A Comparison of 2 Disease Burden Assessment Methods (3D Volume Versus the Number of Lesions) for Prognostication of Survival in Metastatic Melanoma: Implications for the Characterization of Oligometastatic Disease.

PURPOSE: Oligometastatic disease (OMD), generally defined by the presence of ≤5 metastatic lesions, represents an intermediate state between localized and widespread metastatic disease. This study aimed to question the conventional definition of OMD and assess the significance of the total volume and loci of metastases in characterizing OMD using an unselected metastatic melanoma cohort. METHODS AND MATERIALS: We identified 86 consecutive patients with metastatic melanoma who received pembrolizumab monotherapy from 2015 to 2020. We retrospectively contoured the gross tumor volumes of all metastatic lesions on baseline and follow-up imaging. The number, total volume, and loci information of metastases was collected. The primary endpoint was overall survival. A density histogram plot was used for tumor characteristic descriptions, and classification analysis using the decision tree and random forest methods was performed to determine the optimal combination of prognostic factors in the clinical setting. RESULTS: A total of 2728 gross tumor volumes were delineated. On baseline imaging, the median number and total volume of metastases was 7 (interquartile range, 3-17) and 28.4 cc (interquartile range, 8.4-88.78), respectively. The lymph node was the most common metastatic site (n = 46, 54%), followed by the lungs (n = 32, 37%), liver (n = 23, 27%), and bones (n = 21, 24%). Two-year overall survival rates of patients with 1 to 5, 6 to 10, 11 to 20, and >20 metastases were 58%, 47%, 31%, and 14%, respectively, and with ≤10, 11 to 30, 31 to 130, and >130 cc of metastatic volume were 64%, 43%, 33%, and 25%, respectively. K-adaptive partitioning revealed that the optimal cutoff was 20 and 37.9 cc. Decision tree and random forest analyses revealed that volume and loci (brain and liver metastases) were the most important factors (Harrell's C-index, 0.78). CONCLUSIONS: The OMD state could represent a continuous spectrum of disease burden instead of a binary phenomenon. We propose integrating the volumetric and spatial information of metastases into the characterization of OMD and the stratification tool of clinical trials in the metastatic setting, although external validation studies are needed.

A Radiological Assessment of Chronic Subdural Hematomas.

Chronic subdural hematoma (CSDH), which generally occurs in elderly patients, is a frequently diagnosed condition in neurosurgical departments. Computed tomography (CT) and magnetic resonance imaging (MRI) are the most preferred diagnostic modalities for CSDH assessment. With early diagnosis and adequate management, CSDH may show favorable prognosis in majority of the patients; however, recurrence after surgery can occur in a significant number of patients. The recently increasing number of CSDH studies could reveal the prognostic factors affecting CSDH recurrence. Particularly, radiological characteristics regarding the internal architecture of CSDH are considered closely associated with recurrence in surgically treated CSDH patients. In this literature review, we evaluated the various diagnostic modalities of CSDH and its radiological characteristics on CT and MRI. Furthermore, we summarized the prognostic factors of recurrence for the hematoma type based on the radiological findings.

Assessment of radiation-induced otitis media in patients with parotid gland malignancy.

BACKGROUND: Otitis media with effusion (OME) is a known side effect of radiation therapy in patients with head and neck cancer. AIMS/OBJECTIVES: To investigate the incidence rate and clinical course of radiation-induced OME, we have reported on the long-term characteristics of OME in patients with parotid gland malignancy. MATERIAL AND METHODS: This cohort study assessed 200 patients who underwent post-parotidectomy radiation therapy from January 2010 to December 2019 in a tertiary referral center. Postoperative radiation therapy was performed at 6 weeks post-surgery. Serial magnetic resonance images were collected to detect otitis media. Two blinded otologists individually assessed data from radiation therapy initiation to 36 months of post-radiation therapy. RESULTS: A total of 121 patients were enrolled (male, 61 [50.4%]; mean age, 46.98 ± 15.69 years), of which 14 developed otitis media (11.6%) within 6 months after radiation therapy. Spontaneous remission occurred without intervention within 1 year, excluding one patient who sustained otitis media for 2 years. CONCLUSIONS AND SIGNIFICANCE: Radiation-induced OME occurred in 11.6% of patients and it remitted within 1 year without intervention. Therefore, cooperation between otolaryngologists and radiation oncologists is required and invasive intervention should be considered with careful risk-benefit evaluation.

The Effect of Global Surgery Fellowship for Tertiary Hospital Professionals from Myanmar: Current Issues and Future Challenges.

OBJECTIVE: As the surgical burden of diseases grows higher than ever, the development of skilled surgeons and surgery teams is of fundamental importance. However, there is scarce evidence of the effectiveness of surgical training programs. Our study aims to evaluate the effectiveness of a global surgery fellowship program. DESIGN: In 2018, Myanmar subspecialty surgeons were trained for a 3-month in tertiary hospital of Korea. We evaluated the reactions, learning, and transfer of the 11 trainees using Kirkpatrick's Evaluation Model. SETTING: Myanmar and Korean tertiary hospital. PARTICIPANTS: Eleven participants of fellowship from Myanmar. RESULTS: Participants' overall reaction scores were 4.45 ± 0.52 out of 5.00. Regarding overall competency, the trainees assessed themselves as at an "advanced beginner level" (3.63 ± 1.38 out of 10.00) at the beginning and at a "competent level" (5.40 ± 1.70 out of 10.00) after the training (p for difference = 0.014). The trainees stated that their transfer in clinical practice was between "quite applicable" and "I am very sure that I can do this" (3.39 ± 0.61 out of 4.00). Their transfer in education was second, ranked around "quite applicable" (3.21 ± 0.77 out of 4.00), and their transfer in research was last and ranked "applicable, but just a little" (2.81 ± 0.67 out of 4.00). However, in our online survey, native and foreign trainers had mixed opinions about the transfer of training and were not entirely confident in the trainees' competency. Trainees felt that there were multifactorial challenges for transfer and cited infrastructure, facilities, human resources, perioperative care, and financing. CONCLUSIONS: Surgical trainees reported high-level satisfaction and increased knowledge after training. However, further onsite surgical experiences are necessary for a successful transfer to the real setting. Challenges for such transfers were multifactorial, and surgical care must be systemically strengthened.

Status of Emergency Signal Functions in Myanmar Hospitals: A Cross-Sectional Survey.

INTRODUCTION: Low- and middle-income countries (LMICs) have a large percentage of global mortality and morbidity rates from non-communicable diseases, including trauma. The establishment and development of emergency care systems is crucial for addressing this problem. Defining gaps in the resources and capacity to provide emergency healthcare in LMICs is essential for proper design and operation of ECS (emergency care services) reinforcement programs. Myanmar has particular challenges with road access for providing timely emergency medical care, and a shortage of trained health workers. To examine the ECS capacity in Myanmar, we used the Emergency Care Assessment Tool (ECAT), which features newly developed tools for assessing sentinel conditions and signal functions (key interventions to address morbidity and mortality) in emergency care facilities. METHODS: ECAT is composed of six emergent sentinel conditions and corresponding signal functions. We surveyed a total of nine hospitals in five states in Myanmar. A constructed survey sheet was delivered by e-mail, and follow-up interviews were conducted via messenger to clarify ambiguous answers. RESULTS: We categorized the nine participating institutions according to predefined criteria: four basic-level hospitals; four intermediate-level; and one advanced-level hospital. All basic hospitals were weak in trauma care, and two of 12 signal functions were unavailable. Half of the intermediate hospitals showed weakness in trauma care, as well as critical care such as shock management. Only half had a separate triage area for patients. In contrast, all signal functions and resources listed in ECAT were available in the advanced-level hospital. CONCLUSION: Basic-level facilities in Myanmar were shown to be suboptimal in trauma management, with critical care also inadequate in intermediate facilities. To reinforce signal functions in Myanmar health facilities, stakeholders should consider expanding critical functions in selected lower-level health facilities. A larger scale survey would provide more comprehensive data to improve emergency care in Myanmar.

Maternal and newborn health services utilization in Jimma Zone, Southwest Ethiopia: a community based cross-sectional study.

BACKGROUND: Majority of causes of maternal and newborn mortalities are preventable. However, poor access to and low utilization of health services remain major barriers to optimum health of the mothers and newborns. The objectives of this study were to assess maternal and newborn health services utilization and factors affecting mothers' health service utilization. METHODS: A community based cross-sectional survey was carried out on randomly selected mothers who gave birth within a year preceding the survey. The survey was supplemented with key informant interviews of experts/health professionals. Multivariable logistic model was used to identify factors associated with service utilization. Adjusted odds ratios (AORs) were used to assess the strength of the associations at p-value ≤0.05. The qualitative data were summarized thematically. RESULTS: A total of 789 (99.1% response rate) mothers participated in the study. The proportion of the mothers who got at least one antennal care (ANC) visit, institutional delivery and postnatal care (PNC) were 93.3, 77.4 and 92.0%, respectively. Three-forth (74.2%) of the mothers started ANC lately and only 47.5% of them completed ANC4+ visits. Medium (4-6) family size (AOR: 2.3; 95% CI: 1.1, 4.9), decision on ANC visits with husband (AOR: 30.9; 95% CI: 8.3, 115.4) or husband only (AOR: 15.3; 95%CI: 3.8, 62.3) and listening to radio (AOR: 2.5; 95%CI: 1.1, 5.6) were associated with ANC attendance. Mothers whose husbands read/write (AOR: 1.6; 95% CI: 1.1, 2.), attended formal education (AOR: 2.8; 95% CI: 1.1, 6.8), have positive attitudes (AOR: 10.2; 95% CI: 25.9), living in small (AOR: 3.0; 95% CI: 1.2, 7.6) and medium size family (AOR: 2.3; 95% CI: 1.2, 4.1) were more likely to give birth in-health facilities. The proportion of PNC checkups among mothers who delivered in health facilities and at home were 92.0 and 32.5%, respectively. The key informants mentioned that home delivery, delayed arrival of the mothers, unsafe delivery settings, shortage of skilled personnel and supplies were major obstacles to maternal health services utilization. CONCLUSIONS: Health information communication targeting husbands may improve maternal and newborn health services utilization. In service training of personnel and equipping health facilities with essential supplies can improve the provider side barriers.

The characteristics of pediatric emergency department visits in Korea: An observational study analyzing Korea Health Panel data.

OBJECTIVE: We investigated the characteristics of pediatric emergency department (ED) patients in Korea and determined factors associated with hospital admission after ED treatment. METHODS: Korea Health Panel data from 2008 through 2013 were analyzed retrospectively; we included patients under 18 years old who visited the ED at least once. We collected patient and household epidemiologic data such as sex, age group, region of residence, disability, chronic disease, household income quintile, national health insurance type, use of private insurance, and annual frequency of ED visits. We also examined data related to each ED visit, such as reason for visit, medical service provided, and hospital size/ownership. We then investigated which factors were correlated with case disposition (discharge home or hospital admission) after ED treatment. RESULTS: In total, 3,160 pediatric ED visits occurred during the six-year period. Males (57.5%) and children aged 0-5 years (47.7%) made more visits than females and older children, respectively. The proportion of ED visits for disease (67.7%) was much higher than for injury or poisoning (32.2%), and 452 cases (14.3%) required hospital admission. For hospital admission, the odds ratio (OR) of females was 0.73 compared to males, and the OR of children aged 6-11 was 0.68 compared to children aged 0-5. The OR of capital residents was 0.69 compared to province residents, and the OR of the highest income quintile was 0.51 compared to the lowest quintile. The OR of children with private insurance coverage was 0.49 compared to those lacking private insurance, and the OR of ED visits due to disease was 1.82 compared to visits due to injury/poisoning. CONCLUSION: This analysis of clinical and demographic characteristics of pediatric ED visits and hospital admissions can serve as the foundation of future prospective studies required for establishing appropriate policies for the Korean pediatric emergency medical system.

Prognostic Value of Cardiac MR Imaging for Preoperative Assessment of Patients with Severe Functional Tricuspid Regurgitation.

Purpose To explore the prognostic value of cardiac magnetic resonance (MR) imaging in predicting postoperative cardiac death in patients with severe functional tricuspid regurgitation (TR). Materials and Methods This study was approved by the institutional review board, and written informed consent was obtained from all patients. Prospectively collected data included cardiac MR images, New York Heart Association (NYHA) functional class, a comprehensive laboratory test, and clinical events over the follow-up period in 75 consecutive patients (61 women and 14 men; mean age ± standard deviation, 59 years ± 9) undergoing corrective surgery for severe functional TR. Cox proportional hazards models were used to assess the association between cardiac MR parameters and outcomes. Results During a median follow-up period of 57 months (range, 21-82 months), cardiac mortality and all-cause mortality were 17.3% and 26.7%, respectively, with a surgical mortality of 6.7%. Cardiac death risk was lower with a higher right ventricular (RV) ejection fraction (EF) on cardiac MR images (hazard ratio per 5% higher EF = 0.790, P = .048). By adjusting for confounding variables, RV EF remained a significant predictor for cardiac death (P < .05) and major postoperative cardiac events (P < .05). The area under the receiver operating characteristic curve (AUC) confirmed the incremental role of RV EF on cardiac MR images in the prediction of postoperative cardiac death (AUC, 0.681-0.771; P = .041) and major postoperative cardiac events (AUC, 0.660-0.745; P = .044) on top of NYHA class. RV end-systolic volume index was also independently associated with these outcomes but failed to increase the AUC significantly. Conclusion Preoperative assessment of cardiac MR imaging-based RV EF provides independent and incremental prognostic information in patients undergoing corrective surgery for severe functional TR. (©) RSNA, 2016 Online supplemental material is available for this article.

The CHA2DS2VASc score can be used to stratify the prognosis of acute myocardial infarction patients irrespective of presence of atrial fibrillation.

BACKGROUND: The CHA2DS2VASc score has been used to evaluate the risk of thromboembolic events in atrial fibrillation. However, because all the components of CHA2DS2VASc are important cardiovascular risk factors, we decided to evaluate the effectiveness of CHA2DS2VASc score as a long-term predictor for prognosis in acute myocardial infarction (AMI) patients. METHODS: We enrolled 15,681 AMI patients for the Korean Working Group in Acute Myocardial Infarction (KORMI) consecutively and analyzed retrospectively. We divided the all the patients into four groups according to CHADS2VASc score (Group I: 0-1, n=3317; Group II: 2-3, n=6794; Group III: 4-5, n=4457; Group IV: 6-9, n=1113). The cardiac event was defined as the sum of all-cause mortality and recurrence of myocardial infarction. RESULTS: As the risk score increased, the incidence of cardiac events was higher at 1, 6, 12, and 24 months. The cardiac event-free survival rate was lower as the risk score increased (Group I vs Group II, p<0.001; Group II vs Group III, p<0.001; Group III vs Group IV, p=0.037). After adjusting confounding variables, the Cox-regression multivariate analysis showed that the CHA2DS2VASc score was an independent predictor for the long-term prognosis in total AMI patients (p<0.001, hazard ratio=1.414 per scale). CONCLUSION: The AMI patients with higher CHA2DS2VASc score had worse cardiovascular outcome. Therefore, CHADS2VASc score can be used to stratify AMI patients according to long-term prognosis irrespective of presence of atrial fibrillation.

Direct observation of cooperative protein structural dynamics of homodimeric hemoglobin from 100 ps to 10 ms with pump-probe X-ray solution scattering.

Proteins serve as molecular machines in performing their biological functions, but the detailed structural transitions are difficult to observe in their native aqueous environments in real time. For example, despite extensive studies, the solution-phase structures of the intermediates along the allosteric pathways for the transitions between the relaxed (R) and tense (T) forms have been elusive. In this work, we employed picosecond X-ray solution scattering and novel structural analysis to track the details of the structural dynamics of wild-type homodimeric hemoglobin (HbI) from the clam Scapharca inaequivalvis and its F97Y mutant over a wide time range from 100 ps to 56.2 ms. From kinetic analysis of the measured time-resolved X-ray solution scattering data, we identified three structurally distinct intermediates (I(1), I(2), and I(3)) and their kinetic pathways common for both the wild type and the mutant. The data revealed that the singly liganded and unliganded forms of each intermediate share the same structure, providing direct evidence that the ligand photolysis of only a single subunit induces the same structural change as the complete photolysis of both subunits does. In addition, by applying novel structural analysis to the scattering data, we elucidated the detailed structural changes in the protein, including changes in the heme-heme distance, the quaternary rotation angle of subunits, and interfacial water gain/loss. The earliest, R-like I(1) intermediate is generated within 100 ps and transforms to the R-like I(2) intermediate with a time constant of 3.2 ± 0.2 ns. Subsequently, the late, T-like I(3) intermediate is formed via subunit rotation, a decrease in the heme-heme distance, and substantial gain of interfacial water and exhibits ligation-dependent formation kinetics with time constants of 730 ± 120 ns for the fully photolyzed form and 5.6 ± 0.8 µs for the partially photolyzed form. For the mutant, the overall kinetics are accelerated, and the formation of the T-like I(3) intermediate involves interfacial water loss (instead of water entry) and lacks the contraction of the heme-heme distance, thus underscoring the dramatic effect of the F97Y mutation. The ability to keep track of the detailed movements of the protein in aqueous solution in real time provides new insights into the protein structural dynamics.

Assessment of haemodynamic effects of surgical correction for severe functional tricuspid regurgitation: cardiac magnetic resonance imaging study.

AIMS: There has been growing attention for the development of functional tricuspid regurgitation (TR) long after left-sided valve surgery. We attempted to determine the long-term haemodynamic effects of corrective surgery for severe functional TR in patients who had prior left-sided valve surgery using cardiac magnetic resonance imaging (CMR). METHODS AND RESULTS: Thirty-one patients with severe functional TR (TR fraction of 46.0+/-16.2% by CMR) were analysed. CMR was performed within 1 month before and at a median 27.0 months after surgery. Long after TR surgery, 28 of the 31 patients had no or mild residual TR, two had mild-to-moderate TR, and one showed moderate TR. Remarkable reductions in the right ventricular (RV) end-diastolic volume index (RV-EDVI) (177.4+/-59.1 mL/m(2) vs. 118.2+/-31.2 mL/m(2), P<0.001) and end-systolic volume index (RV-ESVI) (88.5+/-30.1 mL/m(2) vs. 67.2+/-31.0 mL/m(2), P=0.002) were observed, whereas RV ejection fraction (RV-EF) showed no change (49.7+/-8.3% vs. 44.9+/-12.5%, P=0.09). Pre-operative RV-EDVI (R=-0.86, P<0.001) and RV-ESVI (R=-0.55, P=0.001) were significantly associated with their respective changes after corrective surgery. Post-surgery, a normal RV-EF was achieved in 14 patients (42.5%). Pre-operative RV-EDVI of 164 mL/m(2) effectively discriminated patients with normal RV-EF from those without post-surgery, with a sensitivity of 77% and a specificity of 72% (P=0.01). A significant rise in the left ventricular (LV) EDVI and cardiac index (CI) was found after surgery (from 92.9+/-24.4 to 123.2+/-31.6 mL/m(2) for LV-EDVI, P<0.001; from 3.8+/-1.3 to 4.2+/-0.8 L/min/m(2) for CI, P=0.03). Functional capacity as assessed by NYHA class showed a significant improvement from 2.7+/-0.6 before surgery to 2.0+/-0.6 long after surgery (P<0.001). CONCLUSION: Successful TR surgery can remarkably reduce RV volumes and preserve RV systolic function. In addition, successful TR surgery led to a significant rise in LV preload and CI, which may significantly contribute to a significant amelioration in the functional capacity of the patients. It seems that RV volume measurement by CMR is helpful for determining optimal timing for TR surgery.