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.

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.

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.

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.

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.

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.

Failure to achieve therapeutic levels with high-dose posaconazole tablets potentially due to enhanced clearance.

Aim To describe a case of persistent sub-therapeutic posaconazole levels in setting of salvage chemotherapy for relapsed acute myeloid leukemia. Case details A 57-year-old male was admitted for the management of relapsed acute myeloid leukemia and ongoing pulmonary aspergillosis. While continuing on posaconazole tablet 300 mg daily, he received a course of salvage chemotherapy. The initial steady state posaconazole trough level was therapeutic at 0.84 mg/L (target >0.70 mg/L). However, after five days, the level had dropped to 0.40 mg/L, coinciding with hyperbilirubinemia and hypoalbuminemia. Bilirubin level peaked at 36 µm/L (normal high <20 µm/L), albumin levels were consistently low, averaging at 25 g/L (range 33-46 g/L). The patient had been compliant and there were no underlying gastrointestinal conditions identified which might have potentially affected posaconazole absorption. Outcome An increase in posaconazole dose failed to achieve target levels and treatment was changed to voriconazole. However, levels were surprisingly supra-therapeutic, resulting in side effects and substantial dose reduction was required. Conclusion Failure to achieve target posaconazole levels despite increased dosing may be attributed to factors other than impaired oral absorption. Enhanced metabolism and clearance could be associated with hypoalbuminemia and hyperbilirubinemia. Further case studies, including PK modelling, are required to confirm this effect.

Vitamin D, Low-Grade Inflammation and Cardiovascular Risk in Young Children: A Pilot Study.

Vitamin D has anti-inflammatory properties, and deficiency is prevalent in children. There is a paucity of data regarding vitamin D status and its correlation with low-grade inflammation and vasculature. We prospectively enrolled 25 children, 9-11 years old (13 male); 21 obese. Eight atherosclerosis-promoting risk factors were scored as categorical variables with the following thresholds defining abnormality: body mass index Z score ≥ 1.5; systolic blood pressure ≥ 95th percentile (for age, sex, and height); triglyceride ≥ 100 mg/dL; low-density lipoprotein cholesterol (LDL-C) ≥ 110 mg/dL; high-density lipoprotein cholesterol ≤ 45 mg/dL; hemoglobin A1C (HBA1C) ≥ 5.5; 25-hydroxyvitamin D [25(OH) D] ≤ 30 ng/mL, and tobacco smoke exposure. High-sensitivity C-reactive protein (hsCRP) was measured to assess low-grade inflammation and classified as low- (<1 mg/L), average- (1-3 mg/L), and high-risk (>3 to <10 mg/L) groups. The proportion of children within each hsCRP group who had above threshold risk factors was calculated. Carotid artery ultrasound was performed to measure carotid artery intima-media thickness (CIMT). Median (range) for 25(OH) D was 24 (17-45) ng/mL. Eighteen were either 25 (OH) D deficient (<20 ng/mL) or insufficient (20-30 ng/mL), and seven were sufficient (>30 ng/mL). hsCRP was 1.7 (0.2-9.1) mg/L, with 11 being <1.0 mg/L, 8 between 1.0-3.0 and 6 > 3.0 to < 10.0 mg/L. Risk factor score was 3.9 ± 1.7 out of eight. 25(OH) D levels did not correlate with hsCRP or CIMT. While vitamin D deficiency, inflammation, and risk factors coexist at a very young age, causative mechanisms remain unclear.

CLINICAL PROFILE OF EXPANDED DENGUE SYNDROME IN CHILDREN.

The objective is to study the clinical profile and outcome of expanded dengue syndrome (EDS) in children. We conducted a retrospective cohort study and enrolled consecutive children (1 month to 18 years) who presented with dengue fever for over 1 year. The diagnosis of dengue fever was confirmed by the presence of dengue NS1 antigen and/or dengue IgM positivity. Subsequently, we identified children exhibiting EDS according to the revised World Health Organization guidelines (2011). We compared the clinical and laboratory profiles of children diagnosed with EDS and those without EDS. Of 178 children with dengue fever, 33 (18.5%) had EDS [95% confidence interval (CI): 13.1%-25.0%]. In these 33 children, neurological involvement was the most common manifestation [n = 16/33 (49%, 95% CI: 32%-65%)], namely encephalopathy, febrile seizures and encephalitis, respectively. Gastrointestinal involvement was the second most common [n = 10/33 (30%, 95% CI: 17%-47%)], which included fulminant hepatic failure, acalculous cholecystitis and acute pancreatitis. Renal presentation [n = 7 (21%, 95% CI: 10%-37%)] was limited to acute kidney injury. Children with EDS were significantly anemic and had leukocytosis, hyperkalemia, azotemia, hyperbilirubinemia, raised serum transaminases and fluid-refractory shock than their non-EDS counterparts. Children with EDS had a trend toward higher mortality (P = 0.07) and the survivors had a longer duration of hospital stay (5 days vs. 4 days in non-EDS, P = 0.001). In conclusion, we observed a high prevalence (18.5%) of EDS among children hospitalized for dengue fever. The common manifestations of EDS include neurological, renal and gastrointestinal involvement. Children with EDS showed a trend toward higher mortality and longer duration of hospital stay than children without EDS.

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.

Clonal hematopoiesis of indeterminate potential as a prognostic factor: a systematic review and meta-analysis.

ABSTRACT: With advances in sequencing, individuals with clonal hematopoiesis of indeterminate potential (CHIP) are increasingly being identified, making it essential to understand its prognostic implications. We conducted a systematic review of studies comparing the risk of clinical outcomes in individuals with and without CHIP. We searched MEDLINE and EMBASE and included original research reporting an outcome risk measure in individuals with CHIP, adjusted for the effect of age. From the 3305 studies screened, we included 88 studies with 45 to 470 960 participants. Most studies had a low-to-moderate risk of bias in all domains of the Quality in Prognostic Factor Studies tool. Random-effects meta-analyses were performed for outcomes reported in at least 3 studies. CHIP conferred an increased risk of all-cause mortality (hazard ratio [HR], 1.34; 95% confidence interval, 1.19-1.50), cancer mortality (HR, 1.46; 1.13-1.88), composite cardiovascular events (HR, 1.40; 1.19-1.65), coronary heart disease (HR, 1.76; 1.27-2.44), stroke (HR, 1.16; 1.05-1.28), heart failure (HR, 1.27; 1.15-1.41), hematologic malignancy (HR, 4.28; 2.29-7.98), lung cancer (HR, 1.40; 1.27-1.54), renal impairment (HR, 1.25; 1.18-1.33) and severe COVID-19 (odds ratio [OR], 1.46; 1.18-1.80). CHIP was not associated with cardiovascular mortality (HR, 1.09; 0.97-1.22), except in the subgroup analysis restricted to larger clones (HR, 1.31; 1.12-1.54). Isolated DNMT3A mutations did not increase the risk of myeloid malignancy, all-cause mortality, or renal impairment. The reasons for heterogeneity between studies included differences in definitions and measurements of CHIP and the outcomes, and populations studied. In summary, CHIP is associated with diverse clinical outcomes, with clone size, specific gene, and inherent patient characteristics important mediators of risk.

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.

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.

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.

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.