Cohort Of Patients Research Articles

Three-dimensional virtual model for robot-assisted partial nephrectomy: a propensity-score matching analysis with a contemporary control group.

To compare two cohorts of patients submitted to robot-assisted partial nephrectomy (RAPN) with vs without the use of three-dimensional virtual models (3DVMs). We screened a prospective consecutive cohort of 152 patients submitted to RAPN with 3DVM and 1264 patients submitted to RAPN without 3DVM between 2019 and 2022. Propensity score matching analysis (PSMA) was applied. Primary endpoint was to evaluate whereas RAPNs with 3DVM were superior in terms of functional outcomes at 12-month. Secondary endopoints were to compare perioperative and oncological outcomes. Multivariable logistic regression analyses (MVA) tested the associations of clinically significant eGFR drop and 3DVMs. Subgroups analysis was performed for PAUDA-risk categories. 100 patients for each group were analyzed after PSMA. RAPN with 3DVM presented a higher rate of selective/no clamping procedure (32% vs 16%, p = 0.03) and a higher enucleation rate (40% vs 29%, p = 0.04). As concern to primary endopoint, 12-month functional preservation performed better within 3DVM group in terms of creatinine serum level (median 1.2 [IQR 1.1-1.4] vs 1.6 [IQR 1.1-1.8], p = 0.03) and eGFR (median 64.6 [IQR 56.2-74.1] vs 52.3 [IQR 49.2-74.1], p = 0.03). However, this result was confirmed only in the PADUA ≥ 10 renal masses. Regarding secondary endpoints, no significative difference emerged between the two cohorts. MVA confirmed 3DVM as a protective factor for clinically significant eGFR drop only in high-risk (PADUA ≥ 10) masses. RAPN performed with the use of 3DVM assistance resulted in lower incidence of global ischemia and higher rate of enucleations. The positive impact of such technology was found at 12-month only in high-risk renal masses.

The Patient Activation Measure-13 (PAM-13) in an oncology patient population: psychometric properties and dimensionality evaluation.

Accurate assessment and enhancement of health-related skills among oncology patients are pivotal for optimizing cancer care. The Patient Activation Measure (PAM-13), a questionnaire designed to reflect an individual's knowledge, skills, and confidence in self-healthcare management, has been validated across diverse countries and settings. Concerns have been raised regarding the cross-situational applicability, as patients with specific diseases and cultural backgrounds interpret questionnaire items differently. This study aimed to examine the structural validity and psychometric properties of the PAM-13 in an oncological patient cohort. Baseline data from a longitudinal non-randomized controlled study involving cancer out-patients (n = 1,125) from Comprehensive Cancer Centres in Southern Germany were analysed. The German version of the PAM-13 was employed. With classical test and item response theory methods data quality, reliability, convergent and structural validity, as well as psychometric properties were assessed. Exploratory (EFA) and confirmatory factor analyses (CFA) were employed to investigate the postulated unidimensionality of the underlying construct. With a partial credit model (PCM) we examined item fit, targeting, local independence and differential item functioning. Participants were predominantly female (73.0%) with a breast cancer diagnosis (41.3%). While items were generally well-accepted, ceiling effects were observed and a high mean PAM-13 score (69.7, SD = 14.2) was noted, potentially compromising responsiveness to interventions. Reliability was adequate (Cronbach's α = 0.81), person and item separation reliability were good to excellent (0.81 and 0.99, respectively). Explorations of the unidimensionality of the construct (EFA, CFA, PCM) yielded inconclusive results, hinting towards a two-factor solution. Item difficulty rankings deviated from the original. No differential item functioning was identified, and local independence was confirmed. While the PAM-13 serves as a valuable instrument for comprehending and promoting health-related skills in cancer patients, the identification of ceiling effects, disordered item-difficulty rankings, and inconclusive findings regarding unidimensionality contribute to the expanding body of evidence, emphasizing the dependency of PAM-13's validity and reliability on distinctive characteristics within the population under investigation. Future research should prioritize refining or adding PAM-13 items to better capture the specific health-related challenges within diverse populations, paving the way for more effective patient engagement strategies in oncology. DRKS00021779.

Discriminating "impaired" from "disordered" contractile response on FLIP panometry by utilizing pressure measurement.

Functional lumen imaging probe (FLIP) panometry evaluates esophageal motility, including the contractile response to distension, that is, secondary peristalsis. Impaired/disordered contractile response (IDCR) is an abnormal, but nonspecific contractile response that can represent either hypomotility or spastic motor disorders on high-resolution manometry (HRM). We hypothesized that FLIP pressure could be incorporated to clarify IDCR and aimed to determine its utility in a cohort of symptomatic esophageal motility patients. 173 adult patients that had IDCR on FLIP panometry and HRM with a conclusive Chicago Classification v4.0 (CCv4.0) diagnosis were included and analyzed as development (n = 118) and validation (n = 55) cohorts. FLIP pressure values were assessed for prediction of either hypomotility or spasm, defined on HRM/CCv4.0. HRM/CCv4.0 diagnoses were normal motility in 48 patients (28%), "hypomotility" (ineffective esophageal motility, absent contractility, or Type I or II achalasia) in 89 (51%), and "spasm" (Type III achalasia, distal esophageal spasm, or hypercontractile esophagus) in 36 (21%). The pressure at esophagogastric junction-distensibility index (DI) (60 mL) was lower in hypomotility (median [interquartile range] 34 [28-42] mmHg) than in spasm (49 [40-62] mmHg; p < 0.001) and had an area under the receiver operating characteristic curve of 0.80 (95% CI 0.73-0.88) for hypomotility and 0.76 (0.69-0.83) for spasm. For "spasm" on HRM, a threshold FLIP pressure of >35 mmHg provided 90% sensitivity (47% specificity) while >55 mmHg provided 93% specificity (40% sensitivity). Pressure on FLIP panometry can help clarify the significance of IDCR, with low-pressure IDCR associated with hypomotility and high-pressure IDCR suggestive of spastic motor disorders.

Coping with modesty during radiotherapy for breast cancer: a multicentric study.

Breast cancer is the most frequently diagnosed tumour, representing nearly 30% of all new cases in women. Radiotherapy (RT) plays a crucial role in the management of breast cancer. The objective of this study is to assess modesty in patients undergoing RT for breast cancer and take their suggestions and ideas into consideration to enhance the quality of treatment in this regard. The study enrolled 555 breast cancer patients undergoing adjuvant RT in three Italian centres. Patients completed a self-test questionnaire assessing their comfort level concerning modesty during therapy and their relationship with strangers and healthcare professionals. The impact of religious views and potential changes in sexuality were also examined. Results showed that modesty was a common concern across the overall cohort of patients, with discomfort in being undressed during RT correlating with discomfort experienced in other daily life situations. Most patients felt more at ease with same sex healthcare workers. Age was also a major factor with younger patients generally feeling more comfortable with healthcare workers of the same age group. Interestingly, the surgical technique used (mastectomy vs. quadrantectomy) did not significantly influence modesty perceptions. Patients provided valuable suggestions to improve privacy and modesty during RT. This study demonstrates that modesty is an important issue for women undergoing RT, which can be influenced by personal characteristics and hospital-related factors. A reflection about the need to address modesty concerns and to incorporate dedicated interventions for protecting patients' physical and emotional well-being is warranted. Initiatives to improve communication, involvement, and body image support should also be integrated into the care path of patients to better their overall therapeutic experience. This study paves the way for broader research and interventions in daily cancer care.

Validation of a risk score to differentiate autoimmune and viral encephalitis: a Nationwide Cohort Study in Denmark.

A score to differentiateautoimmune (AE) and viral encephalitis (VE) early upon admission has recently been developed but needed external validation. The objective of this study was to evaluate the performance of the score in a larger and more diagnostically diverse patient cohort. We conducted a retrospective nationwide and population-based cohort study including all adults with encephalitis of definite viral (2015-2022) or autoimmune aetiology (2009-2022) in Denmark. Variables included in the score-model were extracted from patient records and individual risk scores were assessed. The performance of the score was assessed by receiver-operating characteristics (ROC) curve analyses and calculation of the area under the curve (AUC). A total of 496 patients with encephalitis [AE n = 90, VE n = 287 and presumed infectious encephalitis (PIE) n = 119] were included in the study. The score was highly accurate in predicting cases of AE reaching an AUC of 0.94 (95% CI 0.92-0.97). Having a score ≥ 3 predicted AE with a PPV of 87% and an NPV of 91%. The risk score was found to perform well across aetiological subgroups and applied to the PIE cohort resulted in an AUC of 0.88 (95% CI 0.84-0.93). The excellent performance of the score as reported in the development study was confirmed in this significantly larger and more diverse cohort of patients with encephalitis in Denmark. These results should prompt further prospective testing with wider inclusion criteria.

Neuroimaging with Rotterdam Scoring System and long-term outcomes in severe traumatic brain injury patients.

The Rotterdam Scoring System (RSS) attempts to prognosticate early mortality and early functional outcome in patients with traumatic brain injury (TBI) based on non-contrast head computed tomography (CT) imaging findings. The purpose of this study was to identify the relationship between RSS scores and long-term outcomes in patients with severe TBI. Consecutively treated patients with severe TBI enrolled between 2008 and 2011, in the prospective, observational, Brain Trauma Research Center database were included. The Glasgow Outcome Scale (GOS) was used to measure long-term functional outcomes at three, six, 12, and 24 months. GOS scores were categorized into favorable (GOS = 4-5) and unfavorable (GOS = 1-3) outcomes. RSS scores were calculated at the time of image acquisition. Of the 89 patients included, 74 (83.4%) were male, 81 (91.0%) were Caucasian, and the mean age of the cohort was 41.9±18.5 years old. Patients with an RSS score of 3 and lower were more likely to have a favorable outcome with increased survival rates than patients with RSS scores greater than 3. The RSS score determined on the head CT scan acquired at admission in a cohort of patients with severe TBI correlated with long-term survival and functional outcomes up to two years following injury.

Incidence of incisional hernia in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: an observational clinical study from a tertiary oncology referral care center in India.

An incisional hernia (IH) after major abdominal surgery is an unwanted complication particularly following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC). The frequency of IH among patients treated with CRS and HIPEC remains unexpectedly high in various studies. This study aimed to analyze the incidence, determine the factors contributing to the occurrence of IH, and develop methods to reduce the incidence of IH. We retrospectively analyzed data from a prospectively maintained structured computerized comprehensive database of 360 patients who had undergone CRS and HIPEC after January 2013 and completed two years of follow-up before December 2023. All patients were followed for a minimum period of two years with physical examination and radiological imaging when required and the occurrence of IH was documented. We used SPSS software version 24 to analyze the data using appropriate statistical tests. We set a significance threshold of p < 0.05. Within two years of undergoing CRS and HIPEC, 25 patients (6.9%) out of 360 developed IH, indicating an annual incidence rate of 3.5%. The mean duration of hospitalization for the CRS/HIPEC procedure was 8.4 ± 4.13 days. Fifty-two (14.4%) patients experienced early post-operative surgical complications. The development of IH in our series was significantly associated with obesity (76% vs. 8.4%, P = 0.001), the occurrence of early post-operative surgical complications (48% vs. 12%, P = 0.001), mainly category III complications (44% vs. 7.1%), category IV complications (24% vs. 2.9%) according to Clavien-Dindo classification, post neoadjuvant chemotherapy status (72% vs. 87%, P = 0.045) and need for bowel anastomosis (32% vs. 11%, P = 0.002). The lower incidence of IH following CRS and HIPEC in our patient cohort than in the literature can be attributed to a combination of factors, including the use of meticulous surgical techniques and the use of an abdominal binder postoperatively, particularly in obese patients.

Analysis of short-term ventilation weaning for patients in spontaneous supratentorial intracranial hemorrhage.

Prolonged ventilation is a complication of spontaneous supratentorial hemorrhage patients, but the predictive relationship with successful weaning in this patient cohort is not understood. Here, we evaluate the incidence and factors of ventilation weaning in case of spontaneous supratentorial hemorrhage. We retrospectively studied data from 166 patients in the same hospital from January 2015 to March 2021 and analyzed factors for ventilation weaning. The clinical data recorded included patient age, gender, timing of operation, initial Glasgow Coma Scale (GCS), Intracranial hemorrhage (ICH) score, alcohol drinking, cigarette smoking, medical comorbidity, and the blood data. Predictors of patient outcomes were determined by the Student t test, chi-square test, and logistic regression. We recruited and followed 166 patients who received operation for spontaneous supratentorial hemorrhage with cerebral herniation. The group of successful weaning had 84 patients and the group of weaning failed had 82 patients. The patient's age, type of operation, GCS on admission to the Intensive care unit (ICU), GCS at discharge from the ICU, medical comorbidity was significantly associated with successful weaning, according to Student t test and the chi-square test. According to our findings, patients with stereotaxic surgery, less history of cardiovascular or prior cerebral infarction, GCS >8 before admission to the hospital for craniotomy, and a blood albumin value >3.5 g/dL have a higher chance of being successfully weaned off the ventilator within 14 days.

Incidence of Surgically Managed Post-Tonsillectomy Hemorrhage Associated With NSAID Prescribing for Postoperative Pain Management.

Tonsillectomy ranks high among the most common pediatric surgical procedures in the United States. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), such as ibuprofen, are routinely prescribed to manage post-tonsillectomy pain, but may carry the risk of hemorrhage. This retrospective, longitudinal, secondary-data analysis study compared the incidence of surgically managed post-tonsillectomy hemorrhage (sPTH) in pediatric patients prescribed ibuprofen at Brooke Army Medical Center (BAMC) after tonsillectomy compared to a similar cohort of pediatric patients at the Children's Hospital of Philadelphia (CHOP) not prescribed ibuprofen. Additional regression analysis examined predictors of sPTH at BAMC. The odds of sPTH was lower in patients who were prescribed ibuprofen at BAMC, relative to patients who were not at CHOP (OR 0.57, 95% CI, 0.37, 0.87; P < 0.01). In a generalized linear model evaluating BAMC patient data, there was a lack of a relationship between reason for tonsillectomy (tonsillitis versus tonsillar obstruction), primary procedure (tonsillectomy-only versus tonsillectomy with adenoidectomy), and presence of a co-occurring procedure. Post-tonsillectomy ibuprofen prescribing practices were not associated with an elevated risk of sPTH, relative to patients at CHOP not exposed to ibuprofen.

Numerical Modeling of Flow in the Cerebral Vasculature: Understanding Changes in Collateral Flow Directions in the Circle of Willis for a Cohort of Vasospasm Patients Through Image-Based Computational Fluid Dynamics.

The Circle of Willis (CoW) is a ring-like network of blood vessels that perfuses the brain. Flow in the collateral pathways that connect major arterial inputs in the CoW change dynamically in response to vessel narrowing or occlusion. Vasospasm is an involuntary constriction of blood vessels following subarachnoid hemorrhage (SAH), which can lead to stroke. This study investigated interactions between localization of vasospasm in the CoW, vasospasm severity, anatomical variations, and changes in collateral flow directions. Patient-specific computational fluid dynamics (CFD) simulations were created for 25 vasospasm patients. Computed tomographic angiography scans were segmented capturing the anatomical variation and stenosis due to vasospasm. Transcranial Doppler ultrasound measurements of velocity were used to define boundary conditions. Digital subtraction angiography was analyzed to determine the directions and magnitudes of collateral flows as well as vasospasm severity in each vessel. Percent changes in resistance and viscous dissipation were analyzed to quantify vasospasm severity and localization of vasospasm in a specific region of the CoW. Angiographic severity correlated well with percent changes in resistance and viscous dissipation across all cerebral vessels. Changes in flow direction were observed in collateral pathways of some patients with localized vasospasm, while no significant changes in flow direction were observed in others. CFD simulations can be leveraged to quantify the localization and severity of vasospasm in SAH patients. These factors as well as anatomical variation may lead to changes in collateral flow directions. Future work could relate localization and vasospasm severity to clinical outcomes like the development of infarct.

Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation.

Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

Comparison of outcomes from tunnelled femorally inserted central catheters and peripherally inserted central catheters: a propensity score-matched cohort study.

To compare catheter-related outcomes of individuals who received a tunnelled femorally inserted central catheter (tFICC) with those who received a peripherally inserted central catheter (PICC) in the upper extremities. A propensity-score matched cohort study. A 980-bed tertiary referral hospital in South West Sydney, Australia. In-patients referred to the hospital central venous access service for the insertion of a central venous access device. The primary outcome of interest was the incidence of all-cause catheter failure. Secondary outcomes included the rates of catheters removed because of suspected or confirmed catheter-associated infection, catheter dwell and confirmed upper or lower extremity deep vein thrombosis (DVT). The overall rate of all-cause catheter failure in the matched tFICC and PICC cohort was 2.4/1000 catheter days (95% CI 1.1 to 4.4) and 3.0/1000 catheter days (95% CI 2.3 to 3.9), respectively, and when compared, no difference was observed (difference -0.63/1000 catheter days, 95% CI -2.32 to 1.06). We found no differences in catheter dwell (mean difference of 14.2 days, 95% CI -6.6 to 35.0, p=0.910); or in the cumulative probability of failure between the two groups within the first month of dwell (p=0.358). No significant differences were observed in the rate of catheters requiring removal for confirmed central line-associated bloodstream infection (difference 0.13/1000 catheter day, 95% CI -0.36 to 0.63, p=0.896). Similarly, no significant differences were found between the groups for confirmed catheter-related DVT (difference -0.11 per 1000 catheter days, 95% CI -0.26 to 0.04, p=1.00). There were no differences in catheter-related outcomes between the matched cohort of tFICC and PICC patients, suggesting that tFICCs are a possible alternative for vascular access when the veins of the upper extremities or thoracic region are not viable for catheterisation.

The burden of radiation exposure in congenital heart disease: the Italian cohort profile and bioresource collection in HARMONIC project.

The European-funded Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Pediatrics (HARMONIC) project aims to improve knowledge on the effects of medical exposure to ionizing radiation (IR) received during childhood. One of its objectives is to build a consolidated European cohort of pediatric patients who have undergone cardiac catheterization (Cath) procedures, with the goal of enhancing the assessment of long-term radiation-associated cancer risk. The purpose of our study is to provide a detailed description of the Italian cohort contributing to the HARMONIC project, including an analysis of cumulative IR exposure, reduction trend over the years and an overview of the prospective collection of biological samples for research in this vulnerable population. In asingle-centerretrospective cohort study, a total of 584 patients (323 males) with a median age of 6 (2-13) years, referred at the Pediatric Cardiology in Niguarda Hospital from January 2015 to October 2023, were included. Biological specimens from asubsetof 60 patients were prospectively collected for biobanking atbaseline, immediately post-procedure and after 12months. Two hundred fifty-nine (44%) patients were under 1year old at their first procedure. The median KAP/weight was 0.09Gy·cm2/kg (IQR: 0.03-0.20), and the median fluoroscopy time was 8.10min (IQR: 4.00-16.25). KAP/weight ratio showed a positive correlation with the fluoroscopy time (Spearman's rho = 0.679, p < 0.001). Significant dose reduction was observed either after implementation of an upgraded technology system and a radiation training among staff. The Italian cohort includes 1858 different types of specimens for Harmonic biobank, including blood, plasma, serum, clot, cell pellet/lymphocytes, saliva. In the Italian Harmonic cohort, radiation dose in cardiac catheterization varies by age and procedure type. An institution's radiological protection strategy has contributed to a reduction in radiation dose over time. Biological samples provide a valuable resource for future research, offering an opportunity to identify potential early biomarkers for health surveillance and personalized risk assessment.

Correlation of Patient-Reported Social Determinants of Health With Census Tract Measures of Socioeconomic Disadvantage in Patients With GI Cancers in Eastern North Carolina.

Investigating the impact of social determinants of health (SDOHs) on cancer care in large populations relies on census estimates. Routine clinic SDOH screening provides timely patient-level information which could inform best practices. This study evaluated the correlation between patient-reported SDOH needs and population-level census tract measures. This was a retrospective cross-sectional study of a cohort of adult patients with GI malignancy screened for SDOHs such as financial insecurity, transportation, and food insecurity during initial outpatient evaluation at East Carolina University (formerly Vidant) Health Medical Center in Greenville, NC (November 2020-July 2021). Primary outcomes included number and severity of identified SDOH needs and area deprivation index (ADI) and census tract measures for each patient. Spearman rank correlations were calculated among patient-level needs and between patient-level needs and similar census tract measures. Of 112 patients screened, 58.9% self-identified as White (n = 66) and 41.1% as Black (n = 46). A total of 50.5% (n = 54) resided in a rural county. The collective median state ADI rank was 7 (IQR, 5-9). The median household income was $38,125 in US dollars (USD) (IQR, $31,436-$48,934 [USD]). Only 12.5% (n = 14) reported a moderate or severe financial need. Among reported needs, financial need moderately correlated with food insecurity (coefficient, 0.46; P < .001) and transportation (coefficient, 0.45; P < .001). Overall, census tract measures and reported needs poorly correlated. Lack of transportation correlated with percentage of households without a vehicle (coefficient, 0.18; P = .03) and limited access to healthy foods (coefficient, 0.18; P = .04). Given the poor correlation between reported and census needs, population-level measures may not accurately predict patient-reported needs. These findings highlight the importance of SDOH screening in the clinical setting to reduce health disparities and identify opportunities to improve care delivery.

Very elevated hCGβ (≥10 multiple of the median) in maternal marker screening for Down syndrome: Frequency, etiologies, outcomes, and guidelines.

This aim of this study was to detail maternal and fetal anomalies observed on a national scale in a large French cohort of patients presenting high hCG values (≥10 multiple of the median [MoM]) at Down syndrome screening in order to define clear and optimal guidelines. This is a retrospective multicenter study based on a French annual database of all trisomy 21 screenings. Our study targeted and studied cases with hCG or hCGβ values ≥10 MoM. Complementary exams and outcomes were analyzed. The calculated frequency was 0.05% for hCGβ ≥10 MoM in unselected patients. For this series of 289 cases, a complication of the pregnancy or a poor outcome was observed in 145 cases (51%) as follows: 96 (66%) cases of fetal disease, 23 (16%) of maternal disease, 5 (3.5%) of placental anomalies and 21 (14.5%) of systemic disease concerning mother, fetus and placenta. This study establishes the frequency of hCG or hCGβ values ≥10 MoM, presents a flow chart that optimizes follow-up, and gives clear information for patients presenting with such abnormal values at trisomy 21 screening.

Performance of subcutaneous continuous glucose monitoring in adult critically ill patients receiving vasopressor therapy.

Background Subcutaneous continuous glucose monitoring (CGM) may facilitate glucose control in the ICU. We aimed to assess the accuracy of CGM (Dexcom G6) against arterial blood glucose (ABG) in adult critically ill patients receiving intravenous insulin infusion and vasopressor therapy. We also aimed to assess feasibility and tolerability of CGM in this setting. Methods We included ICU patients receiving mechanical ventilation, insulin, and vasopressor therapy. Numerical accuracy was assessed by the mean absolute relative difference (MARD), overall, across arterial glucose strata, over different noradrenaline equivalent infusion rates, and over time since CGM start. MARD below 14% was considered acceptable. Clinical accuracy was assessed using Clarke Error Grid (CEG) analysis. Feasibility outcome included number and duration of interrupted sensor readings due to signal loss. Tolerability outcome included skin reactions related to sensor insertion or sensor adhesives. Results We obtained 2946 paired samples from 40 patients (18 with type 2 diabetes) receiving a median (IQR) maximum noradrenaline equivalent infusion rate of 0.18 (0.08-0.33) µg/kg/min during CGM. Overall, MARD was 12.7 (95% CI 10.7-15.3) % and 99.8% of CGM readings were within CEG zones A and B. MARD values ≥14% were observed when ABG was outside target range (6-10 mmol/l [108-180 mg/dl]) and with noradrenaline equivalent infusion rates above 0.10 µg/kg/min. Accuracy improved with time after CGM start, reaching MARD values below 14% after 36 hours. We observed four episodes of interrupted sensor readings due to signal loss ranging from 5 to 20 minutes. We observed no skin reactions related to sensor insertion or sensor adhesives. Conclusions In our ICU cohort of patients receiving vasopressor infusion, subcutaneous CGM demonstrated acceptable overall numerical and clinical accuracy. However, suboptimal accuracy may occur outside glucose ranges of 6-10 mmol/l (108-180 mg/dl), during higher dose vasopressor infusion, and during the first 36 hours after CGM start.

Phenotypic amikacin resistance may not indicate poor response to amikacin in Mycobacterium avium complex pulmonary disease.

When using amikacin to treat Mycobacterium avium complex pulmonary disease (MAC-PD), a minimum inhibitory concentration resistance breakpoint of ≥64 mcg/mL is recommended. We explored whether amikacin resistance characterized by phenotypic drug susceptibility testing was associated with clinical outcomes or mutational resistance in a retrospective cohort of patients with MAC-PD. Despite little aminoglycoside exposure, amikacin resistance was common in our MAC-PD patients but was not associated with worse outcomes or rrs gene mutations.

Clinical and economic burden of organ damage among patients with systemic lupus erythematosus in a real-world setting in Germany.

Systemic lupus erythematosus (SLE), a chronic multisystem autoimmune disease, carries high risk of organ damage and burden to healthcare systems. SLE disease modification aims to reduce disease activity with minimal treatment toxicity and preventing or minimizing organ damage development. This real-world study utilizing healthcare administrative claims data assessed organ damage development, associated costs and healthcare resource utilization (HCRU) in patients with SLE in Germany. Claims data from January 1, 2007, to December 31, 2017, were obtained from the Betriebskrankenkassen German Sickness Fund Database. Adults (> 18 years) with a confirmed SLE diagnosis between January 1, 2009, and December 31, 2014, (inclusion period) were included. The index date was calculated based on the first recorded SLE diagnosis during this period. Patients were propensity score-matched (1:3) to a comparator cohort without SLE by age, sex, and comorbidities (Charlson comorbidity index). Organ damage was identified using an algorithm developed based on conditions described in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), using ICD-10-GM diagnostic codes, healthcare procedures, and/or treatments. 2121 patients with SLE and 6308 comparator patients were included (mean follow-up time: 6.4 years). Organ damage prevalence increased from 60.5% at baseline to 83.0% during 6 years of follow-up in all patients with SLE, while 17.0% of patients with SLE did not develop organ damage. Patients with newly confirmed SLE diagnosis without organ damage at baseline were nearly twice as likely to develop organ damage within 5 years versus the comparator cohort (52.0% vs. 27.0%). Total annual costs per patient-year for patients with SLE with organ damage were more than double those of patients with SLE without organ damage; both the number of inpatient admissions and length of stay were higher. The application of a recently developed algorithm allowed us to use claims data to elucidate SLE organ damage, and its associated high clinical and economic burden, in a large, representative sample in Germany. To our knowledge, this is the first European analysis of its kind involving a broad cohort of patients with SLE treated in the routine care setting.

Effectiveness and safety of granulocyte colony-stimulating factor priming regimen for acute myeloid leukemia: A systematic review and meta-analysis of the Clinical Practice Guideline for the use of G-CSF 2022 from the Japan Society of Clinical Oncology.

The outcomes of relapsed or refractory acute myeloid leukemia (AML) remain poor. Although the concomitant use of granulocyte colony-stimulating factor (G-CSF) and anti-chemotherapeutic agents has been investigated to improve the antileukemic effect on AML, its usefulness remains controversial. This study aimed to investigate the effects of G-CSF priming as a remission induction therapy or salvage chemotherapy. We performed a thorough literature search for studies related to the priming effect of G-CSF using PubMed, Ichushi-Web, and the Cochrane Library. A qualitative analysis of the pooled data was performed, and risk ratios (RRs) with confidence intervals (CIs) were calculated and summarized. Two reviewers independently extracted and accessed the 278 records identified during the initial screening, and 62 full-text articles were assessed for eligibility in second screening. Eleven studies were included in the qualitative analysis and 10 in the meta-analysis. A systematic review revealed that priming with G-CSF did not correlate with an improvement in response rate and overall survival (OS). The result of the meta-analysis revealed the tendency for lower relapse rate in the G-CSF priming groups without inter-study heterogeneity [RR, 0.91 (95% CI 0.82-1.01), p=0.08; I2=4%, p=0.35]. In specific populations, including patients with intermediate cytogenetic risk and those receiving high-dose cytarabine, the G-CSF priming regimen prolonged OS. G-CSF priming in combination with intensive remission induction treatment is not universally effective in patients with AML. Further studies are required to identify the patient cohort for which G-CSF priming is recommended.

Twin prime editing mediated exon skipping/reinsertion for restored collagen VII expression in recessive dystrophic epidermolysis bullosa.

Gene editing nucleases, base editors, and prime editors are potential locus specific genetic treatment strategies for recessive dystrophic epidermolysis bullosa (RDEB); however, many RDEB COL7A1 mutations are unique, making the development of personalized editing reagents challenging. 270 of the ∼320 COL7A1 EB mutations reside in exons that can be skipped, and antisense oligonucleotides (ASO) and gene editing nucleases have been used to create in-frame deletions. ASOs are transient and nucleases generate deleterious double stranded DNA breaks (DSB) and uncontrolled mixtures of allele products. We developed a twin prime editing (twinPE) strategy using the PEmax and recently evolved PE6 prime editors and dual prime editing guide RNAs flanking COL7A1 exon five. Prime editing-mediated deletion of exon 5 with a homozygous premature stop codon was achieved in RDEB fibroblasts, keratinocytes, and iPSC with minimal DSBs, and collagen type VII (C7) protein was restored. TwinPE can replace the target exon with recombinase attachment sequences, and we exploited this to re-insert a normal copy of exon 5 using the Bxb1 recombinase. These findings demonstrate that twinPE can facilitate locus-specific, predictable, in-frame deletions and sequence replacement with few DSBs as a strategy that may enable a single therapeutic agent to treat multiple RDEB patient cohorts.