients recruited from inpatient and outpatient populations, using an unsupervised machine learning cluster analysis, with objective and subjective measures as input features. This resulted in three distinct post-COVID clusters. In the largest cluster (69%), cognitive functions were within normal limits, although mild subjective attention and memory complaints were reported. Vaccination was associated with membership in this "normal cognition" phenotype. Cognitive impairment was present in the remaining 31% of the sample but clustered into two differentially impaired groups. In 16% of participants, memory deficits, slowed processing speed, and fatigue were predominant. Risk factors for membership in the "memory-speed impaired" neurophenotype included anosmia and more severe COVID-19 infection. In the remaining 15% of participants, executive dysfunction was predominant. Risk factors for membership in this milder "dysexecutive" neurophenotype included disease-nonspecific factors such as neighborhood deprivation and obesity. Recovery outcomes at 6-month follow-up differed across neurophenotypes, with the normal cognition group showing improvement in verbal memory and psychomotor speed, the dysexecutive group showing improvement in cognitive flexibility, and the memory-speed impaired group showing no objective improvement and relatively worse functional outcomes compared to the other two clusters. These results indicate that there are multiple post-acute neurophenotypes of long COVID, with different etiological pathways and recovery outcomes. This information may inform phenotype-specific approaches to treatment.

Neurophenotypes of COVID-19: Risk factors and recovery outcomes.

Coronavirus disease 2019 (COVID-19) infection is associated with risk of persistent neurocognitive and neuropsychiatric complications. It is unclear whether the neuropsychological manifestations of COVID-19 present as a uniform syndrome or as distinct neurophenotypes with differing risk factors and recovery outcomes. We examined post-acute neuropsychological profiles following SARS-CoV-2 infection in 205 patients recruited from inpatient and outpatient populations, using an unsupervised machine learning cluster analysis, with objective and subjective measures as input features. This resulted in three distinct post-COVID clusters. In the largest cluster (69%), cognitive functions were within normal limits, although mild subjective attention and memory complaints were reported. Vaccination was associated with membership in this "normal cognition" phenotype. Cognitive impairment was present in the remaining 31% of the sample but clustered into two differentially impaired groups. In 16% of participants, memory deficits, slowed processing speed, and fatigue were predominant. Risk factors for membership in the "memory-speed impaired" neurophenotype included anosmia and more severe COVID-19 infection. In the remaining 15% of participants, executive dysfunction was predominant. Risk factors for membership in this milder "dysexecutive" neurophenotype included disease-nonspecific factors such as neighborhood deprivation and obesity. Recovery outcomes at 6-month follow-up differed across neurophenotypes, with the normal cognition group showing improvement in verbal memory and psychomotor speed, the dysexecutive group showing improvement in cognitive flexibility, and the memory-speed impaired group showing no objective improvement and relatively worse functional outcomes compared to the other two clusters. These results indicate that there are multiple post-acute neurophenotypes of COVID-19, with different etiological pathways and recovery outcomes. This information may inform phenotype-specific approaches to treatment.

Neurocognitive Screening in Patients Following SARS-CoV-2 Infection: Tools for Triage.

Background and purpose Cognitive complaints are common in patients recovering from Coronavirus Disease 2019 (COVID-19), yet their etiology is often unclear. We assess factors that contribute to cognitive impairment in ambulatory versus hospitalized patients during the sub-acute stage of recovery. Methods Participants were prospectively recruited from a hospital-wide registry. All patients tested positive for SARS-CoV-2 infection using a real-time reverse transcriptase polymerasechain-reaction assay. Patients ≤ 18 years-of-age and those with a pre-existing major neurocognitive disorder were excluded. Participants completed an extensive neuropsychological questionnaire and a computerized cognitive screen via remote telemedicine platform. Rates of subjective and objective neuropsychological impairment were compared between the ambulatory and hospitalized groups. Factors associated with impairment were explored separately within each group. Results A total of 102 patients (76 ambulatory, 26 hospitalized) completed the symptom inventory and neurocognitive tests 24 ± 22 days following laboratory confirmation of SARSCoV-2 infection. Hospitalized and ambulatory patients self-reported high rates of cognitive impairment (27-40%), without differences between the groups. However, hospitalized patients showed higher rates of objective impairment in visual memory (30% vs. 4%; p=0.001) and psychomotor speed (41% vs. 15%; p=0.008). Objective cognitive test performance was associated with anxiety, depression, fatigue, and pain in the ambulatory but not the hospitalized group. Conclusions Focal cognitive deficits are more common in hospitalized than ambulatory patients. Cognitive performance is associated with neuropsychiatric symptoms in ambulatory but not hospitalized patients. Objective neurocognitive measures can provide essential information to inform neurologic triage and should be included as endpoints in clinical trials.

Disseminated cryptococcosis in a patient with newly diagnosed HTLV-1 infection.

Infection by human T-lymphotropic virus 1 (HTLV-1) is often seen as the cause of chronic infection or lymphoproliferative disorders, but many clinicians do not recognise its association with severe immunosuppression. We report the case of a woman in her 70s from the Caribbean who sought care at the emergency department for weakness, fatigue and weight loss. Further work-up showed atypical lymphocytosis with floral lymphocytes and smudge cells in the peripheral blood smear and hypercalcaemia. Chest CT demonstrated a moderate right pleural effusion. Results of HIV testing were negative, and screening and confirmatory tests for HTLV-1 were positive. Empiric antibiotic therapy was administered, and the patient was discharged home. Five days later, she was readmitted with shortness of breath and severe abdominal pain. A disseminated infection with Cryptococcus neoformans was diagnosed. Despite aggressive intravenous antifungal therapy, the patient died on day 7 of hospitalisation.

Reduction in Health Care Facility-Onset Clostridioides difficile Infection: A Quality Improvement Initiative.

OBJECTIVE: To reduce health care facility-onset (HCFO) Clostridioides difficile infection (CDI) incidence by improving diagnostic stewardship and reducing the inappropriate testing of C difficile assays. PATIENTS AND METHODS: A multidisciplinary team conducted a quality improvement initiative from January 1, 2020, through March 31, 2021. Clostridioides difficile infection and inappropriate testing were identified via electronic health records using predefined criteria related to stool quantity/caliber, confounding medications, and laboratory data. An intervention bundle was designed including (1) provider education, (2) implementation of an appropriate testing algorithm, (3) expert review of C difficile orders, and (4) batch testing of assays to facilitate review and cancellation if inappropriate. RESULTS: Compared with a baseline period from January to September 2020, implementation of our intervention bundle from December 2020 to March 2021 resulted in an 83.6% reduction in inappropriate orders tested and a 41.7% reduction in HCFO CDI incidence. CONCLUSION: A novel prevention bundle improved C difficile diagnostic stewardship and HCFO CDI incidence by reducing testing of inappropriate orders. Such initiatives targeting HCFO CDI may positively affect patient safety and hospital reimbursement.

Neurobrucellosis associated with feral swine hunting in the southern United States.

Although uncommon, Brucella infection can occur outside the areas of high endemicity, such as the USA. In the southern USA, hunters of wild swine are at risk for brucellosis. We present a case of a patient with fever, headache and constitutional symptoms that were ongoing for 11 months. He was diagnosed with neurobrucellosis. The patient was treated successfully with intravenous ceftriaxone, oral doxycycline and oral rifampin therapy. He had persistent neurological sequelae after completing treatment. This case illustrates the high index of suspicion needed to diagnose neurobrucellosis in a non-endemic country because initial symptoms can be subtle. The disease can be treated successfully, but long-lasting neurological sequelae are common.

Tuberculosis presenting as dacryoadenitis in the USA.

A 25-year-old Filipino woman living in the USA was evaluated for a 5-month history of left eye pain and a subsequent orbital mass. Histopathological analysis of the lacrimal mass showed a mixed inflammatory process with necrotising granulomas and positive cultures for Mycobacterium tuberculosis She was treated with antituberculosis therapy, with resolution of symptoms. Tuberculosis dacryoadenitis is extremely rare in the USA and other developed countries. It requires a high degree of clinical suspicion with special attention to the patient's history to make the correct diagnosis. It can be treated successfully with antituberculosis therapy.

Hematochezia: An Uncommon Presentation of Colonic Tuberculosis.

Abdominal tuberculosis (TB) is an uncommon entity in the United States. Colonic TB is reported in 2-3% of patients with abdominal TB. It is frequently misdiagnosed as Crohn's disease or carcinoma of the colon due to their shared clinical, radiographic, and endoscopic presentations. We present a case of a 72-year-old male with colonic tuberculosis presenting as hematochezia. Our patient presented with shortness of breath and weight loss. Chest X-ray demonstrated ill-defined bilateral parenchymal opacities in the perihilar, mid, and lower lung zones. The patient was diagnosed and treated for community acquired pneumonia, with no improvement. Hematochezia complicated by symptomatic hypotension developed later in the course of admission. Colonoscopy revealed multiple ulcers at the anus and transverse and ascending colon as well as the cecum with stigmata of bleeding. Biopsy of a sigmoid ulcer was consistent with colonic tuberculosis. Antitubercular therapy was initiated, but the patient passed away secondary to multiorgan failure 29 days into admission.

Identification of SUMO modification sites in the base excision repair protein, Ntg1.

DNA damaging agents are a constant threat to genomes in both the nucleus and the mitochondria. To combat this threat, a suite of DNA repair pathways cooperate to repair numerous types of DNA damage. If left unrepaired, these damages can result in the accumulation of mutations which can lead to deleterious consequences including cancer and neurodegenerative disorders. The base excision repair (BER) pathway is highly conserved from bacteria to humans and is primarily responsible for the removal and subsequent repair of toxic and mutagenic oxidative DNA lesions. Although the biochemical steps that occur in the BER pathway have been well defined, little is known about how the BER machinery is regulated. The budding yeast, Saccharomyces cerevisiae is a powerful model system to biochemically and genetically dissect BER. BER is initiated by DNA N-glycosylases, such as S. cerevisiae Ntg1. Previous work demonstrates that Ntg1 is post-translationally modified by SUMO in response to oxidative DNA damage suggesting that this modification could modulate the function of Ntg1. In this study, we mapped the specific sites of SUMO modification within Ntg1 and identified the enzymes responsible for sumoylating/desumoylating Ntg1. Using a non-sumoylatable version of Ntg1, ntg1ΔSUMO, we performed an initial assessment of the functional impact of Ntg1 SUMO modification in the cellular response to DNA damage. Finally, we demonstrate that, similar to Ntg1, the human homologue of Ntg1, NTHL1, can also be SUMO-modified in response to oxidative stress. Our results suggest that SUMO modification of BER proteins could be a conserved mechanism to coordinate cellular responses to DNA damage.

Azacitidine as salvage therapy for acute myeloid leukemia in a severely ill patient.

Acute myeloid leukemia (AML) is a hematological malignancy of myeloid progenitor cells that disrupt normal hematopoiesis. Current chemotherapy regimens result in complete remission in many cases; however, there exists no standard efficacious therapy for refractory acute myeloid leukemia. The hypomethylating agent, azacitidine, is effective in a limited number of such cases. We present a 57-year-old Filipino male with acute myeloid leukemia who was refractory to two induction chemotherapy regimens; however, he achieved complete remission after palliative therapy with azacitidine. We report this case to demonstrate the efficacy of azacitidine in refractory acute myeloid leukemia. Although the effectiveness of azacitidine in improving overall survival has been shown, this case demonstrates the effect on remission induction in high risk AML. Further studies are needed to delineate subsets of acute myeloid leukemia in which azacitidine will serve as effective therapy and to identify other targeted agents that may potentiate its effects.