Circadian rhythms of trematode parasites: applying mixed models to test underlying patterns.

Circadian rhythms of parasites and their hosts can influence processes such as transmission, pathology and life cycle evolution. For trematode parasites that depend on free-living infectious stages (i.e. cercariae) to move among host species, the timing of parasite release is hypothesized to increase the likelihood of contacting a host. Yet, a persistent challenge in studying such biorhythms involves selection of appropriate analytical techniques. Here, we extend a generalized linear mixed modelling (GLMM) framework to cosinor analyses, thereby allowing flexibility in the statistical distribution of the response variable, incorporation of multiple covariates and inclusion of hierarchical grouping effects. By applying this approach to 93 snails infected with trematode parasites from freshwater pond ecosystems, we detected non-random rhythms in six of eight species, with variation in both the timing of peak cercariae release (between 5:10 and 21:46 h) and its magnitude (between 13 and 386). The use of GLMM yielded more accurate and precise estimates of the cosinor parameters compared with classical least-squares (LS) based on a simulation-based sensitivity analysis. The sensitivity analysis revealed that the amplitude and rhythm-adjusted mean values from the LS models diverged from the true values at some limits. We highlight the importance of novel analytical approaches for evaluating parasite circadian rhythms and investigating their underlying mechanisms.

Unmasking Carcinoid Syndrome in a Chronic Obstructive Pulmonary Disease (COPD) Patient: A Rare Presentation with Wheezing and Angioedema.

Carcinoid syndrome is a rare condition resulting from neuroendocrine tumors (NETs) that secrete vasoactive substances like serotonin. This report describes the case of a 61-year-old man with a history of chronic obstructive pulmonary disease (COPD) and hypertension who presented with new-onset angioedema, loss of consciousness, and a fall. He had been treated for COPD exacerbations during ER visits without improvement and was unaware of a prior mesenteric carcinoid tumor diagnosis from 2012. The next emergency evaluation revealed significant airway and facial edema necessitating intubation. Imaging and biopsy identified a well-differentiated grade 1 NET with extensive liver metastases. Laboratory tests showed elevated levels of serum serotonin, chromogranin A, and 24-hour urine 5-hydroxyindoleacetic acid (5-HIAA). Post-discharge, a PET scan confirmed metastatic lesions primarily in the liver and small bowel, with an unresectable mesenteric mass. The patient was treated with lanreotide and became symptom-free. This case underscores the need to consider carcinoid syndrome in patients with COPD presenting with unexplained respiratory symptoms, as timely diagnosis and treatment can significantly enhance patient outcomes.

Extensive Unprovoked Thromboembolism in Steroid-Dependent Ulcerative Colitis: A Case Report.

The elevated risk of thromboembolism (TE) in association with inflammatory bowel disease (IBD) is well-established in literature. Herein, we present a case of a 70-year-old patient with steroid-dependent ulcerative colitis who presented with exertional dyspnea and abdominal pain. Investigations revealed extensive bilateral iliac and renal and caval venous thrombosis as well as pulmonary emboli. In addition to the rarity of such a finding in this location, this case serves to remind clinicians of the elevated risk of TE in those with IBD, even among those with IBD that has been in remission, especially in those presenting with unexplained abdominal pain and/or renal injury. TE can be life-threatening and requires a high index of clinical suspicion to establish early diagnosis and prevent propagation.

Bulbar Onset Amyotrophic Lateral Sclerosis in a COVID-19 Patient: A Case Report.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with a largely unknown etiology. In this case, we are presenting an 84-year-old male patient who was admitted for acute hypoxemic respiratory failure secondary to coronavirus disease 2019 (COVID-19) infection. He was neurologically intact. His infection improved and oxygen requirement was gradually weaned off allowing for discharge. However, he was admitted again a month later with progressive dysphagia and aspiration that were confirmed on videofluoroscopic study. He was also found to have mild dysarthria, bulbar muscle weakness, bilateral lower motor neuron facial nerve palsy, diffuse hyporeflexia on four extremities with intact sensory function. Diagnosis of ALS was suspected after extensive workup was pursued and ruled out nutritional, structural, autoimmune, infectious and inflammatory disorders. This case is only the third reported case in medical literature to suggest COVID-19 infection as a triggering/accelerating factor of ALS progression.

Important Clues for the Diagnosis of Anti-LGI1-Antibody Autoimmune Encephalitis: A Case Report.

Anti-leucine-rich-glioma-inactivated 1 (LGI1) antibody autoimmune encephalitis is a rare autoimmune encephalitis. We present a 68-year-old female patient who initially presented with episodic confusion, hallucinations, behavioral changes, and unexplained hyponatremia. History was also remarkable for intermittent abnormal movement affecting the left upper extremity and face. She was initially thought to be suffering from dementia and was discharged home. However, progressive symptoms led to her second admission, where evidence of autonomic dysfunction with episodic bradycardia and persistent symptomatic orthostatic hypotension were evident. Generalized cortical hyperexcitability and subclinical seizures were seen. Diagnosis of LGI1 encephalitis was confirmed with a positive Anti-LGI1 antibody in the cerebrospinal fluid, and treatment with intravenous immunoglobulin and steroids improved her cognitive function. This case helps to highlight important features that should raise early clinical suspicion of LGI1 encephalitis, including unexplained progressive hyponatremia, autonomic dysfunction, and frequent refractory seizures. This can lead to earlier recognition of this condition, where earlier implementation of immunosuppressive therapy is linked to better clinical outcomes and brain structural preservation.

The Clinical Challenge of Refractory Octreotide-Induced Thrombocytopenia in Active Gastrointestinal Bleeding: A Case Report.

The association between octreotide and thrombocytopenia has been documented in the literature but it remains a rare finding. We are reporting a 59-year-old female patient with alcoholic liver cirrhosis who presented with the gastrointestinal tract (GIT) bleeding secondary to esophageal varices. Initial management involved fluid and blood products resuscitation and initiation of both octreotide and pantoprazole infusion. However, the abrupt onset of severe thrombocytopenia was evident within a few hours of admission. Platelet transfusion and discontinuation of pantoprazole infusion failed to correct the abnormality prompting the holding off of octreotide. However, this also failed to control the decline in platelet count and prompted intravenous immunoglobulin (IVIG). This case helps to remind clinicians to closely monitor platelet count once octreotide is initiated. This allows early detection of the rare entity of octreotide-induced thrombocytopenia, which can be life-threatening with extremely low platelet count nadir.

A Probable Catastrophic Antiphospholipid Antibody Syndrome/Thrombotic Storm Presenting As Rapidly Evolving Multifocal Ischemic and Hemorrhagic Strokes: A Case Report.

Catastrophic antiphospholipid antibody syndrome (CAPS) is a life-threatening disorder. It is a rare and severe form of antiphospholipid antibody (APL) syndrome characterized by widespread multisystemic thrombosis. We present a 55-year-old male patient with acute cerebellar hemorrhagic stroke who developed widespread progressive microthrombosis and macrothrombosis manifesting as progressive bilateral ischemic strokes with lower extremities deep vein thrombosis (DVT) and acute renal failure within a week of presentation. The diagnosis and initiation of therapy were established after serological confirmation. This case adds to a limited number of cases of CAPS in literature and is interesting given the rarity of CAPS and thrombotic storm (TS) as well as the lack of inciting factor triggering CAPS/thrombotic syndrome. This case also helps to remind the clinicians of the importance to consider CAPS, even prior to serological confirmation, in those with rapidly progressive thrombotic events, as delayed diagnosis and therapy can yield poor clinical outcomes.

Wernicke Encephalopathy in a Patient With Bipolar Disorder: A Case Report.

Wernicke encephalopathy (WE) is a combination of neurological findings including confusion, ataxia, and ophthalmoplegia. It is most commonly associated with patients who have a history of alcohol abuse. This aspect leads to the majority of cases going undiagnosed in non-alcoholic patients who have other potential thiamine deficiency-causing conditions such as malignancy, chronic kidney disease (CKD) on hemodialysis, hyperemesis gravidarum, and psychiatric disorders leading to starvation and malnourishment. Here we present the case of a 59-year-old female patient with decompensated bipolar disorder who came in with altered mental status and multiple syncopal episodes. On examination, she was completely confused and had a fixed gaze. She was worked up for broad differential diagnoses including stroke, arrhythmias, seizures, drug intoxication, and infections. But due to her severely malnourished appearance, Wernicke's encephalopathy was suspected early on, and she was started on thiamine therapy, to which she responded well. It was also confirmed by an MRI of the brain showing flair in the bilateral medial thalamic region. Therefore, to suspect the presence of WE in non-alcoholic patients with psychiatric disorders and to differentiate behavioral symptoms from delirium and encephalopathy is difficult and requires a high degree of clinical suspicion.

Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia Masquerading as IgM Warm Antibody Autoimmune Hemolytic Anemia in Association With Mycoplasma pneumoniae Infection: A Case Report.

Warm antibody autoimmune hemolytic anemia (AIHA) is mostly of IgG subtype. IgM subtype is extremely rare and has not been reported in association with lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM). We are reporting the case of a 75-year-old female patient who presented with severe hemolytic anemia and Mycoplasma pneumoniae pneumonia (MPP). Cold agglutinin and serum protein electrophoresis (SPEP) were negative but immunofixation was positive for IgM. Ultimately, hemolytic anemia was labeled warm antibody AIHA in association with MPP. She presented again one year later with more severe hemolytic anemia. Persistently elevated IgM was seen in immunofixation and triggered bone marrow biopsy that confirmed LPL/WM. This case highlights the clinical pearl that warm antibody AIHA in association with MPP is a rare entity and more intensive investigation to rule out other etiologies is mandated. Also, this case is rare as it is of IgM subtype warm AIHA and observed in the context of LPL/WM.

Mortality risk in chronic Chagas cardiomyopathy: a systematic review and meta-analysis.

AIMS: This study aimed to estimate the annual mortality risk and its determinants in chronic Chagas cardiomyopathy. METHODS AND RESULTS: We conducted a systematic search in MEDLINE, Web of Science Core Collection, Embase, Cochrane Library, and LILACS. Longitudinal studies published between 1 January 1946 and 24 October 2018 were included. A random-effects meta-analysis using the death rate over the mean follow-up period in years was used to obtain pooled estimated annual mortality rates. Main outcomes were defined as all-cause mortality, including cardiovascular, non-cardiovascular, heart failure, stroke, and sudden cardiac deaths. A total of 5005 studies were screened for eligibility. A total of 52 longitudinal studies for chronic Chagas cardiomyopathy including 9569 patients and 2250 deaths were selected. The meta-analysis revealed an annual all-cause mortality rate of 7.9% [95% confidence interval (CI): 6.3-10.1; I2  = 97.74%; T2  = 0.70] among patients with chronic Chagas cardiomyopathy. The pooled estimated annual cardiovascular death rate was 6.3% (95% CI: 4.9-8.0; I2  = 96.32%; T2  = 0.52). The annual mortality rates for heart failure, sudden death, and stroke were 3.5%, 2.6%, and 0.4%, respectively. Meta-regression showed that low left ventricular ejection fraction (coefficient = -0.04; 95% CI: -0.07, -0.02; P = 0.001) was associated with an increased mortality risk. Subgroup analysis based on American Heart Association (AHA) classification revealed pooled estimate rates of 4.8%, 8.7%, 13.9%, and 22.4% (P < 0.001) for B1/B2, B2/C, C, and C/D stages of cardiomyopathy, respectively. CONCLUSIONS: The annual mortality risk in chronic Chagas cardiomyopathy is substantial and primarily attributable to cardiovascular causes. This risk significantly increases in patients with low left ventricular ejection fraction and those classified as AHA stages C and C/D.

Increased mortality associated with uncontrolled diabetes mellitus in patients with pulmonary cryptococcosis: a single US cohort study.

BACKGROUND: Diabetes mellitus is an established risk factor for bacterial infections, but its role in cryptococcosis is unclear. The study aimed to determine whether uncontrolled diabetes (HbA1c >7%) was an independent risk factor for mortality in cryptococcosis. METHODS: A retrospective case-control study partially matched by age and gender was performed in patients tested for Cryptococcus infection at the University of Colorado Hospital from 2000 to 2019. A multivariable logistic regression model was used to identify mortality predictors. Cox proportional hazard model was used for survival analysis. RESULTS: We identified 96 cases of cryptococcosis and 125 controls. Among cases, cryptococcal meningitis (49.0%) and pneumonia (36.5%) constituted most infections. Cases with pulmonary cryptococcosis with uncontrolled diabetes had a higher mortality at 10 weeks (50% versus 7%, p = 0.006) and 1 year (66.7% versus 13.8%, p = 0.005) compared to pulmonary cases with controlled or no diabetes. Unadjusted Cox proportional hazard model found an increased rate of death for uncontrolled diabetes at 10 weeks [hazard ratio 8.4, confidence interval (CI): 1.4-50.8, p = 0.02] and 1 year (hazard ratio 7.0, CI: 1.7-28.4, p = 0.007) among pulmonary cryptococcosis cases. Multivariable analysis showed a significantly increased odds of 10 weeks [odds ratio (OR) = 4.3, CI: 1.1-16.5, p = 0.035] and 1 year (OR = 5.0, CI: 1.4-18.3, p = 0.014) mortality for uncontrolled diabetes among pulmonary cryptococcosis cases. After adjustment for gender, age, and case/control, for every 1% increase in HbA1c levels, the odds of pulmonary cryptococcosis mortality at 1 year increased by 11% (OR = 1.6, CI 95%: 1.1-2.3, p = 0.006). CONCLUSION: Uncontrolled diabetes is associated with worse outcomes in pulmonary cryptococcosis, including a 4-fold and 6-fold increased odds of death at 10 weeks and 1 year, respectively. Glucose control interventions should be explored to improve clinical outcomes in patients with pulmonary cryptococcosis.

Silicosis With Secondary Spontaneous Pneumothorax in the Western Rajasthan.

Objective Silicosis is one of the common occupational lung diseases caused by crystalline silica respiration. Pneumothorax is one of the most common and morbid complications of silicosis involving lung pleura. It is commonly seen unilaterally in chronic silicosis and can often be lethal. The purpose of this study is to report secondary spontaneous pneumothorax (SSP) in critically ill patients with silicosis. Methods A cross-sectional study was done between January 2019 and June 2019 at Sawai Man Singh (SMS) Medical College in Jaipur, India. A cohort of 50 patients with dyspnea and a history of silicosis were studied. A chest X-ray and sputum for acid fast bacilli were checked on all suspected cases. Results The present study showed that the mean age of patients was 38.7 years, all silicosis patients had dyspnea, and 96% of patients had severe chest pain. The results of chest X-rays concluded the evidence of silicosis. Bilateral pneumothorax was seen in three cases, right-sided pneumothorax in eight cases, and left-sided pneumothorax in 11 cases. The rate of pneumothorax incidence in silicosis patients was about 44%, which is higher than the current evidence. Six patients were managed conservatively with oxygen and bronchodilators, and 16 patients underwent through tube thoracostomy. Conclusion This study highlights the importance of considering spontaneous pneumothorax in patients who are presenting with shortness of breath and/or chest pain especially with a known history of silicosis, as the timely diagnosis can alter the management of this morbid condition which carries a high mortality rate if left untreated, compromising the lung expansion, venous return, cardiac output, oxygenation and eventually leading to death.

Lower Mortality Associated With Adjuvant Corticosteroid Therapy in Non-HIV-Infected Patients With Pneumocystis jirovecii Pneumonia: A Single-Institution Retrospective US Cohort Study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids in these patients is uncertain. This study aimed to determine if corticosteroids would reduce mortality in a cohort of HIV-negative PJP patients. METHODS: We examined a retrospective case series of patients diagnosed with PJP at the University of Colorado Hospital between 1995 and 2019. Data were collected in 71 PJP-infected patients. Twenty-eight patients were HIV-negative, and 43 were infected with HIV. We performed bivariate and forward, stepwise multivariable logistic regressions to identify mortality predictors. RESULTS: Common underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), and solid organ transplantation (10.7%). HIV-negative patients had higher rates and durations of mechanical ventilation and intensive care unit stay. Survival was significantly increased in HIV-negative patients receiving adjuvant corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (P = .034). In an adjusted multivariable model, no adjuvant corticosteroid use was associated with higher mortality (odds ratio, 13.5; 95% CI, 1.1-158.5; P = .039) regardless of HIV status. CONCLUSIONS: We found substantial mortality among HIV-negative patients with PJP, and adjuvant corticosteroid use was associated with decreased mortality. Response to corticosteroids is best established in HIV-infected patients, but emerging reports suggest a similar beneficial response in PJP patients without HIV infection. Further prospective studies may establish a more definitive role of the addition of corticosteroids among HIV-negative patients with PJP.

Ensuring the Safety of Yellow Fever Vaccination in Travelers-The Experience at a Large U.S. Academic Medical Center in Colorado.

Background: Yellow fever (YF) virus has the potential to cause fatal outcomes among at-risk individuals visiting endemic areas. Vaccinating travelers who are at risk is necessary to prevent virus-related life-threatening complications. We lack data on the clinical features of persons seeking YF vaccination. We aim to describe the characteristics of a cohort of persons receiving the YF vaccine before travel. Methods: A retrospective analysis of 964 travelers receiving the YF vaccine (Stamaril®) from Oct 2016 to Jul 2019 was performed at the University of Colorado Hospital, U.S. Percentages, means, and standard deviations were calculated. A multivariate logistic regression model was built to evaluate the association between receiving YF vaccination less than 10 days before departure and visiting friends and relatives (VFR). Results: The average age of the subjects was 39 ± 18 years with a range of nine months to 83 years. Persons who were 60 years of age and older represented 17%. Women consisted of 52%, and most of the travelers were Caucasians (64%). Travelers reported traveling to Africa (57%) or South America (40%). The primary destinations for travelers overall were Kenya (19%), Uganda (11%), and Tanzania (11%) in Africa; and Peru (14%) and Brazil (13%) in South America. The most common reasons for travel included leisure (44%), VFR (18%), and mission trips (10%). Comorbidities included a history of hematologic disorders (4%), HIV infection (2%), and diabetes mellitus (3%). The average duration between vaccine administration and travel was 43 days. Those VFR were two times more likely to receive the YF vaccination <10 days before departure. Conclusions: Identifying the type of travel, itinerary, and underlying medical conditions allows providers to administer the YF vaccine to travelers safely. There is a need to identify strategies to improve the timing of YF vaccination among VFR travelers.

Risk of Chronic Cardiomyopathy Among Patients With the Acute Phase or Indeterminate Form of Chagas Disease: A Systematic Review and Meta-analysis.

Importance: Chagas cardiomyopathy is associated with substantial morbidity and mortality. Precise estimates of the risk of developing cardiomyopathy among patients with the acute or indeterminate chronic forms of Chagas disease are lacking. Objective: To estimate the risk of developing chronic cardiomyopathy in patients with acute and indeterminate chronic forms of Chagas disease. Data Sources: A systematic search in the Cochrane Library, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), Medline, and Web of Science Core Collection databases was conducted from October 8 to October 24, 2018. Studies published between January 1, 1946, and October 24, 2018, that were written in the English, Spanish, and Portuguese languages were included. Search terms included Chagas disease; development of cardiomyopathy; latency duration; and determinants of the Chagas latency period. Study Selection: Longitudinal observational studies of participants diagnosed with the acute phase of Chagas infection or the indeterminate chronic form of Chagas disease who were followed up until the development of cardiomyopathy were included. Studies were excluded if they did not provide sufficient outcome data. Of 10 761 records initially screened, 32 studies met the criteria for analysis. Data Extraction and Synthesis: Critical appraisals of studies were performed using checklists from the Joanna Briggs Institute Reviewer's Manual, and data were collected from published studies. A random-effects meta-analysis was used to obtain pooled estimated annual rates. Data were analyzed from September 11 to December 4, 2019. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for the registration of the protocol, data collection and integrity, assessment of bias, and sensitivity analyses. Main Outcomes and Measures: Main outcomes were defined as the composite of the development of any new arrhythmias or changes in electrocardiogram results, dilated cardiomyopathy and segmental wall motion abnormalities in echocardiogram results, and mortality associated with Chagas disease. Results: A total of 5005 records were screened for eligibility. Of those, 298 full-text articles were reviewed, and 178 of those articles were considered for inclusion in the quantitative synthesis. After exclusions, 32 studies that included longitudinal observational outcomes were selected for the analysis; 23 of those studies comprised patients with the indeterminate chronic form of Chagas disease, and 9 of those studies comprised patients in the acute phase of Chagas infection. The analysis indicated that the pooled estimated annual rate of cardiomyopathy development was 1.9% (95% CI, 1.3%-3.0%; I2 = 98.0%; τ2 [ln scale] = 0.9992) in patients with indeterminate chronic Chagas disease and 4.6% (95% CI, 2.7%-7.9%; I2 = 86.6%; τ2 [ln scale] = 0.4946) in patients with acute Chagas infection. Conclusions and Relevance: Patients with the indeterminate chronic form of Chagas disease had a significant annual risk of developing cardiomyopathy. The annual risk was more than double among patients in the acute phase of Chagas infection.

Duration and determinants of Chagas latency: an etiology and risk systematic review protocol.

OBJECTIVE: The objective of this systematic review is to explore and discuss the latency duration among asymptomatic people with chronic Chagas disease. INTRODUCTION: Studies estimate the latency period of Chagas disease to be approximately 10-30 years. However, new findings may indicate that this latency period is shorter and depends on the presence of clinical factors. This systematic review protocol will explore the duration and factors affecting this latency period to inform treatment, with the potential of improving outcomes. INCLUSION CRITERIA: Eligible studies will include asymptomatic people with indeterminate Chagas disease confirmed through positive serologic testing and the absence of structural cardiomyopathy with no heart failure symptoms and normal electrocardiography results. Studies that involve a longitudinal observation period of participants will be considered. This period must start from the acute acquisition of the infection or an already established indeterminate form of the disease until the development of a primary or secondary cardiac outcome. METHODS: The following electronic databases will be searched: MEDLINE, Embase, Cochrane Library, Web of Science Core Collection and LILACS. The search will include the following concepts: Chagas disease, latency duration and determinants of the Chagas latency period. The languages will be restricted to English, Spanish and Portuguese. Two reviewers will review the selected studies for methodological quality using critical appraisal tools and conduct data extraction. Studies will, where possible, be pooled in a statistical meta-analysis. All data will be presented and synthesized through tables, summaries, figures and charts. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019118019.