Endothelial RUNX3 controls LSEC dysfunction and angiocrine LRG1 signaling to prevent liver fibrosis.

BACKGROUND AND AIMS: Liver fibrosis represents a global health burden, given the paucity of approved antifibrotic therapies. Liver sinusoidal endothelial cells (LSECs) play a major gatekeeping role in hepatic homeostasis and liver disease pathophysiology. In early tumorigenesis, runt-related transcription factor 3 (RUNX3) functions as a sentinel; however, its function in liver fibrosis in LSECs remains unclear. This study aimed to investigate the role of RUNX3 as an important regulator of the gatekeeping functions of LSECs and explore novel angiocrine regulators of liver fibrosis. APPROACH AND RESULTS: Mice with endothelial Runx3 deficiency develop gradual and spontaneous liver fibrosis secondary to LSEC dysfunction, thereby more prone to liver injury. Mechanistic studies in human immortalized LSECs and mouse primary LSECs revealed that IL-6/JAK/STAT3 pathway activation was associated with LSEC dysfunction in the absence of RUNX3. Single-cell RNA sequencing and quantitative RT-PCR revealed that leucine-rich alpha-2-glycoprotein 1 ( LRG1 ) was highly expressed in RUNX3-deficient and dysfunctional LSECs. In in vitro and coculture experiments, RUNX3-depleted LSECs secreted LRG1, which activated HSCs throughTGFBR1-SMAD2/3 signaling in a paracrine manner. Furthermore, circulating LRG1 levels were elevated in mouse models of liver fibrosis and in patients with fatty liver and cirrhosis. CONCLUSIONS: RUNX3 deficiency in the endothelium induces LSEC dysfunction, LRG1 secretion, and liver fibrosis progression. Therefore, endothelial RUNX3 is a crucial gatekeeping factor in LSECs, and profibrotic angiocrine LRG1 may be a novel target for combating liver fibrosis.

Diaphragmatic perforation after transcatheter arterial chemoembolization of hepatocellular carcinoma via inferior phrenic artery: a case report.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) via the inferior phrenic artery has been recognized to have its own therapeutic role without causing serious procedural complications. We report a case of diaphragmatic perforation after repeated TACE sessions conducted via the right inferior phrenic artery. CASE PRESENTATION: A 43-year-old man diagnosed with hepatocellular carcinoma was admitted to the hospital with a chief complaint of cough. The patient underwent TACE via the right inferior phrenic artery 3 months prior and was discharged without specific complications. Physical examination revealed decreased breathing sounds in the right lower lung zone. Chest radiograph demonstrated a small right pleural effusion. Chest CT scan revealed a small diaphragmatic perforation. The patient was unable to undergo surgical exploration, and a follow-up CT scan after 2 months revealed progression of the right diaphragmatic perforation with massive herniation of omental fat into the thoracic cavity. CONCLUSIONS: Although TACE via the inferior phrenic artery is a relatively safe procedure, it can be associated with rare but serious complications after repeated procedures. This is a rare case report of diaphragmatic perforation after TACE via the right inferior phrenic artery. Early recognition and prompt surgical management are essential to prevent catastrophic outcomes.

Ultrasound-Guided Deployment of a Plug-Based Vascular Closure Device in Femoral Arteries with Calcified Plaque or Stenosis.

From January 2019 to January 2020, 106 patients (age, 64.8 ± 14.1 years; male, 63.2%) were included to retrospectively investigate the feasibility and safety of ultrasound-guided deployment of ExoSeal after femoral artery access. Baseline characteristics were not different except for age (P = .022), body mass index (P = .009), and diameter (P < .001) between the calcified plaque or stenosis (CS) group (n = 49) and non-CS group (n = 57). The overall technical and clinical success rates were 96.2% and 100%, respectively. The technical (CS group, 48/49; non-CS group, 54/57) and clinical success rates (100%), time to hemostasis (CS group, 3.21 ± 0.54 min; non-CS group, 3.39 ± 0.71 min), and complication rates (CS group, 1/49; non-CS group, 0/57) were not different between the 2 groups. ExoSeal seems to be safe to use under ultrasound guidance in the femoral arteries with CS.

Satisfying medical and rehabilitation needs positively influences returning to work after a work-related injury: an analysis of national panel data from 2018 to 2019.

BACKGROUND: This study examined how meeting the medical needs of injured workers after initial treatment may affect their return to work, using data from the Panel Study of Workers' Compensation Insurance. METHODS: This study was designed as a longitudinal study, which used data from the second-year, follow-up survey conducted in the secondary cohort of the Panel Study of Workers' Compensation Insurance. The odds ratio (OR) and 95% confidence interval were estimated through binomial and multinomial logistic regression analyses to examine the effects of unmet medical needs on workers' return to original work and return to work overall (including reemployment). RESULTS: The returned to original work OR of workers whose rehabilitation needs were met was 1.35 (1.12-1.63) while the return to work OR was 1.20 (1.03-1.41). The returned to original work OR of workers whose medical needs were met was 1.64 (1.18-2.27) while the return to work OR was 1.39 (1.07-1.80). In terms of disability rating, the return to work ORs of workers with mild disabilities whose medical/rehabilitation needs were not met and those of workers without disabilities were 1.71 (1.17-2.49) and 1.97 (1.27-3.08), respectively. In the case of regular/temporary workers, the returned-to-work ORs of workers whose medical/rehabilitation needs were not met were 1.54 (1.12-2.13) and 1.27 (1.03-1.56), respectively. CONCLUSIONS: For workers who sustained work-related injuries, providing medical accessibility and meeting rehabilitation needs were found to be important predictors of return to work after initial treatment.

Effect of professional certification on employees' return-to-work rate after occupational injuries in Korea: focusing on vulnerable groups.

BACKGROUND: One effective way to improve return-to-work (RTW) performance may be to convince the employer that the worker has the necessary skills. The aim of this paper is to investigate the effect of having a professional certification among workers injured in occupational injuries on their return to work. METHODS: The Panel Study of Workers' Compensation Insurance (PSWCI) targets workers who completed medical care in 2012 after an occupational injury. The study population (n = 2000) was stratified by gender, age, region, disability grade, and rehabilitation service use. A total of 1458 workers were finally selected for this study. The effect of having a certification on RTW status was calculated with an odds ratio and 95% confidence intervals using binomial and multinomial logistic regression analyses. In the binomial logistic regression analysis, the RTW group was made up as a combination of the return to original work and the reemployment groups. RESULTS: The ORs of RTW among those with a certification compared to those without certification were 1.38 (1.16-1.65) in Model 1, 1.25 (1.05-1.50) in Model 2, and 1.22 (1.01-1.47) in Model 3. Among female workers with a certification, the OR of RTW was 4.60 (2.68-7.91), that of return to original work was 3.21 (1.74-5.91), and that of reemployment was 5.85 (3.34-10.27). Among daily workers with a certification, the OR of RTW was 1.32 (1.03-1.69) and that of reemployment was 1.37 (1.07-1.76). CONCLUSION: In conclusion, injured workers with a certification generally had a higher RTW rate. In particular, the RTW rate was higher among female workers and daily workers with a certification than among those without.

Subclassification and Treatment Results of Ethanol Embolotherapy of Type II Arteriovenous Malformations of the Extremity and Body.

PURPOSE: To evaluate the safety and efficacy of ethanol and coil embolization of type II arteriovenous malformation (AVM) according to a new subtype classification. MATERIALS AND METHODS: Eighty-four type II AVMs in the body or extremity of 79 patients who underwent AVM treatment from 1996 to 2017 were retrospectively subclassified according to the angiographic morphology of the draining vein as type IIa (arterioles shunt to focal segment of single draining vein), type IIb (arterioles shunt to venous sac with multiple draining veins), and type IIc (arterioles shunt along long segment of draining vein). Coil and ethanol embolization of the focal or long segment of the draining vein or the venous sac was performed with direct puncture or transvenous approach according to subtype. Treatment outcomes, number of treatment sessions, and complications were analyzed. RESULTS: AVM cure (ie, complete embolization) rates were 95%, 76%, and 65% in types IIa, IIb, and IIc AVMs, respectively. The cure rate of type IIa AVMs was significantly better than that of type IIc AVMs (P = .015). Median numbers of treatment sessions were 1 in types IIa and IIb AVMs and 2.5 in type IIc AVMs, with a significant difference between type IIc and the other 2 types (P < .05). Minor complications occurred in 20% of patents and major complications occurred in 7%. CONCLUSIONS: The cure rate of type IIa AVMs was significantly better than that of type IIc AVMs, which also required significantly more treatment sessions than the other 2 types.

RUNX3 and p53: How Two Tumor Suppressors Cooperate Against Oncogenic Ras?

RUNX family members play pivotal roles in both normal development and neoplasia. In particular, RUNX1 and RUNX2 are essential for determination of the hematopoietic and osteogenic lineages, respectively. RUNX3 is involved in lineage determination of various types of epithelial cells. Analysis of mouse models and human cancer specimens revealed that RUNX3 acts as a tumor suppressor via multiple mechanisms. p53-related pathways play central roles in tumor suppression through the DNA damage response and oncogene surveillance, and RUNX3 is involved in both processes. In response to DNA damage, RUNX3 facilitates p53 phosphorylation by the ATM/ATR pathway and p53 acetylation by p300. When oncogenes are activated, RUNX3 induces ARF, thereby stabilizing p53. Here, we summarize the molecular mechanisms underlying the p53-mediated tumor-suppressor activity of RUNX3.

Core Binding Factor ß Plays a Critical Role During Chondrocyte Differentiation.

Core binding factor ß (Cbfß) is a partner protein of Runx family transcription factors with minimally characterized function in cartilage. Here we address the role of Cbfß in cartilage by generating chondrocyte-specific Cbfß-deficient mice (Cbfb(Δch/Δch) ) from Cbfb-floxed mice crossed with mice expressing Cre from the Col2a1 promoter. Cbfb(Δch/Δch) mice died soon after birth and exhibited delayed endochondral bone formation, shorter appendicular skeleton length with increased proliferative chondrocytes, and nearly absent hypertrophic chondrocyte zones. Immunohistochemical and quantitative real-time PCR analyses showed that the number and size of proliferative chondrocytes increased and the expression of chondrocyte maturation markers at the growth plates, including Runx2, osterix, and osteopontin, significantly diminished in Cbfb(Δch/Δch) mice compared to wild type mice. With regard to signaling pathways, both PTHrP-Ihh and BMP signaling were compromised in Cbfb(Δch/Δch) mice. Mechanistically, Cbfß deficiency in chondrocytes caused a decrease of protein levels of Runx transcription factors by accelerating polyubiquitination-mediated proteosomal degradation in vitro. Indeed, Runx2 and Runx3, but not Runx1, decreased in Cbfb(Δch/Δch) mice. Collectively, these findings indicate that Cbfß plays a critical role for chondrocyte differentiation through stabilizing Runx2 and Runx3 proteins in cartilage.

Prolyl isomerase Pin1-mediated conformational change and subnuclear focal accumulation of Runx2 are crucial for fibroblast growth factor 2 (FGF2)-induced osteoblast differentiation.

Fibroblast growth factor 2 (FGF2) signaling plays a pivotal role in bone growth/differentiation through the activation of osteogenic master transcription factor Runx2, which is mediated by the ERK/MAPK-dependent phosphorylation and the p300-dependent acetylation of Runx2. In this study, we found that Pin1-dependent isomerization of Runx2 is the critical step for FGF2-induced Runx2 transactivation function. We identified four serine or threonine residues in the C-terminal domain of Runx2 that are responsible for Pin1 binding and structural modification. Confocal imaging studies indicated that FGF2 treatment strongly stimulated the focal accumulation of Pin1 in the subnuclear area, which recruited Runx2. In addition, active forms of RNA polymerase-II also colocalized in the same subnuclear compartment. Dipentamethylene thiuram monosulfide, a Pin1 inhibitor, strongly attenuated their focal accumulation as well as Runx2 transactivation activity. The Pin1-mediated structural modification of Runx2 is an indispensable step connecting phosphorylation and acetylation and, consequently, transcriptional activation of Runx2 by FGF signaling. Thus, the modulation of Pin1 activity may be a target for the regulation of bone formation.

MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma.

Osteosarcoma (OS) is a primary bone tumor that is most prevalent during adolescence. RUNX2, which stimulates differentiation and suppresses proliferation of osteoblasts, is deregulated in OS. Here, we define pathological roles of RUNX2 in the etiology of OS and mechanisms by which RUNX2 expression is stimulated. RUNX2 is often highly expressed in human OS biopsies and cell lines. Small interference RNA-mediated depletion of RUNX2 inhibits growth of U2OS OS cells. RUNX2 levels are inversely linked to loss of p53 (which predisposes to OS) in distinct OS cell lines and osteoblasts. RUNX2 protein levels decrease upon stabilization of p53 with the MDM2 inhibitor Nutlin-3. Elevated RUNX2 protein expression is post-transcriptionally regulated and directly linked to diminished expression of several validated RUNX2 targeting microRNAs in human OS cells compared with mesenchymal progenitor cells. The p53-dependent miR-34c is the most significantly down-regulated RUNX2 targeting microRNAs in OS. Exogenous supplementation of miR-34c markedly decreases RUNX2 protein levels, whereas 3'-UTR reporter assays establish RUNX2 as a direct target of miR-34c in OS cells. Importantly, Nutlin-3-mediated stabilization of p53 increases expression of miR-34c and decreases RUNX2. Thus, a novel p53-miR-34c-RUNX2 network controls cell growth of osseous cells and is compromised in OS.

Dynamics of Malaria Incidence in Khyber Pakhtunkhwa, Pakistan: Unveiling Rapid Growth Patterns and Forecasting Future Trends.

BACKGROUND: Malaria remains a formidable worldwide health challenge, with approximately half of the global population at high risk of catching the infection. This research study aimed to address the pressing public health issue of malaria's escalating prevalence in Khyber Pakhtunkhwa (KP) province, Pakistan, and endeavors to estimate the trend for the future growth of the infection. METHODS: The data were collected from the IDSRS of KP, covering a period of 5 years from 2018 to 2022. We proposed a hybrid model that integrated Prophet and TBATS methods, allowing us to efficiently capture the complications of the malaria data and improve forecasting accuracy. To ensure an inclusive assessment, we compared the prediction performance of the proposed hybrid model with other widely used time series models, such as ARIMA, ETS, and ANN. The models were developed through R-statistical software (version 4.2.2). RESULTS: For the prediction of malaria incidence, the suggested hybrid model (Prophet and TBATS) surpassed commonly used time series approaches (ARIMA, ETS, and ANN). Hybrid model assessment metrics portrayed higher accuracy and reliability with lower MAE (8913.9), RMSE (3850.2), and MAPE (0.301) values. According to our forecasts, malaria infections were predicted to spread around 99,301 by December 2023. CONCLUSIONS: We found the hybrid model (Prophet and TBATS) outperformed common time series approaches for forecasting malaria. By December 2023, KP's malaria incidence is expected to be around 99,301, making future incidence forecasts important. Policymakers will be able to use these findings to curb disease and implement efficient policies for malaria control.

Nicotinamide in Combination with EGFR-TKIs for the Treatment of Stage IV Lung Adenocarcinoma with EGFR Mutations: A Randomized Double-Blind (Phase IIb) Trial.

PURPOSE: RUNX3 is a tumor suppressor gene, which is inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, a sirtuin inhibitor, has demonstrated potential in re-activating epigenetically silenced RUNX3 in cancer cells. This study assessed the therapeutic benefits of combining nicotinamide with first-generation EGFR-tyrosine kinase inhibitors (TKI) for patients with stage IV lung cancer carrying EGFR mutations. PATIENTS AND METHODS: We assessed the impact of nicotinamide on carcinogen-induced lung adenocarcinomas in mice and observed that nicotinamide increased RUNX3 levels and inhibited lung cancer growth. Subsequently, 110 consecutive patients with stage IV lung cancer who had EGFR mutations were recruited: 70 females (63.6%) and 84 never-smokers (76.4%). The patients were randomly assigned to receive either nicotinamide (1 g/day, n = 55) or placebo (n = 55). The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. RESULTS: After a median follow-up of 54.3 months, the nicotinamide group exhibited a median PFS of 12.7 months [95% confidence interval (CI), 10.4-18.3], while the placebo group had a PFS of 10.9 months (9.0-13.2; P = 0.2). The median OS was similar in the two groups (31.0 months with nicotinamide vs. 29.4 months with placebo; P = 0.2). Notably, subgroup analyses revealed a significant reduction in mortality risk for females (P = 0.01) and never-smokers (P = 0.03) treated with nicotinamide. CONCLUSIONS: The addition of nicotinamide with EGFR-TKIs demonstrated potential improvements in PFS and OS, with notable survival benefits for female patients and those who had never smoked (ClinicalTrials.gov Identifier: NCT02416739).

Runx2 protein stabilizes hypoxia-inducible factor-1α through competition with von Hippel-Lindau protein (pVHL) and stimulates angiogenesis in growth plate hypertrophic chondrocytes.

The regulation of hypoxia-inducible factor-1α (HIF-1α) during endochondral bone formation is not fully understood. Here, we investigated the cross-talk between HIF-1α and Runt-related transcription factor 2 (Runx2) in the growth plate. Runx2 caused the accumulation of HIF-1α protein in ATDC5 chondrocytes and HEK293 cells under normoxic conditions. Runx2 also increased the nuclear translocation of HIF-1α when coexpressed in HEK293 cells and interacted with HIF-1α at the oxygen-dependent degradation domain (ODDD). In addition, Runx2 competed with von Hippel-Lindau tumor suppressor protein by directly binding to ODDD-HIF-1α and significantly inhibited the ubiquitination of HIF-1α, even though Runx2 did not change the hydroxylation status of HIF-1α. Furthermore, overexpression of Runx2 resulted in the significant enhancement of vascular endothelial growth factor (VEGF) promoter reporter activity and protein secretion. Runx2 significantly increased angiogenic activity in human umbilical vein endothelial cells in vitro. In wild-type mice, HIF-1α and Runx2 were colocalized in hypertrophic chondrocytes in which the cluster of differentiation 31 (CD31) protein was expressed at embryonic day 15.5 (E15.5). In contrast, the expression of HIF-1α was markedly reduced in areas of CD31 expression in Runx2(-/-) mice. These results suggest that Runx2 stabilizes HIF-1α by binding to ODDD to block the interaction between von Hippel-Lindau protein and HIF-1α. In conclusion, Runx2, HIF-1α, and VEGF may regulate vascular angiogenesis spatially and temporally in the hypertrophic zone of the growth plate during endochondral bone formation.

Pin1-mediated Runx2 modification is critical for skeletal development.

Runx2 is the master transcription factor for bone formation. Haploinsufficiency of RUNX2 is the genetic cause of cleidocranial dysplasia (CCD) that is characterized by hypoplastic clavicles and open fontanels. In this study, we found that Pin1, peptidyl prolyl cis-trans isomerase, is a critical regulator of Runx2 in vivo and in vitro. Pin1 mutant mice developed CCD-like phenotypes with hypoplastic clavicles and open fontanels as found in the Runx2+/- mice. In addition Runx2 protein level was significantly reduced in Pin1 mutant mice. Moreover Pin1 directly interacts with the Runx2 protein in a phosphorylation-dependent manner and subsequently stabilizes Runx2 protein. In the absence of Pin1, Runx2 is rapidly degraded by the ubiquitin-dependent protein degradation pathway. However, Pin1 overexpression strongly attenuated uniquitin-dependent Runx2 degradation. Collectively conformational change of Runx2 by Pin1 is essential for its protein stability and possibly enhances the level of active Runx2 in vivo.

Abnormal liver differentiation and excessive angiogenesis in mice lacking Runx3.

Runt-related transcription factor 3 (Runx3) is essential for normal mouse development, and Runx3 knock-out (KO) mice (FVB strain), which die within 24 h after birth, show various organ defects, such as lung hyperplasia. For proper early liver development, angiogenesis and liver cell differentiation mechanisms are necessary in mammals. Previous studies have reported that various signaling molecules, such as vascular endothelial growth factor (VEGF), von Willebrand factor (vWF) and cluster of differentiation 31 (CD31), are closely related to angiogenesis in the developing liver. Proper expression levels of molecules that induce liver cell differentiation, such as phosphorylated Smad2 (pSmad2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), Wilms tumor-1 (WT-1) and CD90 (Thy-1), are necessary for fetal liver development. To confirm the pathogenesis of liver defects caused by the loss of function of Runx3, the localization of proliferating cells was examined in wild-type and Runx3 KO mouse livers at postnatal day 1 (PN1). Specimens were also stained for various liver differentiation markers to confirm the function of Runx3. Moreover, gene expression level was examined by real-time quantitative polymerase chain reaction (RT-qPCR). Our results indicate that VEGF, vWF, CD31, pSmad2, NF-kB, WT-1 and Thy-1 were markedly up-regulated by the loss of Runx3. Therefore, our results indicate that liver development is controlled by Runx3. Clarifying the mechanisms of angiogenesis and liver differentiation might aid in the design of efficient and safe antiangiogenic therapy and gene therapy for liver disorders.

Association Between Initiation of Rehabilitation and Length of Hospital Stay for Workers with Moderate to Severe Work-Related Traumatic Brain Injury.

Background: In workers with moderate to severe work-related traumatic brain injury (wrTBI), this study aimed to investigate the effect of the timing of rehabilitation therapy initiation on the length of hospital stay and the factors that can influence this timing. Methods: We used data obtained from the Republic of Korea's nationwide Workers' Compensation Insurance. In the Republic of Korea, between the years 2010 and 2019, a total of 26,324 workers filed a claim for compensation for moderate to severe wrTBI. Multiple regression modeling was performed to compare the length of hospital stay according to the timing of rehabilitation therapy initiation following wrTBI. According to the timing of the initiation of rehabilitation therapy following TBI, the proportions of healthcare institutions that provided medical care during each admission step were compared. Results: The length of hospital stay for workers who started rehabilitation therapy within 90 days was significantly shorter than that for workers who started rehabilitationment were first admitted to tertiary hospitals. Approximately 39% of patients who received delayed rehabilitation treatment were first admitted to general hospitals, and 28.5% were first admitted to primary hospitals. Conclusions: Our findings demonstrate the importance of early rehabilitation initiation and that the type of healthcare institution that the patient is first admitted to after wrTBI may influence the timing of rehabilitation initiation. The results of this study also emphasize the need to establish a Worker's Compensation Insurance-specialized rehabilitation healthcare delivery system.

Prediction Model for Job Retention According to the Type of Return to Work Among Industrially Injured Workers in Korea.

OBJECTIVES: This study aimed to investigate how the type of return to work after an industrial accident affects job retention. METHODS: Using data from the panel study of workers' compensation insurance first-third, and hazard ratios (HRs) and 95% confidence intervals were calculated for workers leaving their jobs. RESULTS: The HR leaving their jobs were higher in the "reemployed" compared with that in the "returned to original work," with HR of 2.69 (2.33-3.10). According workers' status, the HRs leaving their jobs were higher among the "reemployed" than among those who "returned to original work." Regular and daily workers' HRs were 1.70 (1.37-2.11) and 3.55 (2.96-4.26), respectively. CONCLUSIONS: The findings suggest that to increase job retention rate, protection policies for reemployed workers or support for employers who hire reemployed workers should be considered.

Over- and under-supply of inpatient rehabilitation after stroke without a post-acute rehabilitation system: a nationwide retrospective cohort study.

Introduction: This study aimed to investigate the utilization of post-ischemic stroke rehabilitation prior to the introduction of the post-acute rehabilitation system in South Korea in 2017. Methods: Medical resources utilized for patients with cerebral infarction hospitalized at Regional Cardio-Cerebrovascular Centers (RCCVCs) of 11 tertiary hospitals were tracked until 2019. Stroke severity was classified according to the National Institutes of Health Stroke Scale (NIHSS), and multivariate regression analysis was performed to analyze factors influencing the length of hospital stay (LOS). Results: This study included 3,520 patients. Among 939 patients with stroke with moderate or greater severity, 209 (22.3%) returned home after RCCVC discharge without inpatient rehabilitation. Furthermore, 1,455 (56.4%) out of 2,581 patients with minor strokes with NIHSS scores ≤4 were readmitted to another hospital for rehabilitation. The median LOS of patients who received inpatient rehabilitation after RCCVC discharge was 47 days. During the inpatient rehabilitation period, the patients were admitted to 2.7 hospitals on average. The LOS was longer in the lowest-income group, high-severity group, and women. Conclusion: Before the introduction of the post-acute rehabilitation system, treatment after stroke was both over- and under-supplied, thus delaying home discharge. These results support the development of a post-acute rehabilitation system that defines the patients, duration, and intensity of rehabilitation.

Prevalence of neuropsychiatric disorders in patients with systemic lupus erythematosus in Pakistan: A systematic review and meta-analysis.

Introduction: By conducting a systematic review and meta-analysis, we investigated the prevalence of neuropsychiatric (NP) symptoms among systemic lupus erythematosus (SLE) patients in Pakistan. Methods: In this review work, three electronic databases (Web of Science, MEDLINE, and Google Scholar) and local databases were screened for 20 years from 1 January 2002 to 30 September 2022, to identify the articles evaluating the prevalence of NP symptoms in SLE patients in Pakistan. We performed a random-effects meta-analysis to estimate the prevalence of NPSLE. Statistical heterogeneity was measured by the I2 index, and subgroup meta-analyses were used to access the statistical heterogeneity. Furthermore, meta-regression models were used to examine the associations between prevalence estimates and study characteristics of interest. Three independent authors reviewed existing studies, extracted data, and rated the qualities of selected studies. This review was registered on PROSPERO (Registration no. CRD42022361798). Results: Thirteen studies met the inclusion criteria out of the 322 studies with a total of 2,003 SLE patients for this systematic review and meta-analysis. The prevalence of NP disorders in SLE patients was estimated to be 30.42% (95% CI:18.26-44.11%), with cognitive dysfunction being the most common (31.51%; 95% CI:1.28-76.27%), followed by headache (10.22%; 95% CI: 0.00-33.43%), seizures (5.96%; 95% CI: 3.80-8.53%), psychosis (3.64%; 95% CI: 2.38-5.13%), and neuropathy is the least common (0.86%; 95% CI: 0.00-2.74%). The heterogeneity between studies was significant (p < 0.01). The pooled prevalence of NP disorders among SLE patients was found highest in Punjab (41.21%) and lowest in Sindh (17.60%). Conclusion: Findings from this study revealed that SLE patients have a high prevalence of NP disorders. The most common symptoms were cognitive dysfunctions, headaches, seizures, psychosis, and neuropathy. Clinicians can manage these potentially deadly and disabling diseases more effectively if they understand the incidence of each NP symptom in SLE patients. NP symptoms among SLE patients are at their peak in Pakistan; policymakers should devise preventive strategies to curb the disease. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record. php?RecordID=361798, identifier CRD42022361798.