Recurrent Fever Research Articles

P-07 Unraveling the Mystery-Conn's Syndrome

Abstract Background Conn's syndrome, also known as primary aldosteronism, is a rare disease that can manifest at a young age. Resolving the underlying cause of hypertension is crucial, as seen in this case report. Clinical Case A 17-year-old female patient was admitted with a history of recurrent fever over the past 6 months, bifrontal headaches, palpitations, and myalgia for the past 4 months. Examination revealed resistant hypertension, and laboratory results showed persistent hypokalemia and an elevated aldosterone/renin ratio. CT imaging revealed a left adrenal adenoma. A laparoscopic intervention successfully addressed the uncontrolled hypertension. Histological examination confirmed a diagnosis of a benign adrenal cortical adenoma. Conclusion Post-surgery, the patient's overall condition significantly improved, and blood pressure was effectively controlled. This case report underscores the rare presentation of Conn's syndrome in young individuals and emphasizes the importance of investigating specific underlying causes of hypertension to prevent associated morbidity and mortality.Figure 1.Conns syndrome, CT scan, histology section gross.CECT scan of abdomen and pelvis - left adrenal adenoma gross section - cut section adrenal gland -showing 2 cysts one on medial side 1*1cm and inferiolateral side 1*0.5cm histology of the removed adrenal confirmed diagnosis of benign adrenal cortical adenoma Table 1.Conns syndrome investigations Table 2.Conns syndrome investigations

Disseminated Talaromyces marneffei infection associated with haemophagocytic syndrome in an HIV-negative patient in northern China: a case report

BackgroundTalaromyces marneffei is endemic to eastern India, Southeast Asia, and Guangdong and Guangxi provinces in China. It is common in immunocompromised individuals, especially in HIV-infected patients.Case presentationA 66-year-old male who had a history of hypertension and resided in Shandong Province (Northern China) was admitted for recurrent fever for one month. The patient had recurrent fever, multiple lymphadenopathies, hepatosplenomegaly, a back rash, and a progressive decrease in white blood cells and platelets. Talaromyces marneffei was isolated from peripheral blood and bone marrow after admission, and suspected fungal cells were found via lymph node pathology. The patient’s infection secondary to haemophagocytic syndrome continued to worsen despite antifungal, anti-inflammatory, and symptomatic treatment, leading to death due to multiple-organ failure.ConclusionAlthough rare, infection due to Talaromyces marneffei in HIV-negative patients has been increasing in recent years, and we should be vigilant about “new” infections in nonendemic areas.

Gastric inflammatory myofibroblastic tumor presented with severe anemia and inflammation: a case report

BackgroundInflammatory myofibroblastic tumor (IMT) is a rare stromal tumor, often found in children and young adults, and most commonly occurs in the lungs. Surgical resection is considered the standard treatment for localized IMT, although only limited data exist. Gastric IMT in adults is extremely rare, and there are no established guidelines for its treatment.Case presentationA 69-year-old male presented with persistent fatigue and weakness. Laboratory examination revealed severe anemia and inflammation. Upper gastrointestinal endoscopy at admission revealed a 40-mm type I softish tumor in the lesser curvature of the gastric body, without apparent hemorrhage. Repeated biopsies, including partial resection with snare, failed to give a definitive diagnosis. Computed tomography (CT) revealed a massive lesion at the gastric body, protruding into the gastric lumen, which was consistent with the gastric tumor. After admission, the patient developed anemia refractory to frequent blood transfusions despite the absence of apparent gastrointestinal bleeding. In addition, the patient had recurrent fevers of 38 °C or higher, and persistent high inflammatory levels. Fluorodeoxyglucose-positron emission tomography (FDG-PET) CT 1 month after the first visit exhibited an increased FDG uptake in the gastric tumor. In addition, this CT scan revealed a rapid increase in tumor size to 75 mm. It was suspected that the undiagnosed gastric tumor caused these serious clinical symptoms, and he underwent distal gastrectomy and cholecystectomy. The gross image of the tumor showed an 80-mm cauliflower-like shape with a gelatinous texture. The histopathological diagnosis was IMT. The postoperative course was uneventful, and the patient’s symptoms subsided drastically, improving both anemia and systemic inflammation. The patient has shown no recurrence or relapse of the symptoms over one and a half years.ConclusionsIn this case, the tumor resection finally enabled the diagnosis of IMT and resolved the clinical symptoms. Despite its predominantly benign morphological nature, some cases of IMT present clinically adverse courses. Surgical treatment may lead to its final diagnosis and improvement of clinical symptoms.

Enteric Duplication Cyst –A Rare Congenital Anomaly in Adolescence Presenting as Recurrent Pain Abdomen

Case Report: Presented by Dr. Harleen Bawa and Dr. Parthasarathi Hota, this case involves an 18-year-old male with recurrent abdominal pain, nausea, and fever. Initially suspected of congenital gastrointestinal malformation at 1 year, the patient underwent conservative management until symptoms reappeared. Imaging revealed blind-ended tubular structures attached to the small bowel, prompting further investigation for a definitive diagnosis. Management: An exploratory laparotomy revealed an enteric duplication cyst in the ileal region, 50 cm from the ileocecal junction. Resection of the involved ileum with end-to-end anastomosis was performed. Mesenteric lymphadenopathy and an inflamed appendix were also addressed. Biopsy results indicated changes consistent with chronic appendicitis. In Radiological findings CT images displayed well-defined blind-ended tubular structures arising from the distal ileum, suggesting Meckel’s diverticulum. Fluid density cystic lesions near the duodenum and pancreas raised the possibility of an enteric duplication cyst. Discussion: Enteric duplication cysts, though rare, can manifest with varied symptoms, including recurrent abdominal pain and intestinal obstruction. Imaging techniques such as CT, USG, and technetium pertechnetate scanning aid in diagnosis. Resection of the cyst and adjacent intestine with end-to-end anastomosis is a common surgical approach. The prognosis is excellent when complete excision is possible without compromising intestinal length. Conclusion: Enteric duplication cysts, located along the gastrointestinal tract, may present challenges in diagnosis and management. Surgical intervention, guided by imaging and clinical findings, often leads to favorable outcomes. Awareness of potential complications, such as bowel obstruction and bleeding, is crucial for timely intervention.

Outcome following acute and recurrent rheumatic fever

ABSTRACT Background Rheumatic carditis is the leading cause of permanent disability caused by damage of the cardiac valve. This study aimed to determine the outcome and predictors of valve surgery in patients with acute rheumatic fever (ARF) and recurrent rheumatic fever (RRF). Methods This was a retrospective study of patients diagnosed with ARF and RRF between 2006 and 2021. The predictors of valve surgery were analysed using multivariable Cox proportional regression. Results The median age of patients with ARF and RRF (n=92) was 11 years (range 5–18). Seventeen patients (18%) were diagnosed with RRF. The most common presenting symptoms included clinical carditis (87%), heart failure (HF) (63%), fever (49%) and polyarthralgia (24%). Patients with moderate-to-severe rheumatic carditis (88%) were given prednisolone. After treatment, the severity of valvular regurgitation was reduced in 52 patients (59%). Twenty-three patients (25%) underwent valve surgery. The incidence of HF, RRF, severe mitral regurgitation on presentation, left ventricular enlargement and pulmonary hypertension was greater in the surgical group than in the non-surgical group. Recurrent rheumatic fever (hazard ratio 7.9, 95% CI 1.9–33.1), tricuspid regurgitation (TR) gradient ≥ 42 mmHg (HR 6.3, 95%CI 1.1–38.7) and left ventricular end-diastolic dimension (LVEDD) ≥6 cm (HR 8.7, 95% CI 2.1–35.9) were predictors of valve surgery (multivariable Cox proportional regression analysis). Conclusion Clinical carditis was the most common presenting symptom in patients with ARF and RRF. The majority of patients responded positively to prednisolone. These findings highlight the predictors of valve surgery following ARF, including RRF, TR gradient ≥ 42 mmHg and LVEDD ≥ 6 cm. Abbreviations: ARF: acute rheumatic fever; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; GAS: group A beta-haemolytic Streptococcus; HF: heart failure; HR: hazard ratio; LVEDD: left ventricular end-diastolic dimension; MR: mitral regurgitation; RHD: rheumatic heart disease; RRF: recurrent rheumatic fever; TR: tricuspid regurgitation.

Immunodeficiency 70 (IMD 70)

Background: Immunodeficiency 70 is a rare disease and there are only very few cases in the literature. Case History: Young boy in his early 20’s from Indian subcontinent presented with recurrent episodes of fever, oral ulcers, loss of weight for past 3 years. Four episodes (july 2019, april 2020, APRIL 2021, Jan 2022) of fever, each high grade associated with chills, rigor, nausea, myalgia, throat pain, holo-cranial headache, painful oral ulcers over the tongue and painless over lips. Initial episode of fever was associated with leucopenia (3200) and thrombocytopenia (122000), acute kidney injury (creatinie-3.0) and pyelonephritis, transaminitis. He received 2 weeks of parenteral antibiotics and improved. Subsequent episodes of fever is not associated with any localizing symptoms or signs. No history Suggestive of connective tissue disease. Family history was non contributory. Physical examination: He was febrile (101 degree F), pulse rate 100/minute, respiratory rate 18/minute, tongue ulceration in lateral border, no lymphadenopathy, no organomegaly, normal sytemic examination. Evaluation: The patient was evaluated for chronic infections, hematalogical malignancy, Behcet’s disease, auto inflammatory syndromes like Haplo insufficiency of A20. His complete blood count, electrolytes, renal function test, liver function test urine microscopy, blood culture were normal. CRP was elevated (58 mg/l). Tzanck smear from buccal mucosa was negative. CT thorax and abdomen showed no significant lymphadenopathy, organomegaly, evidence of infections or malignancy. In view of oral ulcers & fever Behcet’s disease was considered and HLA b51 was sent and came negative. Exome genome sequencing was done to diagnose immunodeficiency or autoinflammatory syndromes which came positive for immunodeficiency 70. Treatment: He was treated with colchicine and fever subsided and leucopenia improved Discussion: Immunodeficiency-70 (IMD70) is an autosomal dominant immunologic disorder characterized by severe cutaneous warts on the hands, feet, and face, suggesting increased susceptibility to human papillomavirus (HPV) infection. Affected individuals may also have recurrent bacterial infections like pneumonia, boils, sinusitis, as well as feature of autoinflammation, such as colitis, celiac disease, and retinal vasculitis. Laboratory studies show decreased CD4+ T cells and decreased CD19+ B cells; hypogammaglobulinemia, combined T cell and B cell immunodeficiency characterized by decreased CD4+ T cells, decreased CD19+ B cells, recurrent bacterial infections, and severe cutaneous warts on the hands, feet, and face that has material basis in heterozygous mutation in IVNS1ABP on chromosome 1q25.3.

Cryopyrin-associated periodic fever syndrome (CAPS) presenting as early-onset dementia, lacking typical recurrent fever or skin rash: a case report

A 54-year-old man with a university degree was admitted to our hospital because of a two-year history of progressive dementia. He had familial sensorineural hearing loss and had been treated for epilepsy since his 30s. On admission, he showed severe dementia and parkinsonism without fever or skin rash. Systemic inflammation was evident, and the CSF cell count and IL-6 level were elevated to 53/μl and 307 ‍pg/ml, respectively. Brain MRI demonstrated diffuse brain atrophy. More detailed anamnesis revealed a history of rheumatoid arthritis in childhood and aseptic meningitis in his 20s. Genetic examination for autoinflammatory diseases demonstrated compound heterozygotic mutations in the NLRP3 gene, causing cryopyrin-associated periodic fever syndrome (CAPS). This case was atypical CAPS presenting as early-onset progressive dementia, without recurrent fever or urticaria-like eruption which are usually seen in this disease.

Unraveling the genome: Familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an inherited, autoinflammatory disease with a high prevalence in Middle Eastern and Mediterranean populations including Turks, Iranian, Spanish, Sephardic Jews, Arabs, and other Mediterranean ethnic groups. Autoinflammatory diseases are genetically predetermined disorders with multisystem effects primarily caused by defects in innate immunity. Although primarily known for an autosomal recessive mode of inheritance, there are increasing case reports associated with single Mediterranean fever (MEFV) mutation or dominant transmission. There have been over 300 variants identified in the MEFV gene; however, roughly 9-11 variants are responsible for the phenotypical expression seen with FMF. Symptoms include recurrent episodes of fever of unknown origin, abdominal, chest, or joint pain because of serosal inflammation. Persistent elevations in serum amyloid A can lead to complications like renal amyloidosis, kidney dysfunction, and end-stage kidney disease. Familial Mediterranean fever is diagnosed clinically using the Tel-Hashomer criteria and confirmed through genetic testing. Treatment includes initiation of colchicine with the goal of stopping attacks and preventing renal dysfunction and end-stage kidney disease. Genetic testing helps to identify the specific mutation allowing the provider to create a patient-specific treatment plan, monitor for complications such as renal amyloidosis, and enhance knowledge on the genetic heterogeneity and possible epigenetic factors.

Anti-Synthetase Syndrome: A Rare and Challenging Diagnosis for Interstitial Lung Disease (ILD): A Case Report

Background: ASA syndrome is a rare and complex immune-mediated entity with heterogeneously diverse presentations diagnosed by the presence of antibodies directed against aminoacyl tRNA synthetase (most common anti-JO-1). The clinical manifestations range from myositis, interstitial lung disease (NSIP PATTERN), non-erosive arthritis, unexplained recurrent fever, Raynaud’s phenomenon, mechanics hands involving mainly skin, respiratory and musculoskeletal systems. Case Report: We report a case of 37-year-old female who had multiple admissions for polyarthritis which was symmetrical, progressive, involving large and small joints associated with morning stiffness, relieved by medication temporarily, with subsequent development of respiratory symptoms like cough, fever off and on, shortness of breath, exertional dyspnea, along with cracks on fingers of hands (mechanics hands). Symptoms worsened gradually with time, affecting her daily routine activities like combing hair, changing clothes, exertional dyspnea on taking few steps, debilitating her quality of life. Extensive and detailed workup was done, Anti-Jo-1 antibodies and Anti-SSA/Ro were positive, CPK level raised, serum aldolase raised, HRCT chest showed interstitial lung disease most likely NSIP, ANA negative, ACE levels normal, Bronchial biopsy showed benign respiratory mucosa, no evidence of malignancy was found. Patient was diagnosed with anti-synthetase antibody syndrome and started on pulse therapy with methylprednisolone. Conclusion: This article explores the clinical manifestations, diagnostic criteria, treatment, progression and prognosis of the disease course.

Un cas de syndrome hyper-IgD

AbstractThe recurrent fevers of the child are of etiological diagnosis difficult because they concern metabolic or genetic abnormalities. They are associated with diseases whose pathophysiological mechanisms, and thus biological markers, are beginning to be elucidated. We report the case of a hyper IgD-syndrome, which unlike its name, is not always characterized by an elevation of IgD. The diagnostic procedure and the associated markers are described for an essential diagnosis for the implementation of a treatment.

Temperament Characteristics, Anxiety and Depression in People with Familial Mediterranean Fever

ABSTRACT
 Aim: Familial Mediterranean Fever (FMF) is an autosomal recessive and self-limiting disease. FMF is characterized by recurrent episodes of fever, peritonitis, synovitis and pleuritis. Individuals with chronic illness tend to experience depression or anxiety. It has also been stated that affective temperaments are the basis of mood disorders. The aim of our study is to determine the frequency of anxiety and depression in FMF patients, to determine the dominant temperament type, and to compare the findings with the healthy control group.
 Method: 73 patients with FMF and 30 age- and gender-matched healthy individuals without any systemic disease were included in the study. The hospital anxiety and depression scale were used to measure depression and anxiety, and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego –Autoquestionnaire (TEMPS-A) temperament scale was used to determine the temperament type.
 Results: The number of cases diagnosed with anxiety was 33 (45.2%) in the patient group and 5 (16.6%) in the control group; The number of cases diagnosed with depression was 23 (31.5%) in the patient group and 2 (6.6%) in the control group, and both were also found to be statistically significantly higher. (P values p=0.02 and p=0.002, respectively)
 No statistically significant correlation was found between gender, age, disease duration, regular use of treatment, presence of gene mutation and attack type, and anxiety and depression scores.
 According to the TEMPS-A temperament scale, the percentage of patients diagnosed with depressive temperament (20.5%) was higher than the control group (3.3%), and the difference was statistically significant. (p=0.02).
 Conclusion: When the clinical picture in FMF patients becomes complicated with anxiety or depression or in the presence of a temperament predisposed to these conditions, there may be various problems in patients' compliance and response to treatment. FMF patients should be monitored for accompanying anxiety or depression during follow-up.
 Key Words: Anxiety, Depression, Familial Mediterranean Fever, Temperament

Current Clinical Profile of Acute Rheumatic Fever and Recurrent Acute Rheumatic Fever in Pakistan.

Inclusion of echocardiography as diagnostic tool and polyarthralgia and monoarthritis as major criteria for high-risk populations in the Revised Jones Criteria 2015 is likely to surface substantial variability in clinical manifestations among various populations. This study aimed to compare clinical profile of patients presenting with first and recurrent episodes of acute rheumatic fever (ARF) using most recent criteria. 130 consecutive patients with ARF were included in the study from August 2019 to March 2022. World Heart Federation standardized echocardiographic criteria were used for cardiac evaluation. The socio-demographic variables, clinical details and relevant investigations were recorded. Median age was 13(6-26) years. Male to female ratio was 1.6:1. Majority was of low socioeconomic status (90%) and with > 5 family members in a house (83.8%). 27 patients (20.8%) were with ARF while 103 (79.2%) with recurrent ARF. Carditis was the most common presenting feature (n = 122, 93.8%), followed by polyarthralgia (n = 46, 35.4%), polyarthritis (n = 32, 24.6%), subcutaneous nodules (n = 10, 7.7%), monoarthritis (n = 10, 7.7%), and chorea (n = 5, 3.8%). Monoarthralgia was more common in ARF than recurrence (29.4% vs. 3.2%, p = 0.004). Carditis (97.1% vs. 81.5%, p = 0.01) and congestive cardiac failure (18.5% vs. 5.9%, p = 0.001) were more common in recurrent ARF than ARF. Diagnostic categorization of Jones criteria for different populations has highlighted important variability in clinical presentation of ARF. Monoarthralgia is common in first episode of ARF. Carditis is the most common feature in recurrent ARF. Polyarthralgia is seen with higher frequency that polyarthritis. Subcutaneous nodules seem to be more common in our population.

Ludwig's Angina, Clinical Challenge in Pediatrics. – A Case Report

BACKGROUND: Ludwig's angina is a rapidly progressing cellulitis that occurs in the sublingual, submandibular, and submental spaces, with a high mortality rate due to its potential to obstruct the airway. Its primary cause is odontogenic, with polymicrobial infection being the most common scenario. The occurrence of this condition is less common in the pediatric population, but children are more susceptible to life-threatening complications. THE CASE: A two-year-old male preschooler, with no significant medical history, presented with a clinical picture evolving over six days. This was characterized by recurrent fever spikes (up to a maximum of 38.7 degrees Celsius) and a growing, stony, painful mass in the right cervical region measuring 5cm x 5cm. The patient had not shown improvement despite self-medication with amoxicillin at home. Upon admission to a regional hospital, a fixed, painful, stony mass was found in the right submandibular region. Blood tests revealed leukocytosis with a left shift, positive acute-phase reactants, and a neck ultrasound indicating upper cervical adenitis without abscess formation. Antibiotic treatment was initiated for six days. However, the fever persisted, and there was an increase in the size of the lesion, along with the formation of an abscess and limited neck rotation. Consequently, on the 12th day of illness, the patient was referred to a tertiary-level hospital where a large, fixed, stony lesion was observed in neck regions II and III, with no exclusion of a neoplastic process. The patient also experienced difficulty swallowing, necessitating a liquid diet. It was decided to perform drainage under sedation and a biopsy, which revealed a stony mass in the right neck region II extending into the submental space and midline. There were severe inflammatory changes in the subcutaneous tissue, necrotic lymph nodes, but no abscess was found. Pathological examination showed inflammatory infiltrate, recent hemorrhage and vascular congestion, with the initial suspicion being an infectious process. Flow cytometry of the cervical lymph node showed no alterations in the lymphoid series but an elevation of neutrophils. However, due to the characteristics and location of the lesion, a consultation with pediatric hematologic-oncology was sought, and they considered a low likelihood of malignancy. A tuberculin test was requested and returned negative results. A culture of the lesion also yielded negative results. During hospitalization, the condition was considered Ludwig's angina, and the patient continued to show a progressive reduction in temperature and adenitis. On the 21st day, the patient exhibited a reduction of approximately 90% in the size of the lesion, leading to the discontinuation of antibiotic treatment and subsequent medical discharge. CONCLUSION: Ludwig's angina is an infection that primarily affects the floor of the mouth, progressing rapidly and potentially compromising the patient's airways, thus warranting a medical emergency status. It is uncommon and can be mistaken for neoplastic diseases or other infections, highlighting the need for knowledge about this condition and a high degree of suspicion due to its potentially life-threatening consequences. The goal is to establish appropriate management through a multidisciplinary team, given the complexity of its manifestations.

Tricuspid valve fungal endocarditis in a patient with breast cancer and an implantable chemotherapy venous access port

Fungal endocarditis, a rare and lethal infection, is etiologically connected with Candida and Aspergillus species. Among these two agents, Candida is a common nosocomial infection with increasing rates over the last years and mortality up to 40% in cases of systemic candidiasis. In the present paper, we describe the case of a 58yearold woman with metastatic breast cancer under palliative chemotherapy who was hospitalized for recurrent episodes of fever due to fungal endocarditis of the implantable venous access port. Such cases may elude the attention of the physician and need to be taken into account especially in oncologic patients with implantable devices under chemotherapy regimens. The treatment of Candida endocarditis can be difficult because of the formation of biofilms on prosthetic devices. The prognosis of these patients may be ameliorated with the combination of fungal and invasive treatment.

Tricuspid valve fungal endocarditis in a patient with breast cancer and an implantable chemotherapy venous access port

Fungal endocarditis, a rare and lethal infection, is etiologically connected with Candida and Aspergillus species. Among these two agents, Candida is a common nosocomial infection with increasing rates over the last years and mortality up to 40% in cases of systemic candidiasis. In the present paper, we describe the case of a 58yearold woman with metastatic breast cancer under palliative chemotherapy who was hospitalized for recurrent episodes of fever due to fungal endocarditis of the implantable venous access port. Such cases may elude the attention of the physician and need to be taken into account especially in oncologic patients with implantable devices under chemotherapy regimens. The treatment of Candida endocarditis can be difficult because of the formation of biofilms on prosthetic devices. The prognosis of these patients may be ameliorated with the combination of fungal and invasive treatment.

Tricuspid valve fungal endocarditis in a patient with breast cancer and an implantable chemotherapy venous access port

Fungal endocarditis, a rare and lethal infection, is etiologically connected with Candida and Aspergillus species. Among these two agents, Candida is a common nosocomial infection with increasing rates over the last years and mortality up to 40% in cases of systemic candidiasis. In the present paper, we describe the case of a 58yearold woman with metastatic breast cancer under palliative chemotherapy who was hospitalized for recurrent episodes of fever due to fungal endocarditis of the implantable venous access port. Such cases may elude the attention of the physician and need to be taken into account especially in oncologic patients with implantable devices under chemotherapy regimens. The treatment of Candida endocarditis can be difficult because of the formation of biofilms on prosthetic devices. The prognosis of these patients may be ameliorated with the combination of fungal and invasive treatment.

Evaluating the cost-effectiveness of [18F]FDG-PET/CT for investigation of persistent or recurrent neutropenic fever in high-risk haematology patients

BackgroundA recent randomised trial demonstrated [18F]fluorodeoxyglucose positron-emission tomography in combination with low-dose CT (FDG-PET/CT), compared to standard of care computed tomography (CT) imaging, positively impacted antimicrobial management and outcomes of acute leukaemia and haematopoietic stem cell transplant recipients with persistent and recurrent neutropenic fever. We conducted an economic evaluation from a healthcare perspective alongside the clinical trial.MethodsUnit costs in Australian dollars were applied to all resources used (antimicrobials, diagnostic tests, ICU and hospital bed days). Effectiveness was measured as number of patients with antimicrobial rationalisation, 6-month mortality and quality-adjusted life years (QALYs) derived from patient-reported trial-based health-related quality-of-life. Generalised linear models were used to analyse costs and outcomes. Incremental cost-effectiveness ratios (ICERs) for all outcomes and net monetary benefit (NMB) for QALYs were calculated. We performed bootstrapping with 1000 replications using the recycled predictions method.ResultsThe adjusted healthcare costs were lower for FDG-PET/CT (mean $49,563; 95%CI 36,867, 65,133) compared to CT (mean $57,574; 95% CI 44,837, 73,347). The difference in QALYs between the two groups was small (0.001; 95% CI -0.001, 0.004). When simulated 1000 times, FDG-PET/CT was the dominant strategy as it was cheaper with better outcomes than the standard CT group in 74% of simulations. The estimated NMBs at willingness-to-pay thresholds of $50,000 and $100,000 per QALY were positive, thus FDG-PET/CT remained cost-effective at these thresholds.ConclusionsFDG-PET/CT is cost effective when compared to CT for investigation of persistent/recurrent neutropenic fever in high-risk patients, providing further support for incorporation of FDG-PET/CT into clinical guidelines and funding.Trial registrationThis trial is registered with ClinicalTrials.gov, NCT03429387.

Case Report: Scrub Typhus manifesting as Acute Respiratory Distress Syndrome (ARDS) with corresponding radiological findings

Background Scrub typhus is a life-threatening infectious disease endemic in the Asia-Pacific region. It typically presents with nonspecific symptoms such as fever, headache, and myalgia, making early diagnosis challenging. Acute Respiratory Distress Syndrome (ARDS) is a severe pulmonary condition characterized by acute-onset hypoxemia, bilateral lung infiltrates on radiology, and increased pulmonary capillary permeability. Case Presentation An 18-year-old female student in central India presented with a seven-day history of recurrent fever, chills, dry cough, and severe shortness of breath, escalating to Modified Medical Research Council dyspnea grade III-IV. After unsuccessful local clinic treatment, a chest radiograph revealed bilateral pneumonia. On admission, she displayed tachycardia, tachypnea, hypotension, and hypoxia requiring non-invasive ventilation (NIV). Computed tomography confirmed scrub typhus-associated pneumonia, and serological testing was positive for scrub typhus. She was diagnosed with moderate ARDS and began treatment. Symptomatic improvement was seen in the ICU, and she was discharged on day 10 with radiological and clinical resolution. Management and Outcomes She received intravenous doxycycline and oral azithromycin for scrub typhus and any potential concurrent lung infection. In the ICU, she required continuous NIV and supplemental oxygen, with significant symptomatic improvement, evidenced by reduced tachypnoea and oxygen requirements after 72 hours. She was weaned off NIV and monitored for an additional four days. After satisfactory oxygen saturation on room air, she was discharged on the tenth day. High-resolution CT scan demonstrated resolution of ground glass opacities and consolidation. Sequential chest radiographs exhibited gradual reduction in bilateral alveolar infiltrates over time, in parallel with clinical improvement. Laboratory findings, including reduced CRP and D-dimer values, and a normal hemogram on discharge indicated a resolution of leukopenia. Conclusion This case underscores the importance of early recognition and intervention in scrub typhus-associated ARDS and highlights the utility of timely diagnostic imaging in monitoring the progress of the disease.

A novel 268 kb deletion combined with a splicing variant in IL7R causes of severe combined immunodeficiency in a Chinese family: a case report

BackgroundSevere combined immunodeficiency (SCID) is a group of fatal primary immunodeficiencies characterized by the severe impairment of T-cell differentiation. IL7R deficiency is a rare form of SCID that usually presents in the first months of life with severe and opportunistic infections, failure to thrive, and a high risk of mortality unless treated. Although recent improvements in early diagnosis have been achieved through newborn screening, few IL7R-related SCID patients had been reported in the Chinese population.Case presentationHere, we retrospectively analyzed a case of SCID in a 5-month-old girl with symptoms, including severe T-cell depletion, recurrent fever, oral ulcers, pneumonia, hepatosplenomegaly, bone marrow hemophagocytosis, and bacterial and viral infections. Whole-exome sequencing (WES), quantitative PCR (qPCR), and chromosome microarray analysis (CMA) were performed to identify the patient’s genetic etiology. We identified a 268 kb deletion and a splicing variant, c.221 + 1G > A, in the proband. These two variants of IL7R were inherited from the father and mother.ConclusionsTo our knowledge, this is the first report of whole IL7R gene deletion in combination with a pathogenic splicing variant in a patient with SCID. This deletion also expands the pathogenic variation spectrum of SCID caused by IL7R. The incorporation of exome-based copy number variant analysis makes WES a powerful molecular diagnostic technique for the clinical diagnosis of pediatric patients.

Patterns of Mannose-Binding Lectin (MBL) responses to <i>Plasmodium falciparum</i> infections in hyperendemic settings

Background: malaria caused by Plasmodium falciparum remains a significant and major public health concern in Africa, particularly in hyperendemic regions. Recurrent fevers and high quantities of inflammatory mediators in the circulation define the disease's blood stages. By binding to non-self-pathogen oligosaccharide surfaces, Mannose-Binding Lectin (MBL) and lectin complement pathways trigger innate immune processes and contribute to the formation of adaptive immune responses. Methods: in Sudan, we investigated the varied immune response levels of MBL to the different phases of P. falciparum infection in White Nile and Blue Nile states endemic to malaria. And we looked at the interaction of regulatory Interleukin 6 (IL- 6) cytokines on MBL during infection. Our study was based on a total of 108 cases, in which 86 patients (62.0%) were uncomplicated and (17.6%) were severe, all met the diagnostic criteria and were clinically admitted for malaria infections. For the determination of serum MBL and IL-6 levels, a commercial ELISA kit was employed. Results: the analysis of the results revealed significantly elevated levels of MBL and IL-6 in both severe and uncomplicated cases (p<0.001). And MBL average in contrast to residents, Blue Nile patients had high parasitemia (599.9 ng/mL) and this difference was statistically significant (p-value<0.05). The remarkable positive correlation of IL-6 serum levels with MBL among malaria patients and healthy controls (r=0.399, p<0.001) was noted too. Conclusions: according to the findings of this study, patients living in hyperendemic areas exhibit a different MBL response rate and appear to be more homogeneous in proportion to the density of P. falciparum due to parasitemia. In addition, it is also dependent on the regulatory immune mediator IL-6.