Nevin Manimala

Crit Care. 2024 Nov 24;28(1):383. doi: 10.1186/s13054-024-05167-9.

ABSTRACT

BACKGROUND: Despite the clinical importance of sepsis-associated acute kidney injury (SA-AKI), little is known about its epidemiology. We aimed to investigate the incidence and outcomes of SA-AKI, as well as the risk factors for mortality among patients with severe SA-AKI in critically ill patients.

METHODS: This secondary multicenter, observational, prospective cohort analysis of sepsis in South Korea evaluated patients aged ≥ 19 years admitted to intensive care units with a diagnosis of sepsis. The primary outcome was the incidence of SA-AKI, defined using the new consensus definition of the Acute Disease Quality Initiative 28 Workgroup. Secondary outcomes were in-hospital mortality and risk factors for in-hospital mortality.

RESULTS: Between September 2019 and December 2022, 5100 patients were admitted to intensive care units with a diagnosis of sepsis, and 3177 (62.3%) developed SA-AKI. A total of 613 (19.3%), 721 (22.7%), and 1843 (58.0%) patients had stage 1, 2, and 3 SA-AKI, respectively. Severe SA-AKI (stages 2 and 3 combined) was associated with an increased risk of in-hospital mortality. Adherence to the fluid resuscitation component of the one-hour sepsis bundle was associated with a decreased risk of in-hospital mortality in severe SA-AKI (adjusted odds ratio, 0.62; 95% confidence interval, 0.48-0.79; P < 0.001).

CONCLUSIONS: Of the patients admitted to the intensive care unit for sepsis, 62.3% developed SA-AKI. Severe SA-AKI was associated with an increased risk of mortality. Adherence to the fluid resuscitation component of the one-hour sepsis bundle can potentially improve outcomes in these patients.

PMID:39581988 | DOI:10.1186/s13054-024-05167-9

BMC Med Ethics. 2024 Nov 25;25(1):137. doi: 10.1186/s12910-024-01138-5.

ABSTRACT

BACKGROUND: In 2021, a survey was conducted among doctors and nurses at Landspítali Iceland University Hospital (LIUH) regarding their views on medical assistance in dying (MAID) and the underlying arguments, the inclusion criteria and modality of implementation. Surveys on identically defined study groups in 1995 and 2010 were used for comparison.

METHODS: The survey was sent to 357 doctors and 516 nurses working at LIUH. It included seven questions and several subquestions. Participants’ answers were compared by profession, age group, and specialisation status. Descriptive and inferential statistics were used.

RESULTS: A total of 135 doctors (38% response rate) and 103 nurses (20% response rate) answered the survey, representing 27% of the study group. A total of 145 (61%) participants were positive about MAID, with the most common argument being patient autonomy. The 95% margin of error for this view was ± 6.2%. Compared to 19% in 2010, support for MAID had tripled in 2021 (p < 0.05). Approximately 18% of participants did not support MAID of any kind, mostly due to arguments regarding preserving life or inconsistencies with the role of health care professionals. Finally, 19% of participants were uncertain of their views towards MAID, mostly due to the high level of complexity of the matter.

CONCLUSION: Compared to previous surveys, a large increase in positive attitudes towards MAID was observed among this study population. The results revealed the reasons for participants’ attitudes; weighing patients’ dignity/autonomy against professionals’ duty to “not to kill”/palliate and showing some differences between professions.

PMID:39581987 | DOI:10.1186/s12910-024-01138-5

BMC Bioinformatics. 2024 Nov 23;25(1):363. doi: 10.1186/s12859-024-05982-5.

ABSTRACT

BACKGROUND: Over the last decade the drop in short-read sequencing costs has allowed experimental techniques utilizing sequencing to address specific biological questions to proliferate, oftentimes outpacing standardized or effective analysis approaches for the data generated. There are growing amounts of bacterial 3′-end sequencing data, yet there is currently no commonly accepted analysis methodology for this datatype. Most data analysis approaches are somewhat ad hoc and, despite the presence of substantial signal within annotated genes, focus on genomic regions outside the annotated genes (e.g. 3′ or 5′ UTRs). Furthermore, the lack of consistent systematic analysis approaches, as well as the absence of genome-wide ground truth data, make it impossible to compare conclusions generated by different labs, using different organisms.

RESULTS: We present PIPETS, (Poisson Identification of PEaks from Term-Seq data), an R package available on Bioconductor that provides a novel analysis method for 3′-end sequencing data. PIPETS is a statistically informed, gene-annotation agnostic methodology. Across two different datasets from two different organisms, PIPETS identified significant 3′-end termination signal across a wider range of annotated genomic contexts than existing analysis approaches, suggesting that existing approaches may miss biologically relevant signal. Furthermore, assessment of the previously called 3′-end positions not captured by PIPETS showed that they were uniformly very low coverage.

CONCLUSIONS: PIPETS provides a broadly applicable platform to explore and analyze 3′-end sequencing data sets from across different organisms. It requires only the 3′-end sequencing data, and is broadly accessible to non-expert users.

PMID:39580611 | DOI:10.1186/s12859-024-05982-5

Mol Psychiatry. 2024 Nov 23. doi: 10.1038/s41380-024-02849-2. Online ahead of print.

ABSTRACT

The extent to which bullying victimization is associated with an increased risk of obsessive-compulsive disorder (OCD) has received little empirical attention. This longitudinal, population-based, genetically informative study examined whether self-reported bullying victimization at age 15 was associated with a clinical diagnosis of OCD in the Swedish National Patient Register and with self-reported obsessive-compulsive symptoms (OCS) at ages 18 and 24 in 16,030 twins from the Child and Adolescent Twin Study in Sweden. Using a discordant twin design, including monozygotic (MZ) and dizygotic (DZ) twins, each twin was compared with their co-twin, allowing a strict control of genetic and environmental confounding. At the population level, adjusting for birth year and sex, each standard deviation (SD) increase in bullying victimization was associated with a 32% increase in the odds of an OCD diagnosis (OR, 1.32; 95% CI, 1.21-1.44), of 0.13 SD in OCS at age 18 (β, 0.13; 95% CI, 0.11-0.16), and of 0.11 SD in OCS at age 24 (β, 0.11; 95% CI, 0.07-0.16). While associations tended to persist in the within DZ-twin comparison models, the estimates attenuated and were no longer statistically significant in the within MZ-twin comparisons. These results suggest that the association between bullying victimization and OCD/OCS is likely due to genetic confounding and therefore incompatible with a strong causal effect. Other mechanisms, such as evocative gene-environment correlations, are more plausible explanations for the observed associations.

PMID:39580606 | DOI:10.1038/s41380-024-02849-2

Mol Psychiatry. 2024 Nov 23. doi: 10.1038/s41380-024-02843-8. Online ahead of print.

ABSTRACT

Fear extinction leads to a decrease of originally acquired fear responses after the threat is no longer present. Fear extinction is adaptive and critical for organism’s survival, but deficits in extinction may lead to exaggerated fear in animals or post-traumatic stress disorder (PTSD) in humans. Dopamine has recently emerged as essential for fear extinction and PTSD, however the neural circuits serving this dopamine function are only beginning to be investigated, and the dopamine intracellular signaling pathways are unknown. We generated gastrin-releasing peptide gene knockout (Grp^-/-) mice and found that they exhibit enhanced fear memory in a stress-enhanced fear learning (SEFL) paradigm, which combines stress exposure and fear extinction, two features critical for developing PTSD. Using in vivo fiber photometry to record dopamine signals, we found that the susceptibility of Grp^-/- mice to SEFL is paralleled by an increase in basolateral amygdala (BLA) dopaminergic binding during fear conditioning and early extinction. Combined optogenetics and ex vivo electrophysiology showed an increase in presynaptic ventral tegmental area (VTA)-BLA connectivity in Grp^-/- mice, demonstrating a role of dysregulated input from the VTA on BLA function in the absence of the GRP. When examining gene transcription using RNA-seq and qPCR, we discovered concerted down-regulation in dopamine-related genes in the BLA of Grp^-/- mice following long-term SEFL memory recall that was not observed in naïve conditions. These experiments demonstrate that the GRP regulates dopamine function in stress-enhanced fear processing and identify the Grp as the first gene known to regulate dopaminergic control of fear extinction.

PMID:39580604 | DOI:10.1038/s41380-024-02843-8

Sci Rep. 2024 Nov 23;14(1):29090. doi: 10.1038/s41598-024-80566-0.

ABSTRACT

Patients who develop chimeric antigen receptor (CAR) T-cell-related immune effector cell-associated neurotoxicity syndrome (ICANS) frequently undergo evaluation with electroencephalography (EEG). We hypothesize that EEG features and Synek scale score, a measure of degree of EEG abnormality, are associated with ICANS severity. Here, we performed a retrospective review of 125 adult patients at Memorial Sloan Kettering Cancer Center (MSKCC) who received CAR-T cell therapy from 2010 to 2019, including 53 patients with B-acute lymphoblastic leukemia treated with 1928z CAR T cells (NCT01044069) and 72 patients with large B-cell lymphoma (LBCL) treated with the commercial CAR T products axicabtagene ciloleucel or tisagenlecleucel. We collected video EEG monitoring (27 with B-ALL and 20 with LBCL) and recorded daily EEG features, Synek scores, and ICANS grade for 47 eligible patients. Synek scale and ICANS grade were positively correlated (correlation coefficient 0.47, 95% CI: 0.31-0.60). This was further corroborated in the univariable model associating high Synek scale (3 or 4) with high ICANS grade (OR = 15.2; 95%CI:7.8-29.7, p < 0.0001). EEG features such as discontinuity, absence of posterior dominant rhythm, and presence of generalized sharp waves were statistically significantly associated with higher ICANS grade in univariable models. In the multivariable model, discontinuity (OR = 4.2 (95%CI:1.3-13.8, p = 0.02) and absence of posterior dominant rhythm (OR = 10.5 (95%CI:4.6-23.9, p < 0.0001) were statistically associated with higher ICANS grade. Overall, EEG discontinuity and absence of posterior dominant rhythm were independently associated with higher severity of neurotoxicity. Further, our data suggest that Synek Scale, may be a severity marker for neurotoxicity.

PMID:39580601 | DOI:10.1038/s41598-024-80566-0

Hernia. 2024 Nov 23;29(1):28. doi: 10.1007/s10029-024-03217-3.

ABSTRACT

PURPOSE: The aim of this study was to evaluate quality of life from the preoperative time to six months after surgery of patients who underwent a Shouldice Repair for primary inguinal hernia.

METHODS: After ethical approval, consent was obtained, and data collected from surveys and chart review. The study population was composed of male and female patients aged 16-90 years of age, who had a Shouldice Repair of a primary unilateral inguinal hernia. The EQ-5D-3L, a questionnaire applied to hernia surgery in Canada, was used to determine quality of life at the preoperative and 1 week, 1- and 6-month postoperative time. Data analysis included descriptive statistics, as well as inferential analysis.

RESULTS: From January 2023 to February 2024, 532 participants met the criteria, completed and returned the preoperative survey, and underwent primary inguinal hernia repair. The participants were mostly male (94%) with an average age of 62.18 years and BMI of 24.93 kg/m². The EQ-5D-3L health index scores and EQ-VAS health status at preoperative were 0.83 ± 0.13 and 79.5 ± 12.59. At the 1-month postoperative time, health index scores and health status had significantly increased from preoperative (score:0.91 ± 0.12, p = .001; status 83.56 ± 12.93, p = .001), and continued to significantly increase from baseline at the 6-month postoperative time (score:0.95 ± 0.10, p = .001; status:85.25 ± 12.17, p < .001).

CONCLUSION: Quality of life, as measured by the ED-5D-3L health index score, significantly improved for patients that underwent a Shouldice Repair for an inguinal hernia.

PMID:39580600 | DOI:10.1007/s10029-024-03217-3

Sci Rep. 2024 Nov 23;14(1):29069. doi: 10.1038/s41598-024-80890-5.

ABSTRACT

Percutaneous kyphoplasty (PKP) is an effective, minimally invasive treatment for Kummell’s disease, but challenges like cement leakage, fracture, and displacement remain. This study explores the use of PKP with a mesh-hold bone filling container for this disease.A retrospective analysis was conducted on nine Kummell’s disease cases treated with this technique at a spinal surgery department from June 2016 to May 2022. Pre- and postoperative evaluations included X-rays, CT scans, and 3D reconstructions. Parameters like vertebral heights, kyphotic angle, operation time, blood loss, and bone cement issues were measured. Efficacy was assessed using ODI and VAS scores.Statistical analysis showed no significant difference in posterior vertebral height before and after treatment. All other indexes improved significantly postoperatively and at follow-up. No cement leakage or displacement occurred.PKP with a mesh-hold bone filling container is a promising treatment for Kummell’s disease. It enhances reduction quality, ensures adequate bone cement filling, and reduces issues related to cement leakage, fracture, and displacement.

PMID:39580562 | DOI:10.1038/s41598-024-80890-5

Eur J Hum Genet. 2024 Nov 23. doi: 10.1038/s41431-024-01747-z. Online ahead of print.

ABSTRACT

Polygenic Risk Scores (PRS) are statistical methods estimating part of an individual’s genetic susceptibility to various disease phenotypes. Their potential clinical applications to enhance the prediction, prevention, and risk management of complex conditions motivate current research efforts worldwide. While a growing body of literature has highlighted the scientific and ethical limitations of PRS, the technology’s clinical translation will present both opportunities and challenges for the stakeholders involved. Here, a mixed-method systematic review of empirical studies was performed to gather evidence on the perspectives, attitudes, and experiences of healthcare providers, patients, and the public regarding the use of PRS in healthcare settings. The PRISMA reporting protocol was followed and 24 articles were included. Three major themes were identified. First, we reported on participants’ familiarity with the test, including their knowledge, understanding, and education on PRS’ clinical use. The second theme collects stakeholders’ motivations for taking the test and their perspectives on sensitive issues related to the return of results. Participants’ normative stances regarding the appropriate use of PRS, their benefits, and harms were presented in the third theme. The findings underscore significant knowledge gaps and challenges in the clinical interpretation of PRS among healthcare providers. On the other hand, the provision of genetic counseling benefitted patients’ understanding of PRS results and in most cases, no psychosocial burden was reported. Finally, the review highlights that stakeholders’ perspectives on the clinical use of PRS are highly context-dependent, shaped by population characteristics, disease type, and social factors, emphasizing the need for tailored approaches across diverse healthcare settings.

PMID:39580561 | DOI:10.1038/s41431-024-01747-z

Sci Rep. 2024 Nov 23;14(1):29092. doi: 10.1038/s41598-024-80934-w.

ABSTRACT

To compare the safety and effectiveness of the combination of intelligent intrarenal pressure control platforms and flexible end ureteral access sheath combined with flexible ureteroscopic lithotripsy (FURL) for the treatment of renal stones less than 2 cm with day case mode. From November 2023 to July 2024, a prospective, randomized, double-blind, parallel-controlled study was conducted to recruit 60 patients with upper urinary tract calculi measuring ≤ 2 cm in longest diameter. A total of 60 eligible patients were consecutively enrolled. Based on a pre-generated random number table and allocation scheme using SPSS 27.0, patients were assigned to either the intelligent pressure control group (IFURL, n = 30) or the head bending group (BFURL, n = 30). Blinding measures were implemented for patients, data collectors, statisticians, and analysts, with the allocation results disclosed to the surgeons prior to the start of the procedure in the operating room. The operation duration for IFURL and BFURL was 52.50 (48.00, 60.00) vs. 46.00 (36.00, 56.25), respectively (p = 0.047). Stone free rate (SFR) on the first postoperative day was 73.33% vs. 93.33% for IFURL and BFURL, respectively (p = 0.038). While, SFR was no significant difference between the two groups after two months(90.00% vs. 96.67%, p = 0.301). One patient in IFURL was readmitted after discharge due to fever 2 days post-discharge, and improved after 2 days of anti-infection treatment. One patient in BFURL was readmitted due to lumbar and abdominal pain from urine extravasation, which improved after 3 days of anti-infection treatment. SFR of one-month post-surgery for renal calculi ≤ 2 cm treated with intelligent pressure control and flexible UAS combined with FURL in day surgery mode was similar, with low infection-related complications and rehospitalization rates, showing no statistical difference. However, the overall hospitalization costs for the BFURL was lower than IFURL.

PMID:39580558 | DOI:10.1038/s41598-024-80934-w