Erdheim-Chester Disease: A Case Report of BRAF V600E-Negative, MAP2K1-Positive ECD Diagnosed by Blood Next-Generation Sequencing Assay and a Brief Literature Review.

Erdheim-Chester disease (ECD) is a rare type of non-Langerhans cell histiocytosis. However, its prevalence has increased significantly the past few years due to increased awareness about the disorder, and 1500 cases have been reported worldwide. It is often a multisystemic disease with skeletal, cardiovascular, urologic, renal, retroperitoneal, pulmonary, endocrine, cutaneous, and neurologic involvement. MAPK pathway mutations, such as BRAF activating and MAP2K1 mutations, play a key role in its pathogenesis. In addition to the characteristic clinical, radiological, and histopathological findings, identifying underlying mutations helps diagnose and treat patients with highly effective targeted therapies such as BRAF and MEK inhibitors. We report a case of a man, aged 55 years, with an extensive and prolonged course of an unexplained multisystemic disease, later diagnosed with BRAF V600E-negative and MAP2K1-positive ECD on cell-free DNA testing. Additionally, we review common clinical manifestations, mutations, diagnoses, and targeted therapies for ECD.

Magnetic resonance neurography: is it so complicated that it needs a touch of genius?

KEY POINTS: • Neuropathy imaging is not that complicated or illusive that it needs a touch of genius.• By gaining MR imaging expertise of peripheral nerve lesions and using knowledge of common clinical patterns and diseases, general radiology practitioners can prudently participate in the multidisciplinary care for appropriate and timely management of peripheral neuropathy patients.

Length of stay and cost of care associated with admissions for atrial fibrillation among patients with cancer.

BACKGROUND: The aim of this study is to assess the burden of AF-related hospitalizations inclusive of inflation-adjusted cost-of-care and length-of-stay (LOS) among cancer patients and the impact of direct current cardioversion (DCCV) on these outcomes. METHODS: Using the National Inpatient Sample (NIS), patients hospitalized with either a primary or secondary diagnosis of AF and comorbid cancer were identified and both cost of hospitalization and LOS were evaluated for each group. Subgroup analyses were performed for specific cancer types (breast, lung, colon, prostate and lymphoma), and those receiving DCCV. RESULTS: The prevalence of co-morbid AF was 8.2 million (16%) and 35.5 million (10%) among those with vs. those without cancer, respectively (odds ratio = 1.6, 95% confidence interval = 1.5-1.7; P < 0.001). Over time, both primary and prevalent AF admissions among those with comorbid cancer increased from 1.1% and 12.3% in 2003 to 1.5% and 21% in 2015, respectively. The total cost of hospitalization increased 94.4% among those with AF and comorbid cancer compared to 23.9% among those without cancer. Among the subgroup of patients with comorbid cancer and primary admission for AF undergoing DCCV, length of stay (2.7 vs. 2.2 days; P < 0.001, model 1) and cost of care ($7,093 vs. 6,152; P < 0.001) were both significantly higher. CONCLUSIONS: AF related admissions are increasing for all populations especially amongst those patients with a comorbid diagnosis of cancer, including all cancer subtypes evaluated. Among those patients who underwent DCCV, cancer patients had longer length of stay and increased health care costs.

Temporal muscle thickness as an independent prognostic marker in glioblastoma patients-a systematic review and meta-analysis.

Glioblastoma is the most common primary malignant brain tumor in the adult population. It causes the patient to incur a great deal of malady. Even with the advances in management and the Stupp protocol in place, the prognosis remains grim. There are various parameters to evaluate patients' performance status and frailty pre-operatively, but these are mostly subjective and thus suffer from inter-observer variability. Assessment of sarcopenia serves as an objective parameter to assess the patient's performance status pre-operatively. Temporalis muscle thickness serves as a surrogate to assess sarcopenia in patients with glioblastoma. We conducted a literature review and meta-analysis to determine the prognostic implications of temporalis muscle thickness in 3283 patients with primary glioblastoma. The pooled overall survival hazard's ratio of thick versus thin TMT was 0.54. The pooled progression-free survival hazard's ratio of thick versus thin TMT was 0.38. Thus, the main finding of this study is that thicker temporal muscle is associated with better OS and PFS as compared to thinner temporal muscle. We thus conclude that TMT is a viable surrogate for predicting sarcopenia and survival in primary glioblastoma. TMT measurement is extremely easy and can be incorporated as a part of the routine neurosurgical workflow in these patients. Survival prediction will help inform treatment decisions in glioblastoma patients having poor prognosis, at the initial diagnosis itself.

Unveiling the tale of the tail: an illustration of spinal dysraphisms.

Spinal dysraphism is an umbrella term describing herniation of meninges or neural elements through defective neural arch. They can be broadly categorized into open and closed types. MRI is the investigation of choice to study neural abnormalities and to assess the severity of hydrocephalus and Chiari malformation. Knowledge of the embryology of these disorders is valuable in correctly identifying the type of dysraphism. The aim of surgery is untethering and dural reconstruction. Accurate depiction of the abnormal anatomy in cases of spinal dysraphism is of utmost importance for surgical management of these patients. MRI makes this possible due to its excellent soft tissue contrast resolution and multiplanar capability, allowing the radiologist to evaluate the intricate details in small pediatric spinal structures. Imaging enlightens the surgeons about the status of spinal cord and other associated abnormalities and helps detect re-tethering in operated cases. Besides, antenatal surgery to repair myelomeningoceles has made detection of open dysraphisms on fetal MRI and antenatal ultrasound critical. The purpose of this review is to describe the development of spine, illustrate the myriad imaging features of open and closed spinal dysraphisms, and enlist the reporting points the operating surgeon seeks from the radiologist.

Progressive cardiorespiratory dysfunction in Kv1.1 knockout mice may provide temporal biomarkers of pending sudden unexpected death in epilepsy (SUDEP): The contribution of orexin.

OBJECTIVE: Immediately preceding sudden unexpected death in epilepsy (SUDEP), patients experienced a final generalized tonic-clonic seizure (GTCS), rapid ventilation, apnea, bradycardia, terminal apnea, and asystole. Whether a progressive pathophysiology develops and increases risk of SUDEP remains unknown. Here, we determined (a) heart rate, respiratory rate, and blood oxygen saturation (SaO2 ) in low-risk and high-risk knockout (KO) mice; and (b) whether blocking receptors for orexin, a cardiorespiratory neuromodulator, influences cardiorespiratory function mice or longevity in high-risk KO mice. METHODS: Heart rate and SaO2 were determined noninvasively with ECGenie and pulse oximetry. Respiration was determined with noninvasive airway mechanics technology. The role of orexin was determined within subject following acute treatment with a dual orexin receptor antagonist (DORA, 100 mg/kg). The number of orexin neurons in the lateral hypothalamus was determined with immunohistochemistry. RESULTS: Intermittent bradycardia was more prevalent in high-risk KO mice, an effect that may be the result of increased parasympathetic drive. High-risk KO mice had more orexin neurons in the lateral hypothalamus. Blocking of orexin receptors differentially influenced heart rate in KO, but not wild-type (WT) mice. When DORA administration increased heart rate, it also decreased heart rate variability, breathing frequency, and/or hypopnea-apnea. Blocking orexin receptors prevented the methacholine (MCh)-induced increase in breathing frequency in KO mice and reduced MCh-induced seizures, via a direct or indirect mechanism. DORA improved oxygen saturation in KO mice with intermittent hypoxia. Daily administration of DORA to high-risk KO mice increased longevity. SIGNIFICANCE: High-risk KO mice have a unique cardiorespiratory phenotype that is characterized by progressive changes in five interdependent endpoints. Blocking of orexin receptors attenuates some of these endpoints and increases longevity, supporting the notion that windows of opportunity for intervention exist in this preclinical SUDEP model.

Magnetic resonance neurography and ultrasonogram findings in upper limb peripheral neuropathies.

Peripheral neuropathy is defined as any disease or damage to the peripheral nerves. Imaging modalities are emerging as a complementary tool of choice for diagnosis of peripheral neuropathies. This has been made possible by the advent of high-resolution ultrasound, higher field strength magnets, better surface array coils, and superior software. In addition, imaging plays a pivotal role in deciding the management. They help in determining the continuity and course of the nerve, thereby helping in the pre-surgical mapping of nerve. Imaging studies also help in prognosticating the recovery by determining the event to be acute or chronic. This article describes the imaging findings of various neuropathies affecting upper limb peripheral nerves, broadly categorized as traumatic and non-traumatic. The non-traumatic group is further divided as entrapment, infective, inflammatory and tumors.

Respiratory dysfunction progresses with age in Kcna1-null mice, a model of sudden unexpected death in epilepsy.

OBJECTIVE: Increased breathing rate, apnea, and respiratory failure are associated with sudden unexpected death in epilepsy (SUDEP). We recently demonstrated the progressive nature of epilepsy and mortality in Kcna1-/- mice, a model of temporal lobe epilepsy and SUDEP. Here we tested the hypothesis that respiratory dysfunction progresses with age in Kcna1-/- mice, thereby increasing risk of respiratory failure and sudden death (SD). METHODS: Respiratory parameters were determined in conscious mice at baseline and following increasing doses of methacholine (MCh) using noninvasive airway mechanics (NAM) systems. Kcna1+/+ , Kcna1+/- , and Kcna1-/- littermates were assessed during 3 age ranges when up to ~30%, ~55%, and ~90% of Kcna1-/- mice have succumbed to SUDEP: postnatal day (P) 32-36, P40-46, and P48-56, respectively. Saturated arterial O2 (SaO2 ) was determined with pulse oximetry. Lung and brain tissues were isolated and Kcna1 gene and protein expression were evaluated by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Western blot techniques. Airway smooth muscle responsiveness was assessed in isolated trachea exposed to MCh. RESULTS: Kcna1-/- mice experienced an increase in basal respiratory drive, chronic oxygen desaturation, frequent apnea-hypopnea (A-H), an atypical breathing sequence of A-H-tachypnea-A-H, increased tidal volume, and hyperventilation induced by MCh. The MCh-provoked hyperventilation was dramatically attenuated with age. Of interest, only Kcna1-/- mice developed seizures following exposure to MCh. Seizures were provoked by lower concentrations of MCh as Kcna1-/- mice approached SD. MCh-induced seizures experienced by a subset of younger Kcna1-/- mice triggered death. Respiratory parameters of these younger Kcna1-/- mice resembled older near-SD Kcna1-/- mice. Kcna1 gene and protein were not expressed in Kcna1+/+ and Kcna1+/- lungs, and MCh-mediated airway smooth muscle contractions exhibited similar half-maximal effective concentration( EC50 ) in isolated Kcna1+/+ and Kcna1-/- trachea. SIGNIFICANCE: The Kcna1-/- model of SUDEP exhibits progressive respiratory dysfunction, which suggests a potential increased susceptibility for respiratory failure during severe seizures that may result in sudden death.

Importins and exportins regulating allergic immune responses.

Nucleocytoplasmic shuttling of macromolecules is a well-controlled process involving importins and exportins. These karyopherins recognize and bind to receptor-mediated intracellular signals through specific signal sequences that are present on cargo proteins and transport into and out of the nucleus through nuclear pore complexes. Nuclear localization signals (NLS) present on cargo molecules to be imported while nuclear export signals (NES) on the molecules to be exported are recognized by importins and exportins, respectively. The classical NLS are found on many transcription factors and molecules that are involved in the pathogenesis of allergic diseases. In addition, several immune modulators, including corticosteroids and vitamin D, elicit their cellular responses by regulating the expression and activity of importin molecules. In this review article, we provide a comprehensive list of importin and exportin molecules and their specific cargo that shuttled between cytoplasm and the nucleus. We also critically review the role and regulation of specific importin and exportin involved in the transport of activated transcription factors in allergic diseases, the underlying molecular mechanisms, and the potential target sites for developing better therapeutic approaches.

Giant Pleomorphic Adenoma of Infratemporal Fossa: A Rare Case Report.

Of all the head and neck tumors, salivary gland tumors account to 3%. Pleomorphic adenomas are one of the most common benign tumors arising from major salivary glands, although it could also develop from minor salivary glands situated at accessory sites like nasal cavity, pharynx, parapharyngeal space, lacrimal glands etc. Tumors of infratemporal fossa are quite unusual, mainly because of its hidden location in retromaxillary region. We report an unusual case of 65 years old male presenting with complaint of progressive left cheek swelling for 4 years. FNAC revealed pleomorphic adenoma of minor salivary gland tumor. Intraoperatively a giant lobulated tumor was seen occupying almost whole space of infratemporal fossa, which was removed in-toto via open approach. Patient was kept on regular follow up with no evidence of recurrence reported till date.

Outcomes of Palisade Cartilage Tympanoplasty in Chronic Otitis Media: Our Experience at a Tertiary Care Centre.

To evaluate the anatomical and functional success rates of palisade cartilage tympanoplasty in chronic otitis media. Thirty patients with chronic otitis media with subtotal perforation underwent palisade cartilage tympanoplasty and were assessed prospectively. The outcomes evaluated were graft uptake and hearing gain. Overall graft uptake was 90% with failure in 3 cases. The preoperative mean air conduction threshold was 22.087 ± 6.120 dB which was improved to 13.387 ± 5.253 dB postoperatively at 12 weeks which was statistically significant. The mean postoperative ABG closure was 8.700 dB with a p value of 0.001 which was statistically significant. Palisade cartilage tympanoplasty demonstrates that subtotal perforations, which are at high risk for graft failure, can be treated efficiently and a durable and resistant reconstruction of the tympanic membrane with reasonable hearing can be achieved.

Assessing Correlation Between Thoracic Impedance and Remotely Monitored Pulmonary Artery Pressure in Chronic Systolic Heart Failure.

Background: Heart failure (HF) readmission continues to be a major health problem. Monitoring pulmonary artery pressure (PAP) and thoracic impedance (TI) are the two modalities utilized for early identification of decompensation in HF patients. We aimed to assess the correlation between these two modalities in patients who simultaneously had both the devices. Methods: Patients with history of New York Heart Association class III systolic HF with a pre-implanted intracardiac defibrillator (ICD) capable of monitoring TI and pre-implanted CardioMEMs™ remote HF monitoring device were included. Hemodynamic data including TI and PAPs were measured at baseline and then weekly. Weekly percentage change was then calculated as: Weekly percentage change = (week 2 - week1)/week 1 × 100. Variability between the methods was expressed by Bland-Altman analysis. Significance was determined as a P-value < 0.05. Results: Nine patients met the inclusion criteria. There was no significant correlation between the assessed weekly percentage changes in pulmonary artery diastolic pressure (PAdP) and TI measurements (r = -0.180, P = 0.065). Using Bland-Altman analytic methods, both methods had no significant difference in agreement (0.011±0.094%, P = 0.215). With the linear regression model applied for Bland-Altman analysis, the two methods appeared to have proportional bias without agreement (unstandardized beta-coefficient of 1.91, t 22.9, P ≤ 0.001). Conclusion: Our study demonstrated that variations exist between measurement of PAdP and TI; however, there is no significant correlation between weekly variations between them.

A Rare Presentation of Thyroid Mass as Tubercular Abscess: A Case Report.

Isolated thyroid gland tuberculosis is a rare disease, while even rarer is its presentation as an acute abscess. Here we present the case of a 65-year-old female who presented with a neck swelling which progressed to an abscess with multiple discharging sinuses which was proven to be tubercular abscess on histopathology.

Endoscopic Push-Through Cartilage Myringoplasty for Anterior Perforations.

Introduction: The study aims to evaluate the anatomical and functional success rates of endoscopic push-through cartilage myringoplasty for anterior tympanic membrane (TM) perforations. Materials and Methods: Thirty patients with TM perforations in the anterior quadrant underwent endoscopic push-through cartilage tympanoplasty and underwent prospective evaluation. The graft uptake rate and hearing gain were the outcomes evaluated. Results: Out of the 30 patients, 15 were male, and 15 were female. The mean age was 32.60 ± 13.66 years (from 18-60 years). The overall graft uptake rate was 90%, with failure observed in three cases. The mean preoperative air conduction threshold was 37.9 ± 5.83 dB which improved to 27.66 ± 4.88 dB at 16 weeks post-operation. The mean postoperative ABG closure was 7.28 dB with a p-value of 0.001 which was statistically significant. Conclusions: Endoscopic push-through cartilage myringoplasty is the least invasive, safe, simple, and advantageous for healing TM perforation and hearing restoration.

Temporal Bone Osteomyelitis Masquerading as Malignancy: A Diagnostic Challenge.

Xanthogranulomatous osteomyelitis is a rare chronic inflammatory disorder. Until now, it has only been reported in long bones. To the best of our knowledge, it has never been reported in temporal bone. We present the case of this rare disease in a 64-year-old male involving the temporal bone, presenting with ear pain, discharge, decreased hearing, and granulation tissue in the external auditory canal, mimicking malignancy clinically and radiologically. The patient was unresponsive to medical management and was taken up for surgical debridement, followed by treatment with systemic and topical antibiotics, with a successful outcome. As this disease has not been reported in the literature yet in the temporal bone and mimics malignancy, it must be differentiated on histopathology to establish a definite diagnosis and provide appropriate management. A long-term follow-up is also necessary to recognize the clinical behavior of this disease, as no treatment protocol has been established yet.

A Case Report of Chondromyxoid Fibroma of the Nasal Cavity.

The chondromyxoid fibroma is a benign osseocartilaginous tumor histopathologically characterized by chondroid, fibrous, and myxoid tissues (Nazeer et al. in Skeltal Radiol 25:779-78, 1996). Its occurrence is quite rare, accounting for less than 0.5% of all bone tumors, with 1-5% of cases reported in the head and neck region. We report an unusual case of 25 years old male who presented with progressive swelling over dorsum of nose with bilateral nasal obstruction over 1 year. The histopathological examination was suggestive of chondromyxoid fibroma. The tumor was completely excised via open approach. We report this case owing to the rarity of the disease, sometimes masquerading as invasive/malignant pathology.

Post-Covid Isolated Mandibular Mucormycosis in a Patient with Chronic Kidney Disease: A Case Report.

Mucormycosis is an opportunistic fungal infection which was earlier seen only in immunocompromised patients. With the recent covid pandemic, there had been a drastic surge in cases of mucormycosis worldwide and especially in India. Here, we present an unusual case of biopsy proven invasive mandibular mucormycosis in a patient with chronic kidney disease and a history of COVID-19 infection. The patient was given low-dose amphotericin B and underwent surgical debridement with a successful outcome.