Disseminated Cryptococcal Disease in Liver Cirrhosis

Introduction: Cryptococcus is an environmental yeast that is typically associated with human immunodeficiency virus (HIV), and transplant recipients. Invasive disease has been described in patients with liver disease, however it is not a common occurrence. We describe a case of disseminated Cryptococcus neoformans infection in a patient with liver cirrhosis. Case presentation: 53-year-old male, with history of Hepatitis C infection, liver cirrhosis, Sjogren’s syndrome, venous thromboembolism (VTE), was admitted to the hospital for worsening debility and weakness. In a recent hospital admission for acute kidney injury (AKI), he was found to have spontaneous bacterial peritonitis secondary to Klebsiella pneumoniae and E. coli, and bacteremia with the latter organism. Patient was treated with IV Ertapenem. On latest admission, patient’s model for end-stage liver disease (MELD)-Na was 25. Physical exam was significant for abdominal distention with mild diffuse tenderness, shifting dullness, positive fluid-wave sign, and bilateral 1+ edema to the knee. Peritoneal fluid was positive for Cryptococcus, and multiple blood cultures (total of 6 different days) were positive for Cryptococcus. Lumbar puncture (LP) showed pleocytosis with monocytes predominance, CSF culture positive for Cryptococcus and a CSF Cryptococcal antigen (CrAg) of 1:2560. Patient was treated with Liposomal Amphotericin B and Flucytosine. Repeated LPs showed persistently elevated opening pressures, requiring ventricular-pleural shunt. He finished a course of 4 weeks of induction therapy, followed by transition to oral Fluconazole for consolidation. Discussion: Cryptococcus neoformans is an encapsulated, ubiquitous, opportunistic yeast. Invasive Cryptococcus disease is a rare but highly morbid infection in patients with liver disease. Peritonitis is common in these patients, especially with high MELD-Na scores. Challenges in diagnosis are due to atypical presentation, mild-moderate fluid pleocytosis, and slow culture turnaround time. Meningitis with Cryptococcus poses a high morbidity condition, especially if complications like elevated intracranial pressure arises. Multiple sites of seeding of Cryptococcus neoformans in an immunocompetent patient is rare. Prompt initiation of adequate therapy and close monitoring of complications are key for improvement in patient’s survival. Treatment is prolonged and challenging.https://scholarlycommons.henryford.com/merf2019caserpt/1036/thumbnail.jp

Health disparities in hepatitis C screening and linkage to care at an integrated health system in Southeast Michigan

With recommended screening for hepatitis C among the 1945-1965 birth cohort and advent of novel highly effective therapies, little is known about health disparities in the Hepatitis C care cascade. Our objective was to evaluate hepatitis C screening rates and linkage to care, among patients who test positive, at our large integrated health system. We used electronic medical records to retrospectively identify patients, in the birth cohort, who were seen in 21 Internal Medicine clinics from July 2014 to June 2015. Patients previously screened for hepatitis C and those with established disease were excluded. We studied patients\u27 sociodemographic and medical conditions along with provider-specific factors associated with likelihood of screening. Patients who tested positive for HCV antibody were reviewed to assess appropriate linkage to care and treatment. Of 40,561 patients who met inclusion criteria, 21.3% (8657) were screened, 1.3% (109) tested positive, and 30% (30/100) completed treatment. Multivariate logistic regression showed that African American race, male gender, electronic health engagement, residency teaching clinic visit, and having more than one clinic visit were associated with higher odds of screening. Patients had a significant decrease in the likelihood of screening with sequential interval increase in their Charlson comorbidity index. When evaluating hepatitis C treatment in patients who screened positive, electronic health engagement was associated with higher odds of treatment whereas Medicaid insurance was associated with significantly lower odds. This study shows that hepatitis C screening rates and linkage to care continue to be suboptimal with a significant impact of multiple sociodemographic and insurance factors. Electronic health engagement emerges as a tool in linking patients to the hepatitis C care cascade

Severe COVID 19 Case with Atypical Presentation

Introduction: COVID-19 was brought to the attention of the WHO on December 31st, 2019 and classified a global pandemic on March 11th. As of March 26th, there were 2,856 cases and 60 deaths in Michigan, with 851 cases and 15 deaths in Detroit. Efforts to characterize risk factors for severe disease may improve clinical outcomes and inform resource allocation. Better understanding of the epidemiological and clinical characteristics of COVID-19 are essential to slowing transmission and treating patients. Below we detail the clinical features of a COVID-19 positive patient seen in early March, 2020. Case Report: An 80-year-old female presented to the ED with fevers. She endorsed worsening fevers, watery diarrhea, abdominal pain, and myalgias of one week. She was lethargic and presyncopal for one day prior to presentation. She endorsed contact with sick members at home and denied travel history. Her past medical history was significant for resected colon cancer, T2DM, COPD, HTN, and CAD. She was a former smoker. On exam she was febrile and had lower abdominal tenderness. Her labs showed lymphopenia, thrombocytopenia, and mild hyponatremia. Influenza swab, viral panel, and legionella urine antigen were negative, prompting COVID-19 testing. Chest x-ray showed diffuse reticular opacities. Antibiotics were started and she was admitted on hospital day 2. She developed dyspnea, rales, and increasing oxygen demand through her hospitalization. COVID-19 testing resulted positive by day 4. Infectious disease recommended ribavirin and lopinavir-ritonavir. Her son was informed, and all contacts were advised to isolate for two weeks. On days 5 and 6 she improved clinically, though was not discharged due to concern she would not abide by self-isolation recommendations. Overnight, she had increasing oxygen demand and repeat chest x-ray revealed worsening infiltrates. She was intubated and transferred to the MICU on day 7. Inflammatory markers including LDH, CRP, procalcitonin, lactate, anion gap, aPTT, INR, and D-dimer were elevated. ABG revealed low PaO2 and low pH. Her IL-6 and fibrinogen levels were normal. She continued to decompensate with concern for septic shock, and had worsening bradycardia and hypotension, unresponsive to three vasopressors. On day 7, she expired. Discussion: Our report of a COVID-19 patient that ended in their mortality provides important lessons for providers. The transmission mode was local spread, reflecting high transmissibility among family groups. Fevers are reliably present over the illness course, though seen in under half on presentation. Fatigue is common and was observed in our patient. Cough is common, though was absent here. Diarrhea is an uncommon presenting symptom, reducing initial clinical suspicion and potentially delaying diagnosis. Other characteristics seen in our patient reflect a growing body of evidence supporting high rate of morbidity and mortality in patients with COVID-19. Such populations, including critically ill elderly population, require ICU level care, with marked lymphopenia on admission labs, and elevated inflammatory markers across their hospitalization. Also, investigative treatments including Lopinavir-ritonavir, ribavirin, hydroxychloroquine, and azithromycin have yet to demonstrate clinical efficacy in large randomized controlled trials.https://scholarlycommons.henryford.com/merf2020caserpt/1105/thumbnail.jp

A unique presentation of Cryptococcus neoformans and Pneumocystis jirovecii PJP ) co infection in a newly diagnosed HIV patient

One week prior to demise, a 30 years old smoker male with a past medical history significant for intermittent asthma presented to emergency with shortness of breath, wheezing, productive cough, and generalized fatigue for 1 week. He was afebrile, normotensive, tachycardic and had O2 saturation of 96% on room air. Physical examination showed cachexia, audible wheezes and oropharyngeal erythema. Labs showed WBC 3600/uL with lymphocyte count of 700/uL and mild thrombocytopenia. Chest X ray was clear. Serology was reactive for HIV, pending viral load. Working diagnosis was asthma exacerbation in the setting of a possible viral infection for which he was discharged home to complete a 5-day course of high dose prednisone, with follow up with infectious diseases as an outpatient. Subsequent, HIV viral load after discharge was 194,643 copies/mL. One week later, he presented to the ED with worsening respiratory symptoms, new onset chest pain and vomiting. He was hypotensive, tachycardic, tachypneic, and afebrile. He had leukocytosis of 12,700/uL with neutrophilia, lactate of 6.6, BNP 841. Influenza A, B and RSV, and urine histoplasma antigen were negative. EKG showed abnormal ST segment elevation with concerns for STEMI. Chest CT revealed multifocal, bilateral ground glass and nodular opacities with cystic cavities. Mediastinal and hilar lymphadenopathy was also noted. Pulmonary embolism and pneumothorax were ruled out. Blood gases reflected acute hypoxemic respiratory failure. Vancomycin and Piperacillin/tazobactam were started. A bed side ultrasound showed significantly dilated right ventricle with severely reduced function and hence concerns for cardiogenic component of shock. He was intubated and shortly after developed asystole and expired after prolonged cardiopulmonary resuscitation within twelve hours of admission. At autopsy, gross exam showed bilateral pulmonary congestion, bilateral hilar adenopathy and matted lymph nodes in the mediastinum. Microscopy revealed cryptococcus (mucicarmine positive encapsulated yeast forms) involving intraalveolar and alveolar septal parts of all lobes of the lungs, effacing lymph nodes, and involving microscopic foci in bilateral myocardial ventricles. Modified GMS-positive cup shaped Pneumocystis organisms involved the alveoli of all lung lobes. The lung parenchyma showed minimal inflammatory response. Our case is of an HIV patient with respiratory symptoms found to have pulmonary co-infection with PJP and Cryptococcus neoformans, confirmed on pathology report. This is uncommon in literature. Additionally, this case is unique in reporting the presentation of Cryptococcus neoformans as involving the mediastinal lymph nodes and myocardium.https://scholarlycommons.henryford.com/merf2020caserpt/1122/thumbnail.jp

Delaying escalation of care for a COVID-19 patient

Background: Since being reported on December 31st 2019, COVID-19 has become a pandemic. In Detroit, there are 1075 cases and 23 deaths, as of March 28th, 2020. Rapid identification of the disease is vital as preliminary reports show that multiple ED and clinic visits are associated with worse outcomes, likely due to delayed treatment. Our report describes the course of a COVID-19 patient who required multiple visits prior to diagnosis, and rapidly deteriorated.Case Report: A 63-year old African American man presented to his PCP with sore throat, cough, and body aches. Patient endorsed symptoms for 4 days, no sick contacts, and flu swab was negative. Patient was diagnosed with a viral syndrome and prescribed rest and symptomatic care. The following day he went to the ED with worsening symptoms and hypotension and was sent home. The next day, patient went for a CXR, where he developed SOB. Due to his distress and presence of bilateral pneumonia, he was sent to the ED rule out COVID. At the ED, patient endorsed a fever, SOB, and chills. Patient’s past medical history included asthma, hypertension, and diabetes. On exam, he was febrile but hemodynamically stable. Patient was ill-appearing, with decreased breath sounds on the left. Labs showed leukopenia, lymphopenia, and an AKI. COVID testing was sent. Patient was admitted, with airborne plus precautions, and antibiotics were started.On hospital day 3, patient became persistently febrile and hypoxic. ABG was done which showed a PaO2 of 55.9. Due to worsening respiratory status, patient was intubated and transferred to the MICU. CXR was repeated and showed worsening airspace opacities bilaterally, and small pleural effusions. COVID test came back positive and treatment began with Hydroxychloroquine, and use of remdesivir pending. On hospitalization day 7, patient received remdesivir and tocilizumab, with hopes that reduced systemic inflammation would lead to improvement of his ARDS. Overnight, patient was hypotensive and nonresponsive to fluids. Levophed was begun, and vent settings were increased. On days 9 and 10, due to worsening hypoxia and inability to follow commands, patient was paralyzed to allow for more time to improve inflammation. Patient was placed on max vent settings, and his PaO2 sat was 57. CXR was repeated due to worsening vent requirements and showed no change. Subsequently, patient became tachycardic in the 120s, and hypotensive to the 80s. D-dimer was elevated, and patient desaturated when turned or repositioned. On day 11, patient was found to be hyperkalemic. Nephrology was consulted and determined the hyperkalemia was due to hemolysis secondary to DIC, but the patient was not a candidate for ultrafiltration or intermittent dialysis. Due to absence of clinical improvement, patient was transferred to comfort care, and expired.Discussion: Our report elucidates the importance of rapid identification of a patient with COVID. Our patient had a standard presentation with cough, fever, body aches and sore throat, indicating that the possibility of COVID as the cause for the patient’s presentation should have been considered. During a pandemic it is vital to practice with a high of index of suspicion. The importance of prompt identification of the illness becomes even more salient considering that current treatment approach is primarily symptomatic management, due to lack of clinically effective curative treatments. It may seem overly simplified, but the sooner a patient is able to receive these services, the more likely they are to recover. While our patient had multiple risk factors for deterioration due to COVID, such as HTN, and T2DM, our patient had two opportunities for escalation of care and identification of his underlying pathology that could have improved his prognosis. Further, our report is in line with preliminary findings that African Americans and patientshttps://scholarlycommons.henryford.com/merf2020caserpt/1103/thumbnail.jp

Increasing Incidence of MDROs: An Emerging Global Concern

Introduction: With massive efflux of civilians from violence-stricken countries, the high rates of colonization with multidrug-resistant organisms (MDROs) amongst the refugees is an emerging global concern. Our report describes two Middle Eastern patients who suffered severe traumatic injuries in their home countries, subsequently developing chronic wounds. Upon arrival to the United States, the patients sought treatment in our institution for wound infection with MDRO. Materials and methods: Clinical data was collected from the patients’ charts. Identification and susceptibility testing were performed as part of routine identification/susceptibility test in the clinical microbiology laboratory. MICs performed by manual microbroth dilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines.Time kill curves used to determine in vitro synergy of Pseudomonas aeruginosa isolate in various antibiotic combinations (½ x MIC meropenem plus ½ x MIC colistin, ½ x MIC meropenum plus ½ x MIC colistin plus ½ x MIC rifampin and ½ x MIC meropenem plus ½ x MIC ceftazidime/avibactam). Mueller Hinton II broth was used. Samples were serially diluted at 0, 4 and 24 hours and plated on TSA II agar. Time kill curves were constructed, plotting colony counts over time, with synergy being defined as ≥2-log10 decrease in CFU/ml between the combination and its most active constituent after 24h, the number of surviving organisms in the presence of combination must be ≥2 log10 CFU/ml below the starting inoculum. Results: Patient 1 came from Syria, and patient 2 from Yemen. Both patients’ wound infections were healthcare-associated, with underlying chronic osteomyelitis. Both had multiple risk factors for MDRO, including multiple prior surgeries and antibiotic courses. Patient 1 culture grew CRE Klebsiella and MDR Morganella, and later ESBL Escherichia coli. Patient 2 culture grew Pseudomonas aeruginosa sensitive only to colistin. Patient 1 was treated with ertapenem. Patient 2 received rifampin+meropenen+colistin, the only antibiotic combination demonstrating synergistic killing. Both patients required prolonged therapy, and on follow up were doing well. Conclusions: Colonization with MDRO amongst Middle Eastern immigrants is an alarming phenomenon.In vitro experiments with available antibacterial agents may assist in the choice of therapy for MDRO strains when conventional options are exhausted.https://scholarlycommons.henryford.com/merf2019basicsci/1001/thumbnail.jp

COVID-19 Presenting with Neurological Symptoms

Introduction: Healthcare officials of Wuhan City in China became aware of several pneumonia cases with an unknown etiology in December 2019. A novel coronavirus, SARS-CoV-2, was identified as cause of the disease named Coronavirus disease-19 (COVID-19). SARS-CoV-2 enters cells through a receptor found on pneumocytes, and there is also evidence this receptor is located on neurons and glial cells. Recently, the neurological manifestations of COVID-19 have been described. However, to our knowledge, there are currently no known cases of COVID-19 presenting as cerebellar dysfunction and essential tremor, which we describe here. Case: A 77-year-old obese man with a past medical history of hypertension and essential tremor presented with decreased mentation, episodes of blank staring, bradykinesia, and worsening bilateral hand tremors. He also reported shortness of breath with a cough productive of clear sputum. Physical exam was within normal limits except for tachypnea requiring 4 liters of oxygen, a bilateral essential tremor and dysmetria. All labs were within normal limits. A chest x-ray suggested multifocal pneumonia. A Computed Tomography (CT) scan demonstrated scattered ground glass opacities and multi-lobar pneumonia, while a CT scan of the head was negative. Treatment was initiated for community acquired pneumonia with azithromycin and ceftriaxone. Upon admission, the patient continued to be orientated only to person and place. Subsequent laboratory investigation demonstrated elevated ferritin (1,200 ng/mL), Lactate Dehydrogenase (613 IU/L), C-Reactive Protein (13.2 mg/dL), and low procalcitonin ( Discussion: The respiratory systems – cough, sputum production, and dyspnea – and imaging findings of COVID-19 are well described.7–11 The presented case is unique because, while the patient did display the established symptoms of COVID-19, he also had encephalopathy, bilateral essential tremor, and cerebellar dysfunction. Neurological imaging was negative, and patients with these symptoms would traditionally receive further investigation. Patients with neurological dysfunction secondary to COVID-19 can demonstrate some significant findings on magnetic resonance imaging (MRI) such as enhancement in the leptomeningeal region and bilateral frontotemporal hypoperfusion on perfusion imaging.5However, because of his concomitant respiratory symptoms, and in context of the ongoing COVID-19 pandemic, our patient did not receive further neurological imaging as there was a high index of suspicion. The central and peripheral nervous system manifestations of COVID-19 are documented, but this case demonstrates that COVID-19 can result in cerebellar dysfunction as well. Conclusion: COVID-19 is caused by SARS-CoV-2, a virus that enters host cells via a receptor primarily found on pneumocytes but also neurons and glial cells. As such, the most common presenting symptoms are respiratory. Here we present a case of a patient presenting with neurological dysfunction in addition to the established respiratory symptoms. Highlights: Our patient presented with encephalopathy, worsened essential tremor, and cerebellar dysfunction, which is an unusual presentation of COVID-19.-In an ongoing pandemic, it is important to have a high index of suspicion, even when patients present with atypical symptoms -It is unclear at this time if hydroxychloroquine and azithromycin should be the treatment of choice for COVID-19, but the regimen was successful in this patient.https://scholarlycommons.henryford.com/merf2020caserpt/1049/thumbnail.jp

Coxsackievirus B3 infection early in pregnancy induces congenital heart defects through suppression of fetal cardiomyocyte proliferation

Background Coxsackievirus B (CVB) is the most common cause of viral myocarditis. It targets cardiomyocytes through coxsackie and adenovirus receptor, which is highly expressed in the fetal heart. We hypothesized CVB3 can precipitate congenital heart defects when fetal infection occurs during critical window of gestation. Methods and Results We infected C57Bl/6 pregnant mice with CVB3 during time points in early gestation (embryonic day [E] 5, E7, E9, and E11). We used different viral titers to examine possible dose-response relationship and assessed viral loads in various fetal organs. Provided viral exposure occurred between E7 and E9, we observed characteristic features of ventricular septal defect (33.6%), abnormal myocardial architecture resembling noncompaction (23.5%), and double-outlet right ventricle (4.4%) among 209 viable fetuses examined. We observed a direct relationship between viral titers and severity of congenital heart defects, with apparent predominance among female fetuses. Infected dams remained healthy; we did not observe any maternal heart or placental injury suggestive of direct viral effects on developing heart as likely cause of congenital heart defects. We examined signaling pathways in CVB3-exposed hearts using RNA sequencing, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and immunohistochemistry. Signaling proteins of the Hippo, tight junction, transforming growth factor-β1, and extracellular matrix proteins were the most highly enriched in CVB3-infected fetuses with ventricular septal defects. Moreover, cardiomyocyte proliferation was 50% lower in fetuses with ventricular septal defects compared with uninfected controls. Conclusions We conclude prenatal CVB3 infection induces congenital heart defects. Alterations in myocardial proliferate capacity and consequent changes in cardiac architecture and trabeculation appear to account for most of observed phenotypes

Vaccine coverage and factors associated with vaccine adherence in persons with HIV at an urban infectious disease clinic

Information on vaccination rates and factors associated with adherence in persons with HIV (PWH) is limited. We report vaccine adherence in 653 adult PWH attending an urban Infectious Disease Clinic from January 2015 to December 2021. Vaccines evaluated included influenza, pneumococcal, tetanus, hepatitis A virus (HAV) and hepatitis B virus (HBV), human papillomavirus (HPV), and zoster vaccines. Vaccine reminders were triggered at every visit, and all vaccines were accessible in the clinic. The mean age was 50 y (±SD 13), male gender was 78.6%, and black race was 74.3%. The overall adherence to all recommended vaccines was 63.6%. Vaccine adherence was \u3e90% for influenza, pneumococcal, and tetanus, \u3e80% for HAV and HBV, and ≥60% for HPV and zoster vaccines. The main predictor of adherence to all vaccines was ≥2 annual clinic visits (odds ratio [OR] 3.45; 95% confidence interval [CI] 2.36-5.05; p \u3c .001). Other predictors included an assigned primary care provider within the system (OR 2.89 [95% CI 1.71-5.00, p \u3c .001]) and CD4 \u3e200 cell/mm(3) at entry into care (OR 1.91 [95% CI 1.24-2.94, p = .0003]). Retention in care combined with vaccine reminders and accessibility of vaccines in the clinic can achieve high vaccine uptake in PWH

Outcomes associated with SARS-CoV-2 reinfection in individuals with natural and hybrid immunity

BACKGROUND: Studies comparing SARS-CoV-2 reinfection outcomes among individuals with previous infection (natural immunity) and previous infection plus vaccination (hybrid immunity) are limited. METHODS: Retrospective cohort study comparing SARS-CoV-2 reinfection among patients with hybrid immunity (cases) and natural immunity (controls) from March 2020 to February 2022. Reinfection was defined as positive PCR\u3e 90 days after initial laboratory-confirmed SARS-CoV-2 infection. Outcomes included time to reinfection, symptom severity, COVID-19-related hospitalization, critical COVID-19 illness (need for intensive care unit, invasive mechanical ventilation, or death), length of stay (LOS). RESULTS: A total of 773 (42%) vaccinated and 1073 (58%) unvaccinated patients with reinfection were included. Most patients (62.7%) were asymptomatic. Median time to reinfection was longer with hybrid immunity (391 [311-440] vs 294 [229-406] days, p \u3c 0.001). Cases were less likely to be symptomatic (34.1% vs 39.6%, p = 0.001) or develop critical COVID-19 (2.3% vs 4.3%, p = 0.023). However, there was no significant difference in rates of COVID-19-related hospitalization (2.6% vs 3.8%, p = 0.142) or LOS (5 [2-9] vs 5 [3-10] days, p = 0.446). Boosted patients had longer time to reinfection (439 [IQR 372-467] vs 324 [IQR 256-414] days, p \u3c 0.001) and were less likely to be symptomatic (26.8% vs 38%, p = 0.002) compared to unboosted patients. Rates of hospitalization, progression to critical illness and LOS were not significantly different between the two groups. CONCLUSIONS: Natural and hybrid immunity provided protection against SARS-CoV-2 reinfection and hospitalization. However, hybrid immunity conferred stronger protection against symptomatic disease and progression to critical illness and was associated with longer time to reinfection. The stronger protection conferred by hybrid immunity against severe outcomes due to COVID-19 should be emphasized with the public to further the vaccination effort, especially in high-risk individuals