Survival prediction of glioblastoma patients—are we there yet? A systematic review of prognostic modeling for glioblastoma and its clinical potential

Glioblastoma is associated with a poor prognosis. Even though survival statistics are well-described at the population level, it remains challenging to predict the prognosis of an individual patient despite the increasing number of prognostic models. The aim of this study is to systematically review the literature on prognostic modeling in glioblastoma patients. A systematic literature search was performed to identify all relevant studies that developed a prognostic model for predicting overall survival in glioblastoma patients following the PRISMA guidelines. Participants, type of input, algorithm type, validation, and testing procedures were reviewed per prognostic model. Among 595 citations, 27 studies were included for qualitative review. The included studies developed and evaluated a total of 59 models, of which only seven were externally validated in a different patient cohort. The predictive performance among these studies varied widely according to the AUC (0.58–0.98), accuracy (0.69–0.98), and C-index (0.66–0.70). Three studies deployed their model as an online prediction tool, all of which were based on a statistical algorithm. The increasing performance of survival prediction models will aid personalized clinical decision-making in glioblastoma patients. The scientific realm is gravitating towards the use of machine learning models developed on high-dimensional data, often with promising results. However, none of these models has been implemented into clinical care. To facilitate the clinical implementation of high-performing survival prediction models, future efforts should focus on harmonizing data acquisition methods, improving model interpretability, and externally validating these models in multicentered, prospective fashion.

     

Breast milk feeding rates of mothers of multiples compared to mothers of singletons.

OBJECTIVE: Over 3% of infants born annually in the United States are from a multiple gestation pregnancy, yet there is little data published about the feeding practices of their mothers. The objectives of this study were to determine and compare the rates of breast milk feeding of mothers of multiples and mothers of singletons. METHODS: Stratified random sampling (n = 686) on the basis of plurality of pregnancy and gestational age at delivery was performed on a 1999 birth certificate database in the greater Cincinnati area. We collected information about infant feeding during the first 6 months of life using a retrospective, self-administered questionnaire and phone interview from mothers of term singletons (TS), preterm singletons (PS), term multiples (TM), and preterm multiples (PM). Data were analyzed using chi-square and logistic or multiple regression. RESULTS: We obtained feeding information from 346 mothers (n = 81 TS, 80 PS, 90 TM, and 95 PM). By 3 days postpartum, PM provided breast milk less often than all other groups: TS = 69%, PS = 66%, TM = 73%, PM = 57% (P =.035). Among mothers who initiated breast milk feeding, the geometric mean duration of at least some breast milk feeding was significantly shorter for PM than for all other groups: TS = 23 weeks, PS = 19 weeks, TM = 24 weeks, and PM = 12 weeks (P =.002). CONCLUSIONS: Further evaluation of the potential causes for the lower breast milk feeding rates among PM is needed to develop effective intervention strategies and increase the number of preterm multiple gestation infants receiving breast milk.     

High precision conformal radiotherapy employing conservative margins in childhood benign and low-grade brain tumours.

BACKGROUND AND PURPOSE: To report local control and follow up outcome data of high precision conformal radiotherapy in childhood brain tumours. MATERIALS AND METHODS: Between December 1999 and December 2002, 26 children (17 boys and 9 girls, median age 11.5 years) with incompletely excised or recurrent benign and low-grade brain tumours [13 craniopharyngiomas, 11 low-grade gliomas (LGG) and 2 others] were treated with three-dimensional (3D) conformal radiotherapy (CRT) (12 patients) and stereotactic conformal radiotherapy (SCRT) (14 patients). Gross tumour volume (GTV) included neuro-imaging based visible tumour and/or resected tumour bed. Clinical target volume (CTV) consisted of GTV+ 5 mm margin and planning target volume (PTV) consisted of additional 5 mm margin for CRT and 2 mm for SCRT. Treatment was delivered with 3-9 conformal fixed fields to a median dose of 54 Gy/30 fractions. RESULTS: The actuarial 2 and 3 year disease free and overall survival was 96 and 100%, respectively (median follow up: 25 months, range 12-47 months). Radiological follow up available in 25 patients revealed complete response in 1, partial regression in 10, stable disease in 13 and progression in 1 patient (within the CTV). One patient with craniopharyngioma on a routine imaging revealed a mild asymptomatic cyst enlargement, which resolved with conservative management. A patient with chiasmatic glioma developed cystic degeneration and hydrocephalus 9 months after SCRT requiring cyst drainage and placement of a ventriculoperitoneal shunt. CONCLUSION: High-precision conformal techniques delivering irradiation to a computer generated target volume employing 7-10 mm 3D margins beyond the visible tumour and/or resected tumour bed appear to be safe in children with incompletely resected or recurrent benign and low-grade brain tumours, based on these data.     

Statin-induced necrotizing autoimmune myopathy: a systematic review

Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing autoimmune myopathy in some patients. We reviewed case reports of 80 patients from 2010 to present diagnosed with statin-induced necrotizing autoimmune myopathy (SINAM), aiming to analyze the clinical, physiological, serologic characteristics and outcomes of SINAM. The mean age of these patients was 66 ±9.4, the majority being male (61.3%). All patients reported proximal muscle weakness, and a few had myalgias, extra muscular symptoms such as dysphagia, and pulmonary complications. Most of the patients were on atorvastatin, simvastatin, or rosuvastatin. The mean creatine kinase was 10,094.2 ±7,351.7 U/l, and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme was positive for 93.8% of patients. The majority of patients were started on steroids; other treatments were also used. Prompt cessation of statins and initiation of immunosuppressants reduced morbidity and mortality.     

Transforming growth factor-β signaling modifies the hematopoietic acute inflammatory response to drive bone marrow failure

Bone marrow failure syndromes are characterized by ineffective hematopoiesis due to impaired fitness of hematopoietic stem cells. They can be acquired during bone marrow stress or innate and are associated with driver genetic mutations. Patients with a bone marrow failure syndrome are at higher risk of developing secondary neoplasms, including myelodysplastic syndromes and leukemia. Despite the identification of genetic driver mutations, the hematopoietic presentation of the disease is quite heterogeneous, raising the possibility that non-genetic factors contribute to the pathogenesis of the disease. The role of inflammation has emerged as an important contributing factor, but remains to be understood in detail. In this study, we examined the effect of increased transforming growth factor-b (TGFb) signaling, in combination or not with an acute innate immune challenge using polyinosinc:polycytidilic acid (pIC), on the hematopoietic system without genetic mutations. We show that acute rounds of pIC alone drive a benign age-related myeloid cell expansion and increased TGFb signaling alone causes a modest anemia in old mice. In sharp contrast, increased TGFb signaling plus acute pIC challenge result in chronic pancytopenia, expanded hematopoietic stem and progenitor cell pools, and increased bone marrow dysplasia 3-4 months after stress, which are phenotypes similar to human bone marrow failure syndromes. Mechanistically, this disease phenotype is uniquely associated with increased mitochondrial content, increased reactive oxygen species and enhanced caspase-1 activity. Our results suggest that chronic increased TGFb signaling modifies the memory of an acute immune response to drive bone marrow failure without the need for a preexisting genetic insult. Hence, non-genetic factors in combination are sufficient to drive bone marrow failure.     

Decadal Change in Seroprevalence of Chikungunya Virus Infection in Pune City,India

Chikungunya virus (CHIKV) is an arthropod-borne virus capable of causing large outbreaks. We aimed to determine the decadal change in the extent of chikungunya virus infection from 2009 to 2019. We implemented a prospective cross-sectional survey in Pune City using a 30-cluster approach with probability-proportion-to-size (PPS) sampling, with blood samples collected from 1654 participants in early 2019. The study also included an additional 799 blood samples from an earlier serosurvey in late 2009. The samples were tested by an in-house anti-CHIKV IgG ELISA assay. The overall seroprevalence in 2019 was 53.2% (95% CI 50.7–55.6) as against 8.5% (95% CI 6.5–10.4) in 2009. A fivefold increase in seroprevalence was observed in a decade (p < 0.00001). The seroprevalence increased significantly with age; however, it did not differ between genders. Modeling of age-stratified seroprevalence data from 2019 coincided with a recent outbreak in 2016 followed by the low-level circulation. The mean estimated force of infection during the outbreak was 35.8% (95% CI 2.9–41.2), and it was 1.2% after the outbreak. To conclude, the study reports a fivefold increase in the seroprevalence of chikungunya infection over a decade in Pune City. The modeling approach considering intermittent outbreaks with continuous low-level circulation was a better fit and coincided with a recent outbreak reported in 2016. Community engagement and effective vector control measures are needed to avert future chikungunya outbreaks.     

Travel Distance and Home Dialysis Rates in the United States

♦ Introduction: Rural residence is associated with increased peritoneal dialysis (PD) utilization. The influence of travel distance on rates of home dialysis utilization has not been examined in the United States. The purpose of this study was to determine whether travel distances to the closest home and in-center hemodialysis (IHD) facilities are a barrier to home dialysis.♦ Methods: This was a retrospective cohort study of patients aged ≥ 18 years initiating dialysis between 2005 and 2011. Unadjusted PD and home hemodialysis (HHD) rates were compared by travel distances to both the closest home dialysis and closest IHD facilities. Adjusted PD and HHD utilization rates were examined using multivariable logistic regression models.♦ Results: There were 98,608 patients in the adjusted analyses. 55.5% of the dialysis facilities offered home dialysis. IHD, PD and HHD patients traveled median distances of 5.4, 3.5 and 6.6 miles respectively to their initial dialysis facilities. Unadjusted analyses showed an increase in PD rates and decrease in HHD rates with increased travel distances. Adjusted odds of PD and HHD were 1.6 and 1.2 respectively for a ten mile increase in distance to the closest home dialysis facility, while for distances to the closest IHD facility the odds ratios for both PD and HHD were 0.7 (all p < 0.01).♦ Conclusions: In metropolitan areas, PD and HHD generally increased with increased travel distance to the closest home dialysis facility and decreased with greater distance to an IHD facility. Examination of travel distances to PD and HHD facilities separately may provide further insight on specific barriers to these modalities which can serve as targets for future studies examining expansion of home dialysis utilization.     

Congenital anatomic variants of the kidney and ureter: a pictorial essay

Congenital renal parenchymal and pelvicalyceal abnormalities have a wide spectrum. Most of them are asymptomatic, like that of ectopia, cross fused kidney, horseshoe kidney, etc., while a few of them become complicated, leading to renal failure and death. It is very important for the radiologist to identify these anatomic variants and guide the clinicians for surgical and therapeutic procedures. Cross-sectional imaging with a volume rendered technique/maximum intensity projection has overcome ultrasonography and IVU for identification and interpretation of some of these variants.