Nevin Manimala

Int J Colorectal Dis. 2025 Jan 3;40(1):5. doi: 10.1007/s00384-024-04781-x.

ABSTRACT

PURPOSE: The role of adjuvant chemotherapy in rectal cancer patients downstaged to ypT0-2 N0 after neoadjuvant chemoradiotherapy (CRT), and surgery is still debated. This study investigates the impact of adjuvant chemotherapy on survival outcomes in this patient population.

METHODS: This retrospective study analyzed hospital records of rectal cancer cases from Shefa Al Orman Cancer Hospital between January 2016 and December 2020, focusing on patients downstaged to ypT0-2 N0 after neoadjuvant CRT and surgery. Patients were divided into two groups based on whether they received adjuvant chemotherapy. Baseline characteristics, DFS, and OS were compared, and survival factors were analyzed using univariate and multivariate Cox regression.

RESULTS: Eighty-five patients met the inclusion criteria; 55 received adjuvant chemotherapy, and 30 did not. The median age was 52, but those receiving adjuvant therapy were younger (47 vs. 60 years, P = 0.006). No significant differences were observed in sex, tumor location, or pathology between groups. Although adjuvant chemotherapy showed a trend toward better 3-year DFS (89.5% vs. 81.9%, P = 0.153) and OS (88.1% vs. 84.6%, P = 0.654), these differences were not statistically significant. Univariate and multivariate analyses confirmed no significant effect of adjuvant chemotherapy on DFS or OS, nor were any other variables significantly associated with survival.

CONCLUSION: Adjuvant chemotherapy did not significantly improve DFS or OS in rectal cancer patients downstaged to ypT0-2 N0 following neoadjuvant CRT and surgery. Further studies are needed to define the role of adjuvant therapy in this group.

PMID:39751895 | DOI:10.1007/s00384-024-04781-x

Calcif Tissue Int. 2025 Jan 3;116(1):15. doi: 10.1007/s00223-024-01311-3.

ABSTRACT

Osteogenesis imperfecta (OI) is a group of rare genetic disorders most commonly caused by reduced amount of biologically normal collagen type I, a structural component of the gastrointestinal tract and abdominal wall. The risk of gastrointestinal (GI) disease in individuals with OI is not well understood, despite GI complaints being frequently reported by the OI population. To investigate the risk of GI diseases in individuals with OI. A Danish nationwide register-based cohort study utilizing data from the Danish National Patient Register and the Danish National Prescription Register. All individuals registered with an OI diagnosis in Denmark from 1995 through 2018, along with a reference population matched 1:5 based on sex, birth year, and month. Sub-hazard ratios (SHR) for peptic ulcer disease, diverticular disease, gastrointestinal cancers, intestinal obstruction with ileus, constipation, abdominal wall hernia, and other reasons for abdominal discomfort. The study included 864 individuals with OI (472 women) and 4,276 in the reference population (2,332 women). The SHR was significantly increased for ulcer (3.28 [95% CI 2.21-4.28]), constipation (2.67 [1.91-3.74]), and hernia (among women: 1.85 [1.22-2.80]). Higher SHRs were also observed for inflammatory bowel disease, biliary and pancreatic diseases, appendicitis, and unspecified abdominal pain. SHRs were not statistically significantly increased for diverticular disease, gastrointestinal cancers, intestinal obstruction with ileus, kidney stones or hemorrhoid disease. Individuals with OI have a higher risk of peptic ulcer disease, constipation, hernia among women, inflammatory bowel diseases, biliary and pancreatic diseases, appendicitis, and unspecified abdominal pain, compared with the general population.

PMID:39751887 | DOI:10.1007/s00223-024-01311-3

Aging Dis. 2024 Dec 18. doi: 10.14336/AD.2024.1174. Online ahead of print.

ABSTRACT

Neuroinflammation plays a critical role in Alzheimer’s (AD) and Parkinson’s diseases (PD) onset, pathophysiology, and progression. The aim of our meta-analysis was to review the available literature to assess the role of neuroinflammation in the pathogenesis of the two most common neurological diseases: Parkinson’s disease and Alzheimer’s disease. Two medical databases were searched: Web of Science and PubMed in the period from 2009-2023, where a total of 37 publications that met the inclusion criteria were selected for further evaluation. Both patients with AD and with PD showed statistically significantly higher levels of interleukin IL-6 compared to the control group: p-value of 0.0034 for AD (SMD, 1.17; 95% CI, 0.39-1.96) and p-value of 0.0487 for PD (SMD 0.29 95% Cl 0.00-0.59). In AD patients, statistical significance (for random effect) was also observed for IL-1β, where higher values of this cytokine were recorded in patients compared to controls (p-value <0.001). In turn, in patients with PD, apart from IL-6, statistical significance was also observed for tumor necrosis factor-α (TNF-α) (p= 0.0431, SMD 0.52 95%Cl 0.02-1.02). Significant heterogeneity was also recorded (Q =85.48; P < 0.01; I² = 87%). In both study groups, significant differences in common effect were observed for the anti-inflammatory cytokine IL-10, which could suggest a protective effect of this cytokine in patients with neurodegenerative diseases. The obtained results reinforce the existing clinical evidence that Alzheimer’s and Parkinson’s diseases are accompanied by an inflammatory response, with considerably higher blood levels observed for pro-inflammatory cytokines: IL-6, TNF-α and IL-1β.

PMID:39751856 | DOI:10.14336/AD.2024.1174

CNS Neurosci Ther. 2025 Jan;31(1):e70203. doi: 10.1111/cns.70203.

ABSTRACT

BACKGROUND: Metabolomics offers promise in uncovering potential biomarkers and understanding the pathophysiology of autoimmune encephalitis (AE), which is a cluster of disorders with the host immune system targeting self-antigens expressed in the central nervous system (CNS). In this research, our objective was to explore metabolic characterization in cerebrospinal fluid (CSF) from individuals with AE, aiming to shed light on the pathophysiology of AE.

METHODS: A targeted approach was applied using an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system to study CSF metabolites in patients with AE (n = 18), and control subjects without neurological diseases (n = 17).

RESULTS: A total of 21 potential biomarkers were acquired by getting the intersection of the differential metabolites from univariate statistics and multidimensional statistics between the AE (cell-based assay panel, CBA-panel) group and the control group. Specifically, the levels of pyruvic acid and oxoglutaric acid were notably elevated in the AE(CBA-panel) group compared to those in the control group, indicating that the dysregulated TCA cycle may play a pivotal role in the progression of AE(CBA-panel). Interestingly, 27 potential biomarkers were acquired by getting the intersection of the differential metabolites from univariate statistics and multidimensional statistics between the anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) group and the control group, suggesting that the disparities between patients with greater homogeneity and the controls are amplified. In addition, seven differential metabolites were identified by the univariate statistics between the AE (tissue-based assay, TBA) group and the control group, including alpha-linolenic acid and gamma-linolenic acid, suggesting that dysregulated biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism might be crucial in the AE(TBA) disease course.

CONCLUSION: Collectively, distinct metabolic profiles were evident in the CSF of the AE group compared to the control group, notably involving metabolites associated with mitochondrial dysfunction, which helped to elucidate the pathophysiology of AE.

PMID:39749658 | DOI:10.1111/cns.70203

Ann Med. 2025 Dec;57(1):2447402. doi: 10.1080/07853890.2024.2447402. Epub 2025 Jan 3.

ABSTRACT

BACKGROUND: Cord blood (CB) is widely used in treating haematologic disorders due to its broad availability, tolerance to significant histocompatibility antigen disparities, and low incidence of chronic graft-versus-host disease (cGVHD). The cord blood transplantation (CBT) with anti-thymocyte globulin (ATG)-containing conditioning regimens shows promise in this regard.

METHODS: We conducted a retrospective review of data from patients who underwent CBT at our centre from August 2003 to December 2022. Patients undergoing CBT with ATG were matched with those who received HLA-haploidentical haematopoietic stem cell transplantation (haplo-HSCT). Propensity score matching (PSM) was utilized to form 105 matched pairs (140 patients) for comprehensive trial analysis.

RESULTS: The cumulative incidence of neutrophil and platelet engraftment was significantly lower in the CBT group. Patients in the CBT group exhibited significantly lower incidences of grade II-IV acute GVHD (aGVHD) and cGVHD compared to the haplo-HSCT group (8.57% vs. 29.52%, p = 0.012; 20% vs. 39.05%, p = 0.031). The overall survival (OS) rate for the CBT and haplo-HSCT groups showed no significant difference. In patients with leukaemia, the CBT cohort showed better OS, GVHD-free and relapse-free survival (GRFS), as well as a lower incidence of disease relapse, although there was no statistical difference.

CONCLUSION: Our single-centre retrospective long-term follow-up investigations indicated that although the implantation rate of CBT is lower than that of haplo-HSCT, patients undergoing CBT with ATG-containing conditioning regimens may have a comparable overall survival with a lower risk of GVHD compared to those undergoing haplo-HSCT.

PMID:39749649 | DOI:10.1080/07853890.2024.2447402

Tijdschr Psychiatr. 2024;66(9):527-531.

ABSTRACT

BACKGROUND: Outpatient forensic treatment is generally more focused on diminishing transgressive behavior, rather than the treatment of a specific disorder. However, the indications for prescribing psychotropic medication are usually a specific disorder. Although guidelines are used a large portion of psychopharmacological prescription is off-label.

AIM: To explore the extent of off-label prescribing. The study aimed to address three main questions: What is the percentage of off-label prescribing? Which part of off-label prescribing is based on guidelines and formularies? What is the frequency of pharmacist consultation before prescribing off-label medication?

METHOD: Data for the study were collected by 17 psychiatrists working in the thirteen forensic outpatient clinics of de Waag. The study focused on a sample of 202 adult patients, who were treated between October&nbsp;2022 and May&nbsp;2023.

RESULTS: 72.0% of 350 prescriptions were prescribed off-label. From these 72.0%, 51.4% was based on guidelines and formularies and 20.6% not. In 84,7% off the off-label prescription not based on guidelines and formularies a pharmacist wasn&rsquo;t consulted.

CONCLUSION: This study confirms the high percentage of off-label prescriptions in the forensic psychiatry. However, more than 70% was based on guidelines and formularies.

PMID:39749614

Mult Scler. 2025 Jan 3:13524585241310104. doi: 10.1177/13524585241310104. Online ahead of print.

ABSTRACT

BACKGROUND: Many common symptoms in post-acute sequelae following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) overlap with those of multiple sclerosis (MS). We examined symptoms and performance of the PASC score, developed in the general population, in MS based on infection history.

METHODS: We surveyed North American Research Committee on Multiple Sclerosis (NARCOMS) registry participants regarding infections and categorized participants based on infection history. Symptoms experienced before, during, and after infection were used to identify persistent new symptoms. PASC was defined as a score ⩾ 12 based on the National Institutes of Health (NIH) study RECOVER.

RESULTS: Of 4787 participants surveyed, 2927 were included: 294 (10%) having recent COVID-19; 853 (29.1%) recent non-COVID-19 infection; 246 (8.4%) recent COVID-19 and non-COVID-19 infection; 1534 (52.4%) uninfected, defined as never having COVID-19 nor any infection within the past 6 months. Compared to those uninfected, infection groups reported at least a two-fold increase in fever, cough, loss of smell/taste, and shortness of breath. Based on persistent new symptoms, PASC was identified in only 1.5% of participants with COVID-19.

CONCLUSION: Our study suggests lower than expected prevalence of PASC in MS and a complex association between infections and development of new persistent symptoms following infections. The similar proportions classified with PASC across infection groups shows that symptoms of PASC are common and complicate assessment of PASC in MS.

PMID:39749575 | DOI:10.1177/13524585241310104

Trans R Soc Trop Med Hyg. 2025 Jan 3:trae069. doi: 10.1093/trstmh/trae069. Online ahead of print.

ABSTRACT

BACKGROUND: Snakebite envenoming is a medical emergency that requires rapid access to essential medicines and well-trained personnel. In resource-poor countries, mapping snakebite incidence can help policymakers to make evidence-based decisions for resource prioritisation. This study aimed to characterise the spatial variation in snakebite risk, and in particular to identify areas of relatively high and low risk, in Eastern Province, Rwanda.

METHODS: Snakebite surveillance of people bitten in 2020 was conducted in Eastern Province through household visits and case verification. Geostatistical modelling and predictive mapping were applied to data from 617 villages in six districts to develop sector-level and district-level risk maps.

RESULTS: There were 1217 individuals bitten by snakes across six districts. The estimated population-weighted snakebite incidence in Eastern Province was 440 (95% predictive interval 421 to 460) cases per 100 000 people, corresponding to 13 500 (95% predictive interval 12 950 to 14 150) snakebite events per year. Two sectors in the southwest, Gashanda and Jarama, showed >1500 snakebite events per 100 000 annually. The lowest incidence was observed in the north.

CONCLUSIONS: Considerable differences exist in snakebite risk between sectors in Eastern Province, with the highest risk concentrated in the southwest. Policymakers should consider prioritising resources related to snakebite prevention, essential medicines and health worker training in this region.

PMID:39749566 | DOI:10.1093/trstmh/trae069

Dan Med J. 2024 Nov 20;71(12):A04240264. doi: 10.61409/A04240264.

ABSTRACT

INTRODUCTION: Even though Denmark has the highest contraceptive use (42%) of the Nordic countries, 19% of all pregnancies in Denmark end in termination. Various contraceptive options are available, and unwanted pregnancies therefore ought to be avoidable. This study aimed to investigate if women received counselling and prescriptions for contraception during their termination and if this or other factors impacted their risk of repeat termination.

METHODS: This was an analytical, historical and retrospective cohort study. Data were collected manually from 310 medical records at the Hospital of Southern Jutland between 2016 and 2019.

RESULTS: A total of 82% of patients received contraceptive counselling during their termination, and 35% of these patients received a contraceptive prescription for future use. A total of 17% had a repeat termination within three years after receiving counselling; 23% of the women who did not receive contraceptive counselling experienced one or more repeat pregnancy terminations within the following three-year period. The risk of repeat termination during the follow-up period was significantly higher among the patients with a previous termination.

CONCLUSIONS: The majority of the women received contraceptive counselling at the time of their termination. Women who previously had an abortion were twice as likely to undergo a repeat termination during the follow-up period. Further research is necessary to establish whether counselling and prescription of contraceptives have a significant impact on repeat terminations.

FUNDING: None.

TRIAL REGISTRATION: Approval R. no. 20/22908.

PMID:39749560 | DOI:10.61409/A04240264

Dan Med J. 2024 Nov 20;71(12):A05240316. doi: 10.61409/A05240316.

ABSTRACT

INTRODUCTION: Most postmenopausal women with early-stage oestrogen receptor-positive breast cancer are allocated to five years of endocrine therapy. This treatment is not without adverse effects, which may lead to treatment discontinuation. This study aimed to assess compliance with endocrine therapy among postmenopausal women with early-stage oestrogen receptor-positive breast cancer and examine its association with disease-free survival.

METHODS: This study retrospectively identified a cohort of 360 postmenopausal women diagnosed in the period from 1 January 2015 to 31 December 2017 at Rigshospitalet, Copenhagen, Denmark, with early-stage oestrogen receptor-positive breast cancer in the clinical database of the Danish Breast Cancer Group. Kaplan-Meier was used to estimate compliance and disease-free survival.

RESULTS: A total of 346 patients receiving endocrine therapy were included, 240 were compliant, and 106 were non-compliant. The median follow-up was 6.5 years (95% confidence interval (CI): 6.4-6.7 years). The compliance at 4.5 years was 68.8% (95% CI: 64.1-74.0%). Disease-free survival was significantly higher for the compliant group (adjusted HR = 2.29; 95% CI: 1.34-3.91).

CONCLUSIONS: We found a low compliance at 4.5 years and most discontinuations were due to adverse effects. The study provides evidence that low compliance with endocrine therapy had a negative impact on disease-free survival.

FUNDING: The study was funded by the Danish Cancer Society.

TRIAL REGISTRATION: The study was approved by the research overview of the Capital of Denmark and the Center for Health.

PMID:39749559 | DOI:10.61409/A05240316