Detection of Mpox Virus Using Microbial Cell-Free DNA: The Potential of Pathogen-Agnostic Sequencing for Rapid Identification of Emerging Pathogens.

BACKGROUND: The 2022 global outbreak of Monkeypox virus (MPXV) highlighted challenges with polymerase chain reaction detection as divergent strains emerged and atypical presentations limited the applicability of swab sampling. Recommended testing in the United States requires a swab of lesions, which arise late in infection and may be unrecognized. We present MPXV detections using plasma microbial cell-free DNA (mcfDNA) sequencing. METHODS: Fifteen plasma samples from 12 case-patients were characterized through mcfDNA sequencing. Assay performance was confirmed through in silico inclusivity and exclusivity assessments. MPXV isolates were genotyped using mcfDNA, and phylodynamic information was imputed using publicly available sequences. RESULTS: MPXV mcfDNA was detected in 12 case-patients. Mpox was not suspected in 5, with 1 having documented resolution of mpox >6 months previously. Six had moderate to severe mpox, supported by high MPXV mcfDNA concentrations; 4 died. In 7 case-patients, mcfDNA sequencing detected coinfections. Genotyping by mcfDNA sequencing identified 22 MPXV mutations at 10 genomic loci in 9 case-patients. Consistent with variation observed in the 2022 outbreak, 21 of 22 variants were G > A/C > T. Phylogenetic analyses imputed isolates to sublineages arising at different time points and from different geographic locations. CONCLUSIONS: We demonstrate the potential of plasma mcfDNA sequencing to detect, quantify, and, for acute infections with high sequencing coverage, subtype MPXV using a single noninvasive test. Sequencing plasma mcfDNA may augment existing mpox testing in vulnerable patient populations or in patients with atypical symptoms or unrecognized mpox. Strain type information may supplement disease surveillance and facilitate tracking emerging pathogens.

Pharmacological options for Candida albicans Endocarditis at the roadblock with irrecoverable prosthetics and drug interactions: a case report and review of literature.

BACKGROUND: Candidemia is the fourth most common nosocomial bloodstream infection. Endocarditis from candidemia is a rare but possibly fatal complication. The efficacy of amphotericin and echinocandins for induction and azoles for suppression has been well studied. Source control of infection, including removal of foreign bodies, remains the cornerstone for the success of any antifungal therapy. CASE PRESENTATION: We are describing a case of a 63-years old patient with multiple comorbidities who developed candidemia secondary to Candida albicans. The prospect of curing the fungemia was made difficult by prosthetic devices, including prosthetic heart valves, intracardiac defibrillator, and inferior vena filter, which could not be extracted due to poor cardiovascular status and higher postoperative mortality risk. Combination therapy with amphotericin and 5-Flucytosine (5FC) was used with the first recurrence. Suppression with fluconazole was contraindicated due to prolonged corrected QT (QTc) interval. Isavuconazole was employed for chronic lifelong suppression. CONCLUSION: Retaining prosthetics in higher surgical risk patients presents us with unique clinical and pharmacological challenges regarding breakthrough infections, drug interaction, and side effects from prolonged suppressive therapies.

The diagnostic dilemma for atypical presentation of progressive human Mpox.

BACKGROUND: Human mpox has increasingly been reported worldwide since May 2022, with higher incidence in men who have sex with men (MSM) and persons living with HIV (PLHIV) with presentation typical for generalized macules and papules. CASE PRESENTATION: We are describing a case of human mpox, which presented as widespread, atypical round verrucous lesions that went undiagnosed in the community for six months and was treated with antibacterials and antifungals given the similarity to skin manifestations associated with endemic mycoses. CONCLUSIONS: Suspicion for human mpox should be high in young MSM and PLHIV who present with rash and mpox should be ruled out earlier.

Case report: aseptic meningitis secondary to varicella-zoster virus (VZV) without an exanthem post MMR vaccination.

BACKGROUND: Varicella-zoster virus (VZV) is a known cause of aseptic meningitis, with a predisposition for an immunocompromised population. A dermatomal rash usually accompanies aseptic meningitis secondary to VZV. CASE PRESENTATION: We report the case of a 31-year-old male with a history of chickenpox in childhood and recent shingles who presented with severe frontal headaches secondary to VZV meningitis. The patient had also recently received the measles-mumps-rubella (MMR) vaccine. He recovered without any neurological sequala. CONCLUSION: This case report describes an immunocompetent patient with recent MMR vaccination who developed aseptic meningitis secondary to VZV without any dermatomal involvement (Zoster Sine Herpete).

First case report of acute cholangitis secondary to Cronobacter sakazakii.

INTRODUCTION: Cronobacter sakazakii is an opportunistic Gram-negative, rod-shaped bacterium which may be a causative agent of meningitis in premature infants and enterocolitis and bacteremia in neonates and adults. While there have been multiple cases of C. sakazakii infections, there have been no acute cholangitis cases reported in humans. CASE PRESENTATION: An 81-year-old male with a past medical history of basal cell carcinoma, alcoholic liver cirrhosis, transjugular intrahepatic portosystemic shunt procedure, complicated by staphylococcus bacteremia, pituitary tumor, glaucoma, and hypothyroidism presented to the emergency room with the complaint of diffuse and generalized 10/10 abdominal pain of 1 day's duration. There was a concern for pancreatitis, acute cholangitis, and possible cholecystitis, and the patient underwent a percutaneous cholecystostomy tube placement. Blood cultures from admission and biliary fluid cultures both grew C. sakazakii. The patient was treated with a carbapenem and clinically improved. CONCLUSIONS: The case study described a patient with multiple medical comorbidities that presented with C. sakazakii bacteremia and cholangitis. While this bacterium has been implicated in other infections, we believe this is the first time the bacteria is being documented to have caused acute cholangitis.

Efficacy of PARP Inhibitors as Maintenance Therapy for Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials.

Background: PARP inhibitors have been recently approved by the FDA for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Their effectiveness is seen when used with androgen deprivation therapy in patients with or without deleterious germline and somatic genetic mutations. Objectives: To identify all the randomized controlled trials (RCTs) in which PARP inhibitors have been assessed in the treatment of mCRPC, and to compare the efficacy of PARP inhibitors in these patients with standard-of-care (S/nonhormonal therapies like abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in terms of progression-free survival (PFS) and overall survival (OS). Search strategy: A systemic review search was conducted using PubMed, Embase, and Central Cochrane Registry. Selection criteria: Randomized clinical trials with PARP inhibitors, with or without antihormonal therapy, as the intervention arm, with SOC as control. Data analysis: HRs were calculated for PFS and OS. For effect sizes, a confidence interval of 95% was used, and for statistical significance, a P value of less than .05 was used. Analysis was done using random effects and fixed models and both were reported. Heterogeneity was evaluated using I2 statistic. Results: Three RCTs were included in the analysis. PARP inhibitors showed a statistically significant improvement in OS when calculated using a fixed model (HR, 0.751; 95% CI, 0.582-0.968) but the improvement was not significant when calculated using a random model (HR, 0.758; 95% CI, 0.565-1.017; I2 = 23). Similarly, the improvement in PFS was statistically significant when calculated using a fixed model (HR, 0.626; 95% CI, 0.521-0.752), and no statistical significance was noted with a random model (HR, 0.674; 95% CI, 0.437-1.039; I2 = 80). Conclusions: PARP inhibitors contributed to significant increases in PFS and OS when used with or without antihormonal agents like abiraterone or enzalutamide. This efficacy was pronounced among the patients with deleterious germline or somatic homologous recombination repair gene mutations, although patients without these mutations also showed a better PFS and OS in comparison with SOC therapy.

Case report of peritoneal carcinomatosis of plasma cell origin in a patient with newly diagnosed HIV: A terminal event.

BACKGROUND: B-cell tumors and plasma cell malignancies have been identified in persons living with the human immunodeficiency virus (PLHIV). The literature review has revealed numerous reports of solitary plasmacytomas with metastasis in PLHIV. CASE REPORT: A young patient with no prior medical or surgical history presented with tumor lysis syndrome secondary to metastatic plasma cell Epstein-Baer virus (EBV) related malignancy with peritoneal carcinomatosis. The history and clinical picture promptly led to the diagnosis of HIV. The subsequent hospital course was dismal, and lifespan was cut short by multi-organ failure. CONCLUSION: This case is being reported to highlight the suspicion of HIV in patients presenting acutely with aggressive plasma cell malignancies.

CNS Aspergillosis and Cryptococcosis with Cytomegalovirus Pneumonia in a Patient with Chronic Lymphocytic Leukemia Treated with Acalabrutinib.

Bruton's tyrosine kinase inhibitors (BTKis) are the preferred treatment for chronic lymphocytic leukemia (CLL). Despite their therapeutic benefits, these targeted agents have been associated with an increased risk of invasive infections. We describe a 68-year-old male who developed multiple bacterial, fungal and viral infections while on treatment with acalabrutinib. To our knowledge, this is the first reported case of concomitant CNS infections with Cryptococcus neoformans and Aspergillus fumigatus, along with cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) pneumonia while on acalabrutinib. This case adds to the scarce literature of fungal and bacterial infections associated with acalabrutinib, raising the suspicion that infection risk is a medication class effect for BTKis.

Molnupiravir for the treatment of COVID-19 outpatients: An updated meta-analysis.

BACKGROUND: The majority of available data on molnupiravir come from an unvaccinated COVID-19 population. Therefore, we conducted this meta-analysis to integrate evidence from recent randomized controlled trials (RCTs) as well as observational studies stratified by vaccination status to determine the clinical efficacy and safety of molnupiravir in COVID-19 outpatients. METHODS: We searched PubMed, Embase, the Cochrane Library, medRxiv, and ClinicalTrials.gov from inception to November 2023. We conducted our meta-analysis using RevMan 5.4 with risk ratio (RR) as the effect measure. RESULTS: We included 8 RCTs and 5 observational studies in our meta-analysis. Molnupiravir reduced the risk of all-cause mortality (RR 0.28; 95% CI: 0.20-0.79, I2 = 0%) but did not decrease the hospitalization rate (RR 0.67; 95% CI: 0.45-1.00, I2 = 53%) in the overall population; in the immunized population, no benefits were observed. Molnupiravir lowered the rate of no recovery (RR 0.78; 95% CI: 0.76-0.81, I2 = 0%) and increased virological clearance at day 5 (RR 2.68; 95% CI: 1.94-4.22, I2 = 85%). There was no increase in the incidence of adverse events. CONCLUSIONS: Molnupiravir does not decrease mortality and hospitalization rates in immunized patients with COVID-19. However, it does shorten the disease course and increases the recovery rate. The use of molnupiravir will need to be considered on a case-by-case basis in the context of the prevailing social circumstances, the resource setting, drug costs, and the healthcare burden.

Colchicine for the treatment of patients with COVID-19: an updated systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: We conducted an updated systematic review and meta-analysis to investigate the effect of colchicine treatment on clinical outcomes in patients with COVID-19. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched PubMed, Embase, the Cochrane Library, medRxiv and ClinicalTrials.gov from inception to January 2023. ELIGIBILITY CRITERIA: All randomised controlled trials (RCTs) that investigated the efficacy of colchicine treatment in patients with COVID-19 as compared with placebo or standard of care were included. There were no language restrictions. Studies that used colchicine prophylactically were excluded. DATA EXTRACTION AND SYNTHESIS: We extracted all information relating to the study characteristics, such as author names, location, study population, details of intervention and comparator groups, and our outcomes of interest. We conducted our meta-analysis by using RevMan V.5.4 with risk ratio (RR) and mean difference as the effect measures. RESULTS: We included 23 RCTs (28 249 participants) in this systematic review. Colchicine did not decrease the risk of mortality (RR 0.99; 95% CI 0.93 to 1.05; I2=0%; 20 RCTs, 25 824 participants), with the results being consistent among both hospitalised and non-hospitalised patients. There were no significant differences between the colchicine and control groups in other relevant clinical outcomes, including the incidence of mechanical ventilation (RR 0.75; 95% CI 0.48 to 1.18; p=0.22; I2=40%; 8 RCTs, 13 262 participants), intensive care unit admission (RR 0.77; 95% CI 0.49 to 1.22; p=0.27; I2=0%; 6 RCTs, 961 participants) and hospital admission (RR 0.74; 95% CI 0.48 to 1.16; p=0.19; I2=70%; 3 RCTs, 8572 participants). CONCLUSIONS: The results of this meta-analysis do not support the use of colchicine as a treatment for reducing the risk of mortality or improving other relevant clinical outcomes in patients with COVID-19. However, RCTs investigating early treatment with colchicine (within 5 days of symptom onset or in patients with early-stage disease) are needed to fully elucidate the potential benefits of colchicine in this patient population. PROSPERO REGISTRATION NUMBER: CRD42022369850.

Nigella sativa for the treatment of COVID-19 patients: A rapid systematic review and meta-analysis of randomized controlled trials.

Nigella sativa is an herbal therapy for various afflictions. It has some potential to be a promising option as an efficacious treatment for COVID-19 patients that can contribute to global healthcare as a relatively cheap therapy but evidence of its use from randomized controlled trials (RCTs) is limited. Therefore, to explore the effect of N. sativa in combating COVID-19, we undertook this meta-analysis. We searched several databases to retrieve all RCTs investigating N. sativa for the treatment of COVID-19 as compared to placebo or standard care. We used RevMan 5.4 for all analyses with risk ratio (RR) or odds ratio (OR) as the effect measures. We included a total of seven RCTs in this review. N. sativa significantly reduced the risk of all-cause mortality in patients with COVID-19 compared to the control group (RR 0.27, 95% CI: 0.10 to 0.72; I 2 = 0%). N. sativa significantly reduced the rate of viral PCR positivity (RR 0.62, 95% CI: 0.39 to 0.97; I 2 = 0%). We did not find any significant difference in the risk of hospitalization (RR 0.26, 95% CI: 0.04 to 1.54; I 2 = 0%) and the rate of no recovery (OR 0.48, 95% CI: 0.20 to 1.15; I 2 = 84%) between the two groups. N. sativa is an easily available herbal medicine that may decrease the risk of mortality and improve virological clearance in COVID-19 patients. However, our results are limited by the small number of RCTs available. Further large-scale RCTs are needed to better understand the anti-inflammatory and antiviral effects of N. sativa in COVID-19 patients.

Risk of Invasive Fungal Infections in Patients With Chronic Lymphocytic Leukemia Treated With Bruton Tyrosine Kinase Inhibitors: A Case-Control Propensity Score-Matched Analysis.

Background: Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitor (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom a BTKi is now the first-line recommended therapy. Methods: We queried TriNetX, a global research network database, to identify adult patients with CLL using the International Classification of Diseases, Tenth Revision code (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs. Results: Among 5358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi versus 3.5% among patients not on a BTKi at 5 years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of Pneumocystis jirovecii pneumonia (PJP) (0.5% vs 0.3%, P = .02) and invasive candidiasis (3.5% vs 2.7%, P = .012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively. Conclusions: We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are, however, low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKis are required to identify at-risk patients and preventive, cost-effective interventions.

Immune thrombocytopenic purpura and legionella infection: A case report highlighting the association.

Immune thrombocytopenic purpura (ITP) can be acquired or secondary to other drugs, infections, or autoimmune disorders. Legionella is a known intracellular organism that causes Legionnaire's disease and affects the lungs. Presented is the first case showing a direct association between Legionella and ITP. Our patient was a 61-year-old female with a past medical history of asthma whose clinical presentation was consistent with pneumonia secondary to Legionella. Her hospital course was complicated by critical bleeding with severe thrombocytopenia. She responded to antibiotics, steroids, and intravenous immunoglobulins (IVIG). Our case suggests an association between ITP and Legionella and emphasizes its timely diagnosis for appropriate treatment.

Rare Case of Reversible Pulmonary Arterial Hypertension Secondary to Cyclophosphamide and Doxorubicin Chemotherapy.

Pulmonary arterial hypertension (PAH), characterized as a resting mean pulmonary artery pressure greater than 25 mmHg, is due to the narrowing of the pulmonary arteries, which can be idiopathic, inherited, or drug-related. Alkylating agents, including cyclophosphamide, are a risk factor for developing the pulmonary veno-occlusive disease. Drug-induced PAH is extremely rare. A 59-year-old female with newly diagnosed invasive ductal carcinoma of the right breast and high-grade ductal carcinoma in situ of the left breast was initiated treatment with doxorubicin and cyclophosphamide. About one week after receiving the first cycle, the patient developed worsening lower extremity edema and shortness of breath. She was then hospitalized, and a transthoracic echocardiogram and coronary angiogram revealed PAH. The team then changed the breast cancer treatment regimen to Taxol and carboplatin, and PAH was resolved in a follow-up echocardiogram after five months. This report has described the first case of PAH directly related to cyclophosphamide and doxorubicin. It is imperative to promptly recognize this rare but important side-effect as early diagnosis and response can potentially reverse the disease progression.

An Unusual Case of Hemorrhagic Pleuropericarditis After COVID-19 Vaccination.

As coronavirus disease 2019 (COVID-19) vaccines are being increasingly administered worldwide, subsequent side effects, such as myocarditis, pericarditis, and myopericarditis, are becoming increasingly more common. Our case describes a 64-year-old male who developed chest pain and shortness of breath one week after receiving the Moderna (Cambridge, Massachusetts) COVID-19 mRNA vaccine. He was found to have a large, left-sided pleural effusion and a small pericardial effusion. The patient underwent thoracentesis and video-assisted thoracoscopic procedure with chest tube placement, which drained bloody pleural and pericardial fluid. He was treated with a course of colchicine. Subsequent imaging revealed the resolution of pericardial and pleural effusions, along with the resolution of symptoms.

Management of acute chest syndrome in patients with sickle cell disease: a systematic review of randomized clinical trials.

INTRODUCTION: Acute chest syndrome (ACS) accounts for the highest mortality in Sickle cell disease patients. Early diagnosis and timely management of ACS results in better outcomes. However, the effectiveness of most treatment modalities for ACS management has not been established. AREAS COVERED: To review the treatment modalities management protocols and highlight the effectiveness of each option a literature search was done. Randomized controlled trials that assessed the efficacy of different treatment modalities in ACS management in SCD patients were chosen and reviewed. EXPERT OPINION: 11 randomized controlled trials were found that evaluated the efficacy of incentive spirometry, positive expiratory pressure device, intravenous dexamethasone, oral vs. intravenous morphine, inhaled nitric oxide, unfractionated heparin, and blood transfusion in the prevention or treatment of ACS. Although there are guidelines for ACS treatment, the available evidence is very limited to delineating the effectiveness of various interventions in ACS management. More high-quality studies and trials with a larger patient population can benefit this area to support the recommendations with stronger evidence.

An Unfortunate Case of Takotsubo Cardiomyopathy During Plasmapheresis for Myasthenia Crisis.

A literature review shows scarce reports of myasthenic crises (MC) complicated by Takotsubo cardiomyopathy (TC). This patient cohort (0.11%) has higher all-cause mortality and prolonged in-hospital course. We present a rare case of a 72-year-old man who developed cardiogenic shock post-plasmapheresis for myasthenia crisis. He became hemodynamically unstable and developed acute respiratory failure requiring intubation 30 minutes after completion of plasma exchange. Serum troponin peaked at 3.19 ng/mL while an emergent 12-lead electrocardiogram (EKG) showed new-onset diffuse ST-segment elevation. Hypokinesis of the entire apex, anterior septum, mid-and apical inferior septum, and mid-and apical inferior wall consistent with Takotsubo cardiomyopathy was seen on bedside echocardiogram. The patient received a continuous infusion of norepinephrine and vasopressin. The hospital course was complicated by multiorgan failure and eventual demise. This case highlights MC and the potential of plasma exchange therapy to induce TC.