Tuberculosis the great masquerader.

With increased use of disease-modifying antirheumatic drugs, screening for latent tuberculosis infection is more important than ever. However, even with appropriate screening, reactivation of tuberculosis can occur in patients who have had significant epidemiological exposures. Herein, we present a case of a seventy-four-year-old woman with severe rheumatoid arthritis on long-term disease-modifying antirheumatic drugs who developed cryptic miliary tuberculosis. Histopathological findings from an abdominal lymph node biopsy showed caseating granulomas which were initially attributed to her rheumatoid arthritis given screening tests and sputum acid-fast cultures were negative for tuberculosis. It was not until tuberculosis spondylitis developed that the diagnosis was finally elucidated. This case highlights the need for clinicians to be vigilant about discussing historical epidemiological exposures to tuberculosis instead of relying solely on screening testing.

Successful Use of Salvage Bacteriophage Therapy for a Recalcitrant MRSA Knee and Hip Prosthetic Joint Infection.

Prosthetic joint infections are a serious complication of joint replacement surgery due to the significant morbidity and financial burden that is associated with conventional treatments. When patients fail the gold standard two-stage revision surgery, very limited, well-defined standardized approaches are available. Herein, we discuss the case of a sixty-four-year-old woman who had a recalcitrant MRSA prosthetic joint infection of her knee and hip that failed repeated conventional surgical and medical treatments. Only after receiving intraoperative and intravenous bacteriophage therapy was the patient able to achieve cure of her prosthetic joint infections, as demonstrated by the lack of clinical recurrence and sterility of intraoperative cultures while off antibiotics. This case reinforces that bacteriophage therapy holds promise in the treatment of prosthetic joint infections and more specifically in complicated cases who have failed conventional surgical and medical interventions.

Kinetics of SARS-CoV-2 antibody responses pre-COVID-19 and post-COVID-19 convalescent plasma transfusion in patients with severe respiratory failure: an observational case-control study.

AIMS: While the SARS-CoV-2 pandemic may be contained through vaccination, transfusion of convalescent plasma (CCP) from individuals who recovered from COVID-19 (CCP) is considered an alternative treatment. We investigate if CCP transfusion in patients with severe respiratory failure increases plasma titres of SARS-CoV-2 antibodies and improves clinical outcomes. METHODS: Patients with COVID-19 (n=34) were consented for CCP transfusion and serial blood draws pretransfusion and post-transfusion. Plasma SARS-CoV-2 antireceptor binding domain (RBD) IgG and IgM titres were measured by ELISA serially, and compared with serial plasma titre levels from control patients (n=68). The primary outcome was survival at 30 days, and secondary outcomes were length of ventilator and/or extracorporeal membrane oxygenation (ECMO) support, length of stay (LOS) in the hospital and in the intensive care unit (ICU). Outcomes were compared with matched control patients (n=34). Kinetics of antibodies and clinical outcomes were compared using LOess regression and ORs, respectively. RESULTS: Prior to CCP transfusion, 74% of patients were anti-RBD seropositive for IgG (median 1:3200), and 81% were anti-RBD IgM seropositive (median 1:320), while 16% were seronegative. The kinetics of antibody titres in CCP recipients were similar to controls. CCP recipients presented with similar survival, duration on ventilatory and/or ECMO support, as well as ICU and hospital LOS compared with controls. CONCLUSIONS: CCP transfusion did not increase the kinetics of SARS-CoV2 antibodies and did not result in improved clinical outcomes in patients with COVID-19 with severe respiratory failure, suggesting that CCP may not be indicated in this category of patients.

SARS-CoV-2 Vaccination During Pregnancy: A Complex Decision.

As the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines passed UK and US regulatory milestones in late 2020 and early 2021, multiple professional societies offered recommendations to assist pregnant and breastfeeding people as they choose whether to undergo vaccination. Despite such guidance, the lack of data describing vaccine safety, immunogenicity, and efficacy in pregnant and breastfeeding people has made this decision challenging for many. However, even considering the paucity of data, the known risks of coronavirus disease 2019 during pregnancy likely outweigh the not yet fully elucidated risks of SARS-CoV-2 vaccines, which have reassuring safety and efficacy profiles among nonpregnant people.

Impact of a division-wide bundle on hospital-acquired Clostridioides difficile cases, antibiotic days of therapy, testing appropriateness, and associated financial costs.

INTRODUCTION: Updated international guidelines recommend the use of a two-step algorithm (glutamate dehydrogenase [GDH] or nucleic-acid amplification test [NAAT] plus toxin) rather than NAAT alone for the diagnosis of Clostridioides difficile (formerly Clostridium difficile) infections. The goal of our project was to evaluate the impact of a new bundle on the rate of hospital-acquired C. difficile infections (CDIs), hospital-acquired CDI standardized infection ratio (SIR), antibiotic days of therapy (DOT), and financial cost. MATERIALS AND METHODS: The new bundle was implemented in April 2018. This bundle was implemented across five hospitals in Catholic Health Initiatives (CHI) Texas Division. The bundle included a switch from NAAT to a two-step process (GDH and toxin). We placed the new test in an order panel which included enteric isolation and required indications for C. difficile testing. We used quarterly data pre- and post-intervention to calculate SIR and DOT. RESULTS: In the pre-intervention period, 15.5% of the total 3513 C. difficile NAAT was positive. In the post-intervention period, 5.7% of a total of 2845 GDH and toxin assays was positive for both GDH and toxin (P < 0.0001). SIR, which adjusts for denominator and change in testing methodology, also dropped from 1.02 to 0.43. The estimated cost associated with positive C. difficile cases dropped from 1,932,150 USD to 1,113,800 USD with an estimated yearly cost saving of 794,150 USD. Compliance with enteric isolation improved from 73.1% to 92.5% (P = 0.008). CONCLUSION: The new testing bundle led to a marked reduction in hospital-acquired CDI and unnecessary treatment, reduction in C. difficile testing, an increase in compliance with enteric isolation, and significant cost savings.

Diagnosis of Yersinia enterocolitica Infection in Cancer Patients With Diarrhea in the Era of Molecular Diagnostics for Gastrointestinal Infections.

BACKGROUND: Yersinia enterocolitica is an uncommon cause of diarrhea, mesenteric adenitis and bacteremia in the United States. There is limited information regarding the clinical course in immunocompromised patients. We describe the clinical presentations and outcomes in patients with cancer with Y. enterocolitica diagnosed at a US cancer center before and after introduction of gastrointestinal multiplex panel (GIMP) nucleic acid amplification tests (NAATs). METHODS: We reviewed medical records of all patients with Y. enterocolitica isolated from cultures or identified by means of NAATs from 2000 to 2018. We then extracted demographic information, clinical characteristics, treatment, and overall mortality rate at 30 days after the diagnosis of yersiniosis. RESULTS: We identified 17 cases: 6 cases by culture before April 2016 and 11 cases by NAATs after that; 4 of the latter were confirmed by means of culture (36%). This represented an 8-fold increase for overall detection and a 3-fold increase in culture-proved infections when adjusted per 1000 admissions. The most common presenting symptom was diarrhea (11 of 14 [79%]), followed by abdominal pain (9 of 14 [64%]) and nausea and vomiting (6 of 14 [43%]). In 1 patient, the infection resolved spontaneously; the other patients received antibiotic treatment, the majority with a fluoroquinolone. The 30-day mortality rate was 7.1%, and the cause of death was a complication of advanced cancer. CONCLUSION: Since implementing use of the GIMP, we observed an increase in Y. enterocolitica cases, possibly related to increasing number of patients with cancer at our institution who are receiving intensive immunosuppression, increased testing due to ease and availability, and increased sensitivity of NAATs. GIMP NAATs are redefining the epidemiology of Y. enterocolitica infection in patients with cancer.

Clinical characteristics and risk factors of pulmonary hypertension associated with chronic respiratory diseases: a retrospective study.

BACKGROUND: Chronic respiratory disease-associated pulmonary hypertension (PH) is an important subtype of PH, which lacks clinical epidemiological data in China. METHODS: Six hundred and ninety three patients hospitalized from 2010 to 2013 were classified by echocardiography according to pulmonary arterial systolic pressure (PASP): mild (36≤ PASP <50 mmHg); moderate (50≤ PASP <70 mmHg) and severe (PASP ≥70 mmHg). RESULTS: Dyspnea (93.51%) was the most common symptom. Hemoptysis observed in the severe group (6.42%) was significantly higher than the other two groups (P<0.05). COPD (78.35%), lung bullae (44.16%), tuberculosis (including obsolete pulmonary tuberculosis) (38.82%), and bronchiectasis (30.45%) were frequently present. Mild group occupied the highest proportion (84.7%) in COPD, while severe group occupied the highest proportion (19.3%) in pulmonary embolism (P<0.01). Age, partial pressure of oxygen (PaO2), hematocrit (HCT), partial pressure of carbon dioxide (PaCO2), increase of N-terminal pro brain natriuretic peptide (NT-proBNP) and right ventricular (RV) diameter (>20 mm) were associated with moderate-to-severe PH, while RV [odds ratio (OR) =3.53, 95% CI, 2.17-5.74], NT-proBNP (OR=2.44, 95% CI, 1.51-3.95), HCT (OR=1.03, 95% CI, 1.00-1.07) and PaCO2 (OR=1.01, 95% CI, 1.00-1.03) were independent risk factors. CONCLUSIONS: PH related to respiratory diseases is mostly mild to moderate, and the severity is associated with the category of respiratory disease. Increased HCT can be an independent risk factor for PH related to chronic respiratory diseases.

Chronic hypoxia increases TRPC6 expression and basal intracellular Ca2+ concentration in rat distal pulmonary venous smooth muscle.

BACKGROUND: Hypoxia causes remodeling and contractile responses in both pulmonary artery (PA) and pulmonary vein (PV). Here we explore the effect of hypoxia on PV and pulmonary venous smooth muscle cells (PVSMCs). METHODS: Chronic hypoxic pulmonary hypertension (CHPH) model was established by exposing rats to 10% O2 for 21 days. Rat distal PVSMCs were isolated and cultured for in vitro experiments. The fura-2 based fluorescence calcium imaging was used to measure the basal intracellular Ca2+ concentration ([Ca2+]i) and store-operated Ca2+ entry (SOCE). Quantitative RT-PCR and western blotting were performed to measure the expression of mRNA and levels of canonical transient receptor potential (TRPC) protein respectively. RESULTS: Hypoxia increased the basal [Ca2+]i and SOCE in both freshly dissociated and serum cultured distal PVSMCs. Moreover, hypoxia increased TRPC6 expression at mRNA and protein levels in both cultured PVSMCs exposed to prolonged hypoxia (4% O2, 60 h) and distal PV isolated from CHPH rats. Hypoxia also enhanced proliferation and migration of rat distal PVSMCs. CONCLUSIONS: Hypoxia induces elevation of SOCE in distal PVSMCs, leading to enhancement of basal [Ca2+]i in PVSMCs. This enhancement is potentially correlated with the increased expression of TRPC6. Hypoxia triggered intracellular calcium contributes to promoted proliferation and migration of PVSMCs.