Active surveillance of serious adverse events following transfusion of COVID-19 convalescent plasma.

BACKGROUND: The reported incidence of adverse reactions following Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) transfusion has generally been lower than expected based on the incidence of transfusion reactions that have been observed in studies of conventional plasma transfusion. This raises the concern for under-reporting of adverse events in studies of CCP that rely on passive surveillance strategies. MATERIALS AND METHODS: Our institution implemented a protocol to actively identify possible adverse reactions to CCP transfusion. In addition, we retrospectively reviewed the charts of inpatients who received CCP at Stanford Hospital between May 13, 2020 and January 31, 2021. We determined the incidence of adverse events following CCP transfusion. RESULTS: A total of 49 patients received CCP. Seven patients (14%) had an increased supplemental oxygen requirement within 4 h of transfusion completion, including one patient who was intubated during the transfusion. An additional 11 patients (total of 18, 37%) had increased oxygen requirements within 24 h of transfusion, including 3 patients who were intubated. Six patients (12%) fulfilled criteria for transfusion-associated circulatory overload (TACO). CONCLUSION: Using an active surveillance strategy, we commonly observed adverse events following the transfusion of CCP to hospitalized patients. It was not possible to definitively determine whether or not these adverse events are related to CCP transfusion. TACO was likely over-diagnosed given overlap with the manifestations of COVID-19. Nevertheless, these results suggest that the potential adverse effects of CCP transfusion may be underestimated by reports from passive surveillance studies.

Characteristics and Outcomes of Coronavirus Disease Patients under Nonsurge Conditions, Northern California, USA, March-April 2020.

Limited data are available on the clinical presentation and outcomes of coronavirus disease (COVID-19) patients in the United States hospitalized under normal-caseload or nonsurge conditions. We retrospectively studied 72 consecutive adult patients hospitalized with COVID-19 in 2 hospitals in the San Francisco Bay area, California, USA, during March 13-April 11, 2020. The death rate for all hospitalized COVID-19 patients was 8.3%, and median length of hospitalization was 7.5 days. Of the 21 (29% of total) intensive care unit patients, 3 (14.3% died); median length of intensive care unit stay was 12 days. Of the 72 patients, 43 (59.7%) had underlying cardiovascular disease and 19 (26.4%) had underlying pulmonary disease. In this study, death rates were lower than those reported from regions of the United States experiencing a high volume of COVID-19 patients.

Fatal Emmonsia sp. Infection and Fungemia after Orthotopic Liver Transplantation.

We report a fatal case of disseminated Emmonsia sp. infection in a 55-year-old man who received an orthotopic liver transplant. The patient had pneumonia and fungemia, and multisystem organ failure developed. As human habitats and the number of immunocompromised patients increase, physicians must be aware of this emerging fungal infection.

Prevention and control of neglected tropical diseases: overview of randomized trials, systematic reviews and meta-analyses.

OBJECTIVE: To analyse evidence from randomized controlled trials (RCTs) on the prevention and control of neglected tropical diseases (NTDs) and to identify areas where evidence is lacking. METHODS: The Cochrane Central Register of Controlled Trials and PubMed were searched for RCTs and the Cochrane Database of Systematic Reviews and PubMed were searched for meta-analyses and systematic reviews, both from inception to 31 December 2012. FINDINGS: Overall, 258 RCTs were found on American trypanosomiasis, Buruli ulcer, dengue, geohelminth infection, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis or trachoma. No RCTs were found on cysticercosis, dracunculiasis, echinococcosis, foodborne trematodes, or human African trypanosomiasis. The most studied diseases were geohelminth infection (51 RCTs) and leishmaniasis (46 RCTs). Vaccines, chemoprophylaxis and interventions targeting insect vectors were evaluated in 113, 99 and 39 RCTs, respectively. Few addressed how best to deliver preventive chemotherapy, such as the choice of dosing interval (10) or target population (4), the population coverage needed to reduce transmission (2) or the method of drug distribution (1). Thirty-one publications containing 32 systematic reviews (16 with and 16 without meta-analyses) were found on American trypanosomiasis, dengue, geohelminths, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, schistosomiasis or trachoma. Together, they included only 79 of the 258 published RCTs (30.6%). Of 36 interventions assessed, 8 were judged effective in more than one review. CONCLUSION: Few RCTs on the prevention or control of the principal NTDs were found. Trials on how best to deliver preventive chemotherapy were particularly rare.

No differences in outcomes with stopping or continuing antibiotic suppression in periprosthetic joint infections.

The data on long-term antibiotic use following debridement, antibiotics, and implant retention (DAIR) for treatment of periprosthetic joint infections are limited. In this single-center retrospective study, we show that patients with eventual cessation of antibiotic suppression after DAIR had similar outcomes to those who remained on chronic antibiotic suppression.

Anticytokine Autoantibodies and Fungal Infections.

Anticytokine autoantibodies (ACAAs) can cause adult onset immunodeficiencies which mimic primary immunodeficiencies and can present as refractory and severe fungal infections. This paper provides an overview of the role of innate immunity, including key cytokines, in fungal infections and then describes four clinical scenarios where ACAAs are associated with severe presentations of a fungal infection: (1) Talaromyces marneffei infection and anti-interferon-γ, (2) histoplasmosis and anti-interferon-γ, (3) Cryptococcus gattii infection and anti-GM-CSF, and (4) mucocutaneous candidiasis and anti-IL-17A/F (IL-22). Testing for ACAAs and potential therapeutic options are discussed.

Selecting a high-dose antibiotic-laden cement knee spacer.

Prosthetic joint infection [PJI] after total knee arthroplasty (TKA) remains a common and challenging problem for joint replacement surgeons and patients. Once the diagnosis of PJI has been made, patient goals and characteristics as well as the infection timeline dictate treatment. Most commonly, this involves a two-stage procedure with the removal of all implants, debridement, and placement of a static or dynamic antibiotic spacer. Static spacers are commonly indicated for older, less healthy patients that would benefit from soft tissue rest after initial debridement. Mobile spacers are typically used in younger, healthier patients to improve quality of life and reduce soft-tissue contractures during antibiotic spacer treatment. Spacers are highly customizable with regard to antibiotic choice, cement variety, and spacer design, each with reported advantages, drawbacks, and indications that will be covered in this article. While no spacer is superior to any other, the modern arthroplasty surgeon must be familiar with the available modalities to optimize treatment for each patient. Here we propose a treatment algorithm to assist surgeons in deciding on treatment for PJI after TKA.

Disparities and Trends in Routine Adult Vaccination Rates Among Disaggregated Asian American Subgroups, National Health Interview Survey 2006-2018.

Introduction: Vaccination rates may be improved through culturally tailored messages, but little is known about them among disaggregated Asian American subgroups. We assessed the vaccination rates for key vaccines among these subgroups. Methods: Using the National Health Interview Survey, we analyzed recent vaccination rates (2015-2018, n=188,250) and trends (2006-2018) among Asians (Chinese [n=3,165], Asian Indian [n=3,525], Filipino [n=3,656], other Asian [n=5,819]) and non-Hispanic White adults (n=172,085) for 6 vaccines (the human papillomavirus, hepatitis B, pneumococcal, influenza, tetanus-diphtheria [tetanus], and shingles vaccines). We controlled demographic, socioeconomic, and health-related variables in multivariable logistic regression and predicted marginal modeling analyses. We also computed vaccination rates among Asian American subgroups on the 2015-2018 National Health Interview Survey data stratified by foreign-born and U.S.-born status. We used Joinpoint regression to analyze trends in vaccination rates. All analyses were conducted in 2021 and 2022. Results: Among Asians, shingles (29.2%; 95% CI=26.6, 32.0), tetanus (53.7%; 95% CI=51.8, 55.6), and pneumococcal (53.8%; 95% CI=50.1, 57.4) vaccination rates were lower than among non-Hispanic Whites. Influenza (47.9%; 95% CI=46.2, 49.6) and hepatitis B (40.5%; 95% CI=39.0, 42.7) vaccination rates were similar or higher than among non-Hispanic Whites (48.4%; 95% CI=47.9, 48.9 and 30.7%; 95% CI=30.1, 31.3, respectively). Among Asians, we found substantial variations in vaccination rates and trends. For example, Asian Indian women had lower human papillomavirus vaccination rates (12.9%; 95% CI=9.1, 18.0) than all other Asian subgroups (Chinese: 37.9%; 95% CI=31.1, 45.2; Filipinos: 38.7%; 95% CI=29.9, 48.3; other Asians: 30.4%; 95% CI=24.8, 36.7) and non-Hispanic Whites (36.1%; 95% CI=34.8, 37.5). Being male, having lower educational attainment and income, having no health insurance or covered by public health insurance only, and lower frequency of doctor visits were generally associated with lower vaccine uptakes. Foreign-born Asian aggregate had lower vaccination rates than U.S.-born Asian aggregate for all vaccines except for influenza. We also found subgroup-level differences in vaccination rates between foreign-born and U.S.-born Asians. We found that (1) foreign-born Chinese, Asian Indians, and other Asians had lower human papillomavirus and hepatitis B vaccination rates; (2) foreign-born Chinese and Filipinos had lower pneumococcal vaccination rates; (3) foreign-born Chinese and Asian Indians had lower influenza vaccination rates; and (4) all foreign-born Asian subgroups had lower tetanus vaccination rates. Conclusions: Vaccination rates and trends differed among Asian American subgroups. Culturally tailored messaging and interventions may improve vaccine uptakes.

Prosthetic joint infections caused by Mycobacterium avium complex: a series of five cases.

Prosthetic joint infection (PJI) due to Mycobacterium avium complex (MAC) is a rare entity. There is limited guidance on management strategies and outcomes. In this paper, we describe the demographics, comorbidities, and clinical course of five patients at two academic institutions, constituting the largest series described to date.

Articulating vs Static Spacers for Native Knee Infection in the Setting of Degenerative Joint Disease.

BACKGROUND: Patients with advanced knee arthritis who develop a septic joint are not adequately treated with irrigation and debridement and intravenous antibiotics because of antecedent cartilage damage. The gold standard treatment has been a 2-stage approach. The periprosthetic joint infection literature has demonstrated the superiority of articulating spacers, and metal-on-poly (MOP) spacers are being used with increasing frequency. The purpose of this study was to compare the postoperative outcomes of patients with infected, arthritic knees treated by a 2-stage approach to those of patients who received single-stage treatment with a MOP spacer. METHODS: Sixteen patients with native knee septic arthritis treated with an antibiotic spacer between 1998 and 2019 were reviewed. Demographic data, clinical data, knee motion, Knee Society score, Timed-Up-and-Go, and pain scores were collected. Survivorship of final implants was compared. RESULTS: Six of 16 knees (38%) received single-stage treatment, and 10 received 2-stage treatment (62%). Five of 6 MOP spacers (83%) were retained at a mean follow-up of 3 ± 1.2 years. Nine of 10 (90%) receiving static spacers had subsequent reconstruction, with 9 (100%) surviving at mean follow-up of 7 ± 3.2 years. The patients who received MOP spacers trended toward greater terminal flexion, higher Knee Society score, and faster Timed-Up-and-Go at final follow-up. CONCLUSION: Infection in a native, arthritic knee may be effectively treated using single-stage MOP spacer. Postoperative outcomes of single-stage MOP spacers compare favorably to staged static spacers and with those undergoing revision surgery for other indications. Longer follow-up is needed to evaluate durability of MOP spacers.

Lactate and procalcitonin levels in peripartum women with intraamniotic infection.

BACKGROUND: Pregnant women are vulnerable to infection as their immune response is modulated. OBJECTIVE: Serum biomarkers are used to diagnose and manage severe infections, but data on their utility during labor are limited. We compared lactate and procalcitonin levels in women with and without an intraamniotic infection to determine whether they are useful biomarkers for infection during labor. STUDY DESIGN: We performed a prospective, observational cohort study of term, singleton pregnancies admitted with planned vaginal delivery in 2019 at a university medical center. The lactate and procalcitonin levels were determined during early labor, within 2 hours following delivery, and on postpartum day 1. Women with an intraamniotic infection in addition had their lactate and procalcitonin levels determined following an intraamniotic infection diagnosis. Samples were processed immediately in the hospital clinical laboratory. The primary outcome was the mean lactate level following delivery. The secondary outcomes were the lactate and procalcitonin levels at other time points. Comparisons based on infection status were performed using multivariate linear regressions. RESULTS: A total of 22 women with intraamniotic infection and 29 uninfected women were included. The mean early labor lactate level (1.47 vs 1.49 mmol/L) and mean procalcitonin level (0.048 vs 0.039 ng/mL) did not differ and were normal in the uninfected and intraamniotic infection groups. The mean lactate level was highest following delivery for women in both the uninfected and intraamniotic infection groups (2.00 vs 2.33 mmol/L; adjusted P=.08; 95% confidence interval, 0.98-1.53). The lactate level returned to normal by postpartum day 1 and did not differ significantly based on the infection status at any time point in the adjusted models. The procalcitonin level following delivery was higher among women with vs without an intraamniotic infection (0.142 vs 0.091 ng/mL; adjusted P=.03). The procalcitonin level rose further in both the intraamniotic infection and uninfected groups on postpartum day 1 (0.737 vs 0.408 ng/mL; adjusted P=.05). CONCLUSION: The lactate level is not significantly elevated in pregnant women with an intraamniotic infection above the physiological increase that is observed in women without infection at delivery. The procalcitonin level is elevated at delivery in women with an intraamniotic infection and warrants further investigation as a peripartum infection marker.

Recurrent Multifocal Mycoplasma orale Infection in an Immunocompromised Patient: A Case Report and Review.

A young woman with mixed connective tissue disease complicated by erosive arthritis, secondary hypogammaglobulinemia due to rituximab, and a history of many infectious complications developed multiple nonhealing wounds, polyarticular joint pain, and leukocytosis. Radiographic studies demonstrated multiple scattered areas of osteomyelitis and complex abscesses. Purulent fluid drained from multiple sites did not yield a microbiologic diagnosis by standard culture technique, but Mycoplasma orale was ultimately identified using 16 S ribosomal RNA gene amplification and sequencing. We describe this unique case and review the literature.

The routine use of synovial alpha-defensin is not necessary.

AIMS: To establish the utility of adding the laboratory-based synovial alpha-defensin immunoassay to the traditional diagnostic work-up of a prosthetic joint infection (PJI). METHODS: A group of four physicians evaluated 158 consecutive patients who were worked up for PJI, of which 94 underwent revision arthroplasty. Each physician reviewed the diagnostic data and decided on the presence of PJI according to the 2014 Musculoskeletal Infection Society (MSIS) criteria (yes, no, or undetermined). Their initial randomized review of the available data before or after surgery was blinded to each alpha-defensin result and a subsequent randomized review was conducted with each result. Multilevel logistic regression analysis assessed the effect of having the alpha-defensin result on the ability to diagnose PJI. Alpha-defensin was correlated to the number of synovial white blood cells (WBCs) and percentage of polymorphonuclear cells (%PMN). RESULTS: Intraobserver reliability and interobserver agreement did not change when the alpha-defensin result was available. Positive alpha-defensin results had greater synovial WBCs (mean 31,854 cells/µL, SD 32,594) and %PMN (mean 93.0%, SD 5.5%) than negative alpha-defensin results (mean 974 cells/µL, SD 3,988; p < 0.001 and mean 39.4% SD 28.6%; p < 0.001). Adding the alpha-defensin result did not alter the diagnosis of a PJI using preoperative (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.14 to 1.88; p = 0.315) or operative (OR 0.52, CI 0.18 to 1.55; p = 0.242) data when clinicians already decided that PJI was present or absent with traditionally available testing. However, when undetermined with traditional preoperative testing, alpha-defensin helped diagnose (OR 0.44, CI 0.30 to 0.64; p < 0.001) or rule out (OR 0.41, CI 0.17 to 0.98; p = 0.044) PJI. Of the 27 undecided cases with traditional testing, 24 (89%) benefited from the addition of alpha-defensin testing. CONCLUSION: The laboratory-based synovial alpha-defensin immunoassay did not help diagnose or rule out a PJI when added to routine serologies and synovial fluid analyses except in cases where the diagnosis of PJI was unclear. We recommend against the routine use of alpha-defensin and suggest using it only when traditional testing is indeterminate. Cite this article: Bone Joint J 2020;102-B(5):593-599.

West Nile virus encephalitis in GATA2 deficiency.

We report a male with longstanding warts who presented with severe West Nile virus encephalitis (WNVE) and recovered after interferon alfa-2b and intravenous immunoglobulin. He was later found to have GATA2 deficiency and underwent successful hematopoietic stem cell transplant.

Neglected tropical diseases: survey and geometry of randomised evidence.

OBJECTIVE: To assess the quantity and distribution of evidence from randomised controlled trials for the treatment of the major neglected tropical diseases and to identify gaps in the evidence with network analysis. DESIGN: Systematic review and network analysis. DATA SOURCES: Cochrane Central Register of Controlled Trials and PubMed from inception to 31 August 2011. STUDY SELECTION: Randomised controlled trials that examined treatment of 16 neglected tropical diseases or complications thereof published in English, French, Spanish, Portuguese, German, or Dutch. RESULTS: We identified 971 eligible randomised trials. Leishmaniasis (184 trials, 23,039 participants) and geohelminth infections; 160 trials, 46,887 participants) were the most studied, while dracunculiasis (nine trials, 798 participants) and Buruli ulcer (five trials, 337 participants) were least studied. Relative to its global burden of disease, lymphatic filariasis had the fewest trials and participants. Only 11% of trials were industry funded. Either a single trial or trials with fewer than 100 participants comprised the randomised evidence for first or second line treatments for Buruli ulcer, human African trypanosomiasis, American trypanosomiasis, cysticercosis, rabies, echinococcosis, New World cutaneous leishmaniasis, and each of the foodborne trematode infections. Among the 10 disease categories with more than 40 trials, five lacked sufficient head to head comparisons between first or second line treatments. CONCLUSIONS: There is considerable variation in the amount of evidence from randomised controlled trials for each of the 16 major neglected tropical diseases. Even in diseases with substantial evidence, such as leishmaniasis and geohelminth infections, some recommended treatments have limited supporting data and lack head to head comparisons.

Antiparasitic therapy.

Parasitic diseases affect more than 2 billion people globally and cause substantial morbidity and mortality, particularly among the world's poorest people. This overview focuses on the treatment of the major protozoan and helminth infections in humans. Recent developments in antiparasitic therapy include the expansion of artemisinin-based therapies for malaria, new drugs for soil-transmitted helminths and intestinal protozoa, expansion of the indications for antiparasitic drug treatment in patients with Chagas disease, and the use of combination therapy for leishmaniasis and human African trypanosomiasis.