A multi-institutional meningioma MRI dataset for automated multi-sequence image segmentation.

Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by expert manually refined segmentations of three distinct meningioma sub-compartments: enhancing tumor, non-enhancing tumor, and surrounding non-enhancing T2/FLAIR hyperintensity. Basic demographic data are provided including age at time of initial imaging, sex, and CNS WHO grade. The goal of releasing this dataset is to facilitate the development of automated computational methods for meningioma segmentation and expedite their incorporation into clinical practice, ultimately targeting improvement in the care of meningioma patients.

CURRENT CONCEPTS IN THE MANAGEMENT OF BOXER'S FRACTURE.

Fractures of the metacarpal particularly the 5th metacarpal is quite common among all hand fractures and has a high incidence in male adult population. Proper management of these fractures plays a key role in rehabilitation and early return to work thus reducing the economic burden. Treatment of these injuries depends on the type of injury: whether it is a closed/open fracture, degree of angulation at the fracture site and also mal-rotation and shortening of the finger. Non-operative management is suitable for fractures which are closed, non-displaced and without angulation or rotation. Open fractures, fractures with angulation and/or mal-rotation and fractures with neuro-vascular injury are more suitable for operative management. The acceptable angulation for conservative management for most studies is 70 degrees. Buddy strapping with a Futura splint provides good functional results. In fractures requiring operative intervention, K-wire fixation is a minimally invasive method of fixation, which in most cases has good functional results. Plate and screw fixation, however, is preferred for cases with significant comminution or multiple metacarpal fractures.

THE ROLE OF DISTAL LOCKING IN INTRAMEDULLARY NAILS FOR HIP FRACTURE FIXATION: A REVIEW OF CURRENT LITERATURE.

Traditionally, it was believed that both proximal and distal locking are essential for achieving stability during intra-medullary fixation for extra-capsular hip fractures. However, recent literature has presented varying perspectives on the necessity of distal locking. Distal locking plays a significant role in managing hip fractures with uncertainties regarding longitudinal and rotational stability. This includes cases of comminuted intertrochanteric fractures with subtrochanteric extension, reverse oblique and high oblique fractures, broad medullary canals, comminution of the lateral wall, diaphyseal fractures, and large posteromedial fragments extending below the level of the lesser trochanter. In stable pertrochanteric fractures, with the lag screw passing through the lateral cortex of the distal fragment, may not require a distal locking screw. Distal locking has been associated with potential complications, including irritation of the fascia lata, prolonged operation time, increased radiation exposure, greater blood loss, implant loosening, secondary femoral stress fractures, and damage to the femoral artery. Thus, although distal locking is of doubtful significance in stable pertrochanteric fractures it is essential in unstable fracture patterns.

Limitations of antifungal prophylaxis in preventing invasive Candida surgical site infections after liver transplant surgery.

Invasive primary Candida surgical site infections (IP-SSIs) are a common complication of liver transplantation, and targeted antifungal prophylaxis is an efficient strategy to limit their occurrence. We performed a retrospective single-center cohort study among adult single liver transplant recipients at Duke University Hospital in the period between 1 January 2015 and 31 December 2020. The study aimed to determine the rate of Candida IP-SSI according to the peri-transplant antifungal prophylaxis received. Of 470 adult single liver transplant recipients, 53 (11.3%) received micafungin prophylaxis, 100 (21.3%) received fluconazole prophylaxis, and 317 (67.4%) did not receive systemic antifungal prophylaxis in the peri-transplant period. Ten Candida IP-SSIs occurred among 5 of 53 (9.4%) micafungin recipients, 1 of 100 (1.0%) fluconazole recipients, and 4 of 317 (1.3%) recipients who did not receive antifungal prophylaxis. Our study highlights the limitations of antifungal prophylaxis in preventing invasive Candida IP-SSI after liver transplant surgery. We hypothesize that pathogen, host, and pharmacokinetic-related factors contributed to the occurrence of Candida IP-SSI despite antifungal prophylaxis. Our study reinforces the need for a risk-based, multi-pronged approach to fungal prevention, including targeted antifungal administration in patients with risks for invasive candidiasis and close monitoring, especially among patients with surgically complex procedures, with timely control of surgical leaks.

How has the COVID-19 pandemic affected patients with primary bladder cancer?

PURPOSE: The COVID-19-induced effects of primary bladder cancer (BC) patients have not yet been clarified. The aim of this study was to investigate the effects of the pandemic on the diagnosis, treatment, and follow-up of primary BC patients. MATERIAL AND METHODS: A retrospective single-center analysis was made of all patients who underwent diagnostic and surgical procedures due to primary BC between November 2018 and July 2021. A total of 275 patients were identified and allocated to one of the groups: Pre-COVIDBC (BC diagnosed before the COVID-19 pandemic) or COVIDBC (during the pandemic). RESULTS: The BC patients diagnosed during the pandemic were mostly at higher stages (T2) (p = 0.04), the risk of non-muscle invasive BC (NMIBC) was higher (p = 0.02), and recurrence and progression scores were increased (p = 0.001) compared to patients diagnosed before the pandemic. The time to surgery from diagnosis (p = 0.001) and symptom duration (p = 0.04) were significantly prolonged during the pandemic and the rate of follow-up significantly decreased (p = 0.03). CONCLUSIONS: The study results highlight the significant increase in muscle invasive BC and the very high risk of NMIBC in patients presenting during the COVID-19 pandemic.

ANTECEDENTES: Los efectos inducidos por la COVID-19 en pacientes con cáncer de vejiga primario no están aclarados actualmente. OBJETIVO: Investigar los efectos de la pandemia en el diagnóstico, el tratamiento y el seguimiento del cáncer de vejiga primario. MÉTODO: Se realizó un análisis retrospectivo unicéntrico de todos los pacientes que se sometieron a procedimientos diagnósticos y quirúrgicos por cáncer primario de vejiga durante noviembre de 2018 y julio de 2021. Se incluyeron 275 pacientes en el estudio. Los pacientes fueron asignados a uno de dos grupos: pre-COVIDBC (antes de la pandemia) o COVIDBC (durante la pandemia). RESULTADOS: Los pacientes con cáncer de vejiga diagnosticados durante la pandemia se encontraban en su mayoría en estadios más altos (T2) (p = 0.04), el grupo de riesgo era más alto en el cáncer de vejiga no invasivo del músculo (p = 0.02), y la recurrencia y las puntuaciones de progresión aumentaron (p = 0.001) en comparación con antes del período pandémico. Además, el tiempo hasta la cirugía desde el diagnóstico (p = 0.001) y la duración de los síntomas (p = 0.04) aumentaron considerablemente durante la pandemia, y la tasa de seguimiento disminuyó significativamente (p = 0.03). CONCLUSIONES: Destaca el aumento significativo del cáncer de vejiga invasivo del músculo y del cáncer de vejiga no invasivo del músculo de muy alto riesgo durante la pandemia.

Rapid Cytological Diagnosis With Evaluation of Pre- and Post-Therapeutic Fungal Morphological Characteristics in Mucormycosis.

Background: Mucormycosis necessitates rapid diagnosis and treatment. Microscopy and culture have been considered the gold standard for diagnosis but both take time of 3 - 5 days. KOH mount is another method for fungal identification that takes 1 - 2 h, but it has its own limitations. This study evaluated crush smear as a means of rapid cytological diagnosis. Methods: Biopsy tissue (pre-treatment) from clinically suspicious mucormycosis patients (n = 52) was received in normal saline and crush/imprint smears were prepared; the remaining tissue was processed as routine biopsy specimen. After the rapid initial cytological identification, the patients were managed according to the standard clinical protocol. Random post-therapeutic biopsy samples of some of these patients (n = 19) were also obtained and again evaluated cytologically. Results: Crush smears showed sensitivity/specificity of 77.7%/75.0% with histopathology and 72.2%/62.5% with culture, respectively, while KOH mount had values of 71.4%/70.5% with histopathology and 79.3%/69.5% with culture, respectively. Degenerative fungal morphological characteristics and cellular inflammatory infiltrate (predominantly neutrophilic) in the vicinity of fungal hyphae were compared in pre- and post-treatment groups, and we found a statistically significant difference (P < 0.05) between them. Conclusion: Our preliminary results suggest that crush smear cytology is a simple, rapid, cost-effective and easily available method for diagnosing mucormycosis. Moreover, crush smears also demonstrated morphological alteration in hyphal structure and accompanying immune cell infiltration which may provide valuable insights into mechanism of therapy/host immune response against fungal pathogen.

Cost-Effectiveness Analysis of COVID-19 Vaccination in Low- and Middle-Income Countries.

Background: WHO reported that 5.5 million people died in the world because of COVID-19. One of the efforts to mitigate the pandemic is administrating the vaccines globally. Objective: The objective of this study was to review cost-effectiveness analysis of COVID-19 vaccination in low- and middle-income countries (LMICs). Methods: We searched PubMed and EBSCO for the eligible studies with inclusion criteria using cost-effectiveness analysis, free full text, low-middle-income countries, and the publication date since the last year. Four reviewers conducted the review independently. Results: The review identified four articles meeting the eligibility criteria. The settings were LMICs. Different perspectives and economic modelling used by the countries confirmed a similar result. They all explained that vaccination could prevent the infection spread and mortality caused by COVID-19 and showed high cost-effectiveness values. Conclusion: Administering COVID-19 vaccines was cost-effective and even cost-saving. The studies found that vaccination was more cost-effective in reducing the spread of the COVID-19 virus and the mortality it caused than no vaccination.

Prescription Patterns of Novel Antihyperglycemic Medications.

BACKGROUND: Glucagon-like peptide-1 agonists (GLP-1a) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are recommended in carefully selected patients with type 2 diabetes. This study will assess prescription of these medications and investigate predictors of prescription. METHODS: This retrospective cross-sectional study included 31,354 patients. Data including sociodemographic descriptors, clinical histories, medications, and health insurance providers were extracted from a health system's administrative databases. Variables to be associated with prescription of a GLP-1a or SGLT-2i were assessed using a multivariable logistic regression model. RESULTS: Mean age was 62.58 years and 40.8% identified as African American. Only 3.4% were prescribed a GLP-1a and 2.1% received a SGLT-2i. Logistic regression demonstrated lower odds of receiving either medication in the highest age-group (70 to 79 years) (GLP-1a: odds ratio [OR] 0.44, P < .01, SGLT-2i: OR 0.39, P < .01) and in African Americans (GLP-1a: OR 0.64, P < .01, SGLT-2i: OR 0.28, P < .01). Atherosclerotic cardiovascular disease was not associated with GLP-1a prescription (P = .54) and conferred lower odds of being prescribed SGLT-2i (OR 0.68, P < .01). History of chronic kidney disease conferred lower odds of receiving GLP-1a and was not associated with the odds of receiving SGLT-2i. CONCLUSIONS: Prescription of GLP-1a and SGLT-2i medications was low as compared with existing literature. Advanced age and African American race were negatively associated with prescription of these medications. Contrary to guideline recommendations; atherosclerotic cardiovascular disease and chronic kidney disease were not positively associated with prescription.

Delayed coil migration into oropharynx following endovascular coiling of a traumatic carotid cavernous fistula: management considerations.

Carotid-cavernous fistulas (CCFs) are abnormal vascular shunts between the carotid artery and the cavernous sinus. A 37-year-old male presented with a traumatic CCF and basal skull fracture extending through the medial wall of the cavernous sinus and sphenoid sinus. The CCF was treated with endovascular coiling. Three months after this procedure, he was found to have coil migration through the traumatic sphenoid defect into the pharynx. He underwent urgent endonasal endoscopic surgery to disconnect and remove the extruded coil. Post-operative coil migration is a rare but serious complication following endovascular treatment of traumatic CCF.

Parents' Knowledge, Attitude, and Practice on Childhood Vaccination During the COVID-19 Pandemic in Indonesia.

BACKGROUND: Vaccination is known to have an enormous impact on improving child health. In Indonesia, the government has included several vaccines in the national immunization program. OBJECTIVE: This study aimed to investigate parents' knowledge, attitude, and practice on childhood immunization during the COVID-19 pandemic in Indonesia. METHODS: A valid and reliable questionnaire was delivered to approximately 276 parents in Jakarta and Bandung, representing the epicenter of the pandemic. This study was conducted from June 2020 to February 2021. The correlations between parents' knowledge, attitudes, and practice with the characteristics of the respondents were investigated. In addition, multiple regression analysis was performed to identify the variables associated with good vaccination practice. RESULTS: The results showed that the mean scores of parents' knowledge, attitude, and practice on childhood vaccinations were 7.22 (± 1.30) out of 9 points, 3.93 (± 0.31) out of 4 points, and 3.59 (± 0.97) out of 5 points, respectively. Respondents graduated from university were more knowledgeable than those graduated from senior high school (p-value <0.05). Employed participants had better scores in knowledge and practice, compared to unemployed participants (p-value <0.05). CONCLUSION: In conclusion, this study found positive correlations between participants' knowledge and attitude, knowledge and practice, and attitude and practice on childhood vaccination during the COVID-19 pandemic in Indonesia.

Prevalence of hepatitis B & C infections in prospective blood donors deferred due to history of jaundice.

Background & objectives: As per national guidelines, prospective blood donors with a history of jaundice of unknown cause are deferred permanently to prevent the transmission of hepatitis B and C. The validity of this guideline was tested by comparing prevalence rates of hepatitis B and C in prospective blood donors deferred due to a history of jaundice, with that of donors who were found fit. Methods: Blood samples of 212 consecutive donors (male, n=203) deferred due to a history of jaundice were studied for hepatitis B and C by rapid test kits as well as by chemiluminescence (n=115) or ELISA (n=97). Consecutive healthy donors (n=549; male, n=518) were also studied by ELISA (n=266) or chemiluminescence (n=283). Results: The cumulative prevalence detected by rapid test kit and ELISA/chemiluminescence tests of hepatitis B (n=10) and C (n=2) among donors deferred due to a history of jaundice (n=212) was 5.7 per cent [95% confidence interval (CI): 2.9, 9.9]. The prevalence of reactive results among healthy donors (n=549) by ELISA/chemiluminescence tests was 3.3 per cent (95% CI: 1.9, 5.2), which included hepatitis B (n=15) and hepatitis C (n=3) cases. Compared to healthy donors, the odds of seropositivity among jaundice-deferred donors was 1.7 (95% CI: 0.8, 3.6), P=0.15. For rapid test-negative deferred donors, the odds of seropositivity by ELISA/chemiluminescence declined to 0.4 (0.1, 1.5), P=0.19. Interpretation & conclusions: The prevalence rates of hepatitis B and C in prospective blood donors deferred due to a history of jaundice of unknown aetiology did not differ significantly from that in healthy donors. The current practice of permanently deferring such donors depletes valuable donor pool. A strategy of rejecting only those donors who are found reactive on pre-donation testing by rapid test needs further validation.

Role of ferritin and oxidative stress index in gestational diabetes mellitus.

OBJECTIVES: To investigate the role of serum ferritin and oxidative stress in the development of GDM and to assess their relationship with the ensuing hyperglycemia. METHODS: A case-control study was carried on 90 non-anemic pregnant women of 20-40 years with a gestation of 24-28 weeks. Study group (n = 65) was identified according to the Diabetes in Pregnancy Study Group India (DIPSI) criteria (2-h plasma glucose ≥ 140 mg/dl) and controls (n = 25) having 2-h plasma glucose < 120 mg/dl. DIPSI 2-h plasma glucose, HbA1c and serum ferritin were measured and oxidative stress index (OSI) was calculated. Statistical tests were performed using SPSS version 25.0. RESULTS: Pre-pregnancy BMI showed a significant difference between control and study group. DIPSI 2 h blood glucose, HbA1c, serum ferritin and OSI were significantly higher in study group compared to control group. Both 2 h blood glucose and HbA1c were positively correlated with serum ferritin and OSI, serum ferritin and OSI were also positively correlated with each other. CONCLUSION: Higher pre-pregnancy BMI elevates serum ferritin, which in turn increases the OSI. Both ferritin and oxidative stress raises 2 h blood glucose and HbA1c in GDM patients possibly by causing in-vivo pancreatic ß -cell injury and death (ferroptosis). Serum ferritin and OSI could become newer personalized theranostic and monitoring targets in overweight/obese pregnant females especially GDM patients.

Cost-Effectiveness Analysis of Sacubitril/Valsartan Compared to Enalapril for Heart Failure Patients in Indonesia.

OBJECTIVE: Sacubitril/valsartan is a relatively new medication that is more effective than the usual enalapril for heart failure patients with reduced ejection fraction. Therefore, this study aims to determine the cost-effectiveness of sacubitril/valsartan compared to enalapril in Indonesia's healthcare system. METHODS: In this study, a Markov decision-analytic model was developed to estimate the total cost, health outcomes, and cost-effectiveness of sacubitril/valsartan compared to enalapril from Indonesia's healthcare perspective. The input parameters for the cost-effectiveness were predominantly from the PARADIGM-HF trial. Subsequently, the country-specific data were synthesized for medication and hospitalization costs, cardiovascular and non-cardiovascular death, as well as re-hospitalization rate. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) gained was estimated to determine the cost-effectiveness. Deterministic and probabilistic sensitivity analyses were conducted to assess the impact of parameter uncertainty. RESULTS AND DISCUSSION: In the base case, sacubitril/valsartan was more costly and effective than enalapril with a total cost of IDR 91,783,325,865 (USD 6,487,522) vs IDR 68,101,971,241 (USD 4,813,653) and a total QALYs of 19,680 vs 18,795, resulting in an ICER of IDR 26,742,098 (USD 1890). Based on the willingness to pay threshold GDP per capita in Indonesia, it can be considered cost-effective. The most influential drivers of cost-effectiveness in deterministic sensitivity analysis were risk of mortality outside hospitalization, hospital admission rate, and cost of sacubitril/valsartan. The vast majority of simulation results from probabilistic analysis suggested that sacubitril/valsartan was likely resulted in higher cost and improved QALYs compared with enalapril, indicating the robustness of the model. CONCLUSION: Based on the current price in Indonesia, sacubitril/valsartan can be considered a cost-effective option, although this depends heavily on the willingness to pay threshold. Further studies that incorporate real-world evidence with sacubitril/valsartan are needed to inform the decision-making process.

Mandibular mucormycosis following SARS-CoV-2 infection - A case report and review of literature.

BACKGROUND: The second wave of COVID-19 pandemic has seen an unprecedented rise in the number of mucormycosis cases worldwide and in India particularly. This otherwise rare fungal infection has become an endemic among patients who have recovered from recent SARS-CoV-2 infection. Among the different types of mucormycosis, rhino-orbital-cerebral involvement has mainly been observed in the recent surge of cases. Very few cases of mucormycosis of mandible have been reported in literature and none in COVID-19 patients. We report a case of isolated mandibular mucormycosis in a COVID- 19 patient, with no other predisposing comorbidities.Case report.A 39 year old patient recently recovered from COVID-19 presented with typical symptoms of osteomyelitis which was confirmed using computed tomography of face. He underwent thorough debridement and curettage and tissue was sent for culture, special staining and biopsy. RESULT: Diagnosis of mucormycosis was confirmed based on postoperative biopsy and special staining. He was further managed with complete course of appropriate antifungal therapy. CONCLUSION: Mucormycosis is a fulminant and aggressive infection which requires prompt diagnosis and intervention. Early referral to a maxillofacial surgeon by physicians and general dental practitioners on seeing signs and symptoms of secondary fungal infections involving maxilla or mandible in patients with history of SARS-CoV-19 infection can improve prognosis.

A phase I study of binimetinib (MEK 162), a MEK inhibitor, plus carboplatin and pemetrexed chemotherapy in non-squamous non-small cell lung cancer.

INTRODUCTION: MEK inhibition is a potential therapeutic strategy in non-small cell lung cancer (NSCLC). This phase I study evaluates the MEK inhibitor binimetinib plus carboplatin and pemetrexed in stage IV non-squamous NSCLC patients (NCT02185690). METHODS: A standard 3 + 3 dose-escalation design was used. Binimetinib 30 mg BID (dose level 1 [DL1]) or 45 mg BID (dose level 2 [DL2]) was given with standard doses of carboplatin and pemetrexed using an intermittent dosing schedule. The primary outcome was determination of the recommended phase II dose (RP2D) and safety of binimetinib. Secondary outcomes included efficacy, pharmacokinetics, and an exploratory analysis of response based on mutation subtype. RESULTS: Thirteen patients (6 DL1, 7 DL2) were enrolled: 7 KRAS, 5 EGFR, and 1 NRAS mutation. The RP2D was binimetinib 30 mg BID. Eight patients (61.5%) had grade 3/4 adverse events, with dose limiting toxicities in 2 patients at DL2. Twelve patients were evaluated for response, with an investigator-assessed objective response rate (ORR) of 50% (95% CI 21.1%-78.9%; ORR 33.3% by independent-review, IR), and disease control rate 83.3% (95% CI 51.6%-97.9%). Median progression free survival (PFS) was 4.5 months (95% CI 2.6 months-NA), with a 6-month and 12-month PFS rate of 38.5% (95% CI 19.3%-76.5%) and 25.6% (95% CI 8.9%-73.6%), respectively. In an exploratory analysis, KRAS/NRAS-mutated patients had an ORR of 62.5% (ORR 37.5% by IR) vs. 25% in KRAS/NRAS wild-type patients. In MAP2K1-mutated patients, the ORR was 42.8%. CONCLUSION: The addition of binimetinib to carboplatin and pemetrexed appears to have manageable toxicity with evidence of activity in advanced non-squamous NSCLC.

Plasticity, ligand conformation and enzyme action of Mycobacterium smegmatis MutT1.

Mycobacterium smegmatis MutT1 (MsMutT1) is a sanitation enzyme made up of an N-terminal Nudix hydrolase domain and a C-terminal domain resembling a histidine phosphatase. It has been established that the action of MutT1 on 8-oxo-dGTP, 8-oxo-GTP and diadenosine polyphosphates is modulated by intermolecular interactions. In order to further explore this and to elucidate the structural basis of its differential action on 8-oxo-NTPs and unsubstituted NTPs, the crystal structures of complexes of MsMutT1 with 8-oxo-dGTP, GMPPNP and GMPPCP have been determined. Replacement soaking was used in order to ensure that the complexes were isomorphous to one another. Analysis of the structural data led to the elucidation of a relationship between the arrangements of molecules observed in the crystals, molecular plasticity and the action of the enzyme on nucleotides. The dominant mode of arrangement involving a head-to-tail sequence predominantly leads to the generation of NDPs. The other mode of packing arrangement appears to preferentially generate NMPs. This work also provides interesting insights into the dependence of enzyme action on the conformation of the ligand. The possibility of modulating the enzyme action through differences in intermolecular interactions and ligand conformations makes MsMutT1 a versatile enzyme.

Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma.

BACKGROUND: Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial. METHODS: Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers. RESULTS: In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47-0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65-1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13-0.70). CONCLUSIONS: SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS. CLINICAL TRIAL REGISTRATION: ISRCTN71070888; ClinialTrials.gov (NCT03529175).

Impact of Switch Options on the Economics of Pneumococcal Conjugate Vaccine (PCV) Introduction in Indonesia.

As one of Gavi, the Vaccine Alliance (previously the Global Alliance for Vaccines and Immunization), graduating countries, Indonesia is still eligible to access Gavi price for PCV13, PCV10 A and B. This study aims to estimate the economic impact of switch from the existing product/presentation of PCV (single-dose of PCV13) to the new product/presentation of PCV (multi-dose of PCV13, PCV10 A and B) since PCV is one of the most expensive vaccines in the Expanded Program on Immunization (EPI) schedule. Assuming that Gavi-Advance Market Commitment (AMC) price for all PCVs can be accessed in 2021, the use of multi-dose PCV13, PCV10 A and PCV10 B with Gavi-AMC price in 2021-2024 were considered as respective scenarios. The result showed that the scenario assuming the use of single-dose of PCV13 with contract price in 2019-2020 that would be switched into multi-dose of PCV10 B with Gavi-AMC price in 2021-2024 resulted in the highest potential saving, compared with other scenarios. Our analysis suggests an economic advantage to switch from single-dose into a multi-dose presentation. Vaccination coverage, vaccine price, vaccine wastage and additional Gavi-AMC vaccine costs were considered to be the most influential parameter affecting the savings in all scenarios. Applying the effectiveness of PCV13 and PCV10 A on reducing the risk for invasive pneumococcal disease (IPD), potential averted incidence of IPD in children under one year of age during 2019-2024 would be 246,164 and 105,587 in both scenarios. Despite the result confirmed that PCV13 may provide an additional benefit, a more comprehensive economic evaluation study is required to investigate further the comparison of cost-effectiveness values among all PCVs in Indonesia.

A Case Report of the Clinico-radiologic Challenges of Assessing Treatment Response after Stereotactic Radiation of Oligometastases Preceded by Immunotherapy: Pseudoprogression, Mixed Response Patterns, and Opportunities for Precision Radiation.

As immunotherapy continues to translate to the clinic and is combined with existing modalities, such as radiation therapy, novel treatment response patterns have been observed which complicate conventional clinical assessment and management. Herein, we describe a case study of a patient with non-small cell lung cancer treated initially with definitive chemoradiation who subsequently developed oligorecurrent disease which was managed with nivolumab and then comprehensive salvage stereotactic radiation. Serial radiographic assessment had shown worsening at these limited sites of disease after initiating immunotherapy, improvement after radiation, and then heterogeneous response behavior across sites during longer-term follow-up. Given the dual effects ablative radiation may have in the context of global immune checkpoint inhibition, both cytotoxic and synergistic immune-related, assessment of treatment response to such treatment is complicated. Such assessment is further complicated by novel immunotherapy response phenomena, e.g. pseudoprogression, which are being uncovered and are not fully characterized. Current clinical and radiologic assessment strategies are inadequate to interrogate and discern between immunomodulation-influenced response behavior and further diagnostic innovation is warranted to meet the needs of evolving clinical practice in the era of immunotherapy.