Longitudinal Assessment of Retinal Microvasculature in Preclinical Alzheimer's Disease.

Purpose: To investigate if changes in vessel density (VD) and the foveal avascular zone (FAZ) occur in the preclinical phase of Alzheimer's disease (pAD) over time. Methods: Optical coherence tomography angiography (OCTA) was used to image VD and FAZ at baseline and for a follow-up period of 2 years. Positron emission tomography (PET) was used to determine the amyloid beta (Aß) status of participants. Results: The VD and FAZ of 148 participants (54% female) were analyzed at baseline and follow-up (mean time between measurements, 2.24 ± 0.35 years). The mean age of the participants was 68.3 ± 6.0 years at baseline and 70.3 ± 5.9 years at follow-up. Participants were divided into three groups: control group, participants who had negative Aß status at both measurements (Aß-, n = 116); converter group, participants who transitioned from negative to positive between baseline and follow-up (Aß-+, n = 18); and participants who were consistently positive at both visits (Aß++, n = 14). The VD of both Aß+ groups demonstrated non-significant increases over time in both macula and optic nerve head (ONH) regions. The Aß- group was found to be significantly higher in both ONH and macular regions. The VD of the Aß++ group was significantly higher in the macula inner and outer rings compared to the Aß-+ and Aß- groups. No significant change was found in FAZ values over time. Conclusions: Alterations in VD seem to manifest already in pAD, exhibiting distinct variations between the ONH and macula. Further longitudinal studies with a longer follow-up design and known amyloid pathology should be undertaken to validate these observations.

Efficacy of dexmedetomidine in postoperative nausea and vomiting in laparoscopic bariatric surgery: A systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Postoperative nausea and vomiting (PONV) is a common side effect of all types of surgeries, especially so in bariatric surgery. Dexmedetomidine (DX) is an α2-agonist that may be useful as an adjunct prophylactic medication for PONV. This meta-analysis aims to evaluate the efficacy of DX in reducing the incidence and severity of PONV in laparoscopic bariatric surgeries. MATERIALS AND METHODS: Databases were searched for articles with the determined MESH terms and keywords before February 2022. Identified articles were screened and 13 randomised clinical trials (RCTs) were included in this meta-analysis based on the inclusion criteria. Data were extracted from the articles and statistical analysis was performed using Review Manager. RESULTS: Administration of DX significantly reduced the incidence of PONV and Numerical Rating Scale (NRS) scores for PONV. The outcome was probably due to the intrinsic sympatholytic effect of the medication, reduction of postoperative pain and total postoperative opioid usage. DX showed better efficacy as PONV prophylaxis if the duration of surgery was < 120 minutes. Delivery of DX as a continuous infusion without a loading dose before infusion was found to be effective in reducing PONV compared to infusion after a loading dose. CONCLUSION: Administration of DX can reduce the incidence of PONV in patients undergoing laparoscopic bariatric surgery. However, further studies are required to investigate the optimal dose of DX as an antiemetic, considering its side effects to increase the applicability of our results in future guidelines for laparoscopic bariatric surgery.

Phase I PIANO trial-PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes.

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) induces direct DNA damage and immunogenic cell death in patients with gastric cancer peritoneal metastases (GCPM). Combining PIPAC-OX with immune checkpoint inhibition remains untested. We conducted a phase I first-in-human trial evaluating the safety and efficacy of PIPAC-OX combined with systemic nivolumab (NCT03172416). METHODS: Patients with GCPM who experienced disease progression on at least first-line systemic therapy were recruited across three centers in Singapore and Belgium. Patients received PIPAC-OX at 90 mg/m2 every 6 weeks and i.v. nivolumab 240 mg every 2 weeks. Translational studies were carried out on GCPM samples acquired during PIPAC-OX procedures. RESULTS: In total, 18 patients with GCPM were prospectively recruited. The PIPAC-OX and nivolumab combination was well tolerated with manageable treatment-related adverse events, although one patient suffered from grade 4 vomiting. At second and third PIPAC-OX, respectively, the median decrease in peritoneal cancer index (PCI) was -5 (interquartile range: -12 to +1) and -7 (interquartile range: -6 to -20) and peritoneal regression grade 1 or 2 was observed in 66.7% (6/9) and 100% (3/3). Translational analyses of 43 GCPM samples revealed enrichment of immune/stromal infiltration and inflammatory signatures in peritoneal tumors after PIPAC-OX and nivolumab. M2 macrophages were reduced in treated peritoneal tumor samples while memory CD4+, CD8+ central memory and naive CD8+ T-cells were increased. CONCLUSIONS: The first-in-human trial combining PIPAC-OX and nivolumab demonstrated safety and tolerability, coupled with enhanced T-cell infiltration within peritoneal tumors. This trial sets the stage for future combinations of systemic immunotherapy with locoregional intraperitoneal treatments.

Oral health assessment of epilepsy patients from a tertiary hospital in Asia.

INTRODUCTION: Oral health problems are frequently overlooked in patients with epilepsy. We evaluate the oral health status of epilepsy patients from a tertiary teaching hospital. MATERIALS AND METHODS: We conducted a cross-sectional study of epilepsy patients from the neurology clinic, Hospital Canselor Tuanku Muhriz, Kuala Lumpur. The dental assessment included the decayed, missing and filled teeth (DMFT) criteria, as well as the plaque and periodontal status by dentists. RESULTS: A total of 151 patients were recruited. The median age of onset of epilepsy was 16 (IQR 7-30) years, with generalised seizures at 59.6% and focal seizures in 40.4% of patients. Fair or poor oral health was present in 59 (39.1%) and gingivitis was seen in 65 (43%). The median DMFT decayed (D), missing (M) and filled teeth (FT) was 3 (IQR 1- 7). The median age of patients with fair or poor oral health was older (40 years, IQR 31-51) than the patients with excellent or good oral health (33 years, IQR 26-45), (p=0.014). Multivariate logistic regression analysis showed that carbamazepine (Odds Ratios, OR: 3.694; 95% Confidence Intervals, 95%CI: 1.314, 10.384) and hypertension (OR 6.484; 95%CI: 1.011, 41.594) are the risk factors for fair or poor oral health. Phenytoin use is 4.271 times more likely to develop gingivitis (OR 4.271; 95% CI: 1.252, 14.573). CONCLUSION: Factors that contribute to fair or poor oral health include age, antiseizure medications like phenytoin and carbamazepine, and hypertension. Effective preventive strategies should be implemented to maintain oral health in epilepsy patients.

Rationale and design of the BeyeOMARKER study: prospective evaluation of blood- and eye-based biomarkers for early detection of Alzheimer's disease pathology in the eye clinic.

BACKGROUND: Alzheimer's disease (AD) is a common, complex and multifactorial disease that may require screening across multiple routes of referral to enable early detection and subsequent future implementation of tailored interventions. Blood- and eye-based biomarkers show promise as low-cost, scalable and patient-friendly tools for early AD detection given their ability to provide information on AD pathophysiological changes and manifestations in the retina, respectively. Eye clinics provide an intriguing real-world proof-of-concept setting to evaluate the performance of these potential AD screening tools given the intricate connections between the eye and brain, presumed enrichment for AD pathology in the aging population with eye disorders, and the potential for an accelerated diagnostic pathway for under-recognized patient groups. METHODS: The BeyeOMARKER study is a prospective, observational, longitudinal cohort study aiming to include individuals visiting an eye-clinic. Inclusion criteria entail being ≥ 50 years old and having no prior dementia diagnosis. Excluded eye-conditions include traumatic insults, superficial inflammation, and conditions in surrounding structures of the eye that are not engaged in vision. The BeyeOMARKER cohort (n = 700) will undergo blood collection to assess plasma p-tau217 levels and a brief cognitive screening at the eye clinic. All participants will subsequently be invited for annual longitudinal follow-up including remotely administered cognitive screening and questionnaires. The BeyeOMARKER + cohort (n = 150), consisting of 100 plasma p-tau217 positive participants and 50 matched negative controls selected from the BeyeOMARKER cohort, will additionally undergo Aß-PET and tau-PET, MRI, retinal imaging including hyperspectral imaging (primary), widefield imaging, optical coherence tomography (OCT) and OCT-Angiography (secondary), and cognitive and cortical vision assessments. RESULTS: We aim to implement the current protocol between April 2024 until March 2027. Primary outcomes include the performance of plasma p-tau217 and hyperspectral retinal imaging to detect AD pathology (using Aß- and tau-PET visual read as reference standard) and to detect cognitive decline. Initial follow-up is ~ 2 years but may be extended with additional funding. CONCLUSIONS: We envision that the BeyeOMARKER study will demonstrate the feasibility of early AD detection based on blood- and eye-based biomarkers in alternative screening settings, and will improve our understanding of the eye-brain connection. TRIAL REGISTRATION: The BeyeOMARKER study (Eudamed CIV ID: CIV-NL-23-09-044086; registration date: 19th of March 2024) is approved by the ethical review board of the Amsterdam UMC.

[Colonic interposition with vascular anastomosis for upper digestive tract reconstruction after surgery for hypopharyngeal cancer with esophageal cancer].

Objective: To investigate the feasibility, safety and effectiveness of colonic interposition with vascular anastomosis in reconstructing the entire esophagus and hypopharynx after resection of hypopharyngeal cancer with esophageal cancer. Methods: We conducted a retrospective analysis of 4 male patients with simultaneous multiple primary cancers of the hypopharynx and esophagus, aged 47 to 58, treated in the Department of Head and Neck Surgery at the Hunan Cancer Hospital from February to August 2019. All cases underwent total hypopharyngectomy and total esophagectomy, of whom, three cases presented with total laryngectomy and one case with larynx preservation. Colonic interposition was performed using the left colic artery as a pedicle, with an average colonic length of 48.5 cm. The colon was elevated through the esophageal bed to the neck, and the branch of the colonic mesenteric artery was anastomosed to one of the neck arteries, including the inferior thyroid artery in one case, the transverse cervical artery in two cases, and the superior thyroid artery in one case, and all venous anastomoses were performed with the internal jugular veins. Results: The postoperative neck and abdominal wounds healed well without anastomotic leakage, and all patients were able to resume a regular oral diet within 21-30 days postoperatively. During the follow-up of 48-52 months, two cases died due to tumor recurrence, while the remaining two cases were disease-free survivals. Conclusion: Colonic interposition with vascular anastomosis is a safe and reliable reconstruction method suitable for repairing long-segment upper digestive tract defects after resection of hypopharyngeal cancer with esophageal cancer.

Laser Excitation of the

LiSrAlF_{6} crystals doped with ^{229}Th are used in a laser-based search for the nuclear isomeric transition. Two spectroscopic features near the nuclear transition energy are observed. The first is a broad excitation feature that produces redshifted fluorescence that decays with a timescale of a few seconds. The second is a narrow, laser-linewidth-limited spectral feature at 148.382 19(4)_{stat}(20)_{sys} nm [2020 407.3(5)_{stat}(30)_{sys} GHz] that decays with a lifetime of 568(13)_{stat}(20)_{sys} s. This feature is assigned to the excitation of the ^{229}Th nuclear isomeric state, whose energy is found to be 8.355 733(2)_{stat}(10)_{sys} eV in ^{229}Th:LiSrAlF_{6}.

[Study on the application value of fecal SDC2 gene methylation detection in colorectal cancer screening of urban residents in Zengcheng District in Guangzhou City].

Objective: To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (mSDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods: A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. mSDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of mSDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of mSDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results: A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of mSDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of mSDC2 was negatively correlated with the proportion of advanced colorectal neoplasms (χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion: The CRC screening strategy of fecal mSDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of mSDC2 may have a certain suggestion on the malignant degree of intestinal tumors.

[Re-thinking of "pelvirectal space"].

Before the "mesorectal" theory was proposed, the traditional anatomy believed that the "pelvirectal space" belonged to the anal canal and perirectal space, which was independent of the rectal structure, located on both sides of the rectum, above the levator ani, and below the peritoneal reflexion, and was composed of a large amount of fatty tissue filling. With the development of the theory of membrane anatomy and the clarification of the concept of "rectal mesentery", combined with the author's clinical experience, we found that the above-mentioned fat is actually the fat within the mesorectum, as well as the fat tissue of lateral lymph nodes (LLN) such as the internal iliac lymph nodes (No.263) and obturator lymph nodes (No.283) on both sides of the rectal mesentery, rather than the so-called fat tissue within the interstitial space. Therefore, the author believes that the pelvirectal space does not exist. In the anatomical location equivalent to the pelvic rectal space, there is the "superior levator ani space" based on the membrane anatomy theory. From the pelvirectal space to the superior levator anal space, it reflects our further understanding of the anatomy of the rectal mesentery.

Long-term survival following out-of-hospital cardiac arrest in women and men: Influence of comorbidities, social characteristics, and resuscitation characteristics.

AIM: We aimed to study sex differences in long-term survival following out-of-hospital cardiac arrest (OHCA) compared to the general population, and determined associations for comorbidities, social characteristics, and resuscitation characteristics with survival in women and men separately. METHODS: We followed 2,452 Danish (530 women and 1,922 men) and 1,255 Dutch (259 women and 996 men) individuals aged ≥25 years, who survived 30 days post-OHCA in 2009-2015, until 2019. Using Poisson regression analyses we assessed sex differences in long-term survival and sex-specific associations of characteristics mutually adjusted, and compared survival with an age- and sex-matched general population. The potential predictive value was assessed with the Concordance-index. RESULTS: Post-OHCA survival was longer in women than men (adjusted incidence rate ratio (IRR) for mortality 0.74, 95%CI 0.61-0.89 in Denmark; 0.86, 95%CI 0.65-1.15 in the Netherlands). Both sexes had a shorter survival than the general population (e.g., IRR for mortality 3.07, 95%CI 2.55-3.70 and IRR 2.15, 95%CI 1.95-2.37 in Danish women and men). Higher age, glucose lowering medication, no dyslipidaemia medication, unemployment, and a non-shockable initial rhythm were associated with shorter survival in both sexes. Cardiovascular medication, depression/anxiety medication, living alone, low household income, and residential OHCA location were associated with shorter survival in men. Not living with children and bystander cardiopulmonary resuscitation provision were associated with shorter survival in women. The Concordance-indexes ranged from 0.51 to 0.63. CONCLUSIONS: Women survived longer than men post-OHCA. Several characteristics were associated with long-term post-OHCA survival, with some sex-specific characteristics. In both sexes, these characteristics had low predictive potential.

The outcome of 12-week corticosteroid therapy in COVID-19-related diffuse interstitial lung abnormalities.

INTRODUCTION: The efficacy of long-course corticosteroid therapy in treating COVID-19-related diffuse interstitial lung abnormalities (DILA) needs to be better understood. We aimed to investigate the benefits of 12-week corticosteroid treatment in COVID-19-related DILA by evaluating computed tomography (CT) lung severity scores. MATERIALS AND METHODS: This retrospective, single-centre observational study included patients aged 18 years or older admitted with moderate to severe COVID-19 pneumonia who received 12 weeks of oral prednisolone between January 2021 and December 2021. We recorded clinical parameters, baseline CT scores and post-treatment, modified Medical Research Council (mMRC) dyspnoea scale and pulmonary function tests. RESULTS: A total of 330 patients were analysed. The mean (standard deviation, SD) age was 54.6 (14.2) years, and 43% were females. Three-point nine per cent (3.9%) require noninvasive ventilation (NIV), while 14.6% require mechanical ventilation (MV). On follow-up at 12 weeks, the CT patterns showed improvement in ground-glass opacities, perilobular density and consolidation. There was an improvement in the mean (SD) CT score before and after prednisolone therapy, with values of 17.3 (5.3) and 8.6 (5.5), respectively (p<0.001). The median mMRC was 1 (IQR 0-1), and 98.8% had a radiological response. The common side effects of prednisolone therapy were weight gain (13.9%), hyperglycaemia (1.8%) and cushingoid habitus (0.6%). CONCLUSION: A 12-week treatment with prednisolone showed significant improvement in CT scores with minimal residual dyspnoea and was relatively safe. Longer duration of steroids may be beneficial in moderate to severe COVID-19- related DILA.

Healthcare-associated carbapenem-resistant Klebsiella pneumoniae infections are associated with higher mortality compared to carbapenem-susceptible K. pneumoniae infections in the intensive care unit: a retrospective cohort study.

BACKGROUND: Klebsiella pneumoniae (KP) is an opportunistic pathogen causing severe pneumonia and sepsis. Carbapenem-resistant KP (CRKP) has become a major pathogen in many centres. AIM: To investigate the association between carbapenem resistance and the mortality rate, length of stay, and hospital cost in patients with Klebsiella pneumoniae infection. METHODS: The retrospective cohort study was conducted in the intensive care units of a large teaching tertiary hospital in southwest China between January 1st, 2020 and December 31st, 2022. To examine the impact of carbapenem resistance on mortality rates and economic burden, multivariate Cox regression and generalized linear models were constructed. FINDINGS: The study included 282 adult patients with KP infection (135 CSKP; 147 CRKP). CRKP-infected patients demonstrated higher mortality risk (unadjusted hazard ratio (aHR): 1.980; 95% confidence interval (CI): 1.206-3.248; P = 0.007; aHR: 1.767; 95% CI: 1.038-3.005; P = 0.036) compared to CSKP-infected patients. Stratified analysis, according to type of KP infection, revealed that patients with healthcare-associated CRKP infection had a significantly higher mortality risk compared to those with CSKP infection (log-rank P = 0.015). Patients with CRKP infection had longer hospital stays than those infected with CSKP (adjusted mean: 38.74 vs 29.71 days; P = 0.003), and hospital-related expenses were notably higher among CRKP patients than CSKP patients (adjusted cost: £40,126.73 vs 25,713.74; P < 0.001). CONCLUSION: CRKP infections increase mortality rates, prolong hospital stays, and raise healthcare costs. Healthcare facilities should adopt targeted strategies, including curtailing pre-infection hospitalization periods and managing medications more judiciously.

The association between epidural labour analgesia and postpartum depression: a randomised controlled trial.

There is conflicting evidence regarding the association between epidural labour analgesia and risk of postpartum depression. Most previous studies were observational trials with limited ability to account for confounders. We aimed to determine if epidural analgesia was associated with a significant change in the incidence of postpartum depression in this randomised controlled trial. We enrolled women aged 21-50 years old with a singleton fetus ≥ 36 weeks gestation. Patients were advised regarding available labour analgesic modalities during enrolment (epidural block; intramuscular pethidine; nitrous oxide; or intravenous remifentanil). On request for analgesia, patients were offered the modality that they had been allocated randomly to first. Blinded investigators recorded patient and obstetric characteristics within 24 h of delivery and assessed for postpartum depression at 6-10 weeks following delivery using the Edinburgh Postnatal Depression Scale (score ≥ 13 considered positive for postpartum depression). The modified intention-to-treat population consisted of all patients who received any form of labour analgesia, while per-protocol consisted of patients who received their randomised modality as their first form of labour analgesia. Of 881 parturients allocated randomly (epidural n = 441, non-epidural n = 440), we analysed 773 (epidural n = 389, non-epidural n = 384); 62 (15.9%) of women allocated to epidural group developed postpartum depression compared with 65 (16.9%) women allocate to the non-epidural group. There were no significant differences in the incidence of postpartum depression between the two groups (adjusted risk difference (95%CI) 1.6 (-3.0-6.3%), p = 0.49). Similar results were obtained with per-protocol analysis (adjusted risk difference (95%CI) -1.0 (-8.3-6.3%), p = 0.79). We found no significant difference in the risk of postpartum depression between patients who received epidural labour analgesia and those who utilised non-epidural analgesic modalities.

Reporting standard for describing first responder systems, smartphone alerting systems, and AED networks.

Standardized reporting of data is crucial for out-of-hospital cardiac arrest (OHCA) research. While the implementation of first responder systems dispatching volunteers to OHCA is encouraged, there is currently no uniform reporting standard for describing these systems. A steering committee established a literature search to identify experts in smartphone alerting systems. These international experts were invited to a conference held in Hinterzarten, Germany, with 40 researchers from 13 countries in attendance. Prior to the conference, participants submitted proposals for parameters to be included in the reporting standard. The conference comprised five workshops covering different aspects of smartphone alerting systems. Proposed parameters were discussed, clarified, and consensus was achieved using the Nominal Group Technique. Participants voted in a modified Delphi approach on including each category as a core or supplementary element in the reporting standard. Results were presented, and a writing group developed definitions for all categories and items, which were sent to participants for revision and final voting using LimeSurvey web-based software. The resulting reporting standard consists of 68 core items and 21 supplementary items grouped into five topics (first responder system, first responder network, technology/algorithm/strategies, reporting data, and automated external defibrillators (AED)). This proposed reporting standard generated by an expert opinion group fills the gap in describing first responder systems. Its adoption in future research will facilitate comparison of systems and research outcomes, enhancing the transfer of scientific findings to clinical practice.

Behavioural digital biomarkers enable real-time monitoring of patient-reported outcomes: a substudy of the multicenter, prospective observational SafeHeart study.

INTRODUCTION: Patient-reported outcome measures (PROMs) serve multiple purposes, including shared decision-making and patient communication, treatment monitoring and health-technology assessment. Patient monitoring using PROMs is constrained by recall and non-response bias, respondent burden and missing data. We evaluated the potential of behavioural digital biomarkers obtained from a wearable accelerometer to achieve personalised predictions of PROMs. METHODS: Data from the multicenter, prospective SafeHeart study conducted at Amsterdam University Medical Center in the Netherlands and Copenhagen University Hospital, Rigshospitalet in Copenhagen, Denmark, was used. The study enrolled patients with an implantable cardioverter defibrillator (ICD) between May 2021 and September 2022 who then wore wearable devices with raw acceleration output to capture digital biomarkers reflecting physical behaviour. To collect PROMs, patients received the KCCQ and EQ5D-5 L questionnaire at two instances; baseline and after 6 months. Multivariable Tobit regression models were used to explore associations between digital biomarkers and PROMs, specifically whether digital biomarkers could enable PROM prediction. RESULTS: The study population consisted of 303 patients (mean age 62.9 ± 10.9 years, 81.2% male). Digital biomarkers showed significant correlations to patient-reported physical and social limitations, severity and frequency of symptoms and quality of life. Prospective validation of the Tobit models indicated moderate correlations between the observed and predicted scores for KCCQ (concordance correlation coefficient (CCC) = 0.49, mean difference: 1.07 points) and EQ5D-5 L (CCC = 0.38, mean difference 0.02 points). CONCLUSION: Wearable digital biomarkers correlate with PROMs, and may be leveraged for real-time prediction. These findings hold promise for monitoring of PROMs through wearable accelerometers.

[Reversible bilateral blindness associated with alcoholic ketoacidosis: a case report].

A 51-year-old male with a history of chronic alcoholism presented to the emergency department with an abrupt onset of complete bilateral blindness lasting for one hour. Funduscopic examination yielded unremarkable findings. Systemic evaluations revealed the presence of severe ketoacidosis. The patient spontaneously regained light perception after experiencing total blindness for 3 hours; however, he subsequently developed hypothermia and entered a state of shock. Following treatment with sodium bicarbonate and aggressive fluid resuscitation, his condition stabilized, and there was a rapid improvement in his visual acuity. The diagnosis of alcoholic ketoacidosis was established based on the patient's history of chronic alcohol abuse, physical examination findings, and blood analysis results.

Association of Oral Health with Frailty, Malnutrition Risk and Functional Decline in Hospitalized Older Adults: A Cross-Sectional Study.

BACKGROUND: Poor oral health is known to be associated with adverse outcomes, but the frequency and impact of poor oral health on older adults in the acute inpatient setting has been less well studied. OBJECTIVES: We examined the association between oral health, frailty, nutrition and functional decline in hospitalized older adults. DESIGN: Retrospective cross-sectional study. SETTING AND PARTICIPANTS: We included data from 465 inpatients (mean age 79.2±8.3 years) admitted acutely to a tertiary hospital. METHODS: We evaluated oral health using the Revised Oral Assessment Guide (ROAG), frailty using the Clinical Frailty Scale (CFS), malnutrition risk using the Nutritional Screening Tool (NST) and functional status using a modified Katz Activities of Daily Living (ADL) scale. We examined cross-sectional associations of oral health with frailty, malnutrition risk and functional decline on admission, followed by multivariate logistic regression models evaluating the association between poor oral health and the aforementioned outcomes. RESULTS: 343 (73.8%), 100 (21.5%) and 22 (4.7%) were classified as low, moderate and high risk on the ROAG, respectively. Poorer oral health was associated with greater severity of frailty, functional decline on admission and malnutrition risk. Abnormalities in ROAG domains of voice changes, swallowing difficulty, xerostomia, lips and tongue appearance were more frequently present at greater severity of frailty. Poor oral health was associated with frailty [odds ratio (OR): 1.76, 95% confidence interval (CI) 1.05-2.97; P=0.034]; malnutrition risk [OR: 2.76, 95% CI 1.46-5.19, P=0.002] and functional decline [OR: 1.62, 95% CI 1.01-2.59, P=0.046]. CONCLUSIONS: Poor oral health is significantly associated with frailty, malnutrition risk and functional decline in older inpatients. Oral health evaluation, as part of a comprehensive geriatric assessment may be a target for interventions to improve outcomes. Further research including longitudinal outcomes and effectiveness of specific interventions targeted at oral health are warranted in older adults in the inpatient setting.

Functional and molecular profiling of hematopoietic stem cells during regeneration.

Hematopoietic stem cells (HSCs) enable hematopoietic stem cell transplantation (HCT) through their ability to replenish the entire blood system. Proliferation of HSCs is linked to decreased reconstitution potential, and a precise regulation of actively dividing HSCs is thus essential to ensure long-term functionality. This regulation becomes important in the transplantation setting where HSCs undergo proliferation followed by a gradual transition to quiescence and homeostasis. Although mouse HSCs have been well studied under homeostatic conditions, the mechanisms regulating HSC activation under stress remain unclear. Here, we analyzed the different phases of regeneration after transplantation. We isolated bone marrow from mice at 8 time points after transplantation and examined the reconstitution dynamics and transcriptional profiles of stem and progenitor populations. We found that regenerating HSCs initially produced rapidly expanding progenitors and displayed distinct changes in fatty acid metabolism and glycolysis. Moreover, we observed molecular changes in cell cycle, MYC and mTOR signaling in both HSCs, and progenitor subsets. We used a decay rate model to fit the temporal transcription profiles of regenerating HSCs and identified genes with progressively decreased or increased expression after transplantation. These genes overlapped to a large extent with published gene sets associated with key aspects of HSC function, demonstrating the potential of this data set as a resource for identification of novel HSC regulators. Taken together, our study provides a detailed functional and molecular characterization of HSCs at different phases of regeneration and identifies a gene set associated with the transition from proliferation to quiescence.