Hospital acquired venous thromboembolism in children with sickle cell disease.

Sickle cell disease (SCD) is well recognized as a hypercoagulablestate, however, it remains unclear whether a subgroup of children with SCD at higher risk of venous thromboembolic event (VTE) during hospitalization may benefit from thromboprophylaxis. Our objectives were to describe the clinical characteristics, outcomes and recurrence of hospital acquired VTE in patients with SCD younger than 21 years. This was a single center retrospective study. Data regarding demographics, reason for admission, location of VTE, risk factors like central venous catheter (CVC), intensive care unit (ICU) admission among others were extracted from electronic medical records over a 10-year study period (2011-2021). Recurrence of VTE at 1 and 5 years was assessed. Descriptive statistics were used as indicated. We identified a total of 20 VTE events over the 10-year study period. Six of these events occurred in those younger than 12 years of age. Fourteen (70%) VTE events occurred in the HbSS or HbSßThal0 genotypes compared to 6 (30%) in HbSC. Most common VTE was isolated pulmonary embolism (PE) (n = 10, 50%). VTE were most often associated with acute chest syndrome (ACS) (n = 14, 70%), ICU admissions (n = 10, 50%) and CVC (n = 5/9, 55%). One patient died from the VTE event. One patient with additional underlying risk factors had a recurrent VTE at 13 months. Our study suggests that ICU admission, ACS and presence of CVC increases the risk of VTE in children and young adults with SCD, but larger studies are indicated to validate our findings.

Improving Time to Antibiotic Administration for Pediatric Oncology Patients With New-Onset Fever.

PURPOSE: Time to antibiotic administration (TTA) in <60 minutes for children with neutropenic fever presenting to an emergency room is associated with reduced incidence of sepsis and intensive care admission. As such, TTA is used as a national quality metric for pediatric oncology patients. At our center, in 2020, 19% of the hospitalized patients with a new fever encounter were receiving antibiotics in <60 minutes, prompting a multidisciplinary approach to reach a goal of >90% in all pediatric patients with cancer with a new fever. METHODS: A multidisciplinary team completed four Plan-Do-Study-Act cycles between March 2021 and September 2023. We implemented education initiatives, an updated handoff smartphrase guiding the on-call team, an antibiotic champion (AC) nursing role, a revised fever plan for handoff, a rapid-response team to address new fevers, and an algorithm for blood culture collection. Data were collected, analyzed, and reported biweekly with feedback sought for delays in TTA. RESULTS: There was a total of 639 new fevers in 329 unique oncology patients. As of September 4, 2023, average TTA decreased from 89 minutes at baseline to 46.4 minutes for more than 12 months. The percentage of patients receiving first dose of antibiotic in <60 minutes also increased from 19% to 93.7%, which was sustained as well. The most effective interventions were creation of the AC role and streamlining the blood culture collection process. CONCLUSION: This project demonstrates the importance of multidisciplinary involvement for providing optimal care. Specific implementation of targeted education, an AC role, and development of an algorithm streamlining the processes led to meaningful targeted improvements. Further analyses will explore the impact of these interventions on patient outcomes.

Intracardiac thrombi in pediatrics: anticoagulation approach and treatment outcomes.

Background: Intracardiac thrombi (ICT) are associated with significant morbidity and mortality. Anticoagulation is the first line of treatment and may be complemented by thrombectomy or thrombolysis. However, optimal anticoagulant duration remains ill-defined. High-risk features of ICT that may warrant long-term anticoagulation therapy have not been established. Objectives: To describe anticoagulation duration and patterns of ICT resolution. To identify potential risk factors for persistent ICT despite anticoagulation. Methods: A single-institution retrospective chart review identified patients diagnosed with ICT by echocardiogram between January 2014 and March 2022. Descriptive statistics and logistic regression were used. Results: Fifty-one patients with ICT were identified. Median age at diagnosis was 9.2 years (IQR, 0.4-15.2). The most common underlying diagnoses were congenital heart disease (41%), infection (25%), and malignancy (24%). The majority of ICT were in the right atrium (n = 30). The median longest ICT dimension was 1.5 cm (range, 0.4-4.0). The median duration of anticoagulation was 4.3 months (IQR, 2.2-9.1). Among 48 patients who received anticoagulation as first-line treatment, 32 had partial or complete response with 3 to 6 months of anticoagulation, while remaining 16 patients had no response to anticoagulation. Patients with a central venous line had a delayed resolution of ICT [hazards ratio = 0.45 (95% CI, 0.22-0.93)]. Conclusion: Our study demonstrates the wide variability in duration of anticoagulation for children with ICT. Majority of the individuals benefit from 3-to-6 month treatment; however, individuals with a central venous line may benefit from a longer course of anticoagulation. Further large-scale studies are recommended to validate our findings.

A non-invasive miRNA-based approach in early diagnosis and therapeutics of oral cancer.

Oral or mouth cancer is the 16th most common form of cancer among the world's topmost malignancies. Healthy lifestyle and control of known risk factors can reduce its incidences further. Patients succumb to oral cancer when diagnosed late and lack timely access to tertiary care. Molecular biomarkers might help in early detection of oral cancer. Recently, researchers have identified numerous microRNAs which play a crucial role in promoting and suppressing oral cancers. miRNAs are short non-coding RNA molecules (18-22 nucleotides) that play a pivotal role in regulating gene expression. Understanding the miRNA interplays in oral cancers could augment the development of potential diagnostic, prognostic, and therapeutic tools. Liquid biopsy- a non-invasive approach that has been used lately, allows the determination of miRNAs in biological fluids that play essential roles in tumor suppression and cancer promotion. Herein, we summarize an update on the role of miRNAs in the diagnosis and treatment of oral cancer.

Aberrant expansion of spontaneous splenic germinal centers induced by hallmark genetic lesions of aggressive lymphoma.

Unique molecular vulnerabilities have been identified in the aggressive MCD/C5 genetic subclass of diffuse large B-cell lymphoma (DLBCL). However, the premalignant cell-of-origin exhibiting MCD-like dependencies remains elusive. In this study, we examined animals carrying up to 4 hallmark genetic lesions found in MCD consisting of gain-of-function mutations in Myd88 and Cd79b, loss of Prdm1, and overexpression of BCL2. We discovered that expression of combinations of these alleles in vivo promoted a cell-intrinsic accumulation of B cells in spontaneous splenic germinal centers (GCs). As with MCD, these premalignant B cells were enriched for B-cell receptors (BCRs) with evidence of self-reactivity, displayed a de novo dependence on Tlr9, and were more sensitive to inhibition of Bruton's tyrosine kinase. Mutant spontaneous splenic GC B cells (GCB) showed increased proliferation and IRF4 expression. Mice carrying all 4 genetic lesions showed a >50-fold expansion of spontaneous splenic GCs exhibiting aberrant histologic features with a dark zone immunophenotype and went on to develop DLBCL in the spleen with age. Thus, by combining multiple hallmark genetic alterations associated with MCD, our study identifies aberrant spontaneous splenic GCBs as a likely cell-of-origin for this aggressive genetic subtype of lymphoma.

Sirolimus efficacy in the treatment of critically ill infants with congenital primary chylous effusions.

BACKGROUND: Chylothorax can be a presenting symptom of complex lymphatic anomaly in children and is associated with significant respiratory morbidity. Historically, the traditional pharmacological treatment has been octreotide. There are several treatments that have been utilized in the past few years including sirolimus; however, data regarding their efficacy and outcomes is limited. Furthermore, sirolimus has proven efficacy in complex vascular malformations, and hence, its utility/efficacy in infantile primary chylous effusions warrants further investigation. METHODS: In this retrospective study at Texas Children's Hospital, data were extracted for all infants with chylothorax who were treated with sirolimus between 2009 and 2020. Details regarding underlying diagnosis, comorbidities, and number of days from sirolimus initiation to resolution of effusion were collected. RESULTS: Initially a total of 12 infants were identified. Among them, seven patients had complete data and were included in the study. Reasons for chylous effusions include presumed complex lymphatic anomaly, generalized lymphatic anomaly, and complex congenital lymphatic anomaly. The mean duration of sirolimus treatment needed for chest tube removal was 16 days, with a median of 19 days and range of 7-22 days. No patients had progression of effusions while on sirolimus. CONCLUSION: With close monitoring, sirolimus appears to be an effective therapy for pediatric lymphatic effusions even in critically ill infants. The study also demonstrates shorter duration of chest tube requirement after initiation of sirolimus compared to previous studies. Larger multi-institutional studies are needed to further support our findings.

Arthroscopic Versus Open Management of Diffuse-Type Tenosynovial Giant Cell Tumor of the Knee: A Meta-analysis of Retrospective Cohort Studies.

BACKGROUND: Whether arthroscopic or open surgical management for diffuse-type tenosynovial giant cell tumor (D-TGCT) of the knee is associated with a lower rate of recurrence is unknown. METHODS: PubMed, Scopus, Web of Science, Cochrane, and EMBASE were searched on December 3, 2020. Retrospective studies that reported on recurrence rates for arthroscopic versus open management of D-TGCT were included. A total of 16 studies evaluating 1143 patients with D-TGCT of the knee were included (nopen = 551, narthroscopic = 350 patients, and narthroscopic/open = 23 patients). Random-effects meta-analyses were used to summarize and compare the reported recurrence rates, stratified by approach and overall recurrence. The meta-analysis was registered with PROSPERO. RESULTS: The recurrence rate per year (incidence) for arthroscopic procedures was 0.11 (95% CI 0.08 to 0.16, P < 0.0001) and for open procedures was 0.07 (95% CI 0.04 to 0.13, P < 0.0001). There was a 1.56 times (95% CI 1.04 to 2.34, P = 0.0332) increased risk of recurrence when treating D-TGCT of the knee with an arthroscopic approach. When evaluating only the subset of studies that had data for both arthroscopic and open approaches, the incidence rate per year for arthroscopic procedures was 0.17 (95% CI 0.11 to 0.27, P < 0.0001) and for open procedures was 0.11 (95% CI 0.06 to 0.19, P < 0.0001). The rate of overall complications was 0.04 (95% CI 0.01 to 0.08, P < 0.0001). CONCLUSION: Arthroscopic surgical management of D-TGCT of the knee in our study resulted in a 1.56 times risk of recurrence as compared with the open approach. The percent of overall complications was minimal.

Role of anticoagulation in the management of tumor thrombus: A 10-year single-center experience.

BACKGROUND: Children with cancer diagnosis are overall at a higher risk of thrombosis. For a newly diagnosed blood clot, patients are commonly started on anticoagulants to prevent further extension and embolization of the clot. In the rare instance that a pediatric patient has a tumor thrombus, role of anticoagulation is less clear. PROCEDURE/METHODS: Patients under 21 years of age with a finding of tumor thrombus on imaging from 2010 to 2020 at Texas Children's Hospital were identified and their medical records were reviewed. RESULTS: A total of 50 patients were identified. Most thrombi were incidental findings at diagnosis; however, two patients presented with pulmonary embolism (PE). Inferior vena cava extension was noted in 36% of the patients, and 24% patients had an intracardiac tumor thrombus. Anticoagulation was initiated in 10 patients (20%). There was no difference in the rate of bland thrombus formation and/or embolization in patients who did or did not receive anticoagulation. However, three of the six patients with asymptomatic tumor thrombus who were started on anticoagulation had bleeding complications compared to only two patients in the no anticoagulation cohort (p < .05). CONCLUSION: Children with intravascular extension of solid tumors were not commonly started on anticoagulation at the time of diagnosis, irrespective of the extent of tumor thrombus. Furthermore, we observed a significant trend toward higher incidence of bleeding complications after initiation of anticoagulation for asymptomatic tumor thrombus. There is inadequate evidence at this time to support routine initiation of anticoagulation in pediatric patients with intravascular extension of solid tumors.

Spontaneous expectoration of tumor tissue in primary adenocarcinoma lung.

Spontaneous expectoration of the tissue fragments in primary lung carcinoma is an extremely unusual event. Expectoration of tumor fragments is a significant event that should not be ignored as it serves itself as a noninvasive tool to diagnose underlying malignancy if such samples are immediately preserved and subjected to histopathological examination. More so, expectoration of a large-sized fragment may provide substantial relief from the breathlessness. Reported here is the case of a middle-aged male patient with adenocarcinoma in the right lung, and mass extended up to trachea, who spontaneously coughed out pieces of tumor tissue.

COVID-19: Operational Measures from a Surgeon's Perspective.

Novel corona virus, named as SARS-Cov-2 is the seventh coronavirus causing Corona Virus Disease (COVID-19) in human. It is one of the very few rare events in history of mankind to affect public health at such an enormous scale globally. Whole world is on standstill with this outbreak, which was declared pandemic by WHO in March 2020. All healthcare workers and especially the ones working in vicinity of nasal/oral regions are high risk group to be infected by this airborne virus. Recently, a 62 years old ENT specialist Liang Wudong died while treating patients with COVID in Wuhan city. Numerous reports of health care workers getting infected while serving their patients are coming from all parts of world. As health care providers are struggling to ensure safety and survival of people, their own wellbeing and preventing further spread of infection is also their responsibility. As head and neck surgical specialties are uniquely vulnerable to infection transmission, this communication highlights various instructions and suggestions given by International & National health agencies to safeguard the patient, surgical team, health workers and community. Though the decision regarding treatment is surgeon's discretion, we hope these guidelines will help in decision making.

Compromised counterselection by FAS creates an aggressive subtype of germinal center lymphoma.

Fas is highly expressed on germinal center (GC) B cells, and mutations of FAS have been reported in diffuse large B cell lymphoma (DLBCL). Although GC-derived DLBCL has better overall outcomes than other DLBCL types, some cases are refractory, and the molecular basis for this is often unknown. We show that Fas is a strong cell-intrinsic regulator of GC B cells that promotes cell death in the light zone, likely via T follicular helper (Tfh) cell-derived Fas ligand. In the absence of Fas, GCs were more clonally diverse due to an accumulation of cells that did not demonstrably bind antigen. FAS alterations occurred most commonly in GC-derived DLBCL, were associated with inferior outcomes and an enrichment of Tfh cells, and co-occurred with deficiency in HVEM and PD-L1 that regulate the Tfh-B cell interaction. This work shows that Fas is critically required for GC homeostasis and suggests that loss of Tfh-mediated counterselection in the GC contributes to lethality in GC-derived lymphoma.

Occult carcinoma penis presenting as malignant pleural effusion.

A case of left sided malignant pleural effusion is described in a 41-year-old male, his initial workup for primary site of malignancy was unknown but later found to have hidden squamous cell carcinoma of penis which is one of the rarest site of malignancy that metastasise to pleura. Penile carcinoma manifesting with pleural metastasis and pleural effusion as initial presentation has not been reported previously.

Three-Dimensional Bioprinting: Role in Craniomaxillary Surgery Ethics and Future.

Three-dimensional (3D) printing and bioprinting is gaining lot of momentum, especially in surgical specialties. These two technologies have wide array of applications in presurgical, surgical, and in vitro scenarios. Bioprinting can generate customized patient specific tissue engineered from specialized cells. This technology can be a gold standard in reconstructive and regenerative surgeries, if used in regulated and ethical environment. This communication focuses on basics of these technologies, their role in surgical specialties, ethical issues specific to these technologies, and its future.

Effective targeting of RNA polymerase I in treatment-resistant prostate cancer.

BACKGROUND: Advanced prostate cancers depend on protein synthesis for continued survival and accelerated rates of metabolism for growth. RNA polymerase I (Pol I) is the enzyme responsible for ribosomal RNA (rRNA) transcription and a rate-limiting step for ribosome biogenesis. We have shown using a specific and sensitive RNA probe for the 45S rRNA precursor that rRNA synthesis is increased in prostate adenocarcinoma compared to nonmalignant epithelium. We have introduced a first-in-class Pol I inhibitor, BMH-21, that targets cancer cells of multiple origins, and holds potential for clinical translation. METHODS: The effect of BMH-21 was tested in prostate cancer cell lines and in prostate cancer xenograft and mouse genetic models. RESULTS: We show that BMH-21 inhibits Pol I transcription in metastatic, castration-resistant, and enzalutamide treatment-resistant prostate cancer cell lines. The genetic abrogation of Pol I effectively blocks the growth of prostate cancer cells. Silencing of p53, a pathway activated downstream of Pol I, does not diminish this effect. We find that BMH-21 significantly inhibited tumor growth and reduced the Ki67 proliferation index in an enzalutamide-resistant xenograft tumor model. A decrease in 45S rRNA synthesis demonstrated on-target activity. Furthermore, the Pol I inhibitor significantly inhibited tumor growth and pathology in an aggressive genetically modified Hoxb13-MYC|Hoxb13-Cre|Ptenfl/fl (BMPC) mouse prostate cancer model. CONCLUSION: Taken together, BMH-21 is a novel promising molecule for the treatment of castration-resistant prostate cancer.

Chronic Granulomatous Disease.

Chronic Granulomatous Disease (CGD) is an inherited immunodeficiency disorder characterized by defective functioning of NADPH oxidase enzyme in the phagocytes. This leads to recurrent infections by catalase positive organisms and later, granuloma formation in multiple organs. This condition usually presents in the age group of 2-5 y and is uncommon in neonates. In this case report, we describe a rare case of CGD in a 40-day-old male child who initially presented with a history of erythematous pustular rash on left forearm and refusal to feeds. He remained unresponsive to regular antibiotics. CT chest and abdomen revealed multiple ill-defined lesions suggestive of granulomas or developing abscesses. Immunodeficiency workup showed negative Nitroblue Tetrazolium test and positive Dihydrorhodamine test (flow cytometry). A diagnosis of CGD was then made and treated accordingly. The aim of this report is to highlight the fact that although it is rare for CGD to present at such an early age, but in a neonate with multiple granulomas or abscesses, it should be considered as a differential and worked up accordingly. Early diagnosis and treatment can significantly improve the prognosis.