Thrombocytopenia in Critically Ill Patients: Clinical and Laboratorial Behavior and Its Correlation with Short-term Outcome during Hospitalization.

BACKGROUND: Thrombocytopenia, being among the most common laboratory abnormality, found in Intensive Care Unit (ICU) patients is commonly associated with sepsis and disseminated intravascular coagulation. Declining platelet counts are associated with higher mortality rates. Thus, thrombocytopenia can be used as a prognostic marker in critically ill patients. METHODOLOGY: A prospective observational study was conducted on patients fulfilling the inclusion criteria and were evaluated for complete medical history, clinical, and laboratorial examination. Short-term outcome of the patient was correlated with thrombocytopenia. RESULTS: The incidence of thrombocytopenia in ICU patients was 37.57%, and mortality was 44%. Higher mortality rate was found among patients with acute febrile illnesses, respiratory diseases, and sepsis (P = 0.08, 0.22, 0.41 respectively). The mortality was higher in patients with platelet counts <100,000/µl (P = 0.0008) and whose platelet levels declined on day 3 or 5 (P = 0.0001). CONCLUSIONS: Low as well as declining platelet counts are markers of severity of critical patients and are directly related to prognosis and mortality of patients in ICU.

A novel 2q37 microdeletion containing human neural progenitors genes including STK25 results in severe developmental delay, epilepsy, and microcephaly.

2q37 microdeletion syndrome is a rare syndrome characterized by neurodevelopmental delay, bone, cardiovascular, and neurological alterations. This syndrome is typically associated with loss of genetic material of approximately 100 genes in the 2q37 band. However, the genes associated with neurodevelopmental phenotype in this syndrome are still unknown. We identified a deleted region of 496 kb by whole genome array CGH in a patient who fulfilled criteria for 2q37 microdeletion syndrome with developmental delay, microcephaly, hypoplasia of the corpus callosum, hand wringing, toe walking, and seizures. The deleted segment contains genes that are highly expressed in the developing human cortical plate and the subventricular zone (SVZ) in vivo and human neural progenitors in vitro, including SEPT2, THAP4, ATG4B, PPP1R7, and STK25. Network analysis revealed that STK25 was the most interacting gene associated with neural development in this deletion. Our report narrows the likely causative genomic region for microcephaly and neurodevelopmental delay in 2q37 microdeletion syndrome to a small genomic region enriched with neural progenitor genes that may represent an important locus for the development of the human cortex and corpus callosum.

Nocturnal variant of benign myoclonic epilepsy of infancy: a case series.

Myoclonus is a brief, rapid, involuntary muscle jerk originating in the central nervous system that can be physiological or a symptom of disease. We report a group of five children with excessive myoclonic jerks, only during sleep, and abnormal EEG during the events. Although only one third of the events had EEG epileptiform correlate, the presence of myoclonus without epileptiform EEG correlate has been described in patients with benign myoclonic epilepsy of infancy. We hypothesize that these findings may represent a variant of benign myoclonic epilepsy of infancy.

Assessment of thermal damage for plasmonic photothermal therapy of subsurface tumors.

Plasmonic photothermal therapy (PPTT) involves the use of nanoparticles and near-infrared radiation to attain a temperature above 50 °C within the tumor for its thermal damage. PPTT is largely explored for superficial tumors, and its potential to treat deeper subsurface tumors is dealt feebly, requiring the assessment of thermal damage for such tumors. In this paper, the extent of thermal damage is numerically analyzed for PPTT of invasive ductal carcinoma (IDC) situated at 3-9 mm depths. The developed numerical model is validated with suitable tissue-tumor mimicking phantoms. Tumor (IDC) embedded with gold nanorods (GNRs) is subjected to broadband near-infrared radiation. The effect of various GNRs concentrations and their spatial distributions [viz. uniform distribution, intravenous delivery (peripheral distribution) and intratumoral delivery (localized distribution)] are investigated for thermal damage for subsurface tumors situated at various depths. Results show that lower GNRs concentrations lead to more uniform internal heat generation, eventually resulting in uniform temperature rise. Also, the peripheral distribution of nanoparticles provides a more uniform spatial temperature rise within the tumor. Overall, it is concluded that PPTT has potential to induce thermal damage for subsurface tumors, at depths of upto 9 mm, by proper choice of nanoparticle distribution, dose/concentration and irradiation parameters based on the tumor location. Moreover, intravenous administration of nanoparticles seems a good choice for shallower tumors, while for deeper tumors, uniform distribution is required to attain the necessary thermal damage. In the future, the algorithm may be extended further, involving 3D patient-specific tumors and through mice model-based experiments.

Polypharmacy in Psychiatry: An In-depth Examination of Drug-drug Interactions and Treatment Challenges.

Polypharmacy in psychiatry is an in-depth examination of drug-drug interactions and treatment challenges that explores the intricate landscape of psychiatric polypharmacy, a practice involving the prescription of multiple medications to individuals with mental health disorders. This review is based on the critical aspects of drug-drug interactions and the associated treatment challenges. Psychiatric polypharmacy is motivated by the complexity of mental health conditions, where monotherapy may be insufficient. While it offers potential benefits, the practice raises concerns related to drug interactions that can compromise safety and efficacy. The review delves into the prevalence and clinical indications for psychiatric polypharmacy, thoroughly analyzing drug interactions, treatment challenges, and strategies for mitigation. Real-world case studies illustrate the complexities and outcomes of managing complex medication regimens, while emerging trends in personalized medicine, advancements in psychopharmacology, multidisciplinary approaches, and digital health solutions offer a glimpse into the future of psychiatric polypharmacy. This examination underscores the importance of a patient-centered, evidence-based approach in optimizing psychiatric polypharmacy to achieve therapeutic benefits while minimizing risks.

Gold nanoblackbodies-based multifunctional nanocomposite for multimodal cancer therapy.

Multifunctional nanocomposites are of potential use to achieve complete tumor elimination and, thus, to avoid tumor recurrence. Herein, polydopamine (PDA)-based gold nanoblackbodies (AuNBs) loaded with indocyanine green (ICG) and Doxorubicin (DOX) termed as A-P-I-D nanocomposite were investigated for multimodal plasmonic photothermal-photodynamic-chemotherapy. Upon near-infrared (NIR) irradiation, A-P-I-D nanocomposite showed enhanced photothermal conversion efficiency of 69.2% compared to bare AuNBs (62.9%) due to the presence of ICG, along with ROS (1O2) generation as well as enhanced DOX release. On assessment of therapeutic effects on breast cancer (MCF-7) and melanoma (B16F10) cell lines, A-P-I-D nanocomposite showed significantly lower cell viabilities of 45.5% and 24% compared to 79.3% and 76.8% for AuNBs. Fluorescence images of stained cells revealed characteristic signs of apoptotic mode of cell death, with almost complete damage on A-P-I-D nanocomposite + NIR treated cells. Further, on evaluation of photothermal performance through breast tumor-tissue mimicking phantoms, A-P-I-D nanocomposite provided required thermal ablation temperatures within the tumor along with the potential for the elimination of residual cancerous cells through photodynamic therapy and chemotherapy. Overall, this study demonstrates that A-P-I-D nanocomposite + NIR provides better therapeutic outcome on cell lines and enhanced photothermal performance on breast tumor-tissue mimicking phantoms to be a promising agent for multimodal cancer therapy.

Non-invasive evaluation of buccal respiratory chain enzyme dysfunction in mitochondrial disease: comparison with studies in muscle biopsy.

Making a diagnosis of mitochondrial disease (MD) is extremely challenging and often employs the analysis of respiratory complex (RC) activities in biopsied skeletal muscle. Given both the invasive nature and expense of biopsied-muscle based testing for mitochondrial defects, buccal swab enzyme analysis has been explored as an alternative approach to the more invasive muscle biopsy. Case studies have recently suggested that buccal swabs from patients can be used to accurately assess mitochondrial enzyme activities including RC I and RC IV using a dipstick methodology combined with spectrophotometric analysis. In this study, forty patients with suspected MD who have previously been found to have significant defects in either RC I or RC IV in skeletal muscle were assessed by buccal swab analysis and compared to enzyme values obtained with unaffected controls (n=106) in the same age range. Buccal citrate synthase was used as an indicator of overall mitochondrial content, correlating well with overall buccal mitochondrial frataxin levels and was found to be elevated above control levels in 28% of the patients in this cohort. Of 26 cases with significant muscle RC I deficiency, 20 displayed significantly reduced levels of buccal RC I activity. All 7 of the patients with muscle RC IV deficiency showed significant buccal RC IV defect and 6 of the 7 patients with combined defects in muscle RC I and IV activity levels also exhibited analogous deficiencies in both buccal RC I and RC IV activities. In conclusion, the relatively high correlation (over 82%) of buccal and muscle RC deficiencies further supports the validity of this non-invasive approach as a potentially useful tool in the diagnosis of MD.

Polydopamine Coated Gold Nano Blackbodies for Tumor-Selective Spatial Thermal Damage During Plasmonic Photothermal Cancer Therapy.

Plasmonic photothermal therapy (PPTT), which involves nanoparticles and near-infrared radiation (NIR) to generate confined heat, is a potential technique for selective thermal damage of cancerous tissue. Herein, tumor-selective spatial damage characteristics during polydopamine (PDA) coated gold nano blackbodies (AuNBs) mediated PPTT is investigated through a tumor-tissue mimicking phantom. The spatial temperatures during PPTT were measured within the phantom mimicking the optical scattering of superficial invasive ductal carcinoma (injected with AuNBs) surrounded by a region without AuNBs. The phantom was irradiated using broadband NIR radiation (754-816 nm), and spatial temperatures were measured using thermocouples and an infrared thermal camera. The obtained results demonstrate that the tumor region's temperature was elevated to >50°C in about 2.5 minutes and was maintained thereafter for about 6 minutes, which is well sufficient for the thermal ablation of the tumor. While for the region surrounding the tumor, a temperature of about 40-44°C was attained, which is within safe limits for the said exposure duration. Overall, this study demonstrates that for the considered experimental parameters and tumor dimensions, heat-based thermal damage could be confined to the nanoparticle embedded tumor region while maintaining the safe temperature levels for the surrounding region, i.e., 2 mm beyond the tumor boundary.

Gold nanoblackbodies mediated plasmonic photothermal cancer therapy for melanoma.

Aim: Gold nanoblackbodies (AuNBs)-mediated plasmonic photothermal cancer therapy was investigated through melanoma-bearing mice. Materials & methods: Polydopamine-coated Au nanoclusters were synthesized, termed AuNBs and PEGylated AuNBs (AuNBs-PEG). The photothermal response of AuNBs-PEG was evaluated upon low-intensity broadband near-infrared irradiation (785/62 nm; 0.9 Wcm-2), and cytotoxicity was assessed on B16-F10 cells. Further, the therapeutic potential of intravenously administered AuNBs-PEG was evaluated on B16-F10 melanoma in C57BL/6 mice. Results: AuNBs-PEG showed an excellent photothermal response (photothermal conversion efficiency of 60.3%), robust photothermal stability and no cytotoxicity. For AuNB-mediated plasmonic photothermal therapy, an average temperature of 63°C was attained within 5 min of irradiation, and tumors were eradicated. Conclusion: AuNBs-PEG are promising photothermal agents for treating melanoma through low-intensity broadband near-infrared irradiation.

Early-onset childhood absence epilepsy: is it a distinct entity?

Childhood absence epilepsy (CAE) typically starts between four and seven years of age. Onset before three years is rare and has not been previously reported from North America. We retrospectively reviewed the electroencephalography laboratory database and paediatric neurology clinic records (from January 2000 to June 2009) at our institution in order to identify patients with absence seizures beginning before age three. Information was collected for age, gender, neurodevelopment, antiepileptic drugs (AEDs) used, seizure control, follow-up, and side effects. Of 12 patients identified, mean age at onset was 20.5 months (range: 11 months to two years; follow-up: six months to 11 years). Seven of 12 patients had normal neurodevelopment and five had speech delay. Four patients were seizure-free without AEDs, three were seizure-free with a single AED, and five still had seizures with multiple AEDs. Three patients had recurrences after medication withdrawal. Other previously published series have identified better seizure control than that reported here, however, 16% of the 130 patients so far documented are reported to have poorly controlled epilepsy, indicating that early-onset CAE is not a homogeneous condition. The debate as to whether early-onset CAE is a distinct epilepsy syndrome therefore continues. We believe that early-onset CAE may be a distinct epilepsy syndrome, with some features that overlap with those of typical CAE, as well as unique distinguishing features. Large prospective multicentric studies would be necessary to definitely resolve this matter.

Correlation between child and parental perceptions of health-related quality of life in epilepsy using the PedsQL.v4.0 measurement model.

Health-related quality-of-life measures in childhood epilepsy are typically limited to a particular functional domain, specific age group, parent proxy-report, or child self-report. Generic health-related quality-of-life instruments in paediatric epilepsy comparing child self-reports with simultaneous parent proxy-reports have not been previously investigated. A previously validated generic questionnaire, the Pediatric Quality of Life version 4 (PedsQL.v4.0), was used to prospectively assess parental and child perceptions of health-related quality of life in 100 children with epilepsy. The correlation between child and parental health-related quality-of-life perceptions across all domains was excellent (p < 0.001) and both were significantly lower than those for healthy controls (p < 0.001). Parents' perceptions of their children's health-related quality of life were lower than those for other chronic illnesses (p < 0.001), especially for refractory epilepsy. The presence of neurological or psychiatric comorbidities also had an adverse impact on health-related quality of life. The PedsQL.v4.0 measures health-related quality of life from both the parent's and child's perspective. Ease of use makes this instrument attractive for routine clinical use.

Significance of interictal occipital epileptiform discharges in children.

OBJECTIVE: Interictal occipital epileptiform abnormalities have not been well characterized. The objective of this pilot study was to assess their significance in children. METHODS: A search was performed on the EEG database for the keywords "occipital", "spike", "sharp wave" and "epileptiform". Patients were divided into two groups based on the absence of all (group 1) or presence of any (group 2) of the following criteria: mental retardation, cerebral palsy, neurological deficits, abnormal MRI and/or intractable epilepsy. Special attention was given to the spike/sharp wave amplitude/duration and background slowing. RESULTS: A total of 44 children (eight months to 15 years) were studied. Groups 1 and 2 were each composed of 22 children. Background slowing was more frequent in group 2 (10/22, 45%) compared to group 1 (1/22, 4.5%; p = 0.002). In group 2, 8/22 (36%) had spikes or sharp waves with amplitudes below 50 microV or above 150 microV with a positive predictive value of 89%, and a negative predictive value of 39%. Only 1/22 (4.5%) in group 1 had epileptiform activity outside of the 50-150 microV range. CONCLUSIONS: The presence of very high or low-amplitude occipital epileptiform abnormalities or background slowing may be indicative of encephalopathy.

Glucocorticoid Resistance in Premature Adrenarche and PCOS: From Childhood to Adulthood.

CONTEXT: We hypothesize that impaired glucocorticoid sensitivity (GC sensitivity) plays a role in the development of premature adrenarche (PA) and polycystic ovarian syndrome (PCOS) by increasing androgen synthesis. OBJECTIVE: To study glucocorticoid sensitivity in vitro in subjects with PA and PCOS. PATIENTS AND METHODS: Fourteen subjects (10 girls, 4 boys, 6.9 ± 0.6 years) with PA; 27 subjects with PCOS (17 ± 2.5 years) and 31 healthy controls were enrolled in the study. All subjects and controls underwent GC sensitivity analysis in vitro using a fluorescein labeled-dexamethasone (F-DEX) assay. A GC sensitivity index (GCSI) was calculated as area under the curve of the F-DEX assay results. Subjects were classified as GC resistant if the GCSI ≤ 264 and GC sensitive if the GCSI ≥ 386. RESULTS: In the PA group, 8 of 14 subjects were resistant with GCSI of 179.7 ± 39.9, 4 were within the normal range with GCSI of 299.6 ± 27.9, and 2 had increased GC sensitivity with GCSI of 423.5 ± 47.9. In the PCOS group, 18 of 27 subjects were GC-resistant with GCSI of 180.9 ± 58.2, 8 were within the normal range with GCSI of 310.7 ± 26.4, and 1 had increased GCSI of 395.4. In the PCOS GC-resistant subgroup, cortisol was higher compared with PCOS with normal GCSI (P < 0.05). In the combined PCOS plus female control group, GCSI correlated negatively with cortisol and testosterone (P < 0.05). CONCLUSION: GC resistance was found in more than 50% of patients with PCOS and PA. The findings strongly suggest that GC resistance is associated with states of PA and PCOS.

Undervirilized male infant with in utero exposure to maternal use of high dose antifungal therapy.

BACKGROUND: Antifungals act on fungal sterols structurally similar to human cholesterol. Ketoconazole reversibly suppresses steroidogenesis by inhibiting cytochrome P450 enzymes and interferes with dihydrotestosterone (DHT) activity by binding to the androgen receptor. Hypospadias was reported in infants exposed to nystatin in utero. CASE PRESENTATION: A male infant exposed to antepartum nystatin presented with severe under-undervirilization and transient adrenal corticosteroid abnormalities. He was born in USA at 31 weeks gestation to a mother treated with vaginal Polygynax capsules (nystatin-100,000 international units, neomycin sulphate-35,000 international units and polymyxin B-35,000 international units) for vaginal discharge in the Ivory Coast. She used approximately 60 capsules between the first trimester until delivery. The infant was born with micropenis, chordee, perineo-scrotal hypospadias and bifid scrotum with bilaterally palpable gonads. The karyotype was 46,XY. No Mullerian structures were seen on ultrasound. Serum 17-hydroxyprogesterone (17 OHP) on newborn screening was high (304 ng/ml, normal < 35). Cortisol response to cosyntropin on the 3rd day of life (DOL) was 10 mcg/ml; the subnormal cortisol response may have resulted from prematurity and the predelivery treatment with betamethasone. The elevation of several adrenal corticosteroids was not consistent with any specific enzymatic defect. Hydrocortisone and fludrocortisone were initiated at another hospital for suspected mild glucocorticoid and mineralocorticoid deficiencies. Genetic screening for adrenal and gonadal developmental defects performed when transferred to our care were normal. All medications were gradually discontinued over 5-8 months. Adrenal and testicular responses to cosyntropin and human chorionic gonadotropin (hCG) were normal at 8 months. CONCLUSIONS: We report severe undervirilization in a 46,XY infant born to a mother treated with prolonged and high dose nystatin during pregnancy. This presentation suggests that prolonged antepartum use of high dose nystatin could lead to severe but transient defects in androgen synthesis and/or action possibly by acting as an endocrine disruptor. Further studies are warranted to confirm this finding. Thus, endocrine disruptors should be considered in male newborns with atypical genitalia not explained by common pathologies.

Safety and Efficacy of Brivaracetam in Pediatric Refractory Epilepsy: A Single-Center Clinical Experience.

Brivaracetam is a new antiepileptic drug with limited data in children. The objective of this study was to assess the efficacy/tolerability of brivaracetam. This is a retrospective chart review of children/adolescents with refractory epilepsy treated with brivaracetam from 2016 to 2018. The primary outcome was seizure reduction (decrease in seizure frequency >50%). Twenty-three patients were identified. Mean age at initiation was 12.5 years. Fourteen were females. Epilepsy was focal in 11, generalized in 6, and mixed in 3. Average dose was 3.9 mg/kg/d. The mean duration of treatment was 8.2 months. Eight had greater than 50% decrease in seizure frequency, of which 7 had focal epilepsy, and 1 had Lennox-Gastaut/mixed epilepsy. Two had drowsiness and 3 behavioral complaints. One experienced tingling and dizziness. Our retrospective review suggests that brivaracetam is an effective therapy for refractory focal epilepsy in children older than 4 years of age.

Sleep study abnormalities in children with attention deficit hyperactivity disorder.

The study objective was to describe polysomnographic findings in children with attention deficit hyperactivity disorder (ADHD) with diverse sleep problems. Polysomnographic data were retrospectively analyzed for 33 children (age 3-16 years) with ADHD who had sleep studies performed for diverse sleep complaints. Eight patients (24%) had obstructive sleep apnea, 10 (30%) had periodic limb movements of sleep, 8 (24%) had upper airway resistance syndrome, and 5 (15%) had obstructive hypoventilation. The ADHD group showed decreased sleep efficiency, increased arousal index, increased wake after sleep onset, decreased oxygen saturation nadir, and increased snoring, compared with control subjects. Compared with ADHD children without sleep disordered breathing, those who had sleep disordered breathing were significantly more obese and had more sleep architectural abnormalities (including increased sleep latency, increased rapid eye movement latency, increased wake after sleep onset, and increased arousal index with more oxygen desaturations), although total sleep time and sleep efficiency were not significantly different. Sleep disordered breathing and periodic limb movements of sleep appear to be common among children with ADHD who have symptoms of disturbed sleep.

A case of 5,10-methenyltetrahydrofolate synthetase deficiency due to biallelic null mutations with novel findings of elevated neopterin and macrocytic anemia.

We describe a case of 5,10-methenyltetrahydrofolate synthetase (MTHFS) deficiency characterized by microcephaly, global developmental delay, epilepsy, and cerebral hypomyelination. Whole exome sequencing (WES) demonstrated homozygosity for the R74X mutation in the MTHFS gene. The patient had the unexpected finding of elevated cerebrospinal fluid (CSF) neopterin. The novel finding of macrocytic anemia in this patient may provide a clue to the diagnosis of this rare neurometabolic disorder.

Neuropsychological outcome following thalamic stroke in adolescence: an identical twin comparison.

Objective: Medial thalamic stroke in adults commonly results in severe learning and memory impairments and executive dysfunction, particularly during the acute phase. However, there is limited research on the cognitive recovery from thalamic stroke in physically healthy adolescents. This study aimed to fill this gap in the literature by utilizing a monozygotic twin control to investigate the neuropsychological outcomes of bilateral thalamic stroke in adolescence. Method: We evaluated an otherwise healthy 17-year-old male with a history of premature birth, developmental delay, and learning disability 2 and 7 months after he sustained a bilateral medial/anterior thalamic stroke of unknown etiology. His identical twin brother served as a case control. Results: The patient presented with improvements in many cognitive skills between assessments, most notably processing speed. Despite some mild improvement, however, he presented with significant deficits in fine motor speed/coordination, spatial perception, and rapid naming. Additionally, he exhibited persistent, severe deficits in verbal learning and memory. Relative sparing of executive functions (i.e., planning and set-shifting) and attention on standardized measures in this case may be explained by good underlying health, limited extra-thalamic damage, and/or recovery of function. The effects of thalamic injury resulted in minimal adaptive dysfunction or deterrence from academic or athletic success for the presented case. Conclusions: These results suggest risk for deficits in encoding of new verbal information following bilateral thalamic stroke in adolescence, as well as risk for persistent cognitive deficits despite initial improvements. This is consistent with descriptions of anterograde memory impairments in adults with similar lesions.

Spectrum of polysomnographic abnormalities in children with epilepsy.

This study sought to evaluate polysomnographic abnormalities in a cohort of 40 children with epilepsy who underwent a sleep study because of various sleep complaints. Retrospective analyses included polysomnographic variables, antiepileptic drugs, type of epilepsy, and seizure control. The subgroup with epilepsy and obstructive sleep apnea syndrome was compared with 11 children who manifested uncomplicated obstructive sleep apnea syndrome. Thirty-three patients (83%) exhibited snoring (42.5%), sleep-disordered breathing (obstructive hypoventilation, 12.5%; obstructive sleep apnea, 20%; and upper-airway resistance syndrome, 7.5%), or periodic limb movements of sleep (10%). Children with poor seizure control demonstrated significantly lower sleep efficiency, a higher arousal index, and a higher percentage of rapid-eye-movement sleep compared with children who were seizure-free or exhibited good seizure control. Patients with epilepsy and obstructive sleep apnea had significantly a higher body mass index, longer sleep latency, a higher arousal index, and a lower apnea-hypopnea index, but significantly more severe desaturation compared with patients with uncomplicated obstructive sleep apnea. A significant proportion of children with epilepsy referred for polysomnography with diverse sleep problems manifest sleep-disordered breathing, including obstructive sleep apnea syndrome.