Acute demyelinating encephalomyelitis in a child with pulmonary tuberculosis.

Tuberculosis is a leading cause of mortality in children worldwide. One of the greatest challenges in its management is the difficulty of diagnosis as the manifestations are non-specific and often mimic other illnesses. Neurological infection occurs in approximately 1% of patients diagnosed with tuberculosis, and usually takes the form of tuberculous meningitis or tuberculoma. An 11-year-old girl who was diagnosed with acute disseminated encephalomyelitis, a rare immunological manifestation of tuberculosis, is presented. She recovered completely after a course of high-dose systemic corticosteroids in addition to anti-tuberculosis treatment. Considering the immense burden of this infectious disease, recognition and understanding of the uncommon manifestations are important to enable appropriate and timely treatment.Abbreviations: ADEM: acute disseminated encephalomyelitis; ATT: anti-tuberculosis therapy; CBNAAT: cartridge-based nucleic acid amplification test; CNS: central nervous system; CSF: cerebrospinal fluid; CT: computed tomography; FLAIR: fluid attenuated inversion recovery; IFN: interferon; MRI: magnetic resonance imaging; MTB: Mycobacterium tuberculosis; TB: tuberculosis; TNF: tumour necrosis factor.

Experimental Quantum Channel Discrimination Using Metastable States of a Trapped Ion.

We present experimental demonstrations of accurate and unambiguous single-shot discrimination between three quantum channels using a single trapped ^{40}Ca^{+} ion. The three channels cannot be distinguished unambiguously using repeated single channel queries, the natural classical analogue. We develop techniques for using the six-dimensional D_{5/2} state space for quantum information processing, and we implement protocols to discriminate quantum channel analogues of phase shift keying and amplitude shift keying data encodings used in classical radio communication. The demonstrations achieve discrimination accuracy exceeding 99% in each case, limited entirely by known experimental imperfections.

Spontaneous bacterial peritonitis: A rare manifestation of expanded dengue syndrome.

Abdominal pain is a usual presentation in dengue virus infection. The commonly reported causes of abdominal pain in dengue fever are pancreatitis, peptic ulcer disease, hepatitis, and acalculous cholecystitis. Spontaneous bacterial peritonitis (SBP) is a very unusual and rarely reported cause. The etiology of the acute abdomen along with nonresolving fever in dengue infection should be carefully diagnosed and managed accordingly. We report the case of a young female with no previous comorbidities who presented with complaints of fever and abdominal pain. On detailed investigations, she was diagnosed suffering from SBP, a rare type of expanded dengue syndrome.

Commentary on disparity bias in opioid use disorder treatment: policy change perspective.

Disparities in the healthcare system are a topic of continuous discussion in public health. Despite decades of conversations with regards to health inequities, disparities still plague substance use disorder treatment. Opioid use disorder treatment is no exception as disparities has been attributed to the ingrained and deeply flawed mindset of discrimination. Hence, this review highlights the role of policy with regards to discrimination.

Challenging Cases in Cerebrovascular Disease.

Disorders involving the vascular system of the brain are numerous and sundry. Atherosclerotic thromboembolism of large vessels and lacunar infarctions of small vessel disease are well known. Brain infarction due to cardioembolism is common as well, and even more so when diligently sought. Rupture of intracranial blood vessels results in subarachnoid and intraparenchymal hemorrhage. We present four cases of stroke of uncommon cause and remind clinicians to be open minded to the many possible causes of stroke, in particular because early recognition and treatment is often critical. Case 1 discusses a patient with inflammatory cerebral amyloid angiopathy. The presentation, ability to recur, and current treatment considerations are reviewed. Case 2 discusses microangiopathic thrombotic angiopathy. Diagnosis and treatment are considered. An association with interferon therapy and the evolving terminology of this and related conditions are discussed. Case 3 discusses intracranial hemorrhage secondary to acute promyelocytic leukemia. Patients with acute leukemias require aggressive management of their coagulopathy, thrombocytopenia, and the disease itself. Finally, Case 4 discusses ischemic stroke due to a paradoxical embolism in the setting of a patent foramen ovale (PFO). Both medical and surgical management of a PFO for stroke prevention are considered.

Adrenocorticotropic Hormone Induced Status Dystonicus in a Child with West Syndrome.

Dystonia is a movement disorder characterized by involuntary sustained or intermittent muscle contraction causing repetitive twisting movements and abnormal postures. Status dystonicus (SD) is an enigmatic disease of cryptic etiology. We hereby report a child with West syndrome (WS) who went on to develop SD following intramuscular adrenocorticotropic hormone (ACTH) injection. An 11-month-old male child presented with complaints of flexor spasms for 2 months. The diagnosis of WS was confirmed by electroencephalography (EEG), which showed hypsarrhythmia. Intramuscular ACTH was added, and oral trihexyphenidyl was started for dystonia. On day 7 of ACTH, the child developed frequent opisthotonic posturing. Management protocol for grade IV SD was initiated. Administration of N-terminal of ACTH in rat locus coeruleus has been shown to produce human dystonia-like movement and abnormal posturing. How to cite this article: Singh J, Aulakh R. Adrenocorticotropic Hormone Induced Status Dystonicus in a Child with West Syndrome. Indian J Crit Care Med 2022;26(8):961-962.

Multiplex imaging of human induced pluripotent stem cell-derived neurons with CO-Detection by indEXing (CODEX) technology.

BACKGROUND: Human induced pluripotent stem cell (iPSC) models have been hailed as a breakthrough for understanding disease and developing new therapeutics. The major advantage of iPSC-derived neurons is that they carry the genetic background of the donor, and as such could be more predictive for clinical translation. However, the development of these cell models is time-consuming and expensive and it is thus critical to maximize readout of markers for immunocytochemistry. One option is to use a highly multiplexed fluorescence imaging assay, like CO-Detection by indEXing (CODEX), which allows detection of 50 + targets in situ. NEW METHOD: This paper describes the development of CODEX in neuronal cell cultures derived from human iPSCs. RESULTS: We differentiated human iPSCs into mixed neuronal and glial cultures on glass coverslips. We then developed and optimized a panel of 21 antibodies to phenotype iPSC-derived neuronal subtypes of cortical, dopaminergic, and striatal neurons, as well as astrocytes, and pre-and postsynaptic proteins. COMPARISON WITH EXISTING METHODS: Compared to standard immunocytochemistry, CODEX oligo-conjugated fluorophores circumvent antibody host interactions and allow for highly customized multiplexing. CONCLUSION: We show that CODEX can be applied to iPSC neuronal cultures and developed fixation and staining protocols for the neurons to sustain the multiple wash-stain cycles of the technology. Furthermore, we demonstrate both cellular and subcellular resolution imaging of multiplexed markers in the same sample.

A 16-Year-Old-Girl With Asthma, Palpable Purpura, and Hypereosinophilia.

CASE PRESENTATION: A 16-year-old girl presented to the ED with complaints of loose stools, abdominal pain, and rash over her legs for the last 7 days. There was no history of fever, vomiting, oral ulcers, or mucosal bleeds. In the past, she had received a diagnosis of asthma. She had been taking oral montelukast every day for the past year and using a formoterol-budesonide dry powder inhaler irregularly, only during episodes of acute exacerbations. There was a history of significant but undocumented weight loss. On day 3 of hospital admission, she developed numbness over her right foot.

Effects of life-stage and passive tobacco smoke exposure on pulmonary innate immunity and influenza infection in mice.

Limited data are available on the effects of perinatal environmental tobacco smoke (ETS) exposure for early childhood influenza infection. The aim of the present study was to examine whether perinatal versus adult ETS exposure might provoke more severe systemic and pulmonary innate immune responses in mice inoculated with influenza A/Puerto Rico/8/34 virus (IAV) compared to phosphate-buffered saline (PBS). BALB/c mice were exposed to filtered air (FA) or ETS for 6 weeks during the perinatal or adult period of life. Immediately following the final exposure, mice were intranasally inoculated with IAV or PBS. Significant inflammatory effects were observed in bronchoalveolar lavage fluid of neonates inoculated with IAV (FA+IAV or ETS+IAV) compared to PBS (ETS+PBS or FA+PBS), and in the lung parenchyma of neonates administered ETS+IAV versus FA+IAV. Type I and III interferons were also elevated in the spleens of neonates, but not adults with ETS+IAV versus FA+IAV exposure. Both IAV-inoculated neonate groups exhibited significantly more CD4 T cells and increasing numbers of CD8 and CD25 T cells in lungs relative to their adult counterparts. Taken together, these results suggest perinatal ETS exposure induces an exaggerated innate immune response, which may overwhelm protective anti-inflammatory defenses against IAV, and enhances severity of infection at early life stages (e.g., in infants and young children).

Peripheral Perfusion Index as a Marker of Sepsis in Preterm Neonates.

BACKGROUND: Neonatal sepsis is a major contributor to neonatal mortality in India. Blood culture, the gold standard for the diagnosis of sepsis takes 48-72 h while the serological markers have suboptimal diagnostic test characteristics. Perfusion index (PI) is a real time, non-invasive marker that can detect microcirculatory changes before other clinical manifestation of sepsis. OBJECTIVE: To determine the diagnostic accuracy of PI in detecting hospital-acquired sepsis before overt clinical manifestations. STUDY DESIGN: A prospective observational study conducted in the Neonatal Intensive Care Unit (NICU) of a tertiary care hospital. PARTICIPANTS: Preterm neonates admitted to NICU. METHODS: PI was continuously monitored in all enrolled neonates. Clinical sepsis was defined using the NeonatalKrankenhaus-Infektions-Surveillance-System (NeoKISS). The time of fall of PI below 0.88 and time of clinical sepsis as per NeoKISS were noted and the difference was calculated. RESULTS: Among 65 preterm neonates (gestational age: 31.5 ± 2.6 weeks, birth weight: 1350, IQR 1100-1700 g), a total of 86 events of suspected sepsis were noted, of which 69 were sepsis screen positive. Fifteen events were associated with culture positive sepsis. PI yielded a sensitivity of 89.47% (95% CI 78.48-96.04%), specificity of 56% (95% CI 34.93-75.60%), positive predictive value of 82.26% (95% CI 74.70-87.92%) and negative predictive value of 70% (95% CI 50.36-84.29%) in detection of hospital-acquired sepsis. CONCLUSION: PI might serve as an early, non-invasive marker of hospital-acquired sepsis in preterm neonates.

Correlation between a 10-color flow cytometric measurable residual disease (MRD) analysis and molecular MRD in adult B-acute lymphoblastic leukemia.

BACKGROUND: Measurable residual disease (MRD) monitoring in acute lymphoblastic leukemia (ALL) is an important predictive factor for patient outcome and treatment intensification. Molecular monitoring, particularly with quantitative polymerase chain reaction (qPCR) to measure immunoglobin heavy or kappa chain (Ig) or T-cell receptor (TCR) gene rearrangements, offers high sensitivity but accessibility is limited by expertise, cost, and turnaround time. Flow cytometric assays are cheaper and more widely available, and sensitivity is improved with multi-parameter flow cytometry at eight or more colors. METHODS: We developed a 10-color single tube flow cytometry assay. Samples were subject to bulk ammonium chloride lysis to maximize cell yields with a target of 1 × 106 events. Once normal maturation patterns were established, patient samples were analyzed in parallel to standard molecular monitoring. RESULTS: Flow cytometry was performed on 114 samples. An informative immunophenotype was identifiable in all 22 patients who had a diagnostic sample. MRD analysis was performed on 87 samples. The median lower limits of detection and quantification were 0.004% (range 0.0005%-0.028%) and 0.01% (range 0.001%-0.07%) respectively. Sixty-five samples had concurrent molecular MRD testing, with good correlation (r = 0.83, p < 0.001). Results were concordant in 52 samples, and discordant in 13 samples, including one case where impending relapse was detected by flow cytometry but not Ig/TCR qPCR. CONCLUSIONS: Our 10-color flow cytometric MRD assay provided adequate sensitivity and good correlation with molecular assays. This technique offers rapid and affordable testing in B-ALL patients, including cases where a suitable molecular assay cannot be developed or has reduced sensitivity.

History and Epidemiology of Cancer Pain.

Pain is indelibly associated with the cancer experience. A systematic review and meta-analysis indicate that the prevalence of cancer pain is 55% during anticancer treatment, 66.4% in advanced, metastatic, or terminal disease, and 39.3% after curative treatment.

Alternatives to Student Outbound Mobility-Improving Students' Cultural Competency Skills Online to Improve Global Health Without Travel.

Introduction: Student outbound mobility is a major element in internationalization of medical education and global health education. However, this approach is often criticized, as it is inherently inequitable. Internationalization at home is a newer concept that aims to provide students with international skills and experiences without exchange travel. We report detailed outcomes of an international online program during the COVID-19 pandemic, which aimed to include acquisition of cultural awareness and competency-similar to what the students would have obtained if they had travelled abroad. Method: Sixty-eight students from 12 international universities participated in international small peer group collaborative work, and online networking. Perceived improvement of cultural competency using Likert scale and open-ended questions was used as a measure of success. Furthermore, students' definition of cultural competency in the different countries was obtained. Results: Students improved their cultural competency skills. Data analysis supported statistically significant improvement of the above skills after the program, in comparison to the start of the program. Discussion: Internationalization of medical education can be achieved at home-via structured online peer exchanges-and can provide students with intercultural skills and networking opportunities that are typically achieved via international in-person travel. The above represents a socially just and equitable way to reach all students and can result in improvement of their cultural competency, preparing them for their work in global health, and thereby resulting in improvement of global health. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-021-01332-9.

Infantile Tremor Syndrome Followed by West Syndrome: Effect or Continuation of Spectrum?

BACKGROUND: Infantile tremor syndrome (ITS) is a nutritional deficiency syndrome, frequently reported from the Indian subcontinent caused by vitamin B12 deficiency. The West syndrome (WS), on the other hand, is a type of epileptic encephalopathy with variable etiology. CASE SERIES: We present a series of five children who presented with symptoms consistent with ITS and received standard intramuscular vitamin B12 therapy to which good response was observed. All these children were readmitted with WS with a time lag varying from 2 to 12 months. Magnetic resonance imaging brain and metabolic screen were within normal limits. Three out of five patients responded well to adrenocorticotropic hormone (ACTH), remaining two required additional drugs. We hypothesize that WS could have developed after ITS due to developmental desynchronization. CONCLUSION: In the Indian scenario, it is particularly important to be aware of appearance of WS after ITS, because of high prevalence of ITS and devastating nature of WS.

Treatment practice and outcomes in FLT3-mutant acute myeloid leukemia in the pre-midostaurin era: a real-world experience from Australian tertiary hospitals.

Recent regulatory approval of midostaurin, a FLT3 targeting small molecular inhibitor, will likely lead to increased use of midostaurin in combination with intensive chemotherapy for patients with FLT3-mutant AML. Translation of clinical trial results into everyday practice has its challenges. This study compared the relevance of the trial population and practices studied in the midostaurin registration study (RATIFY) with real-world practice in terms of patient factors, chemotherapy, mutation-specific frequencies and clinical outcomes among patients with FLT3-mutant AML in the pre-midostaurin era (2010-2015) in Australia. We observed substantial diversity of chemotherapy regimens used in the community and limitations of the generalizability of eligibility criteria used in RATIFY (such as age and hyperleukocytosis). This study provides real-world historical data that may be used for comparison with future trial cohorts incorporating FLT3 inhibitors into the management of FLT3-mutant AML and highlights the inherent difficulties in translating clinical trial data into routine practice.

Activity and pharmacology of homemade silver nanoparticles in refractory metastatic head and neck squamous cell cancer.

BACKGROUND: Silver nanoparticles (AgNP) show efficacy in cancer cell lines. We present the first in-human outcome of AgNP in a cancer patient. METHODS: Homemade AgNP solution is manufactured using online instructions by a 78-year old male. He started consuming AgNP while on hospice after he developed nasal cavity squamous cell cancer metastatic to liver and lung. RESULTS: Electron microscopy of AgNP solution revealed bimodal nanoparticle size distribution: 3 and 12 nm. Inductively coupled plasma mass spectrometry showed basal silver ion concentrations of 32 ng/g, rising to 46 ng/g 1 hour after ingesting 60 mL of AgNP solution. Urine showed no AgNP. No toxicities were observed and he had complete radiographic resolution of his cancer. He remains without evidence of cancer 18 months later. CONCLUSIONS: AgNP ingestion was associated with sustained radiographic resolution of cancer. Further testing of AgNP should be done to confirm its efficacy in head and neck cancer.