Functional neural networks stratify Parkinson's disease patients across the spectrum of cognitive impairment.

INTRODUCTION: Cognitive impairment (CI) is a significant non-motor symptoms in Parkinson's disease (PD) that often precedes the emergence of motor symptoms by several years. Patients with PD hypothetically progress from stages without CI (PD-normal cognition [NC]) to stages with Mild CI (PD-MCI) and PD dementia (PDD). CI symptoms in PD are linked to different brain regions and neural pathways, in addition to being the result of dysfunctional subcortical regions. However, it is still unknown how functional dysregulation correlates to progression during the CI. Neuroimaging techniques hold promise in discriminating CI stages of PD and further contribute to the biomarker formation of CI in PD. In this study, we explore disparities in the clinical assessments and resting-state functional connectivity (FC) among three CI stages of PD. METHODS: We enrolled 88 patients with PD and 26 healthy controls (HC) for a cross sectional clinical study and performed intra- and inter-network FC analysis in conjunction with comprehensive clinical cognitive assessment. RESULTS: Our findings underscore the significance of several neural networks, namely, the default mode network (DMN), frontoparietal network (FPN), dorsal attention network, and visual network (VN) and their inter-intra-network FC in differentiating between PD-MCI and PDD. Additionally, our results showed the importance of sensory motor network, VN, DMN, and salience network (SN) in the discriminating PD-NC from PDD. Finally, in comparison to HC, we found DMN, FPN, VN, and SN as pivotal networks for further differential diagnosis of CI stages of PD. CONCLUSION: We propose that resting-state networks (RSN) can be a discriminating factor in distinguishing the CI stages of PD and progressing from PD-NC to MCI or PDD. The integration of clinical and neuroimaging data may enhance the early detection of PD in clinical settings and potentially prevent the disease from advancing to more severe stages.

Enhancing Aircraft Safety through Advanced Engine Health Monitoring with Long Short-Term Memory.

Predictive maintenance holds a crucial role in various industries such as the automotive, aviation and factory automation industries when it comes to expensive engine upkeep. Predicting engine maintenance intervals is vital for devising effective business management strategies, enhancing occupational safety and optimising efficiency. To achieve predictive maintenance, engine sensor data are harnessed to assess the wear and tear of engines. In this research, a Long Short-Term Memory (LSTM) architecture was employed to forecast the remaining lifespan of aircraft engines. The LSTM model was evaluated using the NASA Turbofan Engine Corruption Simulation dataset and its performance was benchmarked against alternative methodologies. The results of these applications demonstrated exceptional outcomes, with the LSTM model achieving the highest classification accuracy at 98.916% and the lowest mean average absolute error at 1.284%.

[Investigation of the Relationship Between Akkermansia Genomic Diversity in Gut Microbiota and Parkinson's Disease Dementia]. / Parkinson Hastaligi Demansi ile Bagirsak Mikrobiyotasindaki Akkermansia Genomik Çesitliligi Arasindaki Iliskinin Incelenmesi.

Although it is known that the relative abundance of Akkermansia, a bacterial genus commonly associated with health, increases in the gut microbiota of Parkinson's disease (PD) patients, the exact reason for this increase remains unclear. This study was aimed to identify potential changes in Akkermansia within the gut microbiota of PD patients in Türkiye. For this purpose, shotgun metagenomics and a novel Akkermansia genus-specific amplicon sequencing technique was used to investigate the presence of specific Akkermansia strains associated with cognitive impairment (CI) stages in PD and to examine potential genes within these strains. In this context, four gut microbiota samples from Türkiye -three PD with dementia (PDD) and one healthy control without CI (HC)- were analyzed by shotgun metagenomics and metagenome-assembled genomes assigned to Akkermansia genus were reconstructed. Then, a custom database was created by combining these genomes with the Akkermansia genomes in public databases and next generation sequencing (NGS) compatible primers specific to the genus Akkermansia were designed using this database. After optimization of amplification and library preparation steps for genus-specific next generation sequencing, gut microbiota samples from 64 PD patients [32 PDD and 32 PD with mild CI (PD-MCI)] and 26 HCs were analyzed by genus-specific amplicon sequencing. The results revealed the presence of seven strains assigned to Akkermansia muciniphila in gut microbiota samples, two of which showed significant distribution differences (p< 0.05) between demented (PDD) and non-demented groups (PD-MCI, HC). When gene contents of the detected Akkermansia genomes were examined through comparative genomic analysis, the presence of 12 genes only in Akkermansia genomes specific to non-demented groups were predicted. The annotations of these genes showed that they were not reported before with unknown functions. In this study, for the first time, gut microbiota samples from PD patients in Türkiye were analyzed using shotgun metagenomics, a novel genus-specific amplicon sequencing method was developed specifically for the analysis of Akkermansia genus, and then Akkermansia strains and genes potentially associated with CI stages in PD were identified using this method. The results underscore that investigating the species or strain level differences could help better understanding of the changes associated with PD in the human gut microbiota.

Comparison of the effects of open and closed aspiration on end-expiratory lung volume in acute respiratory distress syndrome.

BACKGROUND: Alveoli tend to collapse in patients with acute respiratory distress syndrome (ARDS). Endotracheal aspiration may increase alveolar collapse due to the loss of end-expiratory lung volume (EELV). We aimed to compare the loss of EELV after open and closed suction in patients with ARDS. METHODS: This randomized crossover study included 20 patients receiving invasive mechanical ventilation for ARDS. Open and closed suction were applied in a random order. Lung impedance was measured using electric impedance tomography. The change in end-expiratory lung impedance end of suction and at 1, 10, 20, and 30 min after suction, was used to represent the change in EELV. Arterial blood gas analyses and ventilatory parameters such as the plateau pressure (Pplat), driving pressure (Pdrive), and compliance of the respiratory system (CRS) were also recorded. RESULTS: Less volume loss was noted after closed suction than after open suction (mean ΔEELI: -2661 ± 1937 vs. -4415 ± 2363; mean difference: -1753; 95% CI [-2662, -844]; P = 0.001). EELI returned to baseline 10 min after closed suction but did not return to baseline even 30 min after open suction. After closed suction, the Pplat and Pdrive decreased while the CRS increased. Conversely, the Pplat and Pdrive increased while the CRS decreased after open suction. CONCLUSIONS: Endotracheal aspiration may result in alveolar collapse due to loss of EELV. Given that closed suction is associated with less volume loss at end-expiration without worsening ventilatory parameters, it should be chosen over open suction in patients with ARDS.

Metaproteogenomic analysis of saliva samples from Parkinson's disease patients with cognitive impairment.

Cognitive impairment (CI) is very common in patients with Parkinson's Disease (PD) and progressively develops on a spectrum from mild cognitive impairment (PD-MCI) to full dementia (PDD). Identification of PD patients at risk of developing cognitive decline, therefore, is unmet need in the clinic to manage the disease. Previous studies reported that oral microbiota of PD patients was altered even at early stages and poor oral hygiene is associated with dementia. However, data from single modalities are often unable to explain complex chronic diseases in the brain and cannot reliably predict the risk of disease progression. Here, we performed integrative metaproteogenomic characterization of salivary microbiota and tested the hypothesis that biological molecules of saliva and saliva microbiota dynamically shift in association with the progression of cognitive decline and harbor discriminatory key signatures across the spectrum of CI in PD. We recruited a cohort of 115 participants in a multi-center study and employed multi-omics factor analysis (MOFA) to integrate amplicon sequencing and metaproteomic analysis to identify signature taxa and proteins in saliva. Our baseline analyses revealed contrasting interplay between the genus Neisseria and Lactobacillus and Ligilactobacillus genera across the spectrum of CI. The group specific signature profiles enabled us to identify bacterial genera and protein groups associated with CI stages in PD. Our study describes compositional dynamics of saliva across the spectrum of CI in PD and paves the way for developing non-invasive biomarker strategies to predict the risk of CI progression in PD.

The Impact of CoronaVac Vaccination on 28-day Mortality Rate of Critically Ill Patients with COVID-19 in Türkiye.

Background: Vaccines against coronavirus disease-19 (COVID-19) have been effective in preventing symptomatic diseases, hospitalizations, and intensive care unit (ICU) admissions. However, data regarding the effectiveness of COVID-19 vaccines in reducing mortality among critically ill patients with COVID-19 remains unclear. Aims: To determine the vaccination status and investigate the impact of the COVID-19 vaccine on the 28-day mortality in critically ill patients with COVID-19. Study Design: Multicenter prospective observational clinical study. Methods: This study was conducted in 60 hospitals with ICUs managing critically ill patients with COVID-19. Patients aged ≥ 18 years with confirmed COVID-19 who were admitted to the ICU were included. The present study had two phases. The first phase was designed as a one-day point prevalence study, and demographic and clinical findings were evaluated. In the second phase, the 28-day mortality was evaluated. Results: As of August 11, 2021, 921 patients were enrolled in the study. The mean age of the patients was 65.42 ± 16.74 years, and 48.6% (n = 448) were female. Among the critically ill patients with COVID-19, 52.6% (n = 484) were unvaccinated, 7.7% (n = 71) were incompletely vaccinated, and 39.8% (n = 366) were fully vaccinated. A subgroup analysis of 817 patients who were unvaccinated (n = 484) or who had received two doses of the CoronaVac vaccine (n = 333) was performed. The 28-day mortality rate was 56.8% (n = 275) and 57.4% (n = 191) in the unvaccinated and two-dose CoronaVac groups, respectively. The 28-day mortality was associated with age, hypertension, the number of comorbidities, type of respiratory support, and APACHE II and sequential organ failure assessment scores (p < 0.05). The odds ratio for the 28-day mortality among those who had received two doses of CoronaVac was 0.591 (95% confidence interval: 0.413-0.848) (p = 0.004). Conclusion: Vaccination with at least two doses of CoronaVac within six months significantly decreased mortality in vaccinated patients than in unvaccinated patients.

Coexistence of Cryptococcal Fungemia and Pneumocystis jirovecii Pneumonia in an HIV-Infected Patient: A Case Report.

INTRODUCTION: Opportunistic infections caused by bacteria and fungi are common in human immunodeficiency virus (HIV)-infected patients. Cryptococcus neoformans and Pneumocystis jirovecii are the most common opportunistic infections in immunosuppressed individuals, but their coexistence is rare. To our knowledge, this is the first case presented in Turkey involving the coexistence of C.neoformans fungemia and P.jirovecii pneumonia. CASE PRESENTATION: A 26-year-old male patient presented with a cachectic appearance, cough, sputum, weakness, shortness of breath, and a weight loss of 15 kg in the last three months. It was learned that the patient was diagnosed with HIV three years ago, did not go to follow-ups, and did not use the treatments. CD4 cell count was 7/mm3 (3.4%), CD8 cell count was 100 (54%) mm3, and HIV viral load was 5670 copies/mL. In thorax computed tomography (CT), increases in opacity in diffuse ground glass density in both lungs and fibroatelectasis in lower lobes were observed. With the prediagnosis of P. jiroveci pneumonia, the HIV-infected patient was given trimethoprim-- sulfamethoxazole 15 mg/kg/day intravenously (i.v.). On the 4th day of the patient's hospitalization, mutiplex PCR-based rapid syndromic Biofire (Film Array) blood culture identification 2 (BCID2) test (Biomerieux, France) was applied for rapid identification from blood culture. C. neoformans was detected in the blood culture panel. The treatment that the patient was taking with the diagnosis of C. neoformans fungemia was started at a dose of liposomal amphotericin B 5 mg/kg/- day + fluconazole 800 mg/day. CONCLUSION: While the incidence of opportunistic infections has decreased with antiretroviral therapy (ART), it remains a problem in patients who are unaware of being infected with HIV or who fail ART or refuse treatment. High fungal burden, advanced age, low CD4+ cell count, and being underweight are risk factors for mortality in HIV-positive patients. Our case was a cachectic patient with a CD4 count of 7 cells/mm3. Despite the early and effective treatment, the course was fatal.

Incidence of nosocomial infection and causative microorganism during extracorporeal membrane oxygenation in adult patients, a single center study.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is an organ support whose use is increasing in acute respiratory distress syndrome (ARDS) cases where adequate gas exchange cannot be achieved despite mechanical ventilation. Patients who were followed up on ECMO are at risk for developing nosocomial infections. In this study, we aimed to investigate the incidence of nosocomial infection and define isolated pathogens from microbiological samples in a single center in Turkey. METHODS: Patients who were followed up on ECMO due to ARDS between January 1, 2018, and December 31, 2021, were included in the study. Nosocomial infections that were diagnosed after the first 48 h of ECMO cannulation and after 48 h of ECMO decannulation were accepted as ECMO-related infections. RESULTS: A total of 50 patients with ARDS were followed up with ECMO. Mean age of patients was 46,8 ± 15,4 and 38 (78%) patients were male. A total of 30 patients (60%) had at least one nosocomial infection, for a rate of 37.6 per 1000 ECMO days. COVID-19, steroid treatment, and ECMO duration were found to be associated with nosocomial infections in patients who underwent ECMO support. In multivariate analysis, antibiotic use was found to be protective against nosocomial infection (OR:0.14, 95% CI: 0.03 - 0.70, p = .017). In addition, prolonged ECMO duration was associated with an increased risk of nosocomial infection in multivariate analysis (OR:1.13, 95% CI: 1.03 - 1.23, p = .010). Gram-negative pathogens were isolated dominantly in blood cultures and tracheal secretion samples, followed by fungi and Gram-positive bacteria. CONCLUSION: Patients are prone to nosocomial infections during ECMO. Microorganisms causing nosocomial infections in ECMO patients seem similar to the flora of each center, and this should be taken into account in the choice of empirical antibiotics.

Rheumatological patients' knowledge of, beliefs about, and practices in using phytotherapy: an exploratory study.

Phytotherapy has emerged as a new concept and has quickly and widely spread in recent years. Studies on phytopharmaceuticals in rheumatology practice are very limited. In this study, we aimed to examine the knowledge of, beliefs about, and practices of using phytotherapy in patients who use biologics due to rheumatological disease. In the first part of the questionnaire, there are 11 questions, including the demographic data of the person, and in the second part, there are 17 questions that aim to learn the level of knowledge about phytotherapy and the use of phytopharmaceuticals. The questionnaire was administered face-to-face to patients with rheumatology using biological therapy who gave consent to participate. A total of 100 patients who were followed up with biological therapy were included in the final analysis. Approximately half of participants (48%) received any phytopharmaceuticals during their biologic treatment. Camellia sinensis (green tea) and Tilia platyphyllos were the most preferred phytopharmaceuticals. Gender, age, smoking, duration of disease, and duration of biologic treatment were not found to be associated with the use of phytopharmaceuticals. Of the 100 participants, 69% had information about phytotherapy, and the primary sources of information about phytotherapy were television and social media. Rheumatological diseases cause chronic pain, multiple drug use, and a decrease in quality of life, so the search for alternative treatment methods is frequent in these patients. Studies with a high level of evidence are necessary for healthcare professionals to inform their patients about this topic.

Vaccination status of COVID-19 patients followed up in the ICU in a country with heterologous vaccination policy: A multicenter national study in Turkey.

OBJECTIVE: Vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-2) prevents the development of serious diseases has been shown in many studies. However, the effect of vaccination on outcomes in COVID-19 patients requiring intensive care is not clear. METHODS: This is a retrospective multicenter study conducted in 17 intensive care unit (ICU) in Turkey between January 1, 2021, and December 31, 2021. Patients aged 18 years and older who were diagnosed with COVID-19 and followed in ICU were included in the study. Patients who have never been vaccinated and patients who have been vaccinated with a single dose were considered unvaccinated. Logistic regression models were fit for the two outcomes (28-day mortality and in-hospital mortality). RESULTS: A total of 2968 patients were included final analysis. The most of patients followed in the ICU during the study period were unvaccinated (58.5%). Vaccinated patients were older, had higher Charlson comorbidity index (CCI), and had higher APACHE-2 scores than unvaccinated patients. Risk for 28-day mortality and in-hospital mortality was similar in across the year both vaccinated and unvaccinated patients. However, risk for in-hospital mortality and 28-day mortality was higher in the unvaccinated patients in quarter 4 adjusted for gender and CCI (OR: 1.45, 95% CI: 1.06-1.99 and OR: 1.42, 95% CI: 1.03-1.96, respectively) compared to the vaccinated group. CONCLUSION: Despite effective vaccination, fully vaccinated patients may be admitted to ICU because of disease severity. Unvaccinated patients were younger and had fewer comorbid conditions. Unvaccinated patients have an increased risk of 28-day mortality when adjusted for gender and CCI.

Factors affecting the development of complications in Crohn's disease in patients undergoing intestinal resection.

Surgery is a common form of management for Crohn disease (CD) in the presence of intra-abdominal complications. In this study, we investigated the effect of various factors on the development of postoperative complications in patients who underwent surgery for complicated CD. Patients who underwent surgery between 2011 and 2018 were included in this study. Information on age, sex, presence of extraintestinal findings, operation indications, operation type, and postoperative complications was obtained. Groups with and without postoperative complications were compared according to body mass index, American Society of Anesthesiologists score, comorbidities, smoking status, preoperative drug use, presence of perianal disease, presence of a stoma, synchronous small intestine resection surgery, duration of hospital stay, and preoperative biochemical parameters. A total of 192 patients were included, of which 53.1% were female and 46.9% were male. Patients were indicated for surgery for reasons such as stricture, abscess, fistula, and tumor development. As the surgical method, patients were operated on by open or laparoscopic method (86% and 14%, respectively). Postoperative complications occurred in 30 female and 33 male patients (15.6% and 17.1%, respectively). Patient age, smoking status, steroid use, perianal disease, presence of stoma, and presence of extra intestinal findings were significantly higher in the complicated group. Surgery may be inevitable for CD in the presence of complications. In cases of patient age, smoking, steroid use, perianal disease, stoma opening, and presence of extra intestinal findings, patients with CD who undergo surgery should be followed up closely in terms of the development of complications.

Investigation of Obesity-Related HAdV-36 in NAFLD Patients: a Case-Control Study.

BACKGROUND: HAdV-36 leads to adipocyte proliferation of adipose tissue through E4orf1 gene, leading to the development of obesity and related diseases. We aimed to investigate the presence and any association of HAdV-36 in non-alcoholic fatty liver disease (NAFLD) patients Methods: The patient group was composed of 116 patients; 30 obese patients with NAFLD (BMI > 30 kg/m2), 30 patients with Diabetes Mellitus (DM)+NAFLD (BMI > 30 kg/m2), 16 patients with NAFLD (BMI < 30 kg/m2), and operated obese group with NAFLD (BMI > 30 kg/m2). The control group comprised 81 non-obese healthy adults. Liver adipose tissue samples were obtained in 30 operated NAFLD patients. HAdV-36-DNA, HAdV-36 neutralizing antibodies, serum lipid, and adipokine levels were analyzed. RESULTS: HAdV-36 neutralizing antibodies (HAdV-36 Ab-positive) were detected in 10/116 and 2/81 participants in the study and control groups, respectively; the difference was statistically significant (p < 0.005). LDL, total cholesterol but not adipokine levels were found to be significantly higher in HadV-36 Ab-positive patients (p < 0.05). While HAdV-36 was identified as a risk factor with OR = 4.11 in univariate analyses, there was no significant difference in binary logistic regression analysis. HAdV-36-DNA was detected in the adipose tissue samples of two patients. CONCLUSIONS: We suggest that the presence of HAdV-36 may lead to the development of obesity with the increase in adipose tissue, and diseases such as hyperlipidemia, NAFLD, DM, and metabolic syndrome may develop on the basis of chronic inflammation caused by obesity. Thus, HAdV-36 may be a plausible risk factor for the development of NAFLD.

Differentiation of claustrum resting-state functional connectivity in healthy aging, Alzheimer's disease, and Parkinson's disease.

The claustrum is a sheet-like of telencephalic gray matter structure whose function is poorly understood. The claustrum is considered a multimodal computing network due to its reciprocal connections with almost all cortical areas as well as subcortical structures. Although the claustrum has been involved in several neurodegenerative diseases, specific changes in connections of the claustrum remain unclear in Alzheimer's disease (AD), and Parkinson's disease (PD). Resting-state fMRI and T1-weighted structural 3D images from healthy elderly (n = 15), AD (n = 16), and PD (n = 12) subjects were analyzed. Seed-based FC analysis was performed using CONN FC toolbox and T1-weighted images were analyzed with the Computational Anatomy Toolbox for voxel-based morphometry analysis. While we observed a decreased FC between the left claustrum and sensorimotor cortex, auditory association cortex, and cortical regions associated with social cognition in PD compared with the healthy control group (HC), no significant difference was found in alterations in the FC of both claustrum comparing the HC and AD groups. In the AD group, high FC of claustrum with regions of sensorimotor cortex and cortical regions related to cognitive control, including cingulate gyrus, supramarginal gyrus, and insular cortex were demonstrated. In addition, the structural results show significantly decreased volume in bilateral claustrum in AD and PD compared with HC. There were no significant differences in the claustrum volumes between PD and AD groups so the FC may offer more precise findings in distinguishing changes for claustrum in AD and PD.

Clinical Contribution of Standardized Terminology for Pancreatic Lesions' Cytopathology.

INTRODUCTION: Demonstration of diagnostic contribution of Papanicolaou Society of Cytopathology-standardized nomenclature for pancreaticobiliary cytology (PSC-PC) in endoscopic ultrasonography (EUS) fine-needle biopsy (FNA) biopsies is important for widespread use and further development. METHODS: 179 EUS-FNA biopsies (89: solid, 90: cystic) and PSC-PC categories were compared with surgical definite histopathology and definite clinical diagnosis. Overall risk of malignancy (oROM) was calculated for each PSC-PC category. Diagnostic accuracy was evaluated. RESULTS: The cytopathology of lesions was nondiagnostic in 27%. Ductal dilatation, lymphadenopathy, and solid characteristic (independently) were associated with diagnostic result, while lesion size was not. PSC-PC categories had 89% diagnostic consistency with surgical definite histopathology. Category mismatch was detected in 3 patients (11%), of which 2 had adenocarcinoma. oROM was 14.3% for nondiagnostic group, 46% for cat. III (atypia), and 12% for cat. IVB (neoplastic - other). In terms of malignancy, the PSC-PC system had 100% specificity; PPV, 92% sensitivity, and 81% NPV; and the diagnostic accuracy was 94%. CONCLUSION: Using PSC-PC in EUS-FNA biopsies, pancreatic malignancy can be diagnosed with high diagnostic accuracy. In mucinous cystic lesions, some malignancies may be missed. To predict the malignancy risk of cat. IVB, assessment of dysplasia seems important. Although PSC-PC is not the only parameter in terms of diagnosing malignancy, its contribution to the clinical decision is quite high.

Efficacy and Safety of Ombitasvir/Paritaprevir/ Ritonavir + Dasabuvir ± Ribavirin Combinations in Patients with Genotype 1 Hepatitis C and Inherited Bleeding Disorders.

BACKGROUND: Hepatitis C is one of the leading causes of death in patients with inherited bleeding disorders. Currently, direct-acting antiviral drugs used for the treatment of hepatitis C have become an effective and a reliable option for people with inherited bleeding disorders. The aim of this study is to report the efficacy and safety of ombitasvir + paritaprevir/ritonavir and dasabuvir combination in the treatment of hepatitis C in patients with inherited bleeding disorders. METHODS: In this retrospective study, we evaluated the efficacy and safety of the combination of ombitasvir + paritaprevir/ritonavir and dasabuvir in 10 adult patients with hemophilia A, 4 patients with hemophilia B, and 1 patient with von Willebrand disease who were infected with hepatitis C genotype 1. RESULTS: Five patients had genotype 1a and 10 patients had genotype 1b chronic hepatitis C. One patient had Child A cirrhosis, 14 patients had chronic hepatitis C without cirrhosis. Hepatitis C virus ribonucleic acid was negative in all patients at week 4 and at the end of the treatment. Sustained virologic response was obtained in all patients. Serious side effects were detected in 3 patients, which were intra- muscular bleeding, erosive gastritis-related gastrointestinal bleeding, and pneumonia. CONCLUSION: Ombitasvir + paritaprevir combined with ritonavir and dasabuvir ± ribavirin is an effective treatment for patients infected with genotype 1 hepatitis C who have coagulation disorders. Tolerance and side effects are similar to other treatment options.

Axillary Microbiota Is Associated with Cognitive Impairment in Parkinson's Disease Patients.

Cognitive impairment (CI) is among the most common non-motor symptoms of Parkinson's disease (PD), with a substantially negative impact on patient management and outcome. The development and progression of CI exhibits high interindividual variability, which requires better diagnostic and monitoring strategies. PD patients often display sweating disorders resulting from autonomic dysfunction, which has been associated with CI. Because the axillary microbiota is known to change with humidity level and sweat composition, we hypothesized that the axillary microbiota of PD patients shifts in association with CI progression, and thus can be used as a proxy for classification of CI stages in PD. We compared the axillary microbiota compositions of 103 PD patients (55 PD patients with dementia [PDD] and 48 PD patients with mild cognitive impairment [PD-MCI]) and 26 cognitively normal healthy controls (HC). We found that axillary microbiota profiles differentiate HC, PD-MCI, and PDD groups based on differential ranking analysis, and detected an increasing trend in the log ratio of Corynebacterium to Anaerococcus in progression from HC to PDD. In addition, phylogenetic factorization revealed that the depletion of the Anaerococcus, Peptoniphilus, and W5053 genera is associated with PD-MCI and PDD. Moreover, functional predictions suggested significant increases in myo-inositol degradation, ergothioneine biosynthesis, propionate biosynthesis, menaquinone biosynthesis, and the proportion of aerobic bacteria and biofilm formation capacity, in parallel to increasing CI. Our results suggest that alterations in axillary microbiota are associated with CI in PD. Thus, axillary microbiota has the potential to be exploited as a noninvasive tool in the development of novel strategies. IMPORTANCE Parkinson's disease (PD) is the second most common neurodegenerative disease. Cognitive impairment (CI) in PD has significant negative impacts on life quality of patients. The emergence and progression of cognitive impairment shows high variability among PD patients, and thus requires better diagnostic and monitoring strategies. Recent findings indicate a close link between autonomic dysfunction and cognitive impairment. Since thermoregulatory dysfunction and skin changes are among the main manifestations of autonomic dysfunction in PD, we hypothesized that alterations in the axillary microbiota may be useful for tracking cognitive impairment stages in PD. To our knowledge, this the first study characterizing the axillary microbiota of PD patients and exploring its association with cognitive impairment stages in PD. Future studies should include larger cohorts and multicenter studies to validate our results and investigate potential biological mechanisms.

Stratification of the Gut Microbiota Composition Landscape across the Alzheimer's Disease Continuum in a Turkish Cohort.

Alzheimer's disease (AD) is a heterogeneous disorder that spans a continuum with multiple phases, including preclinical, mild cognitive impairment, and dementia. Unlike for most other chronic diseases, human studies reporting on AD gut microbiota in the literature are very limited. With the scarcity of approved drugs for AD therapies, the rational and precise modulation of gut microbiota composition using diet and other tools is a promising approach to the management of AD. Such an approach could be personalized if an AD continuum can first be deconstructed into multiple strata based on specific microbiota features by using single or multiomics techniques. However, stratification of AD gut microbiota has not been systematically investigated before, leaving an important research gap for gut microbiota-based therapeutic approaches. Here, we analyze 16S rRNA amplicon sequencing of stool samples from 27 patients with mild cognitive impairment, 47 patients with AD, and 51 nondemented control subjects by using tools compatible with the compositional nature of microbiota. To stratify the AD gut microbiota community, we applied four machine learning techniques, including partitioning around the medoid clustering and fitting a probabilistic Dirichlet mixture model, the latent Dirichlet allocation model, and we performed topological data analysis for population-scale microbiome stratification based on the Mapper algorithm. These four distinct techniques all converge on Prevotella and Bacteroides stratification of the gut microbiota across the AD continuum, while some methods provided fine-scale resolution in stratifying the community landscape. Finally, we demonstrate that the signature taxa and neuropsychometric parameters together robustly classify the groups. Our results provide a framework for precision nutrition approaches aiming to modulate the AD gut microbiota. IMPORTANCE The prevalence of AD worldwide is estimated to reach 131 million by 2050. Most disease-modifying treatments and drug trials have failed, due partly to the heterogeneous and complex nature of the disease. Recent studies demonstrated that gut dybiosis can influence normal brain function through the so-called "gut-brain axis." Modulation of the gut microbiota, therefore, has drawn strong interest in the clinic in the management of the disease. However, there is unmet need for microbiota-informed stratification of AD clinical cohorts for intervention studies aiming to modulate the gut microbiota. Our study fills in this gap and draws attention to the need for microbiota stratification as the first step for microbiota-based therapy. We demonstrate that while Prevotella and Bacteroides clusters are the consensus partitions, the newly developed probabilistic methods can provide fine-scale resolution in partitioning the AD gut microbiome landscape.

Frequency, Predisposing Factors, and Clinical Outcome of Azathioprine-Induced Pancreatitis Among Patients With Inflammatory Bowel Disease: Results From a Tertiary Referral Center.

OBJECTIVE: The aim of the study was to identify the frequency of azathioprine-induced acute pancreatitis (AZA-AP) and related factors. METHODS: Seven hundred eighty-seven inflammatory bowel disease (IBD) patients on AZA therapy were retrospectively analyzed. Azathioprine-induced AP was diagnosed with positive imaging and/or an at least 3-fold increased amylase level, in presence of typical abdominal pain. The AZA-AP group was compared with patients on AZA therapy with no history of pancreatitis and 4 numerical adjacent cases with the same diagnosis were selected (group B). RESULTS: Fifty-four patients developed gastrointestinal symptoms (6.9%); however, only half of them (26 of 54) had pancreatitis, except 1, all within the first 2 months under AZA. When the AZA-AP group was compared with group B, only budesonide usage and active smoking were significantly more common in group A (46.2% vs 25%, P = 0.034, and 77% vs 51%, P = 0.017, respectively). Active smoking was the only independent risk factor for AZA-AP development (odds ratio, 3.208 [95% confidence interval, 1.192-8.632]). CONCLUSIONS: All IBD patients developed AZA-AP nearly all within the first 2 months. Azathioprine intolerance may be a hidden diagnosis in at least half of the patients with AZA-AP symptoms. All smoker IBD patients should be monitored closely for AZA-AP development.

The effect of driving pressures in COVID-19 ARDS: Lower may still be better as in classic ARDS.

BACKGROUND: The respiratory dynamics of coronavirus disease 2019 (COVID-19) patients under invasive ventilation are still not well known. In this prospective cohort, we aimed to assess the characteristics of the respiratory system in COVID-19 patients under invasive mechanical ventilation and evaluate their relationship with mortality. METHODS: Fifty-eight COVID-19 patients who underwent invasive mechanical ventilation between March 11, 2020 and September 1, 2020 were enrolled for the present study. Demographics and laboratory values at baseline were recorded. Respiratory variables such as tidal volume, plateau pressure, positive end expiratory pressure, static compliance, and driving pressure were recorded daily under passive conditions. Further, the median values were analyzed. RESULTS: Median age of the patients was 64 years (58-72). Mortality was 60% on day 28. Plateau pressure, driving pressure, and static compliance significantly differ between the survivors and non-survivors. When patients were categorized into two groups based on the median driving pressure (Pdrive) of ≤15 cmH2O or >15 cmH2O during their invasive mechanical ventilation period, there was significantly better survival on day 28 in patients having a Pdrive ≤ 15 cmH2O [28 days (95% CI = 19-28) vs 16 days (95% CI = 6-25), (log-rank p = 0.026). CONCLUSION: COVID-19 related acute respiratory distress syndrome (ARDS) seemed to have similar characteristics as other forms of ARDS. Lung protective ventilation with low plateau and driving pressures might be related to lower mortality.

Cost of Chronic Critically Ill Patients to the Healthcare System: A Single-center Experience from a Developing Country.

BACKGROUND: An increasing number of patients become chronic critically ill (CCI) and dependent on long-term therapies in the intensive care unit (ICU). Mortality and healthcare costs increase in these patients. In order to deal with this problem, the magnitude and risk factors for CCI must first be determined. Therefore, we aimed at evaluating the incidence cost and risk factors for CCI in our ICU. MATERIALS AND METHODS: This retrospective cohort study was compiled by recruiting patients admitted to our ICU between January 1, 2017, and December 31, 2018. Patients with an ICU stay of more than 21 days were defined as CCI. Patients who did not survive in the first 21 days were excluded from the study because it could be not known whether these patients would progress to CCI. During the study period, 1,166 patients were followed up, and 475 (40%) of them were excluded and 691 patients were included in the final analyses. RESULTS: During the study period, 691 patients were included in the study and 152 of them (22%) were CCI. Age, acute physiology and chronic health evaluation (APACHE)-2 score, length of stay, and daily costs were higher in patients with CCI. The cost for a patient with CCI is sixfold that of a patient without CCI. ICU mortality was 47% in patients without CCI and 54% in the CCI patients (p < 0.001). CONCLUSION: CCI affects an increasing number of patients and leads to increased mortality rates and cost. Prolonged duration in ICU may cause complications such as secondary infections, sepsis episodes, and acute renal injury. The treatment of these complications may lead to increased mortality and cost. HOW TO CITE THIS ARTICLE: Yildirim S, Durmaz Y, San Y, Taskiran I, Cinleti BA, Kirakli C. Cost of Chronic Critically Ill Patients to the Healthcare System: A Single-center Experience from a Developing Country. Indian J Crit Care Med 2021;25(5):519-523.