Category: Nevin Manimala

Nature. 2024 Feb 21. doi: 10.1038/s41586-024-07029-4. Online ahead of print.

ABSTRACT

Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks^1-5, give rise to highly divergent lineages^6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)^9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as ‘persistent infections’ as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people^11-14. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.

PMID:38383783 | DOI:10.1038/s41586-024-07029-4

Commun Med (Lond). 2024 Feb 21;4(1):26. doi: 10.1038/s43856-024-00441-x.

ABSTRACT

BACKGROUND: Geographical variations in mood and psychotic disorders have been found in upper-income countries. We looked for geographic variation in these disorders in Colombia, a middle-income country. We analyzed electronic health records from the Clínica San Juan de Dios Manizales (CSJDM), which provides comprehensive mental healthcare for the one million inhabitants of Caldas.

METHODS: We constructed a friction surface map of Caldas and used it to calculate the travel-time to the CSJDM for 16,295 patients who had received an initial diagnosis of mood or psychotic disorder. Using a zero-inflated negative binomial regression model, we determined the relationship between travel-time and incidence, stratified by disease severity. We employed spatial scan statistics to look for patient clusters.

RESULTS: We show that travel-times (for driving) to the CSJDM are less than 1 h for ~50% of the population and more than 4 h for ~10%. We find a distance-decay relationship for outpatients, but not for inpatients: for every hour increase in travel-time, the number of expected outpatient cases decreases by 20% (RR = 0.80, 95% confidence interval [0.71, 0.89], p = 5.67E-05). We find nine clusters/hotspots of inpatients.

CONCLUSIONS: Our results reveal inequities in access to healthcare: many individuals requiring only outpatient treatment may live too far from the CSJDM to access healthcare. Targeting of resources to comprehensively identify severely ill individuals living in the observed hotspots could further address treatment inequities and enable investigations to determine factors generating these hotspots.

PMID:38383761 | DOI:10.1038/s43856-024-00441-x

Neurol Sci. 2024 Feb 22. doi: 10.1007/s10072-024-07368-0. Online ahead of print.

ABSTRACT

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder with fluctuating weakness that causes significant disability and morbidity. Comorbidities may influence the course of MG, particularly in specific subgroups. The aim of this study is to investigate the frequency of comorbidities in MG patients compared to healthy controls (HC) and to evaluate their distribution according to age at disease onset, sex, and disease severity.

METHODS: MG patients attending the University Hospital “Paolo Giaccone” in Palermo and “SS Annunziata” Hospital in Chieti were enrolled; HC were enrolled from the general population. Non-parametric statistics and logistic regression were used to assess the association of specific comorbidities according to age at disease onset, sex, disease subtypes, and severity of the disease.

RESULTS: A total of 356 subjects were included in the study: 178 MG patients (46% F; median age 60 years [51-71]) and 178 sex- and age-matched HC (46% F, median age 59 years [50-66]). Overall, 86% of MG patients and 76% of HC suffered from comorbidities, and MG patients had a higher number of comorbidities compared to HC. Patients with late-onset suffered from more comorbidities than those with early-onset MG. Hypertension was more common in male patients with MG, while thymic hyperplasia, osteoporosis, and autoimmune diseases were more common in females. Respiratory disorders and thymoma were more common in patients with more severe disease (p < 0.05 for all comparisons).

CONCLUSION: MG patients, particularly those with late onset, showed a higher prevalence of comorbidities than HC. Assessment of comorbidities in MG is an essential issue to identify the appropriate treatment and achieve the best management.

PMID:38383750 | DOI:10.1007/s10072-024-07368-0

Neurol Sci. 2024 Feb 21. doi: 10.1007/s10072-024-07386-y. Online ahead of print.

ABSTRACT

PURPOSE: We aim to propose a visual quantitative score for muscle edema in lower limb MRI to contribute to the diagnosis of idiopathic inflammatory myopathy (IIM).

MATERIAL AND METHODS: We retrospectively evaluated 85 consecutive patients (mean age 57.4 ± 13.9 years; 56.5% female) with suspected IIM (muscle weakness and/or persistent hyper-CPK-emia with/without myalgia) who underwent MRI of lower limbs using T2-weighted fast recovery-fast spin echo images and fat-sat T2 echo planar images. Muscle inflammation was evaluated bilaterally in 11 muscles of the thigh and eight muscles of the leg. Edema in each muscle was graded according to a four-point Likert-type scale adding up to 114 points ([11 + 8)] × 3 × 2). Diagnostic accuracy of the total edema score was explored by assessing sensitivity and specificity using the area under the ROC curve. Final diagnoses were made by a multidisciplinary Expert Consensus Panel applying the Bohan and Peter diagnostic criteria whenever possible.

RESULTS: Of the 85 included patients, 34 (40%) received a final diagnosis of IIM (IIM group) while 51 (60%) received an alternative diagnosis (non-IIM group). A cutoff score ≥ 18 was able to correctly classify patients having an IIM with an area under the curve of 0.85, specificity of 96%, and sensitivity of 52.9%.

CONCLUSION: Our study demonstrates that a quantitative MRI score for muscle edema in the lower limbs (thighs and legs) aids in distinguishing IIM from conditions that mimic it.

PMID:38383748 | DOI:10.1007/s10072-024-07386-y

Eur J Nucl Med Mol Imaging. 2024 Feb 22. doi: 10.1007/s00259-024-06646-5. Online ahead of print.

ABSTRACT

PURPOSE: High blood glucose (hBG) in patients undergoing [¹⁸F]FDG PET/CT scans often results in rescheduling the examination, which may lead to clinical delay for the patient and decrease productivity for the department. The aim of this study was to evaluate whether long-axial field-of-view (LAFOV) PET/CT can minimize the effect of altered bio-distribution in hBG patients and is able to provide diagnostic image quality in hBG situations.

MATERIALS AND METHODS: Oncologic patients with elevated blood glucose (≥ 8.0 mmol/l) and normal blood glucose (< 8.0 mmol/l, nBG) levels were matched for tumor entity, gender, age, and BMI. hBG patients were further subdivided into two groups (BG 8-11 mmol/l and BG > 11 mmol/l). Tracer uptake in the liver, muscle, and tumor was evaluated. Furthermore, image quality was compared between long acquisitions (ultra-high sensitivity mode, 360 s) on a LAFOV PET/CT and routine acquisitions equivalent to a short-axial field-of-view scanner (simulated (sSAFOV), obtained with high sensitivity mode, 120 s). Tumor-to-background ratio (TBR) and contrast-to-noise ratio (CNR) were used as the main image quality criteria.

RESULTS: Thirty-one hBG patients met the inclusion criteria and were matched with 31 nBG patients. Overall, liver uptake was significantly higher in hBG patients (SUV_mean, 3.07 ± 0.41 vs. 2.37 ± 0.33; p = 0.03), and brain uptake was significantly lower (SUV_max, 7.58 ± 0.74 vs. 13.38 ± 3.94; p < 0.001), whereas muscle (shoulder/gluteal) uptake showed no statistically significant difference. Tumor uptake was lower in hBG patients, resulting in a significantly lower TBR in the hBG cohort (3.48 ± 0.74 vs. 5.29 ± 1.48, p < 0.001). CNR was higher in nBG compared to hBG patients (12.17 ± 4.86 vs. 23.31 ± 12.22, p < 0.001). However, subgroup analysis of nBG 8-11 mmol/l on sSAFOV PET/CT compared to hBG (> 11 mmol/l) patients examined with LAFOV PET/CT showed no statistical significant difference in CNR (19.84 ± 8.40 vs. 17.79 ± 9.3, p = 0.08).

CONCLUSION: While elevated blood glucose (> 11 mmol) negatively affected TBR and CNR in our cohort, the images from a LAFOV PET-scanner had comparable CNR to PET-images acquired from nBG patients using sSAFOV PET/CT. Therefore, we argue that oncologic patients with increased blood sugar levels might be imaged safely with LAFOV PET/CT when rescheduling is not feasible.

PMID:38383743 | DOI:10.1007/s00259-024-06646-5

Cereb Cortex. 2024 Jan 31;34(2):bhae043. doi: 10.1093/cercor/bhae043.

ABSTRACT

Mild cognitive impairment (MCI) is the initial phase of Alzheimer’s disease (AD). The cognitive decline is linked to abnormal connectivity between different regions of the brain. Most brain network studies fail to consider the changes in brain patterns and do not reflect the dynamic pathological characteristics of patients. Therefore, this paper proposes a method for constructing brain networks based on microstate sequences. It also analyzes the microstate temporal parameters and introduces a new feature, the brain homeostasis coefficient (Bhc), to quantify the stability of patient brain connections. The results showed that microstate class B parameters were higher in the MCI than in the HC group. Additionally, the Bhc values in most channels of the MCI and AD groups were lower than those of the HC group, with the most significant differences observed in the right frontal lobe. These differences were statistically significant (P < 0.05). The findings indicate that connectivity in the right frontal lobe may be most severely disrupted in patients with cognitive impairment. Furthermore, the Montreal Cognitive Assessment score showed a strong positive correlation with Bhc. This suggests that Bhc could be a novel biomarker for evaluating cognitive function in patients with cognitive impairment.

PMID:38383723 | DOI:10.1093/cercor/bhae043

Sci Rep. 2024 Feb 21;14(1):4285. doi: 10.1038/s41598-024-54469-z.

ABSTRACT

Acinetobacter baumannii is currently a serious threat to human health, especially to people with immunodeficiency as well as patients with prolonged hospital stays and those undergoing invasive medical procedures. The ever-increasing percentage of strains characterized by multidrug resistance to widely used antibiotics and their ability to form biofilms make it difficult to fight infections with traditional antibiotic therapy. In view of the above, phage therapy seems to be extremely attractive. Therefore, phages with good storage stability are recommended for therapeutic purposes. In this work, we present the results of studies on the stability of 12 phages specific for A. baumannii under different conditions (including temperature, different pH values, commercially available disinfectants, essential oils, and surfactants) and in the urine of patients with urinary tract infections (UTIs). Based on our long-term stability studies, the most optimal storage method for the A. baumannii phage turned out to be – 70 °C. In contrast, 60 °C caused a significant decrease in phage activity after 1 h of incubation. The tested phages were the most stable at a pH from 7.0 to 9.0, with the most inactivating pH being strongly acidic. Interestingly, ethanol-based disinfectants caused a significant decrease in phage titers even after 30 s of incubation. Moreover, copper and silver nanoparticle solutions also caused a decrease in phage titers (which was statistically significant, except for the Acba_3 phage incubated in silver solution), but to a much lesser extent than disinfectants. However, bacteriophages incubated for 24 h in essential oils (cinnamon and eucalyptus) can be considered stable.

PMID:38383718 | DOI:10.1038/s41598-024-54469-z

Sci Rep. 2024 Feb 21;14(1):4254. doi: 10.1038/s41598-024-54653-1.

ABSTRACT

This study aimed to assess the feasibility and safety of robot-assisted thoracic surgery (RATS) for resecting benign tumors of the cervicothoracic junction. Between 2017 and 2021, a total of 54 patients with benign cervicothoracic junction tumors were included. Among them, 46 underwent RATS while 8 underwent open surgery. Using a propensity score based on four variables (age, sex, comorbidity, and tumor size). The outcomes compared included short-term outcomes such as blood loss, as well as long-term outcomes including respiratory function and patients’ postoperative health-related quality of life. No operative deaths occurred in this study. RATS was associated with less intraoperative blood loss (102 < 380 ml, P = 0.001) and a shorter length of hospital stay (1.8 < 4.8, P < 0.001). After a median follow-up of 37 months, no recurrences were reported, and no statistically significant differences were found in the 3-year survival between the two groups. The postoperative respiratory function of patients with open surgery showed a significant decrease compared to preoperative levels and were lower than those of RATS patients. In terms of health-related quality of life, RATS was associated with a better mean EQ-5D-5L index than open surgery (0.808 > 0.650, P < 0.05). In RATS, tumor sizes > 5 cm (mean ± SD = 0.768 ± 0.111, P = 0.028) and neurogenic tumors (mean ± SD = 0.702 ± 0.082, P < 0.001) remained significantly and independently associated with a lower EQ-5D-5L index. This study demonstrated that robot-assisted thoracic surgery for benign tumors of the cervicothoracic junction is a safe and technically feasible procedure, particularly for tumors < 5 cm and non-neurogenic tumors.

PMID:38383716 | DOI:10.1038/s41598-024-54653-1

Bone Marrow Transplant. 2024 Feb 21. doi: 10.1038/s41409-024-02241-2. Online ahead of print.

ABSTRACT

A randomized study (acronym: MC-FludT.14/L Trial II) demonstrated that fludarabine plus treosulfan (30 g/m²) was an effective and well tolerated conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT) in older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). To further evaluate this regimen, all 252 study patients aged 50 to 70 years were compared with similar patients, who underwent allo-HCT after fludarabine/melphalan (140 mg/m²) (FluMel) or busulfan (12.8 mg/kg)/cyclophosphamide (120 mg/kg) (BuCy) regimens and whose data was provided by the European Society for Blood and Marrow Transplantation registry. In 1:1 propensity-score matched-paired analysis (PSA) of AML patients, there was no difference in 2-year-relapse-incidence after FluTreo compared with either FluMel (n = 110, p = 0.28) or BuCy (n = 78, p = 0.98). However, 2-year-non-relapse-mortality (NRM) was lower compared with FluMel (p = 0.019) and BuCy (p < 0.001). Consequently, 2-year-overall-survival (OS) after FluTreo was higher compared with FluMel (p = 0.04) and BuCy (p < 0.001). For MDS patients, no endpoint differences between FluTreo and FluMel (n = 30) were evident, whereas 2-year-OS after FluTreo was higher compared with BuCy (n = 25, p = 0.01) due to lower 2-year-NRM. Multivariate sensitivity analysis confirmed all significant results of PSA. Consequently, FluTreo (30 g/m²) seems to retain efficacy compared with FluMel and BuCy, but is better tolerated by older patients.

PMID:38383713 | DOI:10.1038/s41409-024-02241-2

Sci Rep. 2024 Feb 21;14(1):4270. doi: 10.1038/s41598-024-54943-8.

ABSTRACT

Colorectal cancer is a prevalent malignancy with global significance. This retrospective study aimed to investigate the influence of stage and tumor site on survival outcomes in 284 colorectal cancer patients diagnosed between 2001 and 2017. Patients were categorized into four groups based on tumor site (colon and rectum) and disease stage (early stage and advanced stage). Demographic characteristics, treatment modalities, and survival outcomes were recorded. Bayesian survival modeling was performed using semi-competing risks illness-death models with an accelerated failure time (AFT) approach, utilizing R 4.1 software. Results demonstrated significantly higher time ratios for disease recurrence (TR = 1.712, 95% CI 1.489-2.197), mortality without recurrence (TR = 1.933, 1.480-2.510), and mortality after recurrence (TR = 1.847, 1.147-2.178) in early-stage colon cancer compared to early-stage rectal cancer. Furthermore, patients with advanced-stage rectal cancer exhibited shorter survival times for disease recurrence than patients with early-stage colon cancer. The interaction effect between the disease site and cancer stage was not significant. These findings, derived from the optimal Bayesian log-normal model for terminal and non-terminal events, highlight the importance of early detection and effective management strategies for colon cancer. Early-stage colon cancer demonstrated improved survival rates for disease recurrence, mortality without recurrence, and mortality after recurrence compared to other stages. Early intervention and comprehensive care are crucial to enhance prognosis and minimize adverse events in colon cancer patients.

PMID:38383712 | DOI:10.1038/s41598-024-54943-8