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Pathological-Features-Modified TNM Staging System Improves Prognostic Accuracy for Rectal Cancer

Dis Colon Rectum. 2023 Dec 26. doi: 10.1097/DCR.0000000000003034. Online ahead of print.

ABSTRACT

BACKGROUND: Variations in survival outcomes are observed in the American Joint Committee on Cancer’s 8th edition TNM staging system.

OBJECTIVE: Machine learning ensemble methods were used to develop and evaluate the effectiveness of a pathological-features-modified tumor node metastasis staging system in predicting survival for patients with rectal cancer by using commonly reported pathological features, such as histological grade, tumor deposits, and perineural invasion, to improve the prognostic accuracy.

DESIGN: This was a retrospective population-based study.

SETTINGS: Data were assessed from the database of the Surveillance, Epidemiology, and End Results Program.

PATIENTS: The study cohort comprised 14,468 rectal cancer patients diagnosed between 2010 and 2015. The development cohort included those who underwent surgery as the primary treatment while patients who received neoadjuvant therapy were assigned to the validation cohort.

MAIN OUTCOME MEASURES: The primary outcome measures included cumulative rectal cancer survival, adjusted hazard ratios, and both calibration and discrimination statistics to evaluate model performance and internal validation.

RESULTS: Multivariable Cox regression analysis identified all three pathological features as prognostic factors, following which patients were categorized into four pathological groups based on the number of pathological features (i.e., 0, 1, 2, and 3). Distinct survival differences were observed among the groups, especially with stage III patients. The proposed pathological-features-modified tumor-node-metastasis staging outperformed the TNM staging in both the development and validation cohorts.

LIMITATIONS: Retrospective in design and lack of external validation.

CONCLUSIONS: The proposed pathological-features-modified tumor-node-metastasis staging could complement the current TNM staging by improving the accuracy of rectal cancer patients’ survival estimation. See Video Abstract.

PMID:38147435 | DOI:10.1097/DCR.0000000000003034

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Underlying features for the enhanced electrostatic strength of the extremophilic malate dehydrogenase interface salt-bridge compared to the mesophilic one

J Biomol Struct Dyn. 2023 Dec 26:1-16. doi: 10.1080/07391102.2023.2295972. Online ahead of print.

ABSTRACT

Malate dehydrogenase (MDH) exists in multimeric form in normal and extreme solvent conditions where residues of the interface are involved in specific interactions. The interface salt-bridge (ISB) and its microenvironment (ME) residues may have a crucial role in the stability and specificity of the interface. To gain insight into this, we have analyzed 218 ISBs from 42 interfaces of 15 crystal structures along with their sequences. Comparative analyses demonstrate that the ISB strength is ∼30 times greater in extremophilic cases than that of the normal one. To this end, the interface residue propensity, ISB design and pair selection, and ME-residue’s types, i.e., type-I and type-II, are seen to be intrinsically involved. Although Type-I is a common type, Type-II appears to be extremophile-specific, where the net ME-residue count is much lower with an excessive net ME-energy contribution, which seems to be a novel interface compaction strategy. Furthermore, the interface strength can be enhanced by selecting the desired mutant from the net-energy profile of all possible mutations of an unfavorable ME-residue. The study that applies to other similar systems finds applications in protein-protein interaction and protein engineering.Communicated by Ramaswamy H. Sarma.

PMID:38147414 | DOI:10.1080/07391102.2023.2295972

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Increased risk of persistent neuropathic pain after traumatic nerve injury and surgery for carriers of a human leukocyte antigen haplotype

Pain. 2023 Dec 22. doi: 10.1097/j.pain.0000000000003143. Online ahead of print.

ABSTRACT

It is not known why some patients develop persistent pain after nerve trauma while others do not. Among multiple risk factors for the development of persistent posttrauma and postsurgical pain, a neuropathic mechanism due to iatrogenic nerve lesion has been proposed as the major cause of these conditions. Because there is some evidence that the human leukocyte antigen (HLA) system plays a role in persistent postsurgical pain, this study aimed to identify the genetic risk factors, specifically among HLA loci, associated with chronic neuropathic pain after traumatic nerve injuries and surgery in the upper extremities. Blood samples were taken to investigate the contribution of HLA alleles (ie, HLA-A, HLA-B, HLA-DRB1, HLA-DQB1, and HLA-DPB1) in a group of patients with persistent neuropathic pain (n = 70) and a group of patients with neuropathy without pain (n = 61). All subjects had intraoperatively verified nerve damage in the upper extremity. They underwent bedside clinical neurological examination to identify the neuropathic pain component according to the present grading system of neuropathic pain. Statistical analyses on the allele and haplotype were conducted using the BIGDAWG package. We found that the HLA haplotype A*02:01-B*15:01-C*03:04-DRB1*04:01-DQB1*03:02 was associated with an increased risk of developing persistent neuropathic pain in the upper extremity (OR = 9.31 [95% CI 1.28-406.45], P < 0.05). No significant associations were found on an allele level when correcting for multiple testing. Further studies are needed to investigate whether this association is on a haplotypic level or if certain alleles may be causing the association.

PMID:38147413 | DOI:10.1097/j.pain.0000000000003143

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Polymorphisms of OPRM1, OPRK1, DCC genes and non-suicidal self-injuries in adults

Zh Nevrol Psikhiatr Im S S Korsakova. 2023;123(12):116-123. doi: 10.17116/jnevro2023123121116.

ABSTRACT

OBJECTIVE: To investigate the associations of OPRM1 gene rs179971, OPRK1 gene rs6473797 and DCC gene rs8084280 polymorphisms with non-suicidal self-injury (NSSI) characteristics and motivations in adults.

MATERIAL AND METHODS: A pilot sample included 28 adult patients with history of NSSI (89.3% (n=25) women, median age (Q1-Q3) – 23 (21.25-25) years). Most patients (78.6%, n=20) had a diagnosis of bipolar disorder. NSSI characteristics and motivations were assessed using the Inventory of Statements about Self-Injury (ISAS) scale. The Childhood Trauma Questionnaire (CTQ) was used to control for childhood trauma – one of the most important environmental factors associated with NSSI. The Baratt Impulsivity Scale (BIS) and the Buss-Perry Aggression Questionnaire (BPAQ) were also used to assess impulsivity and aggression, respectively. RT-PCR was used for genotyping, a genetic effect was assessed using the dominant model. Mann-Whitney U-test, Pearson χ2-test and multiple linear regression were used for statistical analysis.

RESULTS: Carriers of the minor G allele of OPRM1 gene rs1779971 had a higher level of aggression assessed by BPAQ (p=0.02). The minor C allele of OPRK1 gene rs6473797 was associated with an increase of the subjective importance of «Affect regulation» (B=2.23; CI 95% [0.39-4.06]; p=0.022) and «Anti-dissociation» (B=3.31; CI 95% [0.18-6.44]; p=0.039) motivations, whereas the minor T allele of DCC gene rs8084280, on the contrary, was associated with a decrease of the importance of «Affect regulation» (B=-1.74; CI 95% [-3.30 – -0.18]; p=0.032). Moreover, this effect was found after adjusting for diagnosis, sex, age, and the presence of childhood trauma.

CONCLUSIONS: To our knowledge, this is the first study on the association of genetic markers with NSSI motivations. The results of this pilot study demonstrate that OPRK1 and DCC gene polymorphisms can determine differences in motivations for self-harm, however, these results require confirmation in large samples.

PMID:38147391 | DOI:10.17116/jnevro2023123121116

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Initial mental disorders in patients with psychotic of schizophrenia in adolescent

Zh Nevrol Psikhiatr Im S S Korsakova. 2023;123(12):93-98. doi: 10.17116/jnevro202312312193.

ABSTRACT

OBJECTIVE: Clarification of the phenomenology and dynamics of initial mental disorders in patients with psychotic pubertal forms of schizophrenia, identification of the features of these disorders depending on sex.

MATERIAL AND METHODS: The study material was adolescent patients with psychotic forms of schizophrenia. Forty-three people were examined (women 44.2%, median age 14.3 [13.0; 16.8] years). Clinical-anamnestic, clinical-psychopathological, clinical-statistical methods were used.

RESULTS: The duration of the initial stage of the disease ranged from several hours to 5 years (median 0.8 [0.5; 1.7]. The structure of initial disorders was dominated by nonspecific mental disorders characterized by a combination of symptoms of non-psychotic and subpsychotic levels (20 patients – 43.5%; including 12 males – 26% and 8 females – 24.1% ). If behavioral disorders and episodes of psychoactive substance use were significantly more often detected in boys, then dysmorphic phenomena were detected in girls (p<0.05). In accordance with the dynamics of development, acute (n=14 – 32%), subacute (n=21 – 49%), fluctuating (n=8 – 19%) variants of initial disorders are distinguished. Young men turned to a psychiatrist in a more timely manner (already at the stage of prodrome), while girls sought psychiatric help only at the stage of development of psychotic disorders.

CONCLUSION: A psychotic episode in adolescents suffering from schizophrenia developed acutely in a third of cases. In the vast majority of cases, the initial mental disorders that appeared on the eve of acute psychosis was subacute, or differed in a fluctuating course, characterized by clinical polymorphism and multidirectionality. Differences were revealed in the preference for the occurrence of a number of initial disorders in boys and girls, as well as in the timeliness of seeking psychiatric help.

PMID:38147388 | DOI:10.17116/jnevro202312312193

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Impulsivity and aggression in patients at risk for schizophrenia at the stage of remission after the first depressive episode

Zh Nevrol Psikhiatr Im S S Korsakova. 2023;123(12):83-92. doi: 10.17116/jnevro202312312183.

ABSTRACT

OBJECTIVE: To study the phenomenon of impulsivity, its components and aggression in patients at risk for schizophrenia at the stage of remission after the first depressive episode.

MATERIAL AND METHODS: Forty-eight male patients (mean age 19.4±2.9 years) with the first depressive episode (ICD-10 F32.1, F32.2) with attenuated positive, negative and/or disorganized symptoms were examined. According to the severity of impulsivity, the patients were divided into the clinical group (n=26) with pathological impulsivity and the comparison group (n=27) without it. The control group consisted of 41 mentally healthy young men, students of higher education of 1-3 courses, (mean age 19.7±1.6 years). HDRS, SOPS, SANS, Barratt Impulsiveness Scale (BIS-11) and Buss Perry Aggression Questionnaire (BPAQ) were used. Statistical analysis was carried out using the Statistica 12 software.

RESULTS: The differences between the clinical group and the comparison group were determined by the total score of the subscale of general symptoms of SOPS at admission (53 [41.75; 56] and 45.5 [41.75; 51.25], respectively) (U=187.5; p=0.037) and at discharge (28 [19; 37] and 25 [17.75; 29.25] points respectively) (U=166.5; p=0.012), according to the total HDRS score at admission (35 [31; 38] and 29 [26; 34.25]) (U=191.0; p=0.046). In the clinical group, the motor component of impulsivity and the factor of general impulsivity on the BIS-11 correlated with the severity of aggression on the BPAQ (r=0.395, p<0.05 and r=0.635, p<0.05, respectively). Significant differences were revealed in the clinical group depending on the presence of negative symptoms on the corresponding SOPS subscale according to the total BPAQ score (p=0.01). Correlation analysis showed numerous connections: positive between the total aggressiveness score and the duration of depression (p<0.05), negative between the factors of self-control, consistency, attention, and total scores on the SANS and SOPS (p<0.05).

CONCLUSION: We identify the differences in the structure of impulsivity in patients at risk of developing schizophrenia at the stage of remission after the first depressive state, the comparison group and the control group, as well as the relationship of impulsivity factors with individual clusters of psychopathological disorders.

PMID:38147387 | DOI:10.17116/jnevro202312312183

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Intraosseous blockades and local injection of Chondroreparant Hyalripayer combination in low back pain treatment

Zh Nevrol Psikhiatr Im S S Korsakova. 2023;123(12):59-64. doi: 10.17116/jnevro202312312159.

ABSTRACT

OBJECTIVE: Studying the effectiveness of the combined use of intraosseous blockades (IOB) and intramuscular local injection therapy using bottled forms of Chondroreparant Gialripayer 02/10 in patients with lumbar dorsopathy and recurrent back pain syndrome.

MATERIAL AND METHODS: 30 patients (16 men and 14 women) with chronic recurrent lumbar dorsopathy with pain and myofascial syndromes were examined. Group 1 included 17 patients, whose treatment included the use of IOB and intramuscular local injection therapy using bottled forms of Chondroreparant Gialripayer 02/10. Group 2 included 13 patients who received only IOB. To assess the pain syndrome, a visual analogue pain scale (VAS), a Russian version of the McGill Pain Questionnaire (MPBI), and a body diagram questionnaire were used.

RESULTS: After the course of treatment, in both groups there was a decrease in the severity of pain according to VAS, RMBO, and a decrease in the area of pain distribution according to the Body Scheme questionnaire (p<0.05). The values on the RMBO questionnaire in both groups also decreased by more than 2 times compared to the initial value. A statistically more significant regression of pain syndrome and a decrease in disability were noted in group 1 (p<0.05). 2 months after the end of the course of treatment, the pain syndrome did not recur in any patient. Within 3 to 6 months, back pain recurred in 4 (23.5%) patients of the 1st group and in 6 (46.2%) patients of the 2nd group. A total of 90 IOB procedures were performed; no complications or side effects were noted.

CONCLUSION: The combination of IOB and intramuscular local injection therapy using the vial form of Chondroreparant Gialripayer in the treatment of patients with degenerative diseases of the spine and back pain is an effective and safe method of therapy. Such treatment strategy allowed to relieve back pain more effectively and improved long-term clinical outcome.

PMID:38147383 | DOI:10.17116/jnevro202312312159

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Household Health-Related Social Needs in Newborns and Infant Behavioral Functioning at 6 Months

JAMA Pediatr. 2023 Dec 26. doi: 10.1001/jamapediatrics.2023.5721. Online ahead of print.

ABSTRACT

IMPORTANCE: Dysfunctional patterns of behavior during infancy can predict the emergence of mental health disorders later in childhood. The Baby Pediatric Symptom Checklist (BPSC) can identify indicators of behavioral disorders among children aged 0 to 18 months. Understanding the association of early health-related social needs (HRSNs) with poor infant behavioral functioning can inform interventions to promote early childhood mental well-being.

OBJECTIVE: To examine the association between household HRSNs in the first 4 months of life and BPSC results at 6 months.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort analysis of longitudinal electronic health record data. Covariates were selected based on the biopsychosocial ecological model. Logistic regression analyses examined the association of HRSN domains and the number of HRSNs with the 6-month BPSC outcomes. Participants were recruited from 6 primary care clinics within 1 health system. Children aged 5 to 8 months who were evaluated for 6-month well-child visits between March 30, 2021, and June 30, 2022, were included in the study.

EXPOSURE: Responses to the first HRSN screening tool that a caregiver completed for infants between 0 and 4 months of age. HRSN domains were examined individually and as the number of positive HRSNs.

MAIN OUTCOME AND MEASURES: BPSC screen identified for clinical review due to 1 or more elevated subscales (inflexibility, irritability, and difficulty with routines) at 6 months.

RESULTS: A total of 1541 children (mean [SD] age, 6.1 [0.5] months; 775 female [50.3%]) were included in the study. A total of 405 children (26.3%) had a BPSC screen identified for clinical review, and 328 caregivers (21.3%) reported at least 1 HRSN. Food insecurity (174 [11.3%]) and benefits issues (169 [11.0%]) were the most frequently reported HRSN. Children in households with food insecurity had statistically significant higher odds of inflexibility (adjusted odds ratio [aOR], 1.73; 95% CI, 1.14-2.63), difficulty with routines (aOR, 1.64; 95% CI, 1.05-2.57), and irritability (aOR, 1.86; 95% CI, 1.13-3.08) than children in households without food insecurity. Children in households with benefits issues had statistically significant higher odds of difficulty with routines (aOR, 1.70; 95% CI, 1.10-2.65) and irritability (aOR, 1.70; 95% CI, 1.03-2.82). Children in households with 2 or more HRSNs had consistently higher odds of having a BPSC screen identified for clinical review (aOR, 2.16; 95% CI, 1.38-3.39) compared with children with no HRSNs.

CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest that household food insecurity, benefits issues, and the number of HRSNs were significantly associated with a BPSC screen identified for clinical review at 6 months of age. These findings highlight the urgency of intervening on HRSNs in the newborn period to prevent adverse infant behavioral outcomes.

PMID:38147349 | DOI:10.1001/jamapediatrics.2023.5721

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Pet Ownership, Living Alone, and Cognitive Decline Among Adults 50 Years and Older

JAMA Netw Open. 2023 Dec 1;6(12):e2349241. doi: 10.1001/jamanetworkopen.2023.49241.

ABSTRACT

IMPORTANCE: It remains unclear whether pet ownership is associated with cognitive decline and to what extent pet ownership mitigates the association between living alone and cognitive decline.

OBJECTIVE: To explore the association of pet ownership with cognitive decline, the interaction between pet ownership and living alone, and the extent to which pet ownership mitigates the association between living alone and cognitive decline in older adults.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from waves 5 (June 2010 to July 2011) to 9 (from June 2018 to July 2019) in the English Longitudinal Study of Ageing. Participants included adults 50 years and older. Data were analyzed from April 1 to June 30, 2023.

EXPOSURES: Pet ownership and living alone in wave 5.

MAIN OUTCOMES AND MEASURES: In waves 5 to 9, verbal memory and verbal fluency were assessed, and composite verbal cognition was further calculated.

RESULTS: Of the 7945 participants included, the mean (SD) age was 66.3 (8.8) years, and 4446 (56.0%) were women. Pet ownership was associated with slower rates of decline in composite verbal cognition (β = 0.008 [95% CI, 0.002-0.014] SD/y), verbal memory (β = 0.006 [95% CI, 0.001-0.012] SD/y), and verbal fluency (β = 0.007 [95% CI, 0.001-0.013] SD/y). Three-way interaction tests showed that living alone was a significant modifier in all 3 associations. Stratified analyses showed that pet ownership was associated with slower rates of decline in composite verbal cognition (β = 0.023 [95% CI, 0.011-0.035] SD/y), verbal memory (β = 0.021 [95% CI, 0.008-0.034] SD/y), and verbal fluency (β = 0.018 [95% CI, 0.005-0.030] SD/y) among individuals living alone, but not among those living with others. Joint association analyses showed no significant difference in rates of decline in composite verbal cognition, verbal memory, or verbal fluency between pet owners living alone and pet owners living with others.

CONCLUSIONS AND RELEVANCE: In this cohort study, pet ownership was associated with slower rates of decline in verbal memory and verbal fluency among older adults living alone, but not among those living with others, and pet ownership offset the associations between living alone and declining rates in verbal memory and verbal fluency. Further studies are needed to assess whether pet ownership slows the rate of cognitive decline in older adults living alone.

PMID:38147332 | DOI:10.1001/jamanetworkopen.2023.49241

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Clinical features of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with macrophage activation syndrome

Clin Exp Rheumatol. 2023 Dec 12. doi: 10.55563/clinexprheumatol/2537nv. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to describe the clinical features of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) who had macrophage activation syndrome (MAS).

METHODS: We retrospectively examined 44 patients with anti-MDA5-positive DM and compared the clinical features between patients with MAS (n = 11) and those without (n=33). Patients without MAS were selected randomly in the same year as those with MAS at a ratio of 3:1. Among patients with MAS, we compared the features between non-survivors and survivors. We used Fisher’s exact test, Student’s t test, the Mann-Whitney U test and the log-rank test for statistical analysis.

RESULTS: Patients complicated with MAS had a significantly higher incidence of infection, heliotrope sign, Gottron’s papule, V-neck sign, and higher serum levels of ferritin, aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and creatine kinase (CK) than those without MAS (p<0.05). Among the 11 patients with MAS, 4 (36.4%) died after intensive treatment. Deceased patients were older, given more combination therapy with tofacitinib (TOF) and had a higher incidence of rapid progressive interstitial lung disease, infection, heart failure and renal impairment than those who survived (p<0.05).

CONCLUSIONS: Among anti-MDA5-positive DM, Infection, DM typical rashes, and higher serum levels of ferritin, AST, LDH, and CK were more common in patients complicated with MAS. The mortality of patients with MAS was high, particularly among patients who were older, given more combination therapy with TOF, and had RP-ILD, infection, heart failure and renal impairment.

PMID:38147318 | DOI:10.55563/clinexprheumatol/2537nv