Effect of Pneumocystis jirovecii pneumonia prophylaxis on hematologic toxicity in patients receiving chemoradiation for primary brain tumors.

PURPOSE: Diffuse gliomas are managed with radiation and temozolomide; however, this therapy often results in hematologic toxicities. Patients undergoing chemoradiation also risk contracting Pneumocystis jirovecii pneumonia (PJP), and frequently receive prophylaxis against PJP during treatment. Independent of chemoradiation, some PJP prophylaxis drugs have the potential to cause myelosuppression, which could require cessation of chemotherapy. Here, we evaluate differences in the frequency of hematologic toxicities during chemoradiation when patients receive PJP prophylaxis. METHODS: This retrospective chart review evaluated patients with primary brain tumors treated with radiation and concurrent temozolomide. Analyses were performed to assess the effect of the type of PJP prophylaxis on risk for neutropenia, lymphopenia, or thrombocytopenia and the severity of these adverse effects as defined using the Common Terminology Criteria for Adverse Events. RESULTS: Of the 217 patients included in this analysis, 144 received trimethoprim-sulfamethoxazole (TMP/SMX) and 69 received pentamidine. Of the patients who received TMP/SMX, 15.3% developed an absolute neutrophil count < 1500 cells/µL compared with 7.2% of patients receiving pentamidine (p = 0.10). Platelet count < 100,000/µL occurred in 18.1% of patients who received TMP/SMX and 20.3% of patients who received pentamidine (p = 0.70). No significant differences in lymphocyte counts between therapies were seen. Severity of hematologic toxicities were similar between PJP prophylaxis groups. CONCLUSION: These findings suggest that the type of PJP prophylaxis does not significantly affect the risk for hematologic toxicity in brain tumor patients receiving radiation and temozolomide. Additional studies are merited to evaluate the higher rate of neutropenia in patients on TMP/SMX observed in this study.

Guillain-Barré Syndrome Complicated by Posterior Reversible Encephalopathy Syndrome and Reversible Cerebral Vasoconstriction Syndrome.

Introduction: Guillain-Barré syndrome is an immune-mediated inflammatory polyneuritis characterised by rapidly progressive flaccid paralysis. Guillain-Barré syndrome may present with posterior reversible encephalopathy syndrome or reversible cerebral vasoconstriction syndrome in rare cases. Case description: A woman in her 60s with a history of follicular lymphoma presented with a one-week history of difficulty walking and thunderclap headaches. The patient was diagnosed with Guillain-Barré syndrome based on neurological examination, cerebrospinal fluid analysis and nerve conduction findings. Further diagnosis of posterior reversible encephalopathy and reversible cerebral vasoconstriction syndromes was based on imaging findings and headache history. The patient was treated with intravenous immunoglobulin and amlodipine, and symptoms improved. Discussion: We reviewed the literature on Guillain-Barré syndrome associated with posterior reversible encephalopathy and/or reversible cerebral vasoconstriction syndrome. The underlying pathophysiology may involve dysautonomia resulting in unstable blood pressure, and hyponatraemia causing endothelial dysfunction. The SNOOP mnemonic highlights the 'red flags'. This SNOOP mnemonic suggests the possibility of secondary headaches that require imaging studies. In this case, the patient exhibited three SNOOP symptoms: S (history of malignancy: follicular lymphoma), O (sudden-onset headache) and O (over 50 years old). Conclusion: This case highlights the importance of considering coexisting central neurological disorders in patients with Guillain-Barré syndrome. LEARNING POINTS: Guillain-Barré syndrome (GBS) alone rarely causes headaches; therefore, when GBS patients complain of severe headaches, especially when the headache is associated with 'red flags', other complications and differential diagnosis should be considered.Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) can be triggered by GBS.Hyponatraemia, age over 50 years and female gender may be risk factors for developing PRES and RCVS in GBS patients.

Anti-SOX-1 Antibody-Positive Paraneoplastic Limbic Encephalitis Diagnosed During Small Cell Lung Cancer Treatment.

Paraneoplastic neurological syndrome (PNS) mostly presents its symptoms prior to cancer treatment. We present a case of anti-Sry-like high mobility group box 1 (SOX-1) antibody-positive PNS diagnosed during the treatment of small-cell lung cancer (SCLC). A 65-year-old woman with a history of smoking and SCLC (T3N1M0) was hospitalized to receive chemo-radiation therapy. On day 14, the course was complicated by left mastitis associated with febrile neutropenia. Drainage was performed for the left mastitis, and cefepime was initiated. The fever subsided within a few days, but the patient became agitated accompanied by logorrhea. With the exception of mental status, her neurological examination was unremarkable. Due to mildly impaired renal function, cefepime encephalopathy was considered in the differential diagnosis, but the agitation grew worse despite cefepime discontinuation. Further evaluations, including brain magnetic resonance imaging without contrast and cerebrospinal fluid analysis, were unremarkable. Acyclovir and steroid pulse therapy were initiated empirically for herpes simplex virus (HSV) and PNS, respectively. On day 22, acyclovir was discontinued because the HSV polymerase chain reaction test result was negative. On day 26, the serum anti-SOX-1 antibody test was reported to be positive. Other paraneoplastic syndrome-associated antibodies, including anti-amphiphysin, CV2, PNMA2, Ri, Yo, Hu, recoverin, titin, zic 4, GAD 65, Tr, and N-methyl-D-aspartate receptor antibodies, were negative. The agitation improved gradually following the continuation of chemotherapy and steroid treatment. The patient was discharged on day 55 in stable condition. Although PNS mostly presents prior to cancer treatment, it is important to recognize that it may develop during the course of cancer treatment. Evaluation and empirical treatment for PNS should be considered in patients who develop encephalopathy during cancer treatment, as early treatment can lead to a better outcome.

Neurologic involvement in seronegative primary Sjögren's syndrome with positive minor salivary gland biopsy: a single-center experience.

Objective: To assess the demographics, neurologic manifestations, comorbidities, and treatment of patients with seronegative primary Sjögren's syndrome (pSS). Patients and methods: We conducted a retrospective chart review on patients with seronegative pSS evaluated by a neurologist at the University of Utah Health between January 2010 and October 2018. The diagnosis was based on characteristic symptoms, positive minor salivary gland biopsy according to the American-European Consensus Group 2002 criteria, and seronegative antibody status. Results: Of 45 patients who met the study criteria, 42 (93.3%) were Caucasian, and 38 (84.4%) were female. The patients' mean age at diagnosis was 47.8 ± 12.6 (range 13-71) years. Paresthesia, numbness and dizziness, and headache were noted in 40 (88.9%), 39 (86.7%), and 36 patients (80.0%), respectively. Thirty-four patients underwent brain magnetic resonance imaging. Of these, 18 (52.9%) showed scattered nonspecific periventricular and subcortical cerebral white matter T2/fluid-attenuated inversion recovery hyperintense foci. Twenty-nine patients (64.4%) presented to the neurology clinic prior to pSS diagnosis, and the median delay in diagnosis from the first neurology clinic visit was 5 (interquartile ranges 2.0-20.5) months. Migraine and depression were the most common comorbidities in 31 patients (68.9%). Thirty-six patients received at least one immunotherapy, and 39 were on at least one medication for neuropathic pain. Conclusion: Patients often display various nonspecific neurological symptoms. Clinicians should express a high degree of skepticism regarding seronegative pSS and consider minor salivary gland biopsy to avoid delaying diagnosis, as undertreatment can affect patients' quality of life.

GABA-A Receptor Encephalitis After Autologous Hematopoietic Stem Cell Transplant forMultiple Myeloma: Three Cases and Literature Review.

BACKGROUND AND OBJECTIVES: The relationship between autologous hematopoietic stem cell transplant (aHSCT) for multiple myeloma (MM) and anti-GABAA receptor (GABAAR) encephalitis is unknown. We aimed to describe the clinical features, diagnostic process, and outcome of 3 cases of anti-GABAAR encephalitis in patients with a history of prior aHSCT for MM. METHODS: A case series of 3 patients. Anti-GABAAR antibody was tested at the University of Pennsylvania Laboratory. RESULTS: The patients were all male, aged 52 (case 1), 61 (case 2), and 62 (case 3) years at encephalitis symptom onset. The duration between completion of aHSCT and the onset of encephalitis was 43, 18, and 9 months, respectively. All 3 patients presented with new seizures and altered cognitive function. Other symptoms included headache and visual obscurations in cases 1 and 2 and intractable vertigo and mania in case 3. Brain MRI demonstrated nonenhancing multifocal T2-weighted/fluid-attenuated inversion recovery cortical and subcortical hyperintensities in all 3 patients. Cases 2 and 3 underwent brain biopsy before initiating immunomodulatory therapy, which demonstrated nonspecific encephalitis with astrogliosis in the white matter; these 2 patients were started on immunotherapy for the treatment of anti-GABAAR encephalitis after 22 days and 3 months, respectively, from the first presentation. Case 1 was started on empiric immunotherapy within 8 days of presentation without requiring brain biopsy, given characteristic MRI imaging. CSF analysis demonstrated the presence of anti-GABAAR antibodies in all 3 cases. Cases 1 and 3 also tested positive for anti-GABAAR antibodies in the serum (serum test was not performed in case 2). Cases 1 and 2 recovered to work full-time within 1 year. Case 3 reported occasional myoclonic-like movement. DISCUSSION: We highlight the importance of considering anti-GABAAR encephalitis in patients with seizures, multifocal nonenhancing brain lesions, and a history of aHSCT for MM. Awareness in recovered post-aHSCT patients with MM may be crucial because prompt recognition can avoid brain biopsy and delays in treatment. The rapid initiation of immunotherapy while awaiting autoantibody results will likely improve functional outcomes.

Infective Endocarditis-Like Presentation of Felty Syndrome: A Case Report.

Felty syndrome (FS) and infective endocarditis (IE) can present with similar signs and symptoms. FS is a diagnosis of exclusion, which poses a challenge for the clinician since accurate diagnosis is required to treat this condition effectively. A 52-year-old woman with a 15-year history of rheumatoid arthritis (RA) was admitted due to dyspnea and pain in the right ankle and left arm for two weeks. She was hemodynamically stable and afebrile. Physical examination revealed right ankle swelling and tenderness, left forearm tenderness, abdominal distension, and swan-neck finger deformities. Laboratory tests were notable for pancytopenia with a white blood cell (WBC) count of 2900 × 103/µL (absolute neutrophil count (ANC) of 1800/µL). Rheumatoid factor and anti-cyclic citrullinated peptide tests were positive. Synovial fluid analysis of the right ankle showed no crystals or bacteria, and a WBC count of 192 × 103/µL. Left upper extremity computed tomography (CT) revealed two abscesses, in the forearm and elbow, respectively. CT chest and abdomen revealed a wedge-shaped consolidation in the left upper lobe, multiple bilateral pulmonary nodules, and splenomegaly. Abdominal ultrasonography showed portal hypertension with no clear findings of cirrhosis. Blood cultures were negative. Transthoracic echocardiography (TTE) and transesophageal echocardiography showed no vegetation. Incision and drainage were performed for the right ankle swelling, and left forearm and elbow abscesses. Left forearm abscess culture revealed Staphylococcus hemolyticus. Transbronchial needle aspiration and culture of the left upper lobe lesion showed acute and chronic inflammation with no signs of malignancy or microbial growth. Repeat TTE and blood cultures were negative. Bone marrow biopsy and flow cytometry showed no evidence of large granular lymphocytic (LGL) leukemia. The patient was diagnosed with FS complicated by disseminated infections and pulmonary necrobiotic nodules. Empiric ceftriaxone and vancomycin were initiated. The patient was discharged after the resolution of her symptoms. FS is a rare extra-articular presentation of RA with a triad of a > 10-year history of RA, neutropenia (ANC < 2000/µL), and splenomegaly. IE can also present with disseminated infections and splenomegaly. Repeat TTE and blood cultures were performed due to concerns regarding the high mortality rate of IE and the possibility of false-negative echocardiography results. LGL leukemia also presents with RA and neutropenia, which was deemed less likely in our patient based on unremarkable bone marrow biopsy and flow cytometry results. FS is a rare condition. Therefore, it is important to keep its possibility in mind in the setting of RA while performing workup for the most likely conditions.

Recurrent cervical osteomyelitis after radiation therapy in a patient with oropharyngeal cancer.

It is crucial to consider cervical osteomyelitis as a differential diagnosis for neck pain in patients who underwent radiotherapy for early diagnosis and management, thereby preventing the development of potentially debilitating neurologic symptoms.

E-cigarette or vaping product use-associated lung injury: A great COVID-19 mimicker in young adult.

EVALI and COVID-19 share similar clinical and imaging features. Assessing the vaping or e-cigarette use history and conducting urine toxicology tests for high-risk patients are important with increasing COVID-19 cases in young adults.

Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation.

It is known that obese adipose tissues are hypoxic and express hypoxia-inducible factor (HIF)-1α. Although some studies have shown that the expression of HIF-1α in adipocytes induces glucose intolerance, the mechanisms are still not clear. In this study, we examined its effects on the development of type 2 diabetes by using adipocyte-specific HIF-1α knockout (ahKO) mice. ahKO mice showed improved glucose tolerance compared with wild type (WT) mice. Macrophage infiltration and mRNA levels of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor α (TNFα) were decreased in the epididymal adipose tissues of high fat diet induced obese ahKO mice. The results indicated that the obesity-induced adipose tissue inflammation was suppressed in ahKO mice. In addition, in the ahKO mice, serum insulin levels were increased under the free-feeding but not the fasting condition, indicating that postprandial insulin secretion was enhanced. Serum glucagon-like peptide-1 (GLP-1) levels were also increased in the ahKO mice. Interestingly, adiponectin, whose serum levels were increased in the obese ahKO mice compared with the obese WT mice, stimulated GLP-1 secretion from cultured intestinal L cells. Therefore, insulin secretion may have been enhanced through the adiponectin-GLP-1 pathway in the ahKO mice. Our results suggest that the deletion of HIF-1α in adipocytes improves glucose tolerance by enhancing insulin secretion through the GLP-1 pathway and by reducing macrophage infiltration and inflammation in adipose tissue.