Morbidity Score Research Articles

Quality of life in congenital diaphragmatic hernia survivors treated at a non-ECMO centre from 1998 to 2015: a cross-sectional study

BackgroundSurvival of infants with congenital diaphragmatic hernia (CDH) has increased and more insight is warranted on the long-term issues of this condition.MethodsWe conducted a cross-sectional study on consecutively born infants...

Ileal inflammation is reduced due to treatment with a metalloprotease from BmooMP-α-I snake venom in an experimental model of Toxoplasma gondii infection.

The selection process for advanced therapies in patients with inflammatory bowel diseases (IBDs) must prioritize safety, especially when considering new biologic agents or oral molecule modulators. In C57BL/6 mice, oral infection with Toxoplasma gondii induces intestinal inflammation through excessive tumor necrosis factor (TNF) production, making TNF neutralization a potential therapeutic intervention. Considering this, the present study aimed to evaluate the therapeutic effects of BmooMP-α-I, a snake venom metalloprotease isolated from Bothrops moojeni, which could promote TNF hydrolysis, in treating T. gondii-induced ileitis. The results showed that C57BL/6 mice orally infected with 50 cysts of T. gondii from the Me49 strain and treated with BmooMP-α-I exhibited prolonged survival and improved morbidity scores. Additionally, the treatment ameliorated both the macroscopic and microscopic aspects of the intestine, reduced macrophage influx, and decreased the production of inflammatory mediators by mesenteric lymph node cells. These findings provide compelling experimental evidence supporting the ability of BmooMP-α-I to alleviate ileal inflammation. Considering that the currently available therapeutic protocols are not completely effective and often result in side effects, the exploration of alternative strategies involving novel therapeutic agents, as demonstrated in this study, has the potential to significantly enhance the quality of life for patients suffering from inflammatory bowel diseases.

Evaluation of the effects of multiple capture methods and immobilization drugs on mountain lion welfare

AbstractUsing a dataset of 591 capture events between 2001–2019 in California, USA, we examined the impact of capture methods and immobilization drugs on mountain lion (Puma concolor) welfare. The 3 methods used to capture mountain lions were cage traps, trained hounds, and cable restraints. The drugs used to immobilize mountain lions were either tiletamine/zolazepam (Telazol®), ketamine/medetomidine, or ketamine/xylazine. Mortality occurred in 1.4% of captures, with only one mortality out of 310 captures occurring since 2012. We used a logistic regression framework to compare morbidity and vital parameters of mountain lions among the different capture methods and immobilization drugs used. Vomiting (a risk factor for developing aspiration pneumonia) was the most common severe risk factor associated with cage trapping and was only seen with the use of ketamine/medetomidine or ketamine/xylazine. Morbidity scores were not well predicted by any of the variables we accounted for. Animals immobilized with Telazol® were more likely to experience abnormal heart and respiratory rates, as well as high body temperatures, than those immobilized with the other two combinations. Although there are risks associated with each of the capture methods and drug combinations commonly used in mountain lion captures in California, our analyses demonstrated they are all relatively safe when following appropriate animal welfare practices. Our analyses suggested that unaccounted for factors are equally or more important in explaining injury and physiological abnormality rates, and we urge that agencies train personnel in best practices and conservative decision‐making in order to assure that the welfare of the animal takes precedence over collaring. We suggest training on how to choose between several capture techniques, immobilization drugs and monitoring methods and how to reduce both detrimental effects to mountain lions and danger to humans.

A Mouse Model of CD19 CAR - T Cell Therapy Reveals Mechanism of Cytopenia

Immunotherapy with Chimeric Antigen Receptor (CAR) T cells against CD19 can cure patients with refractory B cell lymphoma and leukemia. However, complications of CAR-T cell therapy can cause morbidity. Among the complications of CAR-T cell therapy is cytopenia, i.e. decreased peripheral blood counts of platelets, leukocytes and / or erythrocytes. The exact mechanism of this side - effect is not known, retrospective analysis showed it affects 10-20% of patients and is linked with the severity of cytokine release syndrome (Juluri et al, PMID34666344). We have previously developed a mouse model of CAR-T cell therapy using C56BL/6 mouse expressing human CD19 under a B- Cell specific promoter (Pennell et al, PMID29735365). The recipient mice are heterozygous for human hCD19 on CD45.2 background. Congenic C56BL/6 CD45.1 mice served as T cell donors. The aim of this study was to investigate if the mouse model recapitulates cytopenia seen in patients after CAR-T cell therapy. C56BL/6 recipient mice were treated with lymphodepleting chemotherapy (Cyclophosphamide (CY) 300 mg/kg) and infused with 1) no T cells 2) control T cells transfected with hEGFR 3) T cells transfected with CD19 CAR with hCD137 and hCD3zeta signaling domains. The chosen dose of infused T cells at 0.3E+6 per animal was low, approximately 10x below the lethal dose and 3x less than IC50 dose, to reduce early mortality. The animals were weighed and examined regularly, and appearance and activity were scored from 0 (healthy) to 8 (moribund). Total of 30 animals per group were harvested at 5 time points, 6 mice each, on days 5, 12, 26, 40 and 54. Peripheral blood counts were measured using HemaVet CBC counter. Flow cytometry was performed on blood and bone marrow. Spleens, long bones (femur, tibia) and sternum were harvested for histopathologic assessment. Multiparametric immunohistochemistry (IHC) was performed using Codex (Phenocycler, Akoya). The mice receiving CAR-19 T cells showed significant, but transient loss of weight and transient increase in morbidity score during the first 2 weeks. Mortality was not significantly different between groups: 0, 1 and 2 deceased animals in CY, control T and CAR-T cell groups, respectively. We observed transient significant cytopenia in the CAR-T cell treated mice, with significantly lower platelet counts on day 5 (p<0.05) and lower White Blood Cell counts on days 12 (p<0.06) and day 26 (p<0.05). These changes were associated with 100-fold larger expansion of CAR-T cells in blood as compared to the control hEGFR T cells and 20-fold higher relative expansion of CAR-T cells in the bone marrow. Multiparametric IHC showed loss of B cell follicles and increased density of donor T cells in the CAR-T cells recipients compared to hEGFR T cell control. Pathologic evaluation of sternums revealed individual segments (sternebra) with necrosis of the hematopoietic elements at the first time point (day 5). At subsequent time points there were progressive changes reminiscent of evolution of infarct with organization, proliferation of fibroblasts and fibrosis with increased osteogenesis and finally with regression of mesenchymal elements and reestablishment of hematopoiesis (Figure 1). The number of segments with necrosis and sequalae was significantly higher in the CAR-T cell group as compared to the hEGFR T cell control (p=0.0005). The necrosis of hematopoietic elements within individual sternum segments involved at the most 3 segments out of 6. The involved segments appeared to distribute randomly: either adjacent or separated by viable segments. The necrotic segments showed paucity of erythrocytes with foci of recent erythrocyte extravasation consistent with ischemic infarct. The mouse model of CAR-T cell therapy against CD19 recapitulates cytopenia in early post - treatment period. The observed pattern of necrosis of the hematopoietic elements in entire segments suggests compromised blood supply. We hypothesize sternebra are more susceptible to necrosis due to limited blood supply, separate for each segment. We hypothesize that occlusion of arteries or capillaries in the bone marrow may contribute to the mechanism of cytopenia following CAR-T cell therapy. Prior retrospective analysis linked the cytopenia with increased levels of inflammatory mediators of Cytokine Release Syndrome. The present findings highlight a role of local factors in situ, which may be influenced by systemic cytokines.

Stereotactic Ablative Radiotherapy Boost to Bladder Tumor for Bladder Preservation in Patients with Muscle-Invasive Bladder Cancer

Previous studies showed that selective bladder-sparing approach using TMT is an established therapy of MIBC with outcomes that are comparable to those of radical cystectomy. However, it has been shown that the 5-year local recurrence in the bladder is greater than 40% after TMT. One of the possible reasons was that the RT dose to the bladder tumor or tumor bed was insufficient. Thus, we assessed the effectiveness and safety of Stereotactic Ablative Radiotherapy (SABR) boost to bladder tumor or tumor bed for patients with muscle invasive bladder cancer (MIBC). A total of 59 consecutive patients with cT2-4 bladder cancer underwent transurethral resection of bladder tumor (TURBT). TURBT was visibly complete in 25 cases. Patients received SABR to the tumor or tumor bed in the bladder followed by conventionally fractionated RT (CFRT) to pelvis and total bladder with concomitant weekly radio-sensitizing chemotherapy. During SABR intravesical installation of isovolumetric saline through urinary catheter ensured adequate bladder filling. Response rate was assessed by cystoscopic evaluation and pelvic MRI or CT. Toxicities were reported per the RTOG acute and late Radiation Morbidity Scoring Schema. The median age of all patients was 76 years (35-90 years). All patients completed SBRT boost and 61% patients received concurrent Gemcitabine chemotherapy. After a median follow-up time of 28 months, the rate of local control (LC) at 3 years was 90.0%. The overall survival (OS) and cancer-specific survival (CSS) rates at 3 years were 61.6% and 77.5%, respectively. Of the surviving patients, 84.4% have a disease-free and functioning bladder. Acute grade 3 gastrointestinal (GI) or genitourinary (GU) toxicities occurred in only 1.7% of the patients. Late grade 3 GU toxicity occurred in 5.1% of the patients. No patients experienced grade 4 GI or GU toxicities. SABR boost followed by chemoradiation to the pelvis was found to be a well-tolerated and effective treatment for MIBC patients who are either not candidates for cystectomy or who desire bladder preservation. Randomized study is required to further evaluate this novel tri-modality treatment paradigm.

Role of Enhanced Recovery after Surgery (ERAS) Protocol in the Management of Elderly Patients with Glioblastoma.

Among the already difficult management of neuro-oncological patients, the elderly population remains vulnerable. Because of the pathology and the comorbidities, they present a significantly higher rate of medical issues related to surgical management. Despite this, the surgical option, if feasible, remains the gold standard in these patients, and an Enhanced Recovery After Surgery (ERAS) protocol could improve the postoperative safety of the patients. With this purpose, we prepared this study with the aim of defining the postoperative hospital length of stay (LOS), but also of evaluating the postoperative morbidity, perioperative complications, and postoperative pain scores. This was a retrospective, single-cohort study performed at an academic hospital (Department of Neurosurgery, Neurocenter of South Switzerland, Switzerland) on elderly patients who underwent craniotomy for glioblastoma. Patients were enrolled in a novel ERAS protocol from January 2022 to December 2022. Since this is a feasibility study and a direct comparison was not possible, we used a historical cohort of elderly patients who had undergone elective craniotomy surgery for glioblastoma as a control group. A total of 19 patients treated in our center for glioblastoma multiforme (GBM) who were aged over 75 years were included in this study. Among those, seven were newly recruited patients included in the ERAS protocol, while the remaining twelve were part of a historical cohort of previously treated patients. From a statistical point of view, the two cohorts were comparable in terms of baseline demographics. In the follow-up, it was shown that in the ERAS group, there was a reduction in the use of opioids after the surgical procedures that could be seen at 30 days (36.2% vs. 71.7%, p < 0.001), but also at 3 months, after surgery (33.0% vs. 80.0%, p < 0.001). A significant difference has also been documented in terms of mobilization and ambulation: compared to the historical cohort, in the ERAS group, there was a higher rate of mobilization (60.0% vs. 10.0%, p < 0.001), but also of ambulation (36.1% vs. 10.0%, p < 0.001). The ERAS protocol for the management of glioblastoma in elderly patients seems to be an effective option for reducing LOS in the hospital, as well as for reducing the number of days spent in the ICU, improving the general recovery of the patient, and reducing the costs associated with hospitalization.

Paying for Medical and Social Complexity in Massachusetts Medicaid

The first MassHealth Social Determinants of Health payment model boosted payments for groups with unstable housing and those living in socioeconomically stressed neighborhoods. Improvements were designed to address previously mispriced subgroups and promote equitable payments to MassHealth accountable care organizations (ACOs). To develop a model that ensures payments largely follow observed costs for members with complex health and/or social risks. This cross sectional study used administrative data for members of the Massachusetts Medicaid program MassHealth in 2016 or 2017. Participants included members who were eligible for MassHealth's managed care, aged 0 to 64 years, and enrolled for at least 183 days in 2017. A new total cost of care model was developed and its performance compared with 2 earlier models. All models were fit to 2017 data (most recent available) and validated on 2016 data. Analyses were begun in February 2019 and completed in January 2023. Model 1 used age-sex categories, a diagnosis-based morbidity relative risk score (RRS), disability, serious mental illness, substance use disorder, housing problems, and neighborhood stress. Model 2 added an interaction for unstable housing with RRS. Model 3 added rurality and updated diagnosis-based RRS, medication-based RRS, and interactions between sociodemographic characteristics and morbidity. Total 2017 annual cost was modeled and overall model performance (R2) and fair pricing of subgroups evaluated using observed-to-expected (O:E) ratios. Among 1 323 424 members, mean (SD) age was 26.4 (17.9) years, 53.4% were female (46.6% male), and mean (SD) 2017 cost was $5862 ($15 417). The R2 for models 1, 2, and 3 was 52.1%, 51.5%, and 60.3%, respectively. Earlier models overestimated costs for members without behavioral health conditions (O:E ratios 0.94 and 0.93 for models 1 and 2, respectively) and underestimated costs for those with behavioral health conditions (O:E ratio >1.10); model 3 O:E ratios were near 1.00. Model 3 was better calibrated for members with housing problems, those with children, and those with high morbidity scores. It reduced underpayments to ACOs whose members had high medical and social complexity. Absolute and relative model performance were similar in 2016 data. In this cross-sectional study of data from Massachusetts Medicaid, careful modeling of social and medical risk improved model performance and mitigated underpayments to safety-net systems.

Evaluation of the usefulness of the Clavien-Dindo classification of surgical complications

The Clavien-Dindo (CD) classification is widely used in the reporting of surgical complications in scientific literature. It groups complications based on the level of intervention required to resolve them, and benefits from simplicity and ease of use, both of which contribute its to high inter-rater reliability. It has been validated for use in many specialties due to strong correlation with key outcome measures including length of stay, postsurgical quality of life and case-related renumeration. Limitations of the classification include concerns over differentiating grade III and IV complications and not classifying intraoperative complications. The Comprehensive Complication Index is an adaptation of the CD classification which generates a morbidity score from 0 to 100. It has been proposed as a more effective method of assessing the morbidity burden of surgical procedures. However, it remains less popular as calculations of morbidity are complicated and time-consuming. In recent years there have been suggestions of adaptations to the CD classification such as the Clavien-Dindo-Sink classification, while in some specialties, completely new classifications have been proposed due to evidence the CD classification is not reliable. Similarly, the Surgical Expertise and Validity Evaluation project aims to determine benchmarks against which surgeons may compare their own practice.

Risk Factors and Survival Impact Associated With Documentation of Radiation Therapy Refusal in Patients With Gynecologic Cancer

Radiation therapy (RT) refusal is known to have deleterious effects on survival for multiple cancer types. Factors associated with RT refusal by patients with gynecologic malignancies have not been well described. This study aimed to examine factors associated with and the survival impact of documented RT refusal among patients with gynecologic cancers. This study analyzed data from the National Cancer Database (NCDB) of patients with gynecologic cancers diagnosed between 2004 and 2020. Patients were included if they had complete survival data and a documented RT recommendation by their treating physician in the NCDB. Patients coded as received RT were compared with those coded as refused RT in the NCDB using a multivariate log binomial regression with robust variance to yield incidence rate ratios (IRR). Overall survival was analyzed using a multivariate (MV) Cox proportional hazards model to yield hazard ratios. This study identified 209,976 patients. A total of 5.75% (n=12,081) patients were coded as refusing RT. Multivariable IRR showed that documentation of RT refusal was positively associated with older age (MV IRR, 1.04; 95% CI, 1.041-1.045), Native Hawaiian Pacific Islander race (1.72 [1.27-2.32]), and increased morbidity (score=1: 1.06 [1.02-1.11]; score=2: 1.20 [1.12-1.29]; score ≥3: 1.26 [1.14-1.38]). Negative associations were seen with Hispanic ethnicity (0.74 [0.67-0.80]), having insurance (0.58 [0.53-0.63]), and annual income >$74,063 (0.85 [0.81-0.90]). During the 16-year period, a statistically significant test for trend (P=.001) for increasing RT refusal was noted. RT refusal was associated with a significantly higher risk of death (MV hazard ratio, 1.59 [1.55-1.63]). For patients with gynecologic malignancies diagnosed from 2004 to 2020, an increase in documented RT refusal is associated with decreased overall survival in all disease types. Targeted interventions aimed at mitigating potential sociodemographic barriers to receipt of RT are warranted.

669 Chronological Distribution and Causes of Mortality Following Emergency Laparotomy – an 8 Year Study

Abstract Introduction Emergency laparotomies have variable level of mortality and morbidity worldwide. Studying the causes and times of mortality, could enable better patient care and improve future outcomes. We investigated the mortality data in laparotomy patients, to investigate for trends in mortality and other patient and process characteristics. Method Data for all emergency laparotomies undertaken between 2014 to 2022 were collected prospectively and retrospectively analysed. The primary outcome was inpatient mortality. Demographics, clinical management, and outcome data was analysed using SPSS. Results 1410 laparotomies performed, with an overall crude mortality rate of 11.9%. The P-POSSUM mortality and morbidity scores ranged from 2-99 (mean 42.4) and 40.1-100 (mean 86.6) respectively. The time from operation to death ranged from 24 hours to 123 days (mean = day 11.75), with a uni-modal distribution. In the first 48 hours post-operatively 28.57% (N = 56 patients) died, with a mean age of 70.6 and a mean P-POSSUM of 48.1 (SD 30.6). Bowel perforation (N = 19 patients) and bowel ischaemia (N = 13 patients) where the most common intra-operative finding. The patients that died after 48 hours (N = 116 patients) had a mean age of 73.5 (SD 12.4) and a mean P-POSSUM of 39.6 (SD 29.9, P 0.92), compared to those that survived (N = 1241) with a mean age of 61.4 (SD 16.4) and a mean P-POSSUM of 15.6 (P&amp;gt;0.01). Conclusions Emergency laparotomy has a high level of mortality and morbidity, with the first 48 hours carrying the highest risk, particularly in those with bowel perforation or ischaemia.

Adverse drug reactions and hospital admissions: Large case-control study of patients aged 65-100 years using linked English primary care and hospital data.

Adverse drug reactions (ADRs) are common and a leading cause of injury. However, information on ADR risks of individual medicines is often limited. The aim of this hypothesis-generating study was to assess the relative importance of ADR-related and emergency hospital admission for large group of medication classes. This study was a propensity-matched case-control study in English primary care. Data sources were Clinical Practice Research Databank and Aurum with longitudinal, anonymized, patient level electronic health records (EHRs) from English general practices linked to hospital records. Cases aged 65-100 with ADR-related or emergency hospital admission were matched to up to six controls by age, sex, morbidity and propensity scores for hospital admission risk. Medication groups with systemic administration as listed in the British National Formulary (used by prescribers for medication advice). Prescribing in the 84 days before the index date was assessed. Only medication groups with 50+ cases exposed were analysed. The outcomes of interest were ADR-related and emergency hospital admissions. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CI). The overall population included 121 546 cases with an ADR-related and 849 769 cases with emergency hospital admission. The percentage of hospitalizations with an ADR-related code for admission diagnosis was 1.83% and 6.58% with an ADR-related code at any time during hospitalization. A total of 137 medication groups was included in the main ADR analyses. Of these, 13 (9.5%) had statistically non-significant adjusted ORs, 58 (42.3%) statistically significant ORs between 1.0 and 1.5, 37 (27.0%) between 1.5-2.0, 18 (13.1%) between 2.0-3.0 and 11 (8.0%) 3.0 or higher. Several classes of antibiotics (including penicillins) were among medicines with largest ORs. Evaluating the 14 medications most often associated with ADRs, a strong association was found between the number of these medicines and the risk of ADR-related hospital admission (adjusted OR of 7.53 (95% CI 7.15-7.93) for those exposed to 6+ of these medicines). There is a need for a regular systematic assessment of the harm-benefit ratio of medicines, harvesting the information in large healthcare databases and combining it with causality assessment of individual case histories.

In France, the organization of perinatal care has a direct influence on the outcome of the mother and the newborn: Contribution from a French nationwide study.

To investigate maternal and neonatal outcomes after a delivery in France in 2019, according to hospital characteristics and the impact of distance and time of travel on mother and newborn. All parturients above 18 years of age who delivered in 2019 and were identified in the French health insurance database were included, with their newborns, in this retrospective cohort study. Main outcome measures were Severe Maternal Morbidity score and the Neonatal Adverse Outcome Indicator (NAOI). Among the 733 052 pregnancies included, 10 829 presented a severe maternal morbidity (1.48%) and 77 237 had a neonatal adverse outcome (10.4%). Factors associated with an unfavorable maternal or neonatal outcome were Obstetric Comorbidity Index, primiparity, and cesarean or instrumental delivery. Prematurity was associated with less severe maternal morbidity but more neonatal adverse outcomes. Time of travel above 30 min was associated with a higher NAOI rate. Results suggest the efficiency of regionalization of perinatal care in France, although a difference in both outcomes persists according to unit volume, suggesting the need for a further step in concentrating perinatal care. Perinatal care organization should focus on mapping the territory with high-level, high-volume maternity throughout the territory; this suggests closing down high-volume units and improving low-volume ones to maintain coherent mapping.

Mortality in Patients Undergoing Emergency Laparotomy and its comparison with Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity Scoring

Objective: To evaluate the role of physiological and operative severity score for the enumeration of mortality and morbidity in predicting mortality in patients undergoing emergency laparotomy. Study Design: Prospective Comparative study. Place and Duration of Study: General Surgical Ward 1 and 2, Combined Military Hospital, Rawalpindi, from Jan to Aug, 2018. Methodology: Adult patients between 12 and 60 years of age admitted from Emergency Department in Surgical ward who underwent emergency laparotomy within 48 hours of admission were enrolled in the study. Physiological and operative scores were measured for Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity and predicted mortality calculated. Patients were stratified into three groups according to the predicted mortality. Patients were then followed up 30 days post-operatively and mortality noted. Observed to predicted (O:P) mortality was calculated. Results: A total of 94 patients were enrolled out of which 85 were followed up. All patients were male with a mean age of 56.5±16 years. Most common indication for surgery was intestinal obstruction and gut perforation. Mean duration of admission was 7.97±3.5 days. Out of 85 patients 13 patients died within 30 days of surgery which equals a crude mortality rate of 15.2%. Observed to predicted mortality ratio (O:P) was 0.65. Conclusion: Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity slightly overpredicted the mortality in or study. Still it is a useful tool in risk stratification of patients according to expected outcome and...

Glutaric Aciduria Type 1: Comparison between Diffusional Kurtosis Imaging and Conventional MR Imaging.

Routine MR imaging has limited use in evaluating the severity of glutaric aciduria type 1. To better understand the mechanisms of brain injury in glutaric aciduria type 1, we explored the value of diffusional kurtosis imaging in detecting microstructural injury of the gray and white matter. This study included 17 patients with glutaric aciduria type 1 and 17 healthy controls who underwent conventional MR imaging and diffusional kurtosis imaging. The diffusional kurtosis imaging metrics of the gray and white matter were measured. Then, the MR imaging scores and diffusional kurtosis imaging metrics of all ROIs were further correlated with the morbidity scores and Barry-Albright dystonia scores. The MR imaging scores showed no significant relation to the morbidity and Barry-Albright dystonia scores. Compared with healthy controls, patients with glutaric aciduria type 1 showed higher kurtosis values in the basal ganglia, corona radiata, centrum semiovale, and temporal lobe (P < .05). The DTI metrics of the basal ganglia were higher than those of healthy controls (P < .05). The fractional anisotropy value of the temporal lobe and the mean diffusivity values of basal ganglia in glutaric aciduria type 1 were lower than those in the control group (P < .05). The diffusional kurtosis imaging metrics of the temporal lobe and basal ganglia were significantly correlated with the Barry-Albright dystonia scores. The mean kurtosis values of the anterior and posterior putamen and Barry-Albright dystonia scores were most relevant (r = 0.721, 0.730, respectively). The mean kurtosis values of the basal ganglia had the best diagnostic efficiency with area under the curve values of 0.837 for the temporal lobe, and the mean diffusivity values of the basal ganglia in glutaric aciduria type 1 were lower than those in the control group (P < .05). The diffusional kurtosis imaging metrics of the temporal lobe and basal ganglia were significantly correlated with the Barry-Albright dystonia scores. The mean kurtosis values of the anterior and posterior putamen and Barry-Albright dystonia scores were most relevant (r = 0.721, 0.730, respectively). The mean kurtosis values of the basal ganglia had the best diagnostic efficiency with area under the curve values of 0.837. Diffusional kurtosis imaging provides more comprehensive quantitative information regarding the gray and white matter micropathologic damage in glutaric aciduria type 1 than routine MR imaging scores.

Socioeconomic position, perceived weight, lifestyle risk, and multimorbidity in young adults aged 18 to 35 years: a Multi-country Study

BackgroundMultimorbidity-risk is established early in life, therefore reducing modifiable risk factors such as overweight or obesity may, in part, tackle the burden of multimorbidity in later life.MethodsWe made use of a cross-sectional online survey that included young adults (18-35yrs old) from three countries – Kenya, South Africa, and the United Kingdom (n = 3000). Information pertaining to socio-demographic, health, lifestyle, and perceived weight was collected. Additionally, the sum of affirmed morbidities was used to determine a morbidity score. Likewise, a lifestyle risk score was calculated based on information obtained from questions surrounding four unhealthy lifestyle behaviours, namely current smoking, alcohol consumption, physical inactivity, and overweight/obese weight status as a confirmed clinic condition. We further explored differences in socioeconomic position, and the prevalence of perceived weight, multimorbidity, and lifestyle risk factors between the three countries. We also determined the odds ratio of multimorbidity with perceived weight as a main predictor variable. We furthermore performed a generalised structural equation model to determine whether the association between socioeconomic position and multimorbidity was mediated via perceived weight and/or lifestyle risk.ResultsSocioeconomic position, weight perceptions, lifestyle risk, and multimorbidity varied significantly across the different economic countries. Higher morbidity (by > 11.9%) and lifestyle risk (by > 20.7%) scores were observed in those who reported an overweight weight perception when compared to those with an underweight or normal weight perception. In pooled analyses, the odds ratio in developing 2 or more morbidities increased multiple times in those who perceived themselves as overweight (all models: OR ≥ 2.241 [95% CI ≥ 1.693; ≥ 2.966] p < 0.001), showing a larger odds ratio with high significance in those who reported 3 or more morbidities (all models: OR ≥ 3.656 [95% CI ≥ 2.528; ≥ 5.286] p < 0.001). Furthermore, this study showed that an overweight weight perception partially mediated (p ≤ 0.001) the association between socioeconomic position and multimorbidity.ConclusionsThis study confirmed poorer health outcomes in those who perceived themselves as overweight. The findings from this study further emphasise the importance of targeted intervention strategies directed at raising weight-related awareness and potentiating risk factors, specifically in those who reside in lower economic developed countries.

Impact of an autophagy-inducing peptide on immunogenicity and protection efficacy of an adenovirus-vectored SARS-CoV-2 vaccine

Because of continual generation of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is critical to design the next generation of vaccines to combat the threat posed by SARS-CoV-2 variants. We developed human adenovirus (HAd) vector-based vaccines (HAd-Spike/C5 and HAd-Spike) that express the whole Spike (S)protein of SARS-CoV-2 with or without autophagy-inducing peptide C5 (AIP-C5), respectively. Mice or golden Syrian hamsters immunized intranasally (i.n.) with HAd-Spike/C5 induced similar levels of S-specific humoral immune responses and significantly higher levels of S-specific cell-mediated immune (CMI) responses compared with HAd-Spike vaccinated groups. These results indicated that inclusion of AIP-C5 induced enhanced S-specific CMI responses and similar levels of virus-neutralizing titers against SARS-CoV-2 variants. To investigate the protection efficacy, golden Syrian hamsters immunized i.n. either with HAd-Spike/C5 or HAd-Spike were challenged with SARS-CoV-2. The lungs and nasal turbinates were collected 3, 5, 7, and 14days post challenge. Significant reductions in morbidity, virus titers, and lung histopathological scores were observed in immunized groups compared with the mock- or empty vector-inoculated groups. Overall, slightly better protection was seen in the HAd-Spike/C5 group compared with the HAd-Spike group.

Can the parkland grading scale predict the difficulty of laparoscopic cholecystectomy? A new approach to validation

BackgroundThe Parkland Grading Scale (PGS) is an intraoperative grading scale to stratify gallbladder disease severity during laparoscopic cholecystectomy (LC). We evaluated the usefulness of the PGS in predicting the difficulty levels of LC procedures using a novel approach.MethodsA total of 261 patients diagnosed with cholelithiasis and cholecystitis who underwent LC were assessed. The PGS and the surgical difficulty grading system were used to evaluate surgical procedures by reviewing the operation videos. Clinical baseline characteristics and post-treatment outcomes were also recorded. Differences between the five PGS grades in terms of surgical difficulty scores were analyzed using the Jonckheere-Terpstra test. The relationship between PGS grades and surgical difficulty scores was assessed using Spearman’s Rank correlation. Finally, the linear trends between morbidity scores and PGS grades were evaluated using the Mantel-Haenszel test.ResultsThere was a significant difference in the surgical difficulty scores for the five PGS grades (p < 0.001). In pairwise comparison, each grade (1–5) was significantly different from the others (p < 0.05) in terms of surgical difficulty, except Grade 2 vs. 3 (p = 0.07) and Grade 3 vs. 4 (p = 0.08). There was a significant correlation between PGS grades and surgical difficulty scores (rs = 0.681, p < 0.001). There was also a significant linear association between morbidity and PGS grades (p < 0.001). Spearman’s R value was 0.176 (p = 0.004).ConclusionThe PGS can accurately assess the surgical difficulty level of LC. The precision and conciseness of the PGS make it suitable for use in future research.

Intensity-modulated radiotherapy and cisplatin-based chemotherapy for anal cancer: long-term outcomes at a single institution.

To evaluate oncological outcomes and late toxicities in a retrospective series of patients with locally-extended anal squamous cell carcinoma (ASCC), treated with curative Intensity Modulated Radiotherapy (IMRT) and chemotherapy. ASCC patients who underwent chemo-radiotherapy with IMRT from 2010 to 2020 were included. Oncological outcomes were assessed in terms of overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS) and event-free survival (EFS). Late toxicity was detected according to CTCAE v.5.0 and RTOG late radiation morbidity scoring system. Ninety-five patients were included. Most patients (83%) received chemotherapy with oral Fluoropyrimidine plus Cisplatin. The median follow-up was 5.5years. The OS was 85.2%, 82.1% and 79.3% at 3, 5 and 8years, respectively. The DFS was 73.1%, 70%, and 65.3% at 3, 5 and 8years, respectively; 3, 5 and 8years CFS was 86.2%, 84.3% and 84.3%, respectively. The EFS was 71%, 67.9% and 63.1%, at 3, 5 and 8years, respectively. On univariable analysis, a statistically significant lower OS was found for patients with T3-T4 stage (HR = 4.58, p = 0.005) and overall treatment time (OTT) ≥ 47days (HR = 3.37, p = 0.038). A statistically significant lower DFS was reported for patients with T3-T4 stage (HR = 2.72, p = 0.008) and Serum Squamous Cell Carcinoma Antigen (SCC) value post-RT > 1.5 (HR = 2.90, p = 0.038.). Ten severe late toxicity (≥ G3) events were reported in 8 patients (8.6%). Our data confirm IMRT concomitant with a Cisplatin-based chemotherapy as an effective treatment of ASCC, ensuring acceptable long-term toxicities and good oncological outcomes.

Age, creatinine, and ejection fraction (ACEF) score as predictive values for late non-valvular atrial fibrillation recurrence after radiofrequency ablation

ABSTRACT The clinical risk factors associated with late recurrence in patients with non-valvular atrial fibrillation (AF) (NVAF) undergoing radiofrequency catheter ablation (RFCA) remain unknown. Furthermore, the current prognostic risk score system is commonly used in such patients as a noninvasive method to assess late AF recurrence. According to recent research, the Age, creatinine, and ejection fraction (ACEF) score is a useful risk score for cardiovascular morbidity and mortality. As a result, we hypothesized that pre-ablation ACEF score could be used to assess late recurrence in patients with NVAF. We included 325 NVAF patients undergoing RFCA. During a median follow-up period of 12 months, patients with late AF recurrence had higher ACEF scores (P < .001). The pre-ablation ACEF score was a risk factor for late AF recurrence after RFCA (P = .027). The ACEF score was a predictor of late AF recurrence after RFCA, with an AUC of 0.624 (P = .001). Moreover, the AUC of left atrial diameter (LAD) was 0.7 (P < .001), which was higher than the ACEF score, but no significant difference was found (P = .104). The ACEF score was positively correlated with LAD, advanced age, and B-type natriuretic peptide. In patients with NVAF, the pre-ablation ACEF score is a valuable risk score for assessing late AF recurrence after RFCA, as with LAD.

Comparison of the healthcare-associated infections in intensive care units in Turkey before and during COVID-19

BackgroundSecondary bacterial infections are an important cause of mortality in patients with coronavirus disease 2019 (COVID-19). All healthcare providers acted with utmost care with the reflex of protecting themselves during the COVID-19 period. We aimed to compare the rates of ventilator-associated pneumonia (VAP) and bloodstream infections (BSIs) in our intensive care units (ICUs) before and during the COVID-19 outbreak surges.MethodsThis multicenter, retrospective, cross-sectional study was performed in six centers in Turkey. We collected the patient demographic characteristics, comorbidities, reasons for ICU admission, mortality and morbidity scores at ICU admission, and laboratory test data.ResultsA total of 558 patients who required intensive care from six centers were included in the study. Four hundred twenty-two of these patients (males (62%), whose mean age was 70 [IQR, 58–79] years) were followed up in the COVID period, and 136 (males (57%), whose mean age was 73 [IQR, 61–82] years) were followed up in the pre-COVID period. BSI and VAP rates were 20.7 (19 events in 916 patient days) and 17 (74 events in 4361 patient days) with a −3.8 difference (P = 0.463), and 33.7 (31 events in 919 patient days) and 34.6 (93 events in 2685 patient days) with a 0.9 difference (P = 0.897), respectively. The mortality rates were 71 (52%) in pre-COVID and 291 (69%) in COVID periods.ConclusionProtective measures that prioritize healthcare workers rather than patients and exceed standard measures made no difference in terms of reducing mortality.