Palatal mucormycosis in neutropenic children: A Case Report with Review of Literature

Palatal involvement in mucormycosis is mostly secondary to rhino-orbito-cerebral disease, but rarely can be a primary disease of the oral mucosa. This report presents two rare cases of the isolated palatal mucormycosis in neutropenic children and highlights some of the peculiar features of the primary palatal disease and management-related issues in children. A 12-year-old child, who had completed the dexamethasone-based induction phase of chemotherapy for Near Early T cell precursor acute lymphoblastic leukemia, and a 9-year-old boy with a Late Isolated Medullary relapse of B cell acute lymphoblastic leukemia, who was to receive salvage induction chemotherapy, developed palatal discoloration without any other major complaints. Both had neutropenia and were on antifungal prophylaxis. In vitro staining of the discolored mucosa suggested mucormycosis, which was confirmed by pathological examination of the debrided tissue. Computed tomography, done before debridement, showed no significant sinonasal disease enabling us to proceed with the transoral approach. With the help of adjuvant antifungal therapy, the infection could be contained in both cases. This report, along with the reviewed literature, shows that limited palatal mucormycosis can be effectively treated by early diagnosis and debridement and appropriate antifungal therapy. Also, the role of antifungal prophylaxis amongst neutropenic patients has been briefly discussed here.

Variables Affecting Outcomes After Allogeneic Hematopoietic Stem Cell Transplant for Cerebral Adrenoleukodystrophy

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in early cerebral adrenoleukodystrophy (CALD) can stabilize neurologic function and improve survival but has associated risks including transplant related mortality (TRM), graft failure, and graft-versus-host disease (GVHD). An observational study of 59 patients with median age at allo-HSCT of 8 years addressed impact of donor source, donor match, conditioning regimen, and cerebral disease stage on first allo-HSCT outcomes. Efficacy analyses included 53 patients stratified by disease category: advanced disease (AD; n=16) with Loes score >9 or neurological function score (NFS) >1 and two early disease (ED) cohorts (ED1 [Loes ≤4 and NFS ≤1; n=24] and ED2 [Loes >4-9 and NFS ≤1; n=13]). Survival free of major functional disabilities and without second allo-HSCT at 4 years was significantly higher in the ED (66%) versus AD (41%) cohort (p=0.015) and comparable between ED1 and ED2 cohorts (p=0.991). The stabilization of neurologic function post-transplant was greater in the ED versus AD cohort, with a median change from baseline at 24 months post-allo-HSCT in NFS and Loes score, respectively, of 0 and 0.5 in ED1 (n=13), 0.5 and 0 in ED2 (n=6), and 2.5 and 3.0 (n=4) in AD cohort. TRM was lower in the ED (7%) compared with AD (22%) cohort, however the difference was not significant (p=0.094). Transplant-related safety outcomes were also impacted by transplant-related characteristics: graft failure incidence was significantly higher with unrelated umbilical cord grafts versus matched related donors (MRD) (p=0.039), and acute GVHD and graft failure incidences varied by conditioning regimen. The study is registered to https://clinicaltrials.gov as NCT02204904.

Classification and Characteristics of Mesenchymal Stem Cells and Its Potential Therapeutic Mechanisms and Applications against Ischemic Stroke

Ischemic stroke is a serious cerebral disease that often induces death and long-term disability. As a currently available therapy for recanalization after ischemic stroke, thrombolysis, including intravenous thrombolysis and endovascular therapy, still cannot be applicable to all patients due to the narrow time window. Mesenchymal stem cell (MSC) transplantation therapy, which can trigger neuronal regeneration and repair, has been considered as a significant advance in treatment of ischemic stroke. MSC transplantation therapy has exhibited its potential to improve the neurological function in ischemic stroke. Our review describes the current progress and future perspective of MSC transplantation therapy in ischemic stroke treatment, including cell types, transplantation approaches, therapeutic mechanisms, and preliminary clinical trials of MSC transplantation, for providing us an update role of MSC transplantation in ischemic stroke treatment.

Chromosomal Syndromes

Electroencephalography (EEG) provides useful information for diagnosis, evaluation, and prognosis when patients have cerebral disease or related conditions. It is particularly helpful for evaluation of patients with transient neurologic disorders and altered states of consciousness. EEG electrodes are placed according to the International 10-20 System, which uses the inion and nasion and the ear or mastoid as landmarks to facilitate uniform placement.

Increased Incidence of Thrombosis in a Cohort of Cancer Patients with COVID-19

<b><i>Background:</i></b> Increased rates of thromboembolism (TE) have been reported in patients with COVID-19, even without prior predisposition to thrombosis. Cancer patients are already predisposed to a hypercoagulable state. This study was designed to assess the TE incidence in COVID-19+ patients with active cancer and its impact on survival. <b><i>Methods:</i></b> Data from cancer patients with documented COVID-19 during the dates March 15th–April 10th, 2020, were retrospectively reviewed. Active cancer was defined as disease treated within the past year. Diagnosis and evaluation of thrombosis were done at the clinicians’ discretion. All imaging studies’ reports within 30 days of the COVID-19 positive test were reviewed for identification of new arterial and/or venous TE. Patients were followed for 30 days from the date of COVID-19+ test for development of TE, hospital length of stay (LOS), and mortality. <b><i>Results:</i></b> Of 90 patients, 11 (12.2%) were found to have 13 new TE within 30 days of COVID-19+ test: 8 (8.9%) arterial and 5 (5.6%) venous. Arterial TE was primarily new strokes and/or microvascular cerebral disease (7) with 1 splenic infarct. Venous TE was superficial (1) and deep (3) venous thromboses with 1 pulmonary embolism. Peak D-dimer (DD) values were numerically higher in the TE group versus those with no TE, median peak DD, 7.7 versus 3.2 μg/mL, <i>p</i> = 0.25. Kidney disease was more frequent among patients with TE (72.7%) versus those without TE (31.6%), <i>p</i> = 0.02. Prophylactic or therapeutic anticoagulation (AC) in the inpatient setting was more common among those without TE, any AC, TE versus no TE, 9.1% versus 79.0%, <i>p</i> &#x3c; 0.0001. Only 1 patient on enoxaparin prophylaxis developed TE. Mortality was higher in the TE group than in those without TE (hazard ratio: 2.6; 95% CI [1.2–5.6], <i>p</i> = 0.009). Cancer type, presence of metastases, administration of prior chemotherapy, patient setting (inpatient, intensive care unit, outpatient, emergency department visit), LOS, and ventilation did not correlate with increased incidence of TE. <b><i>Conclusion:</i></b> Cancer patients with COVID-19 have high overall TE rates with a significant incidence of arterial events. TE was associated with worse survival outcomes.

Spinal Tuina Improves Cognitive Impairment in Cerebral Palsy Rats through Inhibiting Pyroptosis Induced by NLRP3 and Caspase-1

Cerebral palsy (CP) is a severe cerebral disease with high mortality and morbidity, which leads to great challenges for the suffering children and their families. Hence, the need for the efficacious and safe treatments is urgent. As a physical therapy arising from traditional Chinese medicine (TCM), Tuina has shown multiple effects on various diseases, including cerebral palsy. Nevertheless, the detailed mechanisms of Tuina on CP remain unknown, which impedes its further clinical application. Herein, we explored the effects of Tuina on CP and its potential mechanisms. Thirty Sprague Dawley (SD) male rats were randomly divided into sham, model, and Tuina groups (model + Tuina). CP rat model was established by hypoxia-ischemia via permanent occlusion of left common carotid artery and hypoxia for 2.5 hours caused by anaerobic environment, which was subsequently followed by onset of Tuina treatment from postnatal day 7 (P7) to P49. After completion of Tuina treatment, the behavioral tests showed that Tuina treatment not only improved the retarded body weight and impaired motor balance function, but also ameliorated weakened learning and memory function of CP rats. Moreover, immunohistochemistry and western blot also revealed a reduced expression of NLRP3 inflammasome and corresponding pyroptosis-related molecules induced by NLRP3 in CP rats after Tuina treatment. Therefore, our study indicated that Tuina treatment may improve impaired neurocognitive function of CP rats, which was possibly realised via inhibiting NLRP3-induced pyroptosis.

Cunninghamella arunalokei a New Species of Cunninghamella from India Causing Disease in an Immunocompetent Individual

Mucormycosis due to Cunninghamella spp. is a rare disease, especially in immunocompetent individuals. Here, we describe the isolation and characterization of a new species of Cunninghamella, causing chronic rhino-orbital-cerebral disease, and review cases of mucormycosis due to Cunninghamella spp. in immunocompetent individuals. The Basic Local Alignment Search Tool (BLAST) analysis of the internal transcribed spacer region (ITS) sequence of isolate NCCPF 890012 showed 90% similarity with Cunninghamella bigelovii, while the large ribosomal subunit (28S) and translation elongation factor-1 alpha (EF-1 alpha) gene sequences showed 98% identity. Further, the phylogenetic analysis with concatenated sequences clustered isolate (NCCPF 890012) closely with C. bigelovii. The ITS sequence showed the maximum variation among three genes analyzed and helped in the new species’ delineation. Comparison of the assembled whole genome of NCCPF 890012 with other Mucorales using 123 single-copy orthologous genes showed clustering within the genus Cunninghamella. Based on these findings, the isolate is considered to be a new species of Cunninghamella and designated as Cunninghamella arunalokei sp. nov. Despite repeated debridement and antifungal treatment, the patient had multiple recurrences with intracranial extension and succumbed to the illness.

Association between comorbid sleep apnoea–hypopnoea syndrome and prognosis of intensive care patients: a retrospective cohort study

ObjectiveIn this study, we investigated the association between comorbid sleep apnoea–hypopnoea syndrome (SAHS) and the prognosis of patients in an intensive care unit (ICU) to determine whether this relationship varies between different disease subgroups.MethodsWe conducted a retrospective cohort study using publicly available information from the critical care database Medical Information Mart for Intensive Care III. Adults (≥18 years of age) who attended the ICU for the first time were enrolled. Demographic information and clinical data were obtained from each patient. The primary outcome was 30-day mortality after ICU admission, and the secondary outcomes were in-hospital and ICU mortality. Multivariate logistic regression and Cox regression analyses were used to examine the associations between SAHS comorbidities and the research outcomes. Propensity score matching was used to adjust for potential confounding variables.ResultsOf the 32 989 patients enrolled, 1918 (5.81%) were diagnosed with SAHS as a comorbid condition. Patients with SAHS had a significantly lower 30-day mortality rate compared with those without SAHS (5.27% vs 13.65%, respectively; p<0.001). The frequency of chronic obstructive pulmonary disease, cerebral disease, cardiovascular disease, hypertension, diabetes mellitus and renal failure was significantly different between the two groups. Patients with SAHS demonstrated significantly longer survival compared with patients without SAHS. Multivariate Cox proportional hazards regression identified a significant relationship between SAHS and mortality within 30 days (adjusted HR=0.610, 95% CI 0.499 to 0.747, p<0.0001).ConclusionSAHS as a comorbid condition decreases the risk of 30-day mortality, in-hospital mortality and ICU mortality among ICU patients.

Acute thromboembolic events (TE) within 30 days of COVID-19 infection in cancer patients.

e18691 Background: Increased rates of TE have been reported in patients (pts) with coronavirus disease (COVID-19), even without prior predisposition to thrombosis. Patients with cancer are already predisposed to a hypercoagulable state. We aimed to assess whether COVID-19 further increased the risk of TE in pts with active cancer at Montefiore Medical Center, Bronx, NY. Methods: The EMR of 90 cancer pts diagnosed with COVID-19 from March 15th to April 10th, 2020 were reviewed. COVID-19 testing was performed by PCR of nasal swab samples. Active cancer was defined as disease treated <1 year. Reports of imaging studies performed <30 days of the COVID-19+ test, either for new symptoms or for other reasons, were reviewed for new arterial (ATE) and/or venous thromboses (VTE). Patient were followed for 30 days from the date of COVID-19+ test for development of TE, hospital length of stay (LOS) and mortality. Results: Of 90 pts, 11 (12.2%) were found to have 13 new TE within 30 days of COVID-19+ test, 8 (8.9%) arterial and 5 (5.6%) venous. Of the 8 ATE, 7 were new strokes and/or microvascular cerebral disease (MCD) and 1 was a spleen infarct (SI). Of the 5 VTE, 3 were deep venous thrombosis, 1 pulmonary embolism (PE) and 1 patient presented with a superficial VTE. Two patients had 2 new TE each; stroke/PE and MCD/SI, respectively. Peak D-dimer (DD) value was higher in the TE group; mean DD (SD), TE vs no TE, 7.1 (3.4) vs 6.4 (7) ug/mL, p=0.03. Pts on either prophylactic or therapeutic anticoagulation (AC) had less TE; AC vs no AC, 9.1% vs 90.9%, p=0.0003. Only 1 pt on Enoxaparin prophylaxis developed TE. Of the 20 pts on therapeutic AC, 25% were newly started due to concern for thrombosis; the rest were already receiving AC for other reasons. Mortality was higher in the TE group; HR, TE vs no TE, 2.6, 95% CI (1.2 - 5.6), p=0.009. There was no correlation of cancer type, disease stage (metastatic or not), administration of prior chemotherapy or immunotherapy, common comorbidities, patient setting (inpatient, ICU, outpatient, ED visit), LOS or ventilation status with increased incidence of TE. Conclusions: Pts with COVID-19 have high rates of TE, and this is true for our pts with cancer. A high incidence of ATE was noted. TE was associated with increased mortality.[Table: see text]