Acute myositis secondary to Epstein-Barr virus in the absence of infectious mononucleosis with severe rhabdomyolysis.

SummaryRhabdomyolysis is characterised by muscle breakdown which causes myoglobin light chain release and can result in renal injury. While some of the most common causes of rhabdomyolysis are trauma related, others include toxins, autoimmune processes or viral aetiologies. We present the case of a 20s-year-old man, with no significant medical history, who presented to the emergency department with a 1-week history of weakness, myalgias, nausea, vomiting and subjective fevers. A review of systems and physical exam were otherwise unremarkable, including being negative for sore throat, dysphagia and lymphadenopathy. On presentation, the patient was noted to have dark urine with a creatine kinase value of 452 458 U/L and an elevated creatinine at 7.23 mg/dL. The patient denied any trauma or increased physical activity. His toxin screen and autoimmune workup were negative. The patient's serological workup was significant for acute Epstein-Barr virus (EBV) infection, without additional viral coinfection or mononucleosis. During his hospitalisation course, the patient was managed with supportive care including haemodialysis. The patient made a full renal recovery and was discharged with scheduled outpatient follow-up. This case highlights the recognition of an acute EBV infection causing rhabdomyolysis in the absence of mononucleosis or concomitant infection.

CT-guided microwave ablation of the nonsurgical aspergilloma.

Background: Aspergillosis is a fungal infection that can lead to development of an aspergilloma, especially in patients with a history of cavitary lung disease. It is generally managed with antifungal therapy followed by surgical intervention. There are, however, limited options for the nonsurgical patient. Microwave ablation is already an effective, minimally invasive treatment being used in some lung malignancies and may be an alternative and definitive treatment in the inoperable patient. Methods: Two patients were considered for microwave ablation following their diagnoses of aspergillosis with hemoptysis. We sought to evaluate the efficacy of CT-guided microwave ablation of an aspergilloma in these patients who were not good candidates for surgical intervention. Results: Two male patients presented with hemoptysis and were found to have an aspergilloma. Case 1 was initially treated with antifungals and did not improve. He proceeded with VATS, and the procedure was aborted intraoperatively secondary to a frozen chest cavity. The patient subsequently elected to undergo CT-guided microwave ablation. He did not experience any immediate complications but was hospitalized for hemoptysis several weeks later. He developed alveolar hemorrhage and ultimately succumbed to PEA arrest.Case 2 was without hemoptysis at follow up and chose to pursue microwave ablation for definitive treatment. Case 2 developed post ablation pneumothorax requiring chest tube placement. Follow-up CT chest imaging was consistent with resolution of the aspergilloma. Conclusion: Microwave ablation is a safe and effective therapeutic approach in the treatment of lung malignancy with no severe or death related complications. There are almost no absolute contraindications. Microwave ablation may be utilized as a therapeutic option in the treatment of an aspergilloma in the non-surgical patient. This novel application may challenge the current gold standard of surgical intervention.

An observational study on the use of long acting buprenorphine (Sublocade) and a Tamper resistant PICC for Outpatient IV antibiotic administration in Patients with serious infections and Opioid Use Disorder; The STOP OUD project.

What is STOP OUD?: The STOP OUD project is an observational study on the use of long-acting buprenorphine (Sublocade) and a Tamper resistant PICC clamp for Outpatient IV antibiotic administration in Patients with serious infections and Opioid Use Disorder (STOP OUD). Background: The US opioid crisis is driving up serious infections related to intravenous drug use. These infections require prolonged courses of antibiotics, often resulting in lengthy hospital stays. Extended hospitalizations for monitored parenteral antibiotics for patients with opioid use disorder are challenging for patients, reduce bed capacity, and are associated with significant cost. This observational study reviews the administration of intravenous (IV) antibiotics in a monitored outpatient setting using long-acting injectable buprenorphine (Sublocade, Indivior Inc., North Chesterfield, VA) and a tamper resistant clamp in patients with opioid use disorder . Methods: Long-acting buprenorphine and a tamper resistant clamp were used to treat patients with serious infections and opioid use disorder as outpatients. Results: Hospital days avoided were 30-days per STOP OUD project participant. Eleven of thirteen STOP OUD project participants completed their antibiotic courses as prescribed, there was no evidence of peripherally inserted central catheter (PICC) tampering, and they rated their care as a mean of 4.9/5 (SD 0.4). Institutional savings per STOP OUD patient was $33,000. Outpatient infusion costs were $9,300 for a net savings of $23,700 per STOP OUD project participant. Infections resolved in all participants. Conclusions: The STOP OUD project reduced hospital length of stay for patients with opioid use disorder and serious infections, and had a favorable financial impact.

A Metatranscriptomics Survey of Microbial Diversity on Surfaces Post-Intervention of cleanSURFACES® Technology in an Intensive Care Unit.

Hospital-acquired infections (HAIs) pose a serious threat to patients, and hospitals spend billions of dollars each year to reduce and treat these infections. Many HAIs are due to contamination from workers' hands and contact with high-touch surfaces. Therefore, we set out to test the efficacy of a new preventative technology, AIONX® Antimicrobial Technologies, Inc's cleanSURFACES®, which is designed to complement daily chemical cleaning events by continuously preventing re-colonization of surfaces. To that end, we swabbed surfaces before (Baseline) and after (Post) application of the cleanSURFACES® at various time points (Day 1, Day 7, Day 14, and Day 28). To circumvent limitations associated with culture-based and 16S rRNA gene amplicon sequencing methodologies, these surface swabs were processed using metatranscriptomic (RNA) analysis to allow for comprehensive taxonomic resolution and the detection of active microorganisms. Overall, there was a significant (P < 0.05) global reduction of microbial diversity in Post-intervention samples. Additionally, Post sample microbial communities clustered together much more closely than Baseline samples based on pairwise distances calculated with the weighted Jaccard distance metric, suggesting a defined shift after product application. This shift was characterized by a general depletion of several microbes among Post samples, with multiple phyla also being reduced over the duration of the study. Notably, specific clinically relevant microbes, including Staphylococcus aureus, Clostridioides difficile and Streptococcus spp., were depleted Post-intervention. Taken together, these findings suggest that chemical cleaning events used jointly with cleanSURFACES® have the potential to reduce colonization of surfaces by a wide variety of microbes, including many clinically relevant pathogens.

A Bite So Bad: Septic Shock Due to Capnocytophaga Canimorsus Following a Dog Bite.

Infection by Capnocytophaga canimorsus (C. canimorsus), a Gram-negative rod found in the normal oral flora of canine and feline species and transmitted through bites or scratches, is a rare phenomenon. Infections most commonly occur in alcoholics and immunocompromised patients. In this report, we describe the case of a middle-aged male with a history of alcohol abuse who presented with septic shock and multisystem organ failure following a suspected dog bite. The patient was a 59-year-old Caucasian male with alcohol abuse disorder who initially presented with encephalopathy and lethargy. The patient had scratches and multiple healing wounds, with a mottled appearance on his extremities. According to his wife, the patient had been playing aggressively with his dog at home. On admission, he was febrile, tachycardic, and saturating in the 80s on ambient air. His extremities rapidly developed diffuse purpura and dry gangrene of all digits along with the tip of his nose and genitals. The patient developed septic shock and multisystem organ failure. Blood cultures initially grew Gram-positive cocci and Gram-negative rods for which broad-spectrum antibiotics were initiated. Follow-up blood cultures were positive for C. canimorsus and the antibiotic regimen was adjusted accordingly. His condition continued to deteriorate. His family opted for comfort measures only and he died soon after. Common sequelae of C. canimorsus infection include septic shock with multisystem organ failure, disseminated purpuric lesions, hypotension, encephalopathy, and acute renal failure. As seen in our patient, C. canimorsus infection should be considered in such patients, particularly if there is a recent history of an animal bite. Prompt initiation of appropriate treatment is essential to improve patient prognosis.

Risk Factors, Clinical Characteristics, and Prognosis of Acute Kidney Injury in Hospitalized COVID-19 Patients: A Retrospective Cohort Study.

Background: Acute kidney injury (AKI) is a serious complication of COVID-19. Methods: Records of hospitalized adult patients with confirmed SARS-CoV-2 infection from 1 March to 31 May 2020 were retrospectively reviewed. Results: Of 283 patients, AKI occurred in 40.6%. From multivariate analyses, the risk factors of AKI in COVID-19 can be divided into: (1) demographics/co-morbidities (male, increasing age, diabetes, chronic kidney disease); (2) other organ involvements (transaminitis, elevated troponin I, ST segment/T wave change on electrocardiography); (3) elevated biomarkers (ferritin, lactate dehydrogenase); (4) possible bacterial co-infection (leukocytosis, elevated procalcitonin); (5) need for advanced oxygen delivery (non-invasive positive pressure ventilation, mechanical ventilation); and (6) other critical features (ICU admission, need for vasopressors, acute respiratory distress syndrome). Most AKIs were due to pre-renal (70.4%) and intrinsic (34.8%) causes. Renal replacement therapy was more common in intrinsic AKI. Both pre-renal (HR 3.2; 95% CI 1.7-5.9) and intrinsic AKI (HR 7.7; 95% CI 3.6-16.3) were associated with higher mortality. Male, stage 3 AKI, higher baseline and peak serum creatinine and blood urea nitrogen were prevalent in intrinsic AKI. Urine analysis and the fractional excretion of sodium and urea were not helpful in distinguishing intrinsic AKI from other causes. Conclusions: AKI is very common in COVID-19 and is associated with higher mortality. Characterization of AKI is warranted due to its diverse nature and clinical outcome.

Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state.

Objective: COVID-19 is a respiratory disease caused by SARS-CoV-2 with the highest burden in the USA. Data on clinical characteristics of patients with COVID-19 in US population are limited. Thus, we aim to determine the clinical characteristics and risk factors for in-hospital mortality from COVID-19. Design: Retrospective observational study. Setting: Single-network hospitals in Pennsylvania state. Participants: Patients with confirmed SARS-CoV-2 infection who were hospitalised from 1 March to 31 May 2020. Primary and secondary outcome measures: Primary outcome was in-hospital mortality. Secondary outcomes were complications, such as acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS). Results: Of 283 patients, 19.4% were non-survivors. The mean age of all patients was 64.1±15.9 years. 56.2% were male and 50.2% were white. Several factors were identified from our adjusted multivariate analyses to be associated with in-hospital mortality: increasing age (per 1-year increment; OR 1.07 (1.045 to 1.105)), hypoxia (oxygen saturation <95%; OR 4.630 (1.934 to 1.111)), opacity/infiltrate on imaging (OR 3.077 (1.276 to 7.407)), leucocytosis (white blood cell >10 109/µL; OR 2.732 (1.412 to 5.263)), ferritin >336 ng/mL (OR 4.016 (1.195 to 13.514)), lactate dehydrogenase >200 U/L (OR 7.752 (1.639 to 37.037)), procalcitonin >0.25 ng/mL (OR 2.404 (1.011 to 5.714)), troponin I >0.03 ng/mL (OR 2.242 (1.080 to 4.673)), need for advanced oxygen support other than simple nasal cannula (OR 4.608-13.889 (2.053 to 31.250)), intensive care unit admission/transfer (OR 13.699 (6.135 to 30.303)), renal replacement therapy (OR 21.277 (5.025 to 90.909)), need for vasopressor (OR 22.222 (9.434 to 52.632)), ARDS (OR 23.810 (10.204 to 55.556)), respiratory acidosis (OR 7.042 (2.915 to 16.949)), and AKI (OR 3.571 (1.715 to 7.407)). When critically ill patients were analysed independently, increasing Sequential Organ Failure Assessment score (OR 1.544 (1.168 to 2.039)), AKI (OR 2.128 (1.111 to 6.667)) and ARDS (OR 6.410 (2.237 to 18.182)) were predictive of in-hospital mortality. Conclusion: We reported the characteristics of ethnically diverse, hospitalised patients with COVID-19 from Pennsylvania state.

Thinking Outside the Lungs: A Case of Disseminated Abdominal Tuberculosis.

BACKGROUND Extrapulmonary tuberculosis (TB) occurs in up to one-fifth of all cases of TB, with abdominal TB accounting for 5% of all cases. It is an uncommon diagnosis in the Western world, where it is primarily identified in immigrant and immunocompromised populations. CASE REPORT We review a case in which a 47-year-old Nepalese woman with a history of cognitive dysfunction secondary to epilepsy presented with decreased appetite and diffuse abdominal pain. She was hypoxic and febrile on initial exam, and imaging indicated lung consolidation, right-sided pleural effusion, and thickening and nodularity of the omentum with patchy wall thickening of the colon. After failing to improve on a standard antibiotic regimen for treatment of pneumonia and colitis, the differential was broadened to include TB. Interferon-g release assay was subsequently found to be positive, and omental and peritoneal biopsies were obtained. The patient was started on an empiric course of rifampin, isoniazid, ethambutol, pyrazinamide, and pyridoxine. Laboratory testing revealed no immunochemical evidence of Mycobacterium species, however, Ziehl-Neelsen acid-fast stain was positive with rare acid-fast bacilli identified. CONCLUSIONS Peritoneal TB carries significant morbidity and mortality if undiagnosed or untreated. Diagnosis is challenging in the absence of a single test that can confirm or exclude this condition. In combination with clinical suspicion, it is crucial to explore history regarding socio-epidemiology (travel, incarceration, occupation, homelessness, sick contacts) and immunological risk (drug use, chemotherapy) in patients with constitutional symptoms.

Lactobacillus rhamnosus Bacteremia in an Immunocompromised Renal Transplant Patient.

Conventionally, Lactobacillus species are considered as low virulence organisms and rarely cause infection in immunocompetent individuals. However, it might be an opportunistic infection source in immunocompromised patients and can cause invasive serious infections. To our knowledge, there are only a handful of cases in the literature reporting primary bloodstream infection caused by Lactobacilli spp. in transplant recipients. Here, we report a case of a kidney transplant recipient with Lactobacillus rhamnosus bacteremia.

Emerging pathogens: A case of Wohlfahrtiimonas chitiniclastica and Ignatzschineria indica bacteremia.

Wohlfahrtiimonas chitiniclastica and Ignatzschineria indica are rare causes of infection in humans and have been linked to infestation with fly larvae in open wounds. Both organisms are emerging causes of disease globally and co-infection resulting in bacteremia is rare. An 82-year-old male with bilateral lower extremity infections was hospitalized due to fall with associated right lower extremity pain. On exam, a maggot infested ulcer was identified on his right lower extremity. On day three of hospitalization, blood cultures grew gram-negative and gram-variable rods, and methicillin-resistant Staphylococcus aureus. Further analysis of the gram negative and gram variable rods revealed W. chitiniclastica and I. indica respectively. Both I. indica and W. chitiniclastica were pan sensitive to all antimicrobials tested with the exception of tetracyclines to which W. chitiniclastica was fully resistant and I. indica was intermediately sensitive. The patient was treated with two weeks of IV ceftriaxone and was discharged with plans to complete a six-week course of IV daptomycin due to MRSA bacteremia. All repeat blood cultures were negative. Until recently W. chitiniclastica and I. indica infections have been documented only in farm and feral animals. Major risk factors for infection include: poor hygiene, open wounds, peripheral vascular disease, and myiasis. Due to the rarity of infection, identification of both organisms can be difficult, therefore a high index of suspicion is required.

The Avise Lupus Test and Cell-bound Complement Activation Products Aid the Diagnosis of Systemic Lupus Erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a multifaceted disease, and its diagnosis may be challenging. A blood test for the diagnosis of SLE, the Avise Lupus test, has been recently commercialized and validated in clinical studies. OBJECTIVES: To evaluate the use of the Avise Lupus test by community rheumatologists. METHODS: The study is a longitudinal, case-control, retrospective review of medical charts. Cases had a positive test result, and controls had a negative result; all patients were anti-nuclear antibodies (ANA) positive but negative for SLE-specific autoantibodies. Features of SLE, diagnosis, and medications at two time points were recorded. RESULTS: Twenty of the 23 cases (87%) and 4 of the 23 controls (17%) were diagnosed with SLE (sensitivity=83%; specificity=86%). More cases than controls (43% vs. 17%) fulfilled 4 American College of Rheumatology (ACR) classification criteria of SLE. Sensitivity of the test was significantly higher than the ACR score (83% vs. 42%, p=0.006). A higher percentage of patients who met the classification criteria had elevated cell-bound complement activation products (CB-CAPs) compared to patients who did not. Anti-rheumatic medications were used in a higher percentage of cases than controls (83% vs. 35% at baseline, p=0.002), suggesting that cases were treated more aggressively early on. CONCLUSION: A positive Avise Lupus test result aids in formulating a SLE diagnosis when diagnosis based on standard-of-care tests and clinical features may be challenging, and impacts patient management. Prospective studies will be performed to better evaluate the clinical utility of the test and of CB-CAPs as biomarkers of SLE.

Septic Arthritis in the Temporomandibular Joint.

UNLABELLED: Septic arthritis of the temporomandibular joint (TMJ) is a rare event that has only been reported a few dozen times worldwide. This case is remarkable for septic arthritis of the TMJ joint in an otherwise healthy male. CASE REPORT: A 24-year-old male presented to the emergency department with periauricular swelling, erythema, fever, myalgia's and generalized joint pain. He had previously sought medical attention and was placed on ciprofloxacin. However, he developed facial swelling and a rash and had to discontinue the antibiotic. On physical exam the patient had a large swelling and tenderness in his left periauricular area, with erythema and deviation of the right mandible which limited his ability to open the mouth. A computed tomography showed mild asymmetric soft tissue swelling in the left pharyngeal region but did not show joint effusion. Subsequent magnetic resonance imaging did show effusion of the joint space. The effusion was drained, and the synovial fluid was submitted for gram stain, culture, and sensitivity. The cultures grew menthicillin sensitive Staphyloccocus Aureus. The patient was discharged to complete a two week course of intravenous (IV) Ceftriaxone and IV Vancomycin via home infusion. CONCLUSION: Septic Arthritis of the TMJ is a rare event with very specific clinical symptoms. Due to the low sensitivity of the computed tomography scan, magnetic resonance imaging should be considered when computed tomography scan is negative for TMJ effusion.

Aeromonas hydrophila Sepsis Associated with Consumption of Raw Oysters.

Introduction. Aeromonas hydrophila is a gram negative bacillus that is native to aquatic environments that is increasingly reported in humans. This case is remarkable for A. hydrophila with an initial presentation of acute pancreatitis. Case Presentation. A 61-year-old male presented to the emergency department with nausea, vomiting, and abdominal pain for two days. His past medical history was significant for alcohol abuse. Initial laboratory examination showed an elevated white blood cell count, elevated lipase, and elevated liver function tests (LFT). Computer tomography (CT) showed peripancreatic inflammatory changes and retroperitoneal free fluid, suggestive of acute pancreatitis. The patient was treated with intravenous (IV) fluids and IV meropenem. After two days, the patient developed sepsis and respiratory failure and was intubated. Blood cultures were positive for Aeromonas hydrophila sensitive to ciprofloxacin which was added to his treatment. Additionally, it was discovered that this patient had recently vacationed in Florida where he consumed raw oysters. He was discharged home on the eighth day of the hospital admission. Conclusion. This is a rare case of A. hydrophila sepsis in an elderly patient with acute pancreatitis and a history of consumption of raw oysters. This case suggests that A. hydrophila can cause disseminated infection in immunocompetent individuals.

Infliximab efficacy in rheumatoid arthritis after an inadequate response to etanercept or adalimumab: results of a target-driven active switch study.

OBJECTIVE: Evaluate efficacy of infliximab with response-driven dosing in patients with active RA. RESEARCH DESIGN AND METHODS: Patients (n = 203) with active RA despite methotrexate + etanercept/adalimumab, participated in this active-infliximab-switch study. Infliximab 3 mg/kg was infused at Weeks 0, 2, 6, 14, and 22 with escalation to 5 or 7 mg/kg depending on EULAR response at Weeks 14 and 22. The primary endpoint was EULAR response at Week 10. Safety was assessed through Week 30. Infliximab levels and antibodies to infliximab (ATI) were measured at Weeks 0, 6, 14, and 26. CLINICAL TRIAL REGISTRATION: NCT 00714493, EudraCT 2007-003288-36. RESULTS: Of 197 evaluable patients, 120/77 previously received etanercept/adalimumab. Baseline mean (SD) swollen and tender joint counts were 17.3 (10.54) and 30.2 (16.89), respectively; mean DAS28-ESR was 6.19 (0.981). At Week 10, 98 (49.7%; 95% CI: 42.6%, 56.9%) patients achieved EULAR response, with a significantly improved DAS28-ESR score (mean [SD] change -1.1 [1.15]; p < 0.001). EULAR response was achieved by 41.7%/62.3% of patients previously receiving etanercept/adalimumab (p = 0.006). At Week 26, 51.8% (95% CI: 44.6%, 58.9%) of patients achieved or maintained EULAR response. Infliximab dose was escalated in 100 patients, 52% of whom achieved EULAR response at Week 26. Median serum concentration levels at Week 26 showed that dose escalation helped EULAR non-responders achieve levels similar to or higher than the levels seen in responders. ATI were associated with lower serum concentrations of infliximab, consistent with lower efficacy rates among ATI-positive patients. CONCLUSION: Infliximab, in treat-to-target settings with individual dose escalation, demonstrated significant efficacy at Weeks 10 and 26 in patients switched to infliximab after inadequate response to etanercept/adalimumab. The observed efficacy indicated that the switch to infliximab and ability to increase dose in a targeted fashion were beneficial. KEY LIMITATIONS: Given the relatively short duration of study follow-up, these safety findings require confirmation in a longer-term study.

A common novel splice variant of SLC22A1 (OCT1) is associated with impaired responses to imatinib in patients with chronic myeloid leukaemia.

Approximately one-third of patients with chronic myeloid leukaemia will fail to achieve or maintain responses to imatinib. Changes in solute carrier family 22 (organic cation transporter), member 1 (SLC22A1, also termed OCT1), the main transporter for imatinib, have been proposed as a possible predictive factor. We analysed SLC22A1 mRNA levels and single nucleotide polymorphisms (SNPs) located in exon 7 in 153 diagnostic whole blood samples from two patient cohorts. The level of SLC22A1 expression did not significantly correlate with imatinib failure or achievement of molecular remission. The SNP 408V>M (g.1222G>A) was present in 65% of patients and was associated in all cases with an eight base-pair insertion (8(+) allele) at the 3' end of exon 7. The latter generates an alternative splice site, leading to a premature stop codon. M420del was found in 33% of patients and never in cis with 8(+) (the 3(-) allele). Significantly longer times to 1% and 0·1% molecular responses (by quantitative reverse transcription polymerase chain reaction) were seen in patients with 8(+) 8(+) or 8(+) N compared to those with the remaining four genotypes (N = no insertion or deletion). Patients lacking 8(+) and 3(-) (NN, 18%) showed the best outcomes overall. Thus, while SLC22A1 expression does not appear to affect response, alterations in its splicing or amino acid sequence may do so.

PP2A-activating drugs selectively eradicate TKI-resistant chronic myeloid leukemic stem cells.

The success of tyrosine kinase inhibitors (TKIs) in treating chronic myeloid leukemia (CML) depends on the requirement for BCR-ABL1 kinase activity in CML progenitors. However, CML quiescent HSCs are TKI resistant and represent a BCR-ABL1 kinase-independent disease reservoir. Here we have shown that persistence of leukemic HSCs in BM requires inhibition of the tumor suppressor protein phosphatase 2A (PP2A) and expression--but not activity--of the BCR-ABL1 oncogene. Examination of HSCs from CML patients and healthy individuals revealed that PP2A activity was suppressed in CML compared with normal HSCs. TKI-resistant CML quiescent HSCs showed increased levels of BCR-ABL1, but very low kinase activity. BCR-ABL1 expression, but not kinase function, was required for recruitment of JAK2, activation of a JAK2/ß-catenin survival/self-renewal pathway, and inhibition of PP2A. PP2A-activating drugs (PADs) markedly reduced survival and self-renewal of CML quiescent HSCs, but not normal quiescent HSCs, through BCR-ABL1 kinase-independent and PP2A-mediated inhibition of JAK2 and ß-catenin. This led to suppression of human leukemic, but not normal, HSC/progenitor survival in BM xenografts and interference with long-term maintenance of BCR-ABL1-positive HSCs in serial transplantation assays. Targeting the JAK2/PP2A/ß-catenin network in quiescent HSCs with PADs (e.g., FTY720) has the potential to treat TKI-refractory CML and relieve lifelong patient dependence on TKIs.