The Development of Myxedema Coma in the Setting of Euthyroid Sick Syndrome: A Diagnostic Dilemma and Review of Management Strategies.

Euthyroid sick syndrome (ESS), also referred to as nonthyroidal illness syndrome, is an intriguing condition characterized by dysregulation of thyroid hormones despite normal thyroid gland function. It is diagnosed by low serum triiodothyronine levels, and, in some cases, other thyroid hormones such as thyroxine and thyroid-stimulating hormone may be affected. This condition arises via various physiologic mechanisms and is associated with intensive care unit (ICU) admissions, caloric deprivation, and severe illness. Myxedema coma (MC) is a rare medical emergency with a high mortality rate. It is caused by severe hypothyroidism, resulting in multiorgan failure with features including adrenal insufficiency, thermal dysregulation, and altered mentation. Generally, it is observed in untreated and poorly managed cases of hypothyroidism. However, stress from infections, surgical procedures, and medical comorbidities may precipitate this condition. It is particularly uncommon to see MC arise in the setting of ESS, especially in a patient with no history of thyroid disease, which makes this diagnosis easy to miss. In our case, a 36-year-old female presented with septic shock and was admitted to the ICU, where she subsequently developed ESS and features of MC. This case report aims to explore the risk factors, features, and diagnostic and therapeutic management of these conditions, as well as the diagnostic challenges that arise when these diseases present simultaneously.

State of the art of sepsis care for the emergency medicine clinician.

Sepsis impacts 1.7 million Americans annually. It is a life-threatening disruption of organ function because of the body's host response to infection. Sepsis remains a condition frequently encountered in emergency departments (ED) with an estimated 850,000 annual visits affected by sepsis each year in the United States. The pillars of managing sepsis remain timely identification, initiation of antimicrobials while aiming for source control and resuscitation with a goal of restoring tissue perfusion. The focus herein is current evidence and best practice recommendations for state-of-the-art sepsis care that begins in the ED.

A Rare Cause of Septicemia After Pork Meat Ingestion.

Streptococcus suis infection in humans occurs due to consuming raw or undercooked pork meat and after contact with pigs. The highest prevalence occurs in Southeast Asian countries, which have the largest pork industry. We report the first case of a 50-year-old healthy male patient from a rural area of São Paulo, Brazil, with septicemia from undercooked pork meat ingestion. The patient was diagnosed at the emergency department with septicemia and multiple organ dysfunctions, including streptococcal toxic shock syndrome. Blood cultures yielded the growth of S. suis. The patient was treated with ceftriaxone and was maintained for two weeks, according to sensitivity tests. The outcome was favorable but developed deafness as a sequela. This report aims to give importance to recognizing this disease regarding typical signs and symptoms and occupational and epidemiological history.

Circular RNAs as potential biomarkers for male severe sepsis.

Circular RNAs (circRNAs) play important roles in many human diseases. However, their role in the development of severe sepsis, a condition that remains one of the main causes of death in intensive care units, has not yet been defined. In this study, we interrogated the molecular mechanisms of circRNAs in severe sepsis. We profiled the expression levels of 5,680 circRNAs in plasma extracted from blood samples of 9 severe sepsis cases or 9 controls (male, age 78 ± 7) using the Human circRNA Array. To enrich protein-coding genes hosting severe sepsis-related circRNAs, we conducted gene ontology and pathways analyses. Out of the identified 760 differentially expressed circRNAs, 404 were upregulated while 356 were downregulated (fold change [FC] ≥2 or ≤-2, and false discovery ratio <0.05). Circ-0008285 (located in exons of CDYL), showed significant upregulation in severe sepsis with an FC of 13.7, and Bonferroni-corrected P < 0.05/5. In silico analysis identified Circ-0008285 interacting microRNAs as well as protein-coding genes. We systematically investigated the differential expression pattern of circRNAs in severe sepsis. The circRNAs we identified might serve as potential biomarkers for diagnosis and prognosis of sepsis.

Transient Acquired Amegakaryocytic Thrombocytopenia in the Setting of Severe Sepsis: A Case Report.

Acquired amegakaryocytic thrombocytopenia (AATP) is a rare disorder in which severely low platelet levels occur due to reduced or complete absence of megakaryocytes in the bone marrow. The pathophysiology of this disease is not fully understood, although anti-thyroid peroxidase antibodies (anti-TPO) binding to cellular-myeloproliferative leukemia (c-mpl) receptors is a proposed mechanism. Currently, no standard published guideline for treatment exists, but immunosuppressive therapies have been used based on the proposed mechanism and associated conditions. We present a case of a 57-year-old male who presented to the hospital with a 3-day history of progressive weakness and dysphagia. He had recently been discharged from an outside health system after evaluation for suspected gastrointestinal bleeding, although esophagogastroduodenoscopy and colonoscopy did not uncover a source of bleeding. Fifteen days later, he was admitted to our hospital for septic shock and acute renal failure with suspected lower gastrointestinal bleeding (melena on presentation). He was found to have a rapidly declining platelet count with a nadir of 0. Due to severe thrombocytopenia, filgrastim was administered. A bone marrow biopsy revealed findings consistent with amegakaryocytosis with otherwise preserved cell lines. Hematologic labs improved with the initiation of appropriate treatment for severe sepsis. After performing an extensive workup, the likely etiology of transient AATP in this case was severe sepsis-induced immune dysregulation and bone marrow suppression.

An Interesting Case of Cholangitis.

Ascariasis is one of the most common parasitic infections in the world. It is mostly asymptomatic; however, rarely when the worms migrate to the biliary tract, they can cause biliary ascariasis. It typically presents with pain abdomen, jaundice, and fever. This case report is about a patient who presented with fever, icterus, breathlessness, loose stools, and altered sensorium but had no abdominal pain. The patient was diagnosed with biliary ascariasis using ultrasound and endoscopic retrograde cholangiopancreatography (ERCP). The patient was treated with endoscopic sphincterotomy and albendazole. The patient remained stable after 10 days. The absence of abdominal pain highlights the variability of the presentation of biliary ascariasis.

Core sepsis-related competencies for medical students: an international consensus by Delphi technique.

BACKGROUND: Sepsis is a life-threatening condition which may arise from infection in any organ system and requires early recognition and management. Healthcare professionals working in any specialty may need to manage patients with sepsis. Educating medical students about this condition may be an effective way to ensure all future doctors have sufficient ability to diagnose and treat septic patients. However, there is currently no consensus on what competencies medical students should achieve regarding sepsis recognition and treatment. This study aims to outline what sepsis-related competencies medical students should achieve by the end of their medical student training in both high or upper-middle incomes countries/regions and in low or lower-middle income countries/regions. METHODS: Two separate panels from high or upper-middle income and low or lower-middle income countries/regions participated in a Delphi method to suggest and rank sepsis competencies for medical students. Each panel consisted of 13-18 key stakeholders of medical education and doctors in specialties where sepsis is a common problem (both specialists and trainees). Panelists came from all continents, except Antarctica. RESULTS: The panels reached consensus on 38 essential sepsis competencies in low or lower-middle income countries/regions and 33 in high or upper-middle incomes countries/regions. These include competencies such as definition of sepsis and septic shock and urgency of antibiotic treatment. In the low or lower-middle income countries/regions group, consensus was also achieved for competencies ranked as very important, and was achieved in 4/5 competencies rated as moderately important. In the high or upper-middle incomes countries/regions group, consensus was achieved in 41/57 competencies rated as very important but only 6/11 competencies rated as moderately important. CONCLUSION: Medical schools should consider developing curricula to address essential competencies, as a minimum, but also consider addressing competencies rated as very or moderately important.

ACR Appropriateness Criteria® Sepsis.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. A search for the underlying cause of infection typically includes radiological imaging as part of this investigation. This document focuses on thoracic and abdominopelvic causes of sepsis. In 2017, the global incidence of sepsis was estimated to be 48.9 million cases, with 11 million sepsis-related deaths (accounting for nearly 20% of all global deaths); therefore, understanding which imaging modalities and types of studies are acceptable or not acceptable is imperative. The 5 variants provided include the most commonly encountered scenarios in the setting of sepsis along with recommendations and data for each imaging study. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

A Case Report of Sepsis Secondary to Perforated Cholecystitis in the Presence of Severe Aortic Stenosis: Diagnosis and Management.

Gallbladder perforation is a rare complication of acute cholecystitis that is associated with significant morbidity and mortality. Many cases of gallbladder perforation are not diagnosed until surgery, as the physical symptoms closely mimic acute cholecystitis. Gallbladder perforation is most common among older males with associated comorbidities, and preoperative assessment of comorbidities, particularly cardiac, is critical to determine the appropriate clinical course. We report a case of a 77-year-old male who presented initially with low blood pressure and right upper quadrant pain (RUQ) after not feeling well for five days. CT of the abdomen/pelvis with IV contrast demonstrated acute perforated cholecystitis, and general surgery was consulted for a cholecystectomy. Due to the patient's past medical history of severe aortic stenosis (AS), cholecystectomy was deferred and a cholecystostomy tube was placed by interventional radiology. This report aims to provide an example of a case of perforated cholecystitis with sepsis and how it can be diagnosed and managed non-surgically in the presence of pre-existing severe AS.

Unusual Acute Appendicitis Complicated by Sepsis, Evisceration, and Ileostomy: A Case Report.

Acute appendicitis stands as a prevalent cause necessitating surgical intervention globally, predominantly affecting young adults and children, with notably lower incidence among the elderly. Timely diagnosis facilitates effective management, mitigating the risk of severe complications. In this report, we present the case of a 59-year-old patient whose delayed diagnosis and consequently delayed surgical treatment led to serious complications. After the appendectomy, the patient, due to developing sepsis, was transferred to the intensive care unit. On the seventh postoperative day, complications were found in the form of wound dehiscence along with perforation of the jejunum. The second surgery involved a classic laparotomy, encompassing partial resection of the small intestine, and the creation of a single-barrel ileostomy. Further conservative treatment was implemented, and drainage of the abscess was performed. After treatment in the ICU, the patient was transferred to the surgical ward for further treatment. During the hospital stay, further conservative treatment was implemented, resulting in the improvement of the patient's general condition and resolution of symptoms. The patient was discharged home in optimal general condition with recommendations. After six months, the patient was brought to the surgical ward for reconstructive surgery to reestablish gastrointestinal continuity, which was carried out successfully.

ACR Appropriateness Criteria® Sepsis

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. A search for the underlying cause of infection typically includes radiological imaging as part of this investigation. This document focuses on thoracic and abdominopelvic causes of sepsis. In 2017, the global incidence of sepsis was estimated to be 48.9 million cases, with 11 million sepsis-related deaths (accounting for nearly 20% of all global deaths); therefore, understanding which imaging modalities and types of studies are acceptable or not acceptable is imperative. The 5 variants provided include the most commonly encountered scenarios in the setting of sepsis along with recommendations and data for each imaging study. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Unraveling the Complexity: Ehrlichiosis-Induced Septic Shock and Acute Respiratory Distress Syndrome.

Human monocytic ehrlichiosis typically presents with nonspecific cold-like symptoms and a history of recent tick exposure, often responding well to early treatment. Here, we present the case of a 67-year-old immunocompetent male who initially presented with fevers, chills, dysuria, and hematuria, leading to admission to the intensive care unit with septic shock and acute respiratory distress syndrome (ARDS), which was later attributed to Ehrlichia chaffeensis infection. Prompt treatment with doxycycline resulted in a full clinical recovery. This case highlights the rare occurrence of severe ehrlichiosis and provides insights into its effective management based on updated literature.

A Case Report of Sepsis-Induced Dilated Cardiomyopathy Secondary to Human Metapneumovirus Infection.

Sepsis is a medical emergency that describes the body's systemic immunological response to an infectious process that can lead to end-stage organ dysfunction and death. Sepsis-induced cardiomyopathy (SICM) is an increasingly recognized form of transient cardiac dysfunction characterized by left ventricular dilation, depressed ejection fraction, and recovery in 10 days without cardiac-related medical intervention. Injury to the myocardium by inflammatory cytokines has been proposed as one of the main causative mechanisms. Human metapneumovirus (hMPV) is a paramyxovirus and a common cause of respiratory tract infection that has been reported to modulate chemical mediators that produce inflammatory cytokines. Extra-pulmonary cardiac complications of hMPV have been reported; but literature on SICM associated with hMPV are very rare. We describe a case of a 43-year-old male with no known cardiac history diagnosed with SICM associated with hMPV. His sepsis was managed in the intensive care unit, and his heart ejection fraction improved within 10 days without the initiation of guideline-directed medical therapy.

Clinical value of TAT, PIC and t-PAIC as predictive markers for severe sepsis in pediatric patients.

Objective: Sepsis in pediatric patients can progress to severe sepsis, and identifying biomarkers of this progression may permit timely intervention to prevent it. This study aimed to investigate the ability of thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC) and tissue-type plasminogen activator-inhibitor complex (t-PAIC) to predict severe sepsis in pediatrics early. Methods: 148 eligible pediatric sepsis patients were enrolled in this study, and were then divided into those who progressed to severe sepsis (n = 50) or not (n = 98). Serum levels of TAT, PIC, and t-PAIC were analysed, and simplified pediatric critical illness score (PCIS) and DIC score were calculated on the day of pediatric sepsis diagnosis. Results: Compared with sepsis patients, severe sepsis patients had higher levels of TAT, PIC and t-PAIC. Correlation analysis revealed that TAT, PIC and t-PAIC were significantly correlated with simplified PCIS and DIC score. ROC curve analysis suggested that TAT, PIC and t-PAIC could serve as biomarkers for predicting severe sepsis with the AUC up to 0.862, 0.759 and 0.851, respectively. Stratified analysis demonstrated that the patients with increased levels of TAT, PIC and t-PAIC had worse illness severity and clinical outcome. Univariate logistic regression analysis revealed that TAT, PIC and t-PAIC were all risk factors for severe sepsis, yet only TAT and t-PAIC were independent risk factors in multivariate model. Conclusions: TAT, PIC and t-PAIC could serve as biomarkers for predicting severe sepsis, and correlated with illness severity in pediatrics, what's more, serum levels of TAT and t-PAIC may be independent risk factors for pediatric severe sepsis.

Outcome of Tocilizumab Treatment in Febrile Neutropenic Children with Severe Sepsis/Septic Shock in a Single-Center Retrospective Case Series.

PURPOSE: To assess the efficacy of an IL-6 blockade with tocilizumab on treatment outcome of severe sepsis/septic shock in children with febrile neutropenia. METHODS: We performed a retrospective study of febrile neutropenic patients younger than 18 years old who developed severe sepsis/septic shock at a single medical center between November 2022 and October 2023. RESULTS: Seven patients with febrile neutropenia complicated with severe sepsis/septic shock were identified. Four of seven patients received tocilizumab in addition to standard of care. The median IL-6 level before administration of tocilizumab was 14,147 pg/mL (range: 672-30,509 pg/mL). All four patients successfully recovered from severe sepsis/septic shock. Three of seven patients received standard of care without tocilizumab. IL-6 levels were checked intwo2 patients, with a median of 1514.5 (range: 838-2191). Only one of three (33%) patients without tocilizumab therapy made a full recovery from severe sepsis/septic shock. The mortality rate was higher in patients without tocilizumab therapy compared to patients with tocilizumab therapy (67% vs. 0%). CONCLUSIONS: Administration of tocilizumab reduced mortality of severe sepsis/septic shock in children with febrile neutropenia. However, it warrants confirmation with a larger number of patients and a longer follow-up.

Non-albicans Candida Infection as a Rare Cause of Emphysematous Pyelonephritis in an Uncontrolled Diabetic Patient: A Case Report.

The uncommon but dangerous condition known as emphysematous pyelonephritis (EPN) usually affects people with diabetes. This potentially fatal illness is characterized by gas-forming necrosis of the kidneys and surrounding tissues, typically brought on by urinary tract bacteria. Fungal EPN, less prevalent than bacterial EPN, has been reported in a few isolated cases. Cultures of the urine or blood often detect the infection. With an 18% fatality rate, EPN is still a serious illness despite advancements in therapy. High suspicion for EPN is critical in diabetic patients experiencing pyelonephritis. Interestingly, women with uncontrolled diabetes seem to be more susceptible. While Escherichia coli is the usual culprit, rare cases involve Candida species. This case report describes a pathogen that is rarely encountered and causes EPN. A diabetic woman in her sixties without prior hospitalizations presented with a sudden fever and excruciating abdominal pain. The patient also complained of abdominal distension with reduced urine output and breathlessness at rest. Investigations revealed left-sided EPN that was "WAN Type 1." We treated the patient according to culture sensitivity with systemic antifungals, percutaneous nephrostomy (PCN), and ureteral stenting (double J stent or DJ stent). Following successful treatment, the patient recovered and was discharged. This case highlights the importance of considering uncommon causes, even in seemingly typical presentations of EPN. Our case is unique as the patient had an infection with non-albicans Candida with a complication of anuric acute kidney injury and uncontrolled diabetes mellitus.

Familial Hemophagocytic Lymphohistiocytosis (FHLH) Perforin Deficiency: A Case Study and Literature Review.

Hemophagocytic lymphohistocytosis (HLH) is a severe and fatal immunological disorder that is either primary (i.e., familial) or secondary (i.e., acquired). The primary type comprises autosomal recessive disorders with gene mutations related to natural killer cells and cytotoxic T-cells, whereas the secondary type is related to other pathological causes, such as Epstein-Barr virus, bacterial or fungal infection, autoimmune conditions or autoinflammatory diseases, metabolic disorders, and cancer. In this report, we discuss a 37-day-old male who was brought to the emergency room with fever, decreased activity, and hepatosplenomegaly, with a strong family history of unknown cause of death for three siblings who died at the ages of one to two months. A whole exome sequencing confirmed the clinical diagnosis of familial HLH due to mutation in the PRF1 gene. We note the special importance of genetic counselling and antenatal screening or early neonatal screening in families affected by HLH, as this case highlights the importance of early diagnosis and intervention of primary HLH.

Circulating micronutrient levels and their association with sepsis susceptibility and severity: a Mendelian randomization study.

Background: Sepsis, a global health challenge, necessitates a nuanced understanding of modifiable factors for effective prevention and intervention. The role of trace micronutrients in sepsis pathogenesis remains unclear, and their potential connection, especially with genetic influences, warrants exploration. Methods: We employed Mendelian randomization (MR) analyses to assess the causal relationship between genetically predicted blood levels of nine micronutrients (calcium, ß-carotene, iron, magnesium, phosphorus, vitamin C, vitamin B6, vitamin D, and zinc) and sepsis susceptibility, severity, and subtypes. The instrumental variables for circulating micronutrients were derived from nine published genome-wide association studies (GWAS). In the primary MR analysis, we utilized summary statistics for sepsis from two independent databases (UK Biobank and FinnGen consortium), for initial and replication analyses. Subsequently, a meta-analysis was conducted to merge the results. In secondary MR analyses, we assessed the causal effects of micronutrients on five sepsis-related outcomes (severe sepsis, sepsis-related death within 28 days, severe sepsis-related death within 28 days, streptococcal septicaemia, and puerperal sepsis), incorporating multiple sensitivity analyses and multivariable MR to address potential heterogeneity and pleiotropy. Results: The study revealed a significant causal link between genetically forecasted zinc levels and reduced risk of severe sepsis-related death within 28 days (odds ratio [OR] = 0.450; 95% confidence interval [CI]: 0.263, 0.770; p = 3.58 × 10-3). Additionally, suggestive associations were found for iron (increased risk of sepsis), ß-carotene (reduced risk of sepsis death) and vitamin C (decreased risk of puerperal sepsis). No significant connections were observed for other micronutrients. Conclusion: Our study highlighted that zinc may emerges as a potential protective factor against severe sepsis-related death within 28 days, providing theoretical support for supplementing zinc in high-risk critically ill sepsis patients. In the future, larger-scale data are needed to validate our findings.

A Case Report of Necrotizing Pneumonia Due to Burkholderia cepacia Syndrome.

Burkholderia cepacia ​​​​​​(B. cepacia) complex is a highly resistant gram-negative pathogen known to cause lung infection in cystic fibrosis, chronic granulomatous disease, and immunocompromised patients. However, it may rarely infect immunocompetent patients as well. Here, we present the case of a 30-year-old male patient who was treated for B. cepacia pneumonia in the hospital, discharged with oral antibiotics, and returned two months later with recurring B. cepacia pneumonia and bacteremia. The patient rapidly declined over the next 24 hours and expired in the intensive care unit. This case is significant as it is one of very few published cases of cepacia syndrome in a patient with no evidence of immunodeficiency. In conclusion, cases of B. cepacia pneumonia must be monitored vigilantly for progression to cepacia syndrome, even in immunocompetent patients. Additional studies regarding optimized antibiotic regimens and effective treatment modalities for B. cepacia infection are warranted.

Hierarchical Capability in Distinguishing Severities of Sepsis via Serum Lactate: A Network Meta-Analysis.

Background: Blood lactate is a potentially useful biomarker to predict the mortality and severity of sepsis. The purpose of this study is to systematically review the ability of lactate to predict hierarchical sepsis clinical outcomes and distinguish sepsis, severe sepsis and septic shock. Methods: We conducted an exhaustive search of the PubMed, Embase and Cochrane Library databases for studies published before 1 October 2022. Inclusion criteria mandated the presence of case-control, cohort studies and randomized controlled trials that established the association between before-treatment blood lactate levels and the mortality of individuals with sepsis, severe sepsis or septic shock. Data was analyzed using STATA Version 16.0. Results: A total of 127 studies, encompassing 107,445 patients, were ultimately incorporated into our analysis. Meta-analysis of blood lactate levels at varying thresholds revealed a statistically significant elevation in blood lactate levels predicting mortality (OR = 1.57, 95% CI 1.48-1.65, I2 = 92.8%, p < 0.00001). Blood lactate levels were significantly higher in non-survivors compared to survivors in sepsis patients (SMD = 0.77, 95% CI 0.74-0.79, I2 = 83.7%, p = 0.000). The prognostic utility of blood lactate in sepsis mortality was validated through hierarchical summary receiver operating characteristic curve (HSROC) analysis, yielding an area under the curve (AUC) of 0.72 (95% CI 0.68-0.76), accompanied by a summary sensitivity of 0.65 (95% CI 0.59-0.7) and a summary specificity of 0.7 (95% CI 0.64-0.75). Unfortunately, the network meta-analysis could not identify any significant differences in average blood lactate values' assessments among sepsis, severe sepsis and septic shock patients. Conclusions: This meta-analysis demonstrated that high-level blood lactate was associated with a higher risk of sepsis mortality. Lactate has a relatively accurate predictive ability for the mortality risk of sepsis. However, the network analysis found that the levels of blood lactate were not effective in distinguishing between patients with sepsis, severe sepsis and septic shock.