Stage N2 Research Articles

Polysomnographic Findings into Sleep Disorders in Essential Tremor and Essential Tremor Plus: A Comparison with Healthy Controls.

To explore sleep patterns in individuals with Essential Tremor (ET) and Essential Tremor Plus (ET-Plus), compared to healthy controls, and assess differences between ET and ET-Plus, given the lack of established polysomnography (PSG) data on these groups and the potential for sleep disturbances to serve as clinical markers. We conducted a prospective cross-sectional study at NIMHANS, Bengaluru, from November 2021 to August 2023 on 45 patients (26 ET, 19 ET-Plus) and 45 controls. Tremor severity was assessed using TETRAS and FTMTRS, and sleep symptoms with ESS, PSQI, Mayo Sleep Questionnaire, RLS-Q, BQ, GAD-7 and PHQ-9. All cases and controls underwent overnight video PSG. Sleep scoring was manually done by a technically adequate sleep researcher and the first author following AASM (2022) guidelines with data analysed using R studio. ET patients exhibited younger onset age (30.8 ± 16.7 years) compared to ET-Plus patients (46.8 ± 11.1 years). ET-Plus had higher TETRAS and FTMRS scores (P < 0.001) than ET. Both ET and ET-Plus patients exhibited poorer sleep quality, excessive daytime sleepiness, REM sleep behavior disorder (RBD), and Restless Legs Syndrome (RLS) symptoms compared to controls. PSG findings supported these clinical observations, showing elevated Apnea-Hypopnea Index (AHI), reduced Total Sleep Time (TST), prolonged REM latency, decreased sleep efficiency, increased N1 stage duration, and reduced N2/N3 durations and percentages in patients versus controls. The study highlights significant sleep architecture abnormalities in both ET and ET-Plus patients as compared to healthy controls, with no differences between the ET groups.

Characteristics of clinical descriptive variables and polysomnographic findings of catathrenia.

Catathrenia has been classified as a sleep-related breathing disorder variant in the third edition of the International Classification of Sleep Disorders, but its validity remains unverified. We analyzed the clinical descriptive variables and polysomnographic findings of catathrenia and discussed the similarities and differences to those of obstructive sleep apnea (OSA), non-REM parasomnias, and sleep bruxism (SB). A retrospective analysis was conducted on 47 patients diagnosed with nocturnal groaning through polysomnography. We examined sex, body mass index, age at symptom onset, weekly symptom frequency, and presence/absence of comorbidities, including OSA, periodic limb movement disorder, non-REM parasomnia, and SB. The groaning event (GE) index was calculated according to sleep position and sleep stage. The distribution of patients with catathrenia did not show sex difference (male/female = 20:27), body mass index was 20.6 ± 3.0 kg/m2, and age of onset was 18.2 ± 7.4 years. The GE index was higher in stages N1 and R than in stage N3 and in the supine position than in the lateral position. There were no cases complicated with non-REM parasomnia, but the complication of SB was observed in 30% of the participants, and SB events appeared immediately before or during the interictal period of the GE episodes in these cases. Given the clinical background, posture- and sleep stage-dependent appearance of GEs, and the relatively high complication rate of SB, catathrenia pathogenesis may be heterogeneous or comprise elements of different sleep disorders.

Impaired Sleep-Dependent Memory Consolidation in Pediatric Narcolepsy Type 1.

Disrupted nighttime sleep (DNS) is common in pediatric Narcolepsy type 1, yet its cognitive impact is unknown. As N2 sleep spindles are necessary for sleep-dependent memory consolidation, we hypothesized that Narcolepsy Type 1 impairs memory consolidation via N2 sleep fragmentation and N2 sleep spindle alterations. We trained 28 pediatric Narcolepsy Type 1 participants and 27 healthy controls (HC) on a spatial declarative memory task before a nocturnal in-lab polysomnogram and then gave them a cued recall test upon awakening in the morning. We extracted wake and sleep stage bout numbers and N2 spindle characteristics from the polysomnogram and conducted mixed model analysis of sleep-dependent memory consolidation to identify group differences. Narcolepsy Type 1 participants had shorter N2 bout durations and associated shorter N2 spindles vs. HC, but other N2 spindle features were similar. Narcolepsy Type 1 participants had worse memory performance post-sleep than HCs after adjusting for age and gender (mean memory consolidation HC: -3.1% ± 18.7, NT1: -15.6 ± 24.8, main effect group x time of testing F=5.3, p=0.03). We did not find significant relationships between sleep-dependent memory consolidation and N2 spindle characteristics. Notably, increased N1% was associated with worse sleep-dependent memory consolidation with results driven by the Narcolepsy Type 1 group. Sleep-dependent memory consolidation is mildly impaired in youth with Narcolepsy Type 1 and findings may be attributed to increases in N1 sleep. Further studies are needed to determine if these findings are generalizable and reversible with sleep-based therapies.

Selection of induction chemotherapy cycles for stage N3 nasopharyngeal carcinoma based on pre-treatment plasma EBV DNA.

This study aimed to explore the selection of induction chemotherapy (IC) cycles for stage N3 nasopharyngeal carcinoma (NPC). We employed propensity score matching (PSM) to categorize patients into 3-cycle and 4-cycle IC groups (IC = 3 and IC = 4). The log-rank and chi-squared tests were used respectively to evaluate the differences in survival and acute toxicities. Survival outcomes including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were evaluated among the two groups. After PSM, each group comprised 99 patients. The IC = 4 group exhibited markedly improved survival outcomes compared with the IC = 3 group. Multivariate analysis revealed that pre-EBV DNA was an independent risk factor affecting PFS and DMFS. For high-risk patients with pre-EBV DNA ≥ 7800 copies/ml, the IC = 4 group demonstrated greater survival compared to the IC = 3 group. Among low-risk patients with pre-EBV DNA < 7800 copies/ml, both groups showed comparable survival outcomes. In terms of acute adverse reactions, the IC = 4 group experienced higher incidences, particularly with grade 2-4 alanine transaminase elevation and thrombocytopenia. For stage N3 NPC, pre-EBV DNA could be a powerful predictor for guiding the selection of IC cycles. The IC = 4 regimen is probably more beneficial to high-risk patients due to superior survival, while for low-risk patients, the IC = 3 regimen may be sufficient.

Survival Outcomes of Neoadjuvant Therapy Followed by Sleeve Lobectomy in Non-Small Cell Lung Cancer

This study was carried out to evaluate the impact of neoadjuvant therapy on long-term survival in non-small cell lung cancer (NSCLC) patients undergoing sleeve lobectomy. A total of 613 patients were retrospectively analyzed, including 124 who received neoadjuvant therapy. A 1:2 Propensity score matching (PSM) method was adopted to create a balanced cohort including 110 with neoadjuvant therapy and 169 without neoadjuvant therapy. Survival was estimated using the Kaplan-Meier method and compared using the Log-rank test and Cox proportional hazards models. Neoadjuvant therapy was associated with improved 3-year DFS (73.6% vs. 54.4%, P<0.001) and OS (80.9% vs. 63.9%, P=0.002) compared to patients without neoadjuvant therapy. Moreover, neoadjuvant chemoimmunotherapy significantly improved 3-year DFS (85.3% vs. 54.4%, P=0.001) and OS (88.2% vs. 63.9%, P=0.006), whereas chemotherapy alone did not show a significant effect. Multivariable Cox regression analysis revealed that neoadjuvant therapy was an independent predictor of improved DFS and OS while pathological N2 stage was independently associated with poorer DFS and OS. Furthermore, subgroup analysis in the neoadjuvant arm revealed that pathological N2 stage was an independent risk factor for DFS (HR, 3.830; 95% CI, 1.687-8.694; P=0.001), and achieving major pathologic response (MPR) was an independent predictor for better OS (HR, 0.120; 95% CI, 0.015-0.933; P=0.043). Neoadjuvant therapy prior to sleeve lobectomy significantly increased DFS and OS in locally advanced NSCLC. Sleeve lobectomy is advisable followed by neoadjuvant therapy, especially with chemoimmunotherapy.

Exploring Molecular Signatures in Early-Stage Pancreatic Ductal Adenocarcinoma: Implications for Patient Management and Therapeutic Strategies

Abstract Introduction/Objective Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges to patient survival, predominantly due to its tendency for late-stage diagnosis and high rates of post-surgical cancer recurrence. Therefore, a comprehensive understanding of the molecular characteristics associated with the early stages of PDAC is imperative. This understanding holds the potential to improve patient treatment strategies by enabling targeted interventions and personalized therapies. Methods/Case Report Initially, RNA-seq datasets of early-stage PDAC cases (stages IA, IB, IIA, and IIB, all without distant metastasis; M0) were extracted from the GEO database. Subsequently, the datasets were analyzed in four distinct groups, and differentially expressed genes were identified within each group. Group 1 compared T1T2 cases with T3 cases (T: primary tumor), irrespective of N status (N: regional lymph nodes), while group 2 compared N0 cases with N1 cases, regardless of T status. Group 3 included comparisons between T1T2N0 cases and T3N0 cases, and group 4 compared T1T2N1 cases with T3N1 cases. Utilizing a Venn diagram, commonalities between gene expression profiles were isolated. Afterward, gene ontology and signaling pathways were determined using KEGG and Enrichr. Finally, a protein network was constructed, and the proteins were evaluated using the GEPIA and TCGA clinical databases. Results (if a Case Study enter NA) The study encompassed a total of 43 cases, with 25 (58.1%) being male and 18 (41.9%) female. The mean age of the participants was 64.4 years. In group 1, the expression levels of MUC5AC, AKAP13, and SPG7 were significantly upregulated in T3 cases. In group 2, STAB1, PDLIM1, and MTUS1 emerged as the top upregulated genes in N1 cases. Group 3 exhibited notable upregulation of CCNL2, CEACAM6, and TSPAN3 in T3N0 cases, while group 4 demonstrated marked upregulation of LTBR, AKAP12, and BOP1 in T3N1 cases. These genes exhibited diverse functions in PDAC progression. They contributed to the regulation of gene expression and cell cycle progression, modulating cell proliferation, inhibiting tumor growth, regulating cell signaling, and were involved in cytoskeletal organization. Conclusion The upregulated genes in cases with the T3 and/or N1 staging components may shed light on the potential mechanisms of progression from stage IA/B to stage IIA/B in PDAC cases. Furthermore, the identified genetic alterations may hold potential therapeutic and prognostic applications for future use in the early stages of PDAC.

Trypanosoma cruzi infection enhances olfactory response in Triatoma pallidipennis Stål (Hemiptera: Triatominae) to compounds potentially useful for insect control.

In Mexico, Triatoma pallidipennis is a major vector of Trypanosoma cruzi, the causative agent of Chagas disease. Current efforts are focused on developing attractants to control these vectors, using volatile substances derived from vertebrate hosts or compounds known to attract hematophagous insects. However, the efficacy of these compounds in attracting parasite-infected triatomines remains to be evaluated. In this study, we assessed the attractant activity of octenol (1-octen-3-ol), nonanal and a mixture of odorants consisting of ammonium hydroxide, lactic acid and hexanoic acid (in a ratio of 1:0.2:0.4 respectively), at concentrations of 1, 10 and 100 ng on the N3, N4 and N5 nymphal stages of T. pallidipennis, both infected and non-infected with T. cruzi. We also evaluated the synergistic effect of the most effective compounds and doses. All experiments were performed in a laboratory using a Y-type glass olfactometer. We found that both infected and non-infected N3 and N4 nymphs were attracted to low doses of octenol, nonanal and the odorant mixture. Particularly noteworthy was the synergistic effect observed between the odorant mixture and nonanal, which significantly increased attraction of T. cruzi-infected individuals. These findings contribute to the development of baited traps utilising these compounds for monitoring triatomines in epidemiological studies or for mass trapping to control these vectors.

Therapeutic and Diagnostic Tactics for Metastases to the Lymph Nodes of the Neck without an Identified Primary Focus

Introduction. Metastatic squamous cell carcinoma from an unknown primary focus accounts for less than 5 % of malignant tumors in the head and neck. Improving the methods of diagnosis can reduce the incidence of this pathology. Materials and methods. A retrospective analysis of the results of diagnosis and treatment of 59 patients with metastasis to the lymph nodes of the neck without an identified primary focus was performed. The proportion of male patients was 86 % (51/59), female — 14 % (8/59). The average age of patients is 61 years. Squamous cell carcinoma prevailed — 79 % (47/59). Results. Metastatically affected lymph nodes were localized in 92 % of cases at levels II and III. The proportion of patients with stages N2, N3 prevailed — 55 % (abs. 26), 32 % (abs. 15), respectively. Overexpression of the P­16 protein in metastatically affected lymph nodes was detected in 70 %, PD­L1 in 48 %, and Epstein­Barr virus (EBV) in 6 %. Ipsilateral diagnostic palatine tonsillectomy of an apparently unchanged tonsil was performed in 15 % (9/59) of cases, revealing the primary site in one instance. Of the special treatment methods, complex and combined treatment prevailed — 55 % (abs. 26). Radiation therapy in an independent version was performed by 48 % of patients, while 76 % received the full course (abs. 16). Combined treatment (a course of Radiation therapy followed by chemotherapy) — in 7 % (abs. 3) 20 % of patients received polychemotherapy. Palliative immunotherapy (pembrolizumab 200 mg IV — 5 courses) was given to 1 patient. The average life expectancy was higher with complex treatment — it was 60 months (95 % CI 43.5–76.4), the median survival is 60 months. Discussion. The main methods of treatment of patients with metastases of squamous cell carcinoma without were radiation therapy in an independent version, as well as complex treatment. Ipsilateral diagnostic palatine tonsillectomy of an apparently unchanged tonsil was performed in 15 % (abs. 9), and allowed to identify the primary focus in 1 case.Conclusion. Metastasis to the lymph nodes of the neck without remains an urgent interdisciplinary problem. Prospective multicenter studies are required to improve and optimize the algorithms for diagnosis and treatment of these patients.

Brian effects of electroacupuncture on sleep quality and cognitive function in patients with insomnia related to cerebral infarction

To observe the effects of electroacupuncture (EA) on sleep quality, sleep structure, and cognitive function in patients with insomnia related to cerebral infarction, and to explore the brain effect mechanism of EA on insomnia related to cerebral infarction. Thirty-six patients with insomnia related to cerebral infarction were randomly divided into an EA group (18 cases, 1 case was eliminated and 1 case dropped out) and a sham acupuncture group (18 cases, 1 case was eliminated and 2 cases dropped out). Both groups received conventional treatment for cerebral infarction. The EA group received EA at Sishencong (EX-HN 1) with continuous waves at a frequency of 2 Hz, at an intensity tolerable to the patient. The sham acupuncture group received sham acupuncture at non-acupoints with the same EA parameters but electrical stimulation was interrupted after 30 s. Both groups were treated for 20 min each session, once daily, 5 days per week, for a total of 4 weeks. Pittsburgh sleep quality index (PSQI), Montreal cognitive assessment-basic (MoCA-B) scores, and short-term memory (STM) encoding test accuracy and average reaction time were observed before and after treatment in the two groups. Polysomnography (PSG) was used to evaluate sleep structure, and electroencephalogram (EEG) data were collected to observe the standardized power value of the Theta frequency band before and after treatment. Compared with before treatment, PSQI score was decreased and MoCA-B score was increased in the EA group after treatment (P<0.001); the EA group had lower PSQI score and higher MoCA-B score than those in the sham acupuncture group (P<0.001, P<0.01). Compared with before treatment, STM encoding test accuracy was increased and average reaction time was shortened in the EA group after treatment (P<0.01, P<0.001); sleep efficiency (SE) was increased (P<0.01), total sleep time (TST), REM, and N3 stages were prolonged (P<0.01, P<0.05), and sleep latency (SL) was shortened (P<0.01). The standardized power value of the Theta frequency band in EEG channels F3, C3, C4, O1 and O2 was decreased (P<0.05). After treatment, the EA group had higher STM encoding test accuracy, shorter average reaction time (P<0.05), higher SE (P<0.01), longer TST, REM and N3 stages (P<0.01), and shorter SL (P<0.01) than those in the sham acupuncture group. There was no statistically significant difference in the standardized power value of the Theta frequency band between the two groups (P>0.05). EA could regulate sleep quality and structure in patients with insomnia related to cerebral infarction, and improve cognitive function, possibly related to the reduction of slow-wave activity in EEG.

Polysomnographic and clinical characteristics of sleep apnea headache patients.

Sleep apnea headache can be defined as a persistent, widespread, throbbing headache that occurs recurrently, is not accompanied by any additional symptoms after waking up, and usually resolves within four hours. Diagnosis of the condition requires confirmation through polysomnography with an apnea-hypopnea index of at least 5, indicating the presence of obstructive sleep apnea syndrome (OSAS). While sleep apnea headaches are common in 10-15% of individuals with OSAS, morning headaches are experienced by 5% of this population. The aim of this study is to examine both polysomnographic and clinical features associated with sleep apnea headache in individuals confirmed to have OSAS by polysomnography. The study was conducted in the sleep center of University of Health Science, Erenköy Mental and Nervous Disease Training and Research Hospital. We have examined the clinical and polysomnographic data of the patients with sleep apnea headache (SAH) diagnosed according to IHS-3 criteria retrospectively and grouped the patients as mild, moderate and severe OSAS. Patients with morning headache except sleep apnea headache and under PAP titration treatment were excluded. The differences between the sleep macro structures of patients with (WSAH) and without sleep apnea headache (WOSAH) were examined. The WSAH group consisted of 384 participants and the control group (WOSAH) consisted of 294 participants The mean age was 46.29 ± 12.18 and 45.08 ± 12.62 years, respectively. Patients in the WSAH group had significantly higher scores on the Epworth Sleepiness Scale (ESS) (p = 0.004) and higher periodic limb movement index (PLMI) (p = 0.014) compared to the WOSAH group. WSAH patients exhibited shorter wake times after sleep onset (WASO) and lower scores on the sleep quality index, in contrast to WOSAH patients. Additionally, within the WSAH group, there was a negative correlation between age and several sleep parameters, including total sleep parameters. A positive correlation was observed between sleep duration (p = 0.009), waking up after sleep (p = 0.043), sleep efficiency (p = 0.001) and apnea-hypopnea index (AHI) (p = 0.018). Additionally, ESS scores were positively correlated with AHI and total awake time (p = 0.000 and p = 0.008, respectively), while negatively correlated with stage N3 sleep percentage and mean minimum oxygen level (p = 0.001 and p = 0.020, respectively) in the WSAH group. The causes and possible mechanisms of sleep apnea headache are not fully clarified and the underlying processes are not fully understood. Sleep apnea headaches appear to be related to disturbances in nocturnal sleep. Dysregulation in regions that modulate sleep and nociception may be one possible mechanism.

Patterns of failure with 18F-DCFPyL PSMA-PET/CT in the post-prostatectomy setting: A regional cohort analysis.

This study aimed to assess the detection rate of prostate cancer recurrence by prostate-specific member antigen positron emission tomography/computed tomography (PSMA PET/CT) with 18F-DCFPyL in patients with residual disease or biochemical recurrence (BCR), and its association with surgical pathology and prostate-specific antigen (PSA) kinetics. Men from South Central Ontario enrolled in the PSMA Registry for Recurrent Prostate cancer (PREP) between April 2019 and December 2021 after radical prostatectomy (RP) and who had 1) pathologic stage N1 or persistent elevated PSA; or 2) BCR (PSA >0.10 ng/mL) where initial postoperative PSA was undetectable were included. A total of 169 men (median age 68 years; interquartile range [IQR] 62-71) with complete data met the above criteria. The median PSA was 0.27 ng/mL (IQR 0.16-0.85) prior to PSMA-PET. Overall positivity rate 59%; when PSA was <0.40 ng/mL, overall positivity rate 42% vs. 85% with PSA ≥0.40 ng/mL (p<0.001). Higher pathologic tumor stage increased detection of regional lymph nodes (LN) (pT2-3a: 32% vs. pT3b: 69%, p<0.001) but not distant metastases (pT2-3a: 12% vs. pT3b: 24%, p=0.15). PSMA-PET detected 18% with prostate bed, 42% with regional LN disease, and 44% with pelvic-only disease. The three most involved LN chains were the internal (21%) and external (20%) iliac, and obturator chains (16%). This prospective study of patients with residual disease or BCR after RP illustrates patterns of failure that could impact diagnosis and postoperative management. Such patients have significant risk of regional LN positivity on PSMA-PET highlighting a need to include pelvic LN within salvage radiotherapy volumes.

Structure of Spectral Composition and Synchronization in Human Sleep on the Whole Scalp: A Pilot Study.

We used numerical methods to define the normative structure of the different stages of sleep and wake (W) in a pilot study of 19 participants without pathology (18-64 years old) using a double-banana bipolar montage. Artefact-free 120-240 s epoch lengths were visually identified and divided into 1 s windows with a 10% overlap. Differential channels were grouped into frontal, parieto-occipital, and temporal lobes. For every channel, the power spectrum (PS) was calculated via fast Fourier transform and used to compute the areas for the delta (0-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-30 Hz) bands, which were log-transformed. Furthermore, Pearson's correlation coefficient and coherence by bands were computed. Differences in logPS and synchronization from the whole scalp were observed between the sexes for specific stages. However, these differences vanished when specific lobes were considered. Considering the location and stages, the logPS and synchronization vary highly and specifically in a complex manner. Furthermore, the average spectra for every channel and stage were very well defined, with phase-specific features (e.g., the sigma band during N2 and N3, or the occipital alpha component during wakefulness), although the slow alpha component (8.0-8.5 Hz) persisted during NREM and REM sleep. The average spectra were symmetric between hemispheres. The properties of K-complexes and the sigma band (mainly due to sleep spindles-SSs) were deeply analyzed during the NREM N2 stage. The properties of the sigma band are directly related to the density of SSs. The average frequency of SSs in the frontal lobe was lower than that in the occipital lobe. In approximately 30% of the participants, SSs showed bimodal components in the anterior regions. qEEG can be easily and reliably used to study sleep in healthy participants and patients.

Unravelling sleep patterns: Supervised contrastive learning with self-attention for sleep stage classification

Sleep data scoring is a crucial and primary step for diagnosing sleep disorders to know the sleep stages from the PSG signals. This study uses supervised contrastive learning with a self-attention mechanism to classify sleep stages. We propose a deep learning framework for automatic sleep stage classification, which involves two training phases: (1) the feature representation learning phase, in which the feature representation network (encoder) learns to extract features from the electroencephalogram (EEG) signals, and (2) the classification network training phase, where a pre-trained encoder (trained during phase I) along with the classifier head is fine-tuned for the classification task. The PSG data shows a non-uniform distribution of sleep stages, with wake (W) (around 30% of total samples) and N2 stages (around 58% and 37% of total samples in Physionet EDF-Sleep 2013 and 2018 datasets, respectively) being more prevalent, leading to an imbalanced dataset. The imbalanced data issue is addressed using a weighted softmax cross-entropy loss function that assigns higher weights to minority sleep stages. Additionally, an oversampling technique (the synthetic minority oversampling technique (SMOTE) (Chawla et al., 2002)[1] ) is applied to generate synthetic samples for minority classes. The proposed model is evaluated on the Physionet EDF-Sleep 2013 and 2018 datasets using Fpz-Cz and Pz-Oz EEG channels. It achieved an overall accuracy of 94.1%, a macro F1 score of 92.64, and a Cohen’s Kappa coefficient of 0.92. Ablation studies demonstrated the importance of triplet loss-based pre-training and oversampling for enhancing performance. The proposed model requires minimal pre-processing, eliminating the need for extensive signal processing expertise, and thus is well-suited for clinicians diagnosing sleep disorders.

Temporal Lobe Epilepsy with Bitemporal Interictal Epileptiform Discharges: Effects of Sleep and Wakefulness

Introduction. Independent bitemporal interictal discharges are often found in patients with temporal lobe epilepsy. The likelihood of registering epileptiform activity (EA) is higher during sleep. Assessment of bitemporal interictal epileptiform discharges (BIEDs) with various discharge predominance ratio is used for presurgical evaluation of epilepsy patients and prediction of surgical outcomes. Our objective was to determine the predominant side (PS) in patients with bitemporal epilepsy using the incidence of epileptiform discharges for each sleep stage. Materials and methods. We analyzed 45 recordings of 10–24 h long-term video-EEG monitoring (LTM) in patients with bitemporal EA. For each recording, the total incidence of EA (IEA) and EA incidence for wakefulness and for each sleep stage were calculated individually. We also assessed the discharge predominance index (DPI) as a ratio of IEA in the predominant and contralateral sides for the entire recording and for each sleep stage. Results. We observed an IEA increase with sleep deepening, with maximum values observed during N2 and N3 sleep stages. The minimum IEA values were recorded during REM sleep; nevertheless, most of the REM sleep discharges were detected on the PS. DPI values were the highest and the most stable during N2 and N3 stages. Conclusion. The findings of our study demonstrate an increase in DPI values with non-rapid eye movement (NREM) sleep deepening in patients with bitemporal localization of EA. Despite the protective effects of REM sleep (i.e., reducing the likelihood of EA), it may be pivotal in lateralization of EA in patients with BIEDs. The PS is generally determined by a higher DPI during N2 and N3 stages.

Impact of mini-dose dexmedetomidine supplemented analgesia on sleep structure in patients at high risk of obstructive sleep apnea: a pilot trial.

Obstructive sleep apnea (OSA) is common in surgical patients and associated with worse perioperative outcomes. To investigate the effect of mini-dose dexmedetomidine supplemented analgesia on postoperative sleep quality pattern in patients at high risk of OSA. A pilot randomized, double-blind, placebo-controlled trial. A tertiary university hospital in Beijing, China. One hundred and fifty-two adult patients who had a STOP-Bang score ≥3 and a serum bicarbonate level ≥28 mmol/L and were scheduled for major noncardiac surgery between 29 January 2021 and 20 September 2022. After surgery, patients were provided with high-flow nasal cannula and randomized in a 1:1 ratio to receive self-controlled opioid analgesia supplemented with either mini-dose dexmedetomidine (median 0.02 μg/kg/h) or placebo. We monitored polysomnogram from 9:00 pm to 6:00 am during the first night. Our primary outcome was the percentage of stage 2 non-rapid eye movement (N2) sleep. Secondary and exploratory outcomes included other postoperative sleep structure parameters, sleep-respiratory parameters, and subjective sleep quality (Richards-Campbell Sleep Questionnaire; 0-100 score range, higher score better). All 152 patients were included in intention-to-treat analysis; 123 patients were included in sleep structure analysis. Mini-dose dexmedetomidine supplemented analgesia increased the percentage of stage N2 sleep (median difference, 10%; 95% CI, 1 to 21%; p = 0.029); it also decreased the percentage of stage N1 sleep (median difference, -10%; 95% CI, -20% to -1%; p = 0.042). Other sleep structure and sleep-respiratory parameters did not differ significantly between the two groups. Subjective sleep quality was slightly improved with dexmedetomidine on the night of surgery, but not statistically significant (median difference, 6; 95% CI, 0 to 13; p = 0.060). Adverse events were similar between groups. Among patients at high risk of OSA who underwent noncardiac surgery, mini-dose dexmedetomidine supplemented analgesia may improve sleep quality without increasing adverse events. Clinicaltrials.gov, identifier NCT04608331.

Alterations in the DTI-ALPS index and choroid plexus volume are associated with clinical symptoms in participants with narcolepsy type 1

BackgroundNarcolepsy type 1 (NT1) is a sleep disorder characterized by excessive daytime sleepiness accompanied by cataplexy. Sleep disorders have been shown to affect the glymphatic system. This study aimed to evaluate changes in the diffusion tensor imaging along the perivascular space (DTI-ALPS) index and choroid plexus (CP) volume in NT1 participants, and to further explore their clinical significance. MethodsWe prospectively enrolled participants diagnosed with NT1 based on cerebrospinal fluid hypocretin-1 concentration and multiple sleep latency tests at our hospital. All participants underwent MRI to allow analysis of the DTI-ALPS index and CP volume. We subsequently performed correlation analyses between the DTI-ALPS index, CP volume, and important clinical parameters, including the Epworth Sleepiness Scale (ESS) score, Narcolepsy Severity Scale (NSS) score, stage rapid eye movement sleep (REM) ratio, stage 1 non-REM (N1) ratio, stage 2 non-REM (N2) ratio, and stage 3 non-REM (N3) ratio, among the NT1 participants. Inter-group and correlation analyses of DTI-ALPS index and CP volume were performed using age, sex, body mass index, and lateral ventricle volume as covariates. ResultsThis study enrolled 41 NT1 participants and 42 healthy controls (HC). The DTI-ALPS index of NT1 participants was significantly lower than HC (1.444±0.119 vs.1.661±0.135, P<0.001), while the CP volume of NT1 participants was significantly larger than those of HC (0.831±0.146 vs. 0.645±0.137, P<0.001). The DTI-ALPS index was negatively correlated with both the ESS (PFDR-corrected<0.001) and NSS scores (PFDR-corrected=0.010), but positively correlated with the Stage N3 ratio (PFDR-corrected=0.033). The CP volume of NT1 participants was positively correlated with ESS (PFDR-corrected=0.047) and NSS scores (PFDR-corrected=0.047), but negatively correlated with the stage N3 ratio (PFDR-corrected=0.047). ConclusionOur study suggests that the DTI-ALPS index was lower and CP volume was larger in NT1 participants. The DTI-ALPS index and CP volume in the NT1 participants were related to disease severity and sleep structure. These findings may provide new insights into the mechanisms underlying NT1.

Necrosis area, Tumor Size, and Lymph Node of Breast Cancer

Background: Breast cancer is the leading cause of cancer deaths in women worldwide in 2020. The high mortality rate is often influenced by various reasons, one of which is patients's prognosis. One of the prognostic factors is necrosis area, caused by hypoxic tumor tissue that can affect tumor growth and metastasis. Therefore, this study aims to determine the relationship between necrosis area with tumor size and lymph node metastasis in breast cancer patients. Methods: This study was an observational analytic with a cross-sectional approach. This research was conducted at the Anatomical Pathology Laboratory of Dr Soedarso Pontianak General Hospital and the Microscopy Laboratory of the Faculty of Medicine Tanjungpura University from September until November 2022. The study sample was 55 slides of Formalin-Fixed Paraffin-Embedded (FFPE). The study was conducted by observing the preparations under a microscope and then analyzed using ImageJ and SPSS software. The independent variable in this study was the necrosis area in the tumor microenvironment, and the dependent variables were tumor size and lymph node metastasis in breast tissue. Results: All study samples were female patients with invasive ductal carcinoma. Breast cancer tends to occur in patients aged 48-55 years. The highest percentage of necrosis area was 21% and the most diagnosed breast tumor size and lymph node metastasis were stage T4 and stage N2. Spearman's rho correlation test showed that there was no relationship between necrosis area and tumor size (p = 0.122; r = 0.16) and lymph node metastasis (p = 0.637; r = 0.18). Conclusions: There is no correlation between necrosis area with tumor size and lymph node metastasis of breast cancer patients in the Anatomical Pathology Laboratory at Dr Soedarso Pontianak General Hospital.

Age-related changes in sleep spindle characteristics in individuals over 75 years of age: a retrospective and comparative study

BackgroundSleep and its architecture are affected and changing through the whole lifespan. We know main modifications of the macro-architecture with a shorter sleep, occurring earlier and being more fragmented. We have been studying sleep micro-architecture through its pathological modification in sleep, psychiatric or neurocognitive disorders whereas we are still unable to say if the sleep micro-architecture of an old and very old person is rather normal, under physiological changes, or a concern for a future disorder to appear. We wanted to evaluate age-related changes in sleep spindle characteristics in individuals over 75 years of age compared with younger individuals.MethodsThis was an exploratory study based on retrospective and comparative laboratory-based polysomnography data registered in the normal care routine for people over 75 years of age compared to people aged 65–74 years. We were studying their sleep spindle characteristics (localization, density, frequency, amplitude, and duration) in the N2 and N3 sleep stages. ANOVA and ANCOVA using age, sex and OSA were applied.ResultsWe included 36 participants aged > 75 years and 57 participants aged between 65 and 74 years. An OSA diagnosis was most common in both groups. Older adults receive more medication to modify their sleep. Spindle localization becomes more central after 75 years of age. Changes in the other sleep spindle characteristics between the N2 and N3 sleep stages and between the slow and fast spindles were conformed to literature data, but age was a relevant modifier only for density and duration.ConclusionWe observed the same sleep spindle characteristics in both age groups except for localization. We built our study on a short sample, and participants were not free of all sleep disorders. We could establish normative values through further studies with larger samples of people without any sleep disorders to understand the modifications in normal aging and pathological conditions and to reveal the predictive biomarker function of sleep spindles.

A spectrum of altered non-rapid eye movement sleep in schizophrenia.

Multiple facets of sleep neurophysiology, including electroencephalography (EEG) metrics such as non-rapid eye movement (NREM) spindles and slow oscillations, are altered in individuals with schizophrenia (SCZ). However, beyond group-level analyses, the extent to which NREM deficits vary among patients is unclear, as are their relationships to other sources of heterogeneity including clinical factors, ageing, cognitive profiles and medication regimens. Using newly collected high-density sleep EEG data on 103 individuals with SCZ and 68 controls, we first sought to replicate our previously reported group-level differences between patients and controls (original N=130) during N2 stage. Then in the combined sample (N=301 including 175 patients), we characterized patient-to-patient variability. We replicated all group-level mean differences and confirmed the high accuracy of our predictive model (AUC=0.93 for diagnosis). Compared to controls, patients showed significantly increased between-individual variability across many (26%) sleep metrics. Although multiple clinical and cognitive factors were associated with NREM metrics, collectively they did not account for much of the general increase in patient-to-patient variability. Medication regimen was a greater contributor to variability. Some sleep metrics including fast spindle density showed exaggerated age-related effects in SCZ, and patients exhibited older predicted biological ages based on the sleep EEG; further, among patients, certain medications exacerbated these effects, in particular olanzapine. Collectively, our results point to a spectrum of N2 sleep deficits among SCZ patients that can be measured objectively and at scale, with relevance to both the etiological heterogeneity of SCZ as well as potential iatrogenic effects of antipsychotic medication.

Clinicopathological characteristics and survival analysis of different molecular subtypes of breast invasive ductal carcinoma achieving pathological complete response through neoadjuvant chemotherapy

BackgroundTo investigate the prognostic differences following the achievement of a pathological complete response (pCR) through neoadjuvant chemotherapy across different molecular subtypes of breast invasive ductal carcinoma.MethodsData from the Surveillance, Epidemiology, and End Results (SEER) were identified for patients undergoing neoadjuvant chemotherapy who achieved pathological complete response for invasive ductal carcinoma of the breast between 2010 and 2019.Comparing the clinicopathological characteristics of patients across different molecular subtypes. Univariate and Cox multivariate analyses were utilized to identify independent predictors of overall survival (OS) and cancer-specific survival (CSS). The Kaplan–Meier method is used to compare OS and CSS among different molecular subtypes. After propensity score matching, subgroup analysis results were presented through forest plots.ResultsThis study included 9,380 patients diagnosed with invasive ductal carcinoma, who were categorized into four molecular subtypes: 2,721 (29.01%) HR + /HER-2 + , 1,661 (17.71%) HR + /HER2-, 2,082 (22.20%) HR-/HER2 + , and 2,916 (31.08%) HR-/HER-2-. HR + /HER-2- subgroup exhibited a significantly higher proportion of patients under 50 years old than the other subtype groups (54.67% vs 40.2%, 50.35% and 51.82%, p < 0.01), and had a higher N2 + N3 stage (11.2% vs 7.24%, 8.69% and 7.48%, p < 0.01). Univariate and multivariate analysis revealed that molecular subtype was the independent risk factor for OS and CSS in patients(p < 0.05). The Kaplan–Meier curves indicated that the HR + /HER-2 + subtype had the highest OS and CSS(p < 0.05). Next, were the HR-/HER-2 + and HR-/HER-2- subtypes, with the HR + /HER-2- group having the lowest OS and CSS(p < 0.05). After propensity score matching, the OS and CSS of patients in the HR + /HER-2 + group remained higher compared to HR + /HER-2- group(p < 0.05).ConclusionsPatients with invasive ductal carcinoma of different molecular subtypes exhibit varying prognoses after achieving pCR to neoadjuvant chemotherapy. Those in the HR + /HER-2- group are younger, have a higher lymph node stage, and the lowest OS and CSS, whereas patients in the HR + /HER-2 + group have the highest OS and CSS.