Use of Fever Duration to Guide Management of Urinary Tract Infection.

BACKGROUND: The appropriate duration of antimicrobial therapy for febrile urinary tract infection (fUTI) in children has not been established. This study examined the optimal duration of treatment for fUTI in children. METHODS: We created a protocol that used fever duration to determine the duration of antibiotic administration. Transvenous antibiotics were administered until 3 days after resolution of fever, followed by oral antibiotics for 1 week. Diagnosis of fUTI was based on a fever of 37.5°C or higher and a quantitative culture of catheterized urine yielded a bacteria count of ≥5 × 104. Acute focal bacterial nephritis (AFBN) and pyelonephritis (PN) were diagnosed on the basis of contrast-enhanced computed tomography (eCT) findings. We retrospectively reviewed treatment outcomes. RESULTS: Of the 78 patients treated according to our protocol, data from 58 were analyzed-49 children (30 boys) had PN and nine (three boys) had AFBN. Blood test results showed that patients with AFBN had significantly higher white blood cell counts and C-reactive protein levels than did those with PN; however, urinary findings and causative bacteria did not differ between groups. Time to resolution of fever and duration of intravenous antibiotic administration were significantly longer in patients with AFBN than in those with PN. However, average duration of AFBN treatment was 14.2 days, which was shorter than the previously reported administration period of 3 weeks. No recurrence was observed in AFBN patients. CONCLUSIONS: A protocol that used fever duration to determine the duration of antimicrobial treatment was useful. Invasive examinations, such as eCT, were not required.

Combining serum microRNAs and machine learning algorithms for diagnosing infectious fever after HSCT.

Infection post-hematopoietic stem cell transplantation (HSCT) is one of the main causes of patient mortality. Fever is the most crucial clinical symptom indicating infection. However, current microbial detection methods are limited. Therefore, timely diagnosis of infectious fever and administration of antimicrobial drugs can effectively reduce patient mortality. In this study, serum samples were collected from 181 patients with HSCT with or without infection, as well as the clinical information. And more than 80 infectious-related microRNAs in the serum were selected according to the bulk RNA-seq result and detected in the 345 time-pointed serum samples by Q-PCR. Unsupervised clustering result indicates a close association between these microRNAs expression and infection occurrence. Compared to the uninfected cohort, more than 10 serum microRNAs were identified as the combined diagnostic markers in one formula constructed by the Random Forest (RF) algorithms, with a diagnostic accuracy more than 0.90. Furthermore, correlations of serum microRNAs to immune cells, inflammatory factors, pathgens, infection tissue, and prognosis were analyzed in the infection cohort. Overall, this study demonstrates that the combination of serum microRNAs detection and machine learning algorithms holds promising potential in diagnosing infectious fever after HSCT.

Endocrine Fever.

Fever is usually thought to be of an infectious or inflammatory etiology. In this brief communication, we explore the multifaceted connections between fever and endocrine dysfunction. Impaired resistance to infection often leads to fever in conditions like diabetes and Cushing's syndrome. Additionally, several endocrine disorders, including hyperthyroidism, subacute thyroiditis, carcinoid syndrome, and pheochromocytoma, can manifest as fever. Furthermore, fever can be an adverse effect of various endocrine treatments, such as bisphosphonates and antithyroid drugs. We refer to these scenarios as 'endocrine fever.' Increased awareness of these clinical associations can aid in prompt diagnosis and management of these conditions.

A woman in her seventies with fever and convulsions. / En kvinne i 70-årene med feber og krampeanfall.

Background: Chagas encephalitis is a rare but severe manifestation of reactivation in patients with chronic Chagas disease. Case presentation: A woman in her seventies who was immunosuppressed after a heart transplant due to Chagas disease was admitted with convulsions, headache and visual disturbances. She developed fever, confusion and repeated convulsions. Pleocytosis was found in spinal fluid. Wet-mount microscopy of spinal fluid revealed motile Trypanosoma cruzi trypomastigotes, and multiple trypomastigotes were seen on a Giemsa-stained smear, confirming reactivation of Chagas disease with meningoencephalitis. Despite benznidazole treatment, she deteriorated, exhibiting pharyngeal paralysis, aphasia and increasing somnolence. Brain CT showed pathology consistent with Chagas encephalitis. Nifurtimox was given as an adjunctive treatment. After a week of treatment, the patient began to improve. She completed 60 days of benznidazole and had regained normal cognitive and neurological function on subsequent follow-up. She had no signs of myocarditis reactivation. Interpretation: Chronic Chagas disease is common among Latin American immigrants in Europe. Reactivation with myocarditis after a heart transplant is well known, while encephalitis is a rare manifestation. We report on a case of Chagas encephalitis in an immunosuppressed patient. Microscopy of parasites in spinal fluid revealed the diagnosis. The WHO provided antiparasitic medications, and despite a severe prognosis, the patient made a full recovery.

Utility of the modified 5-item frailty index as a predictor of postoperative febrile urinary tract infection in patients who underwent ureteroscopy with laser lithotripsy.

PURPOSE: This study aimed to assess the effect of the modified 5-item frailty index on perioperative complications and surgical outcomes in patients who underwent ureteroscopy with laser lithotripsy for upper urinary tract stones. METHODS: Patients who underwent ureteroscopy with laser lithotripsy for upper urinary tract stones between 2019 and 2022 were reviewed retrospectively. Assessment was performed using the modified 5-item frailty index based on medical history (hypertension, diabetes, heart failure, chronic obstructive pulmonary disease) and functional status. Patients were categorized into the high (≥ 2) and low (≤ 1) modified 5-item frailty index groups based on the frailty score. We compared the perioperative complications and surgical outcomes between the two groups. RESULTS: Seventy-one (15.8%) and 393 (84.1%) of the 467 patients were classified into the high and low modified 5-item frailty index groups, respectively. The high modified 5-item frailty index group exhibited a significant association with increased febrile urinary tract infections compared to the low modified 5-item frailty index group [≥ 37.8 °C: 15 (20.3%) vs 13 (3.3%), p < 0.001; ≥ 38 °C: 9 (12.2%) vs 7 (1.8%), p < 0.001]. Surgical outcomes, including operative time and stone-free rate, did not differ significantly between the two groups. CONCLUSION: The modified 5-item frailty index is valuable for predicting postoperative complications, particularly febrile urinary tract infections, after ureteroscopy with laser lithotripsy for upper urinary tract stones. This index allows for practical preoperative risk assessment in patients who underwent ureteroscopy with laser lithotripsy.

Causes and outcomes of non-chemotherapy induced neutropenic fever in hospitalized adults: An observational study.

Neutropenic fever in adults undergoing chemotherapy for cancer treatment is a medical emergency and has been the focus of numerous studies. However, there is a paucity of data about non-chemotherapy induced neutropenic fever (non-CINF). We retrospectively reviewed 383 adults with neutropenic fever hospitalized at one academic medical center between October 2015 and September 2020 to characterize the frequency, causes, and outcomes of non-CINF. Twenty-six percent of cases of neutropenic fever were non-chemotherapy induced. Among these, the major causes of neutropenia were hematologic malignancy, infection, and rheumatologic disease, and the major causes of fever were infections. Patients with non-CINF had a higher 30-day mortality than those with chemotherapy induced neutropenic fever (25% vs 13%, P = .01). Non-CINF constituted > 25% of neutropenic fever events in hospitalized adults and was associated with a high mortality rate.

Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation.

BACKGROUND: Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. METHODS: Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. RESULTS: Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. CONCLUSIONS: Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

Recurrent fever leading to the diagnosis of an angiosarcoma of the adrenal gland: a case report.

BACKGROUND: Angiosarcoma of the adrenal gland is a very rare malignant vascular neoplasm. The clinical symptoms are atypical or completely absent. Angiosarcomas of the adrenal gland are therefore often discovered incidentally, and the diagnosis is made histologically after resection. CASE PRESENTATION: A 46-year-old white Spanish male who was a previous smoker and nondrinker and was slightly overweight (92 kg, 176 cm, body mass index 29.7 kg/m2) with no relevant medical history presented to the internal medicine emergency department of our hospital with an unclear 12 cm tumor of the right adrenal gland. Prior to the computed tomography scan, he had had persistent evening fevers for 4 months and unintentional weight loss of 5 kg. The laboratory results showed anemia and an elevated C-reactive protein, but no hormone production. We performed an open adrenalectomy of the right adrenal gland. Finally, the histologic findings revealed an angiosarcoma of the adrenal gland. CONCLUSION: Even though angiosarcomas of the adrenal gland are rare, the differential diagnosis of an angiosarcoma should be considered if a malignant tumor of the adrenal gland is suspected. Treatment decisions should be made on an interdisciplinary basis and preferably in a specialized center. Owing to the rarity of angiosarcomas of the adrenal gland, it is necessary to continue to share clinical experience to gain a better understanding of this particular tumor entity.

The mayo adhesive probability score predicts postoperative fever and sepsis in retrograde intrarenal surgery.

Infectious complications are among the most common and potentially life-threatening morbidities of retrograde intrarenal surgery (RIRS). Few predictive tools on these complications include radiological signs. The Mayo adhesive probability (MAP) score is an image-based scoring system that incorporates two radiological signs: perinephric fat stranding and perinephric fat thickness. Previous studies have suggested an association between these signs and febrile urinary tract infection (UTI) following lithotripsy. This study aimed to evaluate the predictive factors, including the MAP score, for post-RIRS fever and sepsis. A total of 260 patients who underwent 306 RIRS between October 2019 to December 2023 due to renal or upper ureteral stones were included in this retrospective study. Patient demographics, perioperative characteristics, stone factors, radiological signs, and MAP scores were recorded. Multivariate logistic regression analysis was used to evaluate the risk factors associated with postoperative fever and sepsis. Postoperative fever and sepsis occurred in 20.8% and 8.5% of the patients, respectively. On multivariate analysis, female gender, history of recurrent UTI, larger maximal stone diameter, and higher MAP score were independent risk factors for postoperative fever and sepsis. Identifying the risk factors for post-RIRS infectious complications is imperative to providing the proper perioperative management. The MAP score is a promising, easily calculated, image-based scoring system that predicts post-RIRS fever and sepsis.

Fever and Rash.

Infectious causes of fever and rash pose a diagnostic challenge for the emergency provider. It is often difficult to discern rashes associated with rapidly progressive and life-threatening infections from benign exanthems, which comprise the majority of rashes seen in the emergency department. Physicians must also consider serious noninfectious causes of fever and rash. A correct diagnosis depends on an exhaustive history and head-to-toe skin examination as most emergent causes of fever and rash remain clinical diagnoses. A provisional diagnosis and immediate treatment with antimicrobials and supportive care are usually required prior to the return of confirmatory laboratory testing.

[Workplace-associated fever]. / Arbeitsplatzassoziiertes Fieber oder wenn es doch das Zebra ist .

INTRODUCTION: Febrile conditions often have an infectious etiology. However, there are also fevers associated with occupational exposures. A detailed occupational history can hold the key to the diagnosis. In the case of exposure to organic dusts, the development of hypersensitivity pneumonitis (HP) is possible. Thus, HP should be considered in the presence of interstitial lung disease of unclear etiology. Failure to recognize this can have dramatic consequences and, in extreme cases, lead to lung transplantation. Differentially, organic dust toxic syndrome (ODTS) must be considered. The syndrome of metal fume fever provoked by inhalation of inorganic substances is usually benign and self-limiting. The disease manifests with fever, cough, and flu-like sensations.

Performance of Febrile Infant Algorithms by Duration of Fever.

OBJECTIVES: To analyze the performance of commonly used blood tests in febrile infants ≤90 days of age to identify patients at low risk for invasive bacterial infection (bacterial pathogen in blood or cerebrospinal fluid) by duration of fever. METHODS: We conducted a secondary analysis of a prospective single-center registry that includes all consecutive infants ≤90 days of age with fever without a source evaluated at 1 pediatric emergency department between 2008 and 2021. We defined 3 groups based on caregiver-reported hours of fever (<2, 2-12, and ≥12) and analyzed the performance of the biomarkers and Pediatric Emergency Care Applied Research Network, American Academy of Pediatrics, and Step-by-Step clinical decision rules. RESULTS: We included 2411 infants; 76 (3.0%) were diagnosed with an invasive bacterial infection. The median duration of fever was 4 (interquartile range, 2-12) hours, with 633 (26.3%) patients with fever of <2 hours. The area under the curve was significantly lower in patients with <2 hours for absolute neutrophil count (0.562 vs 0.609 and 0.728) and C-reactive protein (0.568 vs 0.760 and 0.812), but not for procalcitonin (0.749 vs 0.780 and 0.773). Among well-appearing infants older than 21 days and negative urine dipstick with <2 hours of fever, procalcitonin ≥0.14 ng/mL showed a better sensitivity (100% with specificity 53.8%) than that of the combination of biomarkers of Step-by-Step (50.0% and 82.2%), and of the American Academy of Pediatrics and Pediatric Emergency Care Applied Research Network rules (83.3% and 58.3%), respectively. CONCLUSIONS: The performance of blood biomarkers, except for procalcitonin, in febrile young infants is lower in fever of very short duration, decreasing the accuracy of the clinical decision rules.

From fever to action: diagnosis, treatment, and prevention of acute undifferentiated febrile illnesses.

Acute Undifferentiated Febrile Illness (AUFI) presents a clinical challenge, often characterized by sudden fever, non-specific symptoms, and potential life-threatening implications. This review highlights the global prevalence, types, challenges, and implications of AUFI, especially in tropical and subtropical regions where infectious diseases thrive. It delves into the difficulties in diagnosis, prevalence rates, regional variations, and potential causes, ranging from bacterial and viral infections to zoonotic diseases. Furthermore, it explores treatment strategies, preventive measures, and the critical role of the One Health approach in addressing AUFI. The paper also addresses the emerging zoonotic risks and ongoing outbreaks, including COVID-19, Rickettsia spp., and other novel pathogens, emphasizing their impact on AUFI diagnosis and management. Challenges in resource-limited settings are analyzed, highlighting the need for bolstered healthcare infrastructure, enhanced diagnostics, and collaborative One Health strategies. Amidst the complexity of emerging zoonotic threats, this review underscores the urgency for a multifaceted approach to mitigate the growing burden of AUFI, ensuring early diagnosis, appropriate treatment, and effective prevention strategies.

Elevated IL-6 levels in a patient with pheochromocytoma.

Pheochromocytoma is a chromaffin cell-derived adrenal medullary tumour and usually presents with paroxysms of hypertension, palpitations, sweating and headache due to excessive catecholamine release. These tumours can also secrete a variety of bioactive neuropeptides and hormones other than catecholamines, resulting in unusual clinical manifestations. We report a female in her mid-30s who presented with fever, anaemia, thrombocytosis and markedly elevated inflammatory markers. The fever profile, including cultures, was negative. Contrast-enhanced CT of abdomen showed a large solid-cystic right adrenal lesion with elevated plasma-free normetanephrine levels suggestive of pheochromocytoma. The fever persisted despite empirical antibiotics and antipyretics. Interleukin-6 (IL-6) levels were elevated (41.2 pg/mL (3-4 pg/mL)). She was initiated on naproxen (NPX) at a dose of 250 mg two times per day. The patient responded to NPX, and after stabilisation, she underwent an adrenalectomy. There was a complete resolution of fever with normalisation of IL-6 levels postoperatively.

Kikuchi-Fujimoto Disease: A Case Report of Prolonged Fever and Lymphadenopathy in a Young Girl.

Kikuchi-Fujimoto disease (KFD) is a benign and self-limited disorder that usually presents with regional cervical lymphadenopathy and fever. We report a case of a 12-year-old female who complained of fever, night sweating, significant weight loss, and tender right cervical lymph node enlargement for 2 months. A full workup including laboratory tests and imaging studies, an excisional biopsy, and histopathological analysis were done, and the diagnosis of KFD was confirmed. The patient was treated with analgesia and oral prednisolone, resulting in good improvement. A high degree of clinical suspicion is imperative for physicians, given the rarity of the disease and the associated diagnostic challenges.