Global Case Fatality of Bacterial Meningitis During an 80-Year Period: A Systematic Review and Meta-Analysis.

Importance: The impact of vaccination, antibiotics, and anti-inflammatory treatment on pathogen distribution and outcome of bacterial meningitis over the past century is uncertain. Objective: To describe worldwide pathogen distribution and case fatality ratios of community-acquired bacterial meningitis. Data Sources: Google Scholar and MEDLINE were searched in January 2022 using the search terms bacterial meningitis and mortality. Study Selection: Included studies reported at least 10 patients with bacterial meningitis and survival status. Studies that selected participants by a specific risk factor, had a mean observation period before 1940, or had more than 10% of patients with health care-associated meningitis, tuberculous meningitis, or missing outcome were excluded. Data Extraction and Synthesis: Data were extracted by 1 author and verified by a second author. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Random-effects models stratified by age (ie, neonates, children, adults), Human Development Index (ie, low-income or high-income countries), and decade and meta-regression using the study period's year as an estimator variable were used. Main Outcome and Measure: Case fatality ratios of bacterial meningitis. Results: This review included 371 studies performed in 108 countries from January 1, 1935, to December 31, 2019, describing 157 656 episodes. Of the 33 295 episodes for which the patients' sex was reported, 13 452 (40%) occurred in females. Causative pathogens were reported in 104 598 episodes with Neisseria meningitidis in 26 344 (25%) episodes, Streptococcus pneumoniae in 26 035 (25%) episodes, Haemophilus influenzae in 22 722 (22%), other bacteria in 19 161 (18%) episodes, and unidentified pathogen in 10 336 (10%) episodes. The overall case fatality ratio was 18% (95% CI, 16%-19%), decreasing from 32% (95% CI, 24%-40%) before 1961 to 15% (95% CI, 12%-19%) after 2010. It was highest in meningitis caused by Listeria monocytogenes at 27% (95% CI, 24%-31%) and pneumococci at 24% (95% CI, 22%-26%), compared with meningitis caused by meningococci at 9% (95% CI, 8%-10%) or H influenzae at 11% (95% CI, 10%-13%). Meta-regression showed decreasing case fatality ratios overall and stratified by S pneumoniae, Escherichia coli, or Streptococcus agalactiae (P < .001). Conclusions and Relevance: In this meta-analysis with meta-regression, declining case fatality ratios of community-acquired bacterial meningitis throughout the last century were observed, but a high burden of disease remained.

Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial.

Graft-versus-host disease (GVHD) is the most important complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). We performed a prospective randomized, multicenter, phase 3 trial to study whether posttransplant cyclophosphamide (PT-Cy) combined with a short course of cyclosporine A (CsA) would result in a reduction of severe GVHD and improvement of GVHD-free, relapse-free survival (GRFS) as compared with the combination of CsA and mycophenolic acid (MPA) after nonmyeloablative (NMA) matched related and unrelated peripheral blood alloHSCT. Between October 2013 and June 2018, 160 patients diagnosed with a high-risk hematological malignancy and having a matched related or at least 8 out of 8 HLA-matched unrelated donor were randomized and allocated in a 1:2 ratio to CsA/MPA or PT-Cy/CsA; a total of 151 patients were transplanted (52 vs 99 patients, respectively). The cumulative incidence of grade 2 to 4 acute GVHD at 6 months was 48% in recipients of CsA/MPA vs 30% following PT-Cy/CsA (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.82; P = .007). The 2-year cumulative incidence of extensive chronic GVHD was 48% vs 16% (HR, 0.36; 95% CI, 0.21-0.64; P < .001). The 1-year estimate of GRFS was 21% (11% to 32%) vs 45% (35% to 55%), P < .001. With a median follow-up of 56.4 months, relapse incidence, progression-free survival, and overall survival were not significantly different between the 2 treatment arms. PT-Cy combined with a short course of CsA after NMA matched alloHSCT significantly improves GRFS due to a significant reduction in severe acute and chronic GVHD.

Quality of Life Changes After Surgery for Metastatic Spinal Disease: A Systematic Review and Meta-analysis.

STUDY DESIGN: This was a systematic review and meta-analysis. OBJECTIVE: A systematic review and meta-analysis was conducted to assess the quality of life (QoL) after open surgery for spinal metastases, and how surgery affects physical, social/family, emotional, and functional well-being. SUMMARY OF BACKGROUND DATA: It remains questionable to what extent open surgery improves QoL for metastatic spinal disease, it would be interesting to quantify the magnitude and duration of QoL benefits-if any-after surgery for spinal metastases. MATERIALS AND METHODS: Included were studies measuring QoL before and after nonpercutaneous, open surgery for spinal metastases for various indications including pain, spinal cord compression, instability, or tumor control. A random-effect model assessed standardized mean differences (SMDs) of summary QoL scores between baseline and 1, 3, 6, or 9-12 months after surgery. RESULTS: The review yielded 10 studies for data extraction. The pooled QoL summary score improved from baseline to 1 month (SMD=1.09, P<0.001), to 3 months (SMD=1.28, P<0.001), to 6 months (SMD=1.21, P<0.001), and to 9-12 months (SMD=1.08, P=0.001). The surgery improved physical well-being during the first 3 months (SMD=0.94, P=0.022), improved emotional (SMD=1.19, P=0.004), and functional well-being (SMD=1.08, P=0.005) during the first 6 months, and only improved social/family well-being at month 6 (SMD=0.28, P=0.001). CONCLUSIONS: The surgery improved QoL for patients with spinal metastases, and rapidly improved physical, emotional, and functional well-being; it had minimal effect on social/family well-being. However, choosing the optimal candidate for surgical intervention in the setting of spinal metastases remains paramount: otherwise postoperative morbidity and complications may outbalance the intended benefits of surgery. Future research should report clear definitions of selection criteria and surgical indication and provide stratified QoL results by indication and clinical characteristics such as primary tumor type, preoperative Karnofsky, and Bilsky scores to elucidate the optimal candidate for surgical intervention.

Unexpected neurologic complications following a novel lymphoma treatment 'expected' to give rise to neurologic toxicity.

Chimeric antigen receptor (CAR) T-cell therapy is a novel and promising form of cellular immunotherapy using genetically engineered, tumour-specific autologous T cells. CD19-specific CAR T-cells have been shown to be very effective as a treatment for relapsed/refractory B-cell acute lymphoblastic leukaemia and aggressive B-cell non-Hodgkin's lymphoma. ICANS (immune effector cell-associated neurotoxicity syndrome) is one of the most frequently occurring toxicities of CAR T-cell treatment. We describe two cases of patients with neurologic symptoms following CAR T-cell infusion who were suspected to have ICANS, but in fact had cerebral toxoplasmosis and venous sinus thrombosis respectively. The focus on CRS and ICANS after CAR T-cell infusion may lead to less vigilance to the 'normal' threats faced by intensively pretreated patients with lymphoma such as infections and thrombosis. Both cases underscore the importance of a broad and thorough examination of patients if they experience neurologic symptoms after CAR T-cell treatment.

The FOUR score as predictor of outcome in adults with bacterial meningitis.

OBJECTIVES: To evaluate the Full Outline of Unresponsiveness (FOUR) score as a predictor of outcome in adult patients with bacterial meningitis. METHODS: We selected 427 patients from a nationwide, prospective cohort on community-acquired bacterial meningitis included from August 2011 to November 2016. Data on patient history, symptoms and signs on admission, treatment, and outcome were collected. We compare the FOUR score with the Glasgow Coma Scale (GCS) score, performed a receiver operator characteristic curve analysis, and calculated the area under the curve (AUC) of the FOUR and GCS scores for the prediction of unfavorable outcome and mortality. RESULTS: The median FOUR score on admission was 14 (interquartile range [IQR] 12-16), and the median GCS score was 12 (IQR 9-14). The outcome was unfavorable in 135 of 427 (32%) patients, of whom 55 (13%) died. There was a strong correlation between the FOUR score and the GCS score (r = 0.85, p < 0.001). AUCs for the GCS and FOUR scores in the prediction of unfavorable outcome (both 0.64) and mortality (both 0.68) were comparable. Logistic regression analysis showed that the FOUR motor, brainstem, and respiration items were individual predictors of unfavorable outcome and mortality. For the GCS score, only the motor component was predictive, while the FOUR score provided a spectrum of clinical abnormalities in patients with a GCS score of 3. CONCLUSIONS: The FOUR score adds considerably to the prediction of outcome in patients with severe meningitis by means of better testing of the brainstem reflexes and respiration status. Future studies should consider incorporating the FOUR score into clinical assessment.

Baseline Renal Function and Albumin are Powerful Predictors for Allogeneic Transplantation-Related Mortality.

Biomarkers measured in blood chemistry before allogeneic hematopoietic stem cell transplantation (HSCT) may reflect patients' physiological status. We hypothesized that selected markers are predictive for nonrelapse mortality (NRM) following transplantation and could contribute to risk assessment. We investigated the value of pre-HSCT albumin, estimated glomerular filtration rate (eGFR), and alkaline phosphatase (AlkP) in predicting NRM. We retrospectively analyzed clinical and laboratory data from 1217 patients receiving a first HSCT in 2 European centers between 2003 and 2015. Transplantation indications and conditioning regimens were diverse. Patients had a median age of 55 years and hematopoietic cell transplantation comorbidity index (HCT-CI) scores of 0 (24%), 1 to 2 (39%), and ≥3 (37%). Cutoffs of eGFR <60 mL/min, albumin <3.5 g/dL, and AlkP >180 IU/L corresponded with 8.8%, 8.3%, and 6.5% of the patients, respectively. eGFR and albumin were associated with increased risk and higher cumulative incidence of day-100, 1-year, and 2-year NRM, both as continuous or categorized variables. A similar pattern was observed for AlkP, except for day-100 NRM. In multivariable analyses, eGFR and albumin were consistently among the top risk factors for early and late-term NRM, abrogating the role of age. Prediction models for day-100, 1-year, and 2-year NRM based only on HCT-CI resulted in c-statistics of .565, .575, and .577, respectively. Addition of both biomarkers increased c-statistics for day-100, 1-year, and 2-year NRM to .651, .633, and .624, respectively. Albumin and eGFR are prognostic biomarkers for NRM after HSCT and improve the discriminative power of the HCT-CI.

Etanercept for steroid-refractory acute graft-versus-host disease: A single center experience.

BACKGROUND: Acute graft-versus-host disease (aGVHD) is an important complication of allogeneic stem cell transplantation (alloSCT). High dose glucocorticosteroids, are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients. No standard second-line regimen has been established. Different options have been reported, including anti-TNFα antibodies. METHODS: We retrospectively reviewed the outcome of 15 patients with steroid-refractory (SR) aGVHD treated with etanercept at our institution. Patients were transplanted for a hematological malignancy and received either a myeloablative or a non-myeloablative conditioning regimen. Prophylaxis of GVHD consisted of cyclosporin A and mycophenolic acid. RESULTS: Acute GVHD was diagnosed at a median of 61 days post-transplantation. All patients had grade III aGVHD of the gut. Second-line treatment with etanercept was started at a median of 13 days after initiation of first-line therapy. Overall response rate was 53%, with CR in 3 patients and PR in 5 patients. Median overall survival after initiation of treatment with etanercept was 66 days (range 5-267) for the entire group. Median overall survival was 99 days (range 47-267 days) for responders and 17 days (range 5-66 days) for non-responders (p<0.01). Nevertheless, all patients died. Causes of death were progressive GVHD in 7 patients (47%), infection in 6 patients (40%), cardiac death in 1 patient (6.7%) and relapse in 1 patient (6,7%). CONCLUSION: Second-line treatment with etanercept does induce responses in SR-aGVHD of the gut but appears to be associated with poor long-term survival even in responding patients.

The SORG nomogram accurately predicts 3- and 12-months survival for operable spine metastatic disease: External validation.

BACKGROUND AND OBJECTIVES: Externally validate the SORG12 nomogram and SORG classic algorithm at estimating survival in patients with spine metastatic disease, and compare predictive accuracy with other survival algorithms. METHODS: We received data from 100 patients who had surgery for spine metastatic disease at an external institution. Algorithms were accurate if the Area Under Curve (AUC) was >0.70, and we used Receiver Operating Characteristic (ROC) analysis to compare predictive accuracy with other algorithms. RESULTS: The SORG nomogram accurately estimated 3-months (AUC = 0.74) and 12-months survival (AUC = 0.78); it did not accurately estimate 1-month survival (AUC = 0.65). There was no difference in 1-month survival accuracy between the SORG nomogram and SORG classic algorithm (P = 0.162). The SORG nomogram was best at predicting 3-months survival, compared with the Tokuhashi score and SORG classic algorithm (P = 0.009). The SORG nomogram was best at predicting 12-months survival, compared with the Tomita score, Ghori score, Bauer modified score, Tokuhashi score, and SORG classic algorithm (P = 0.033). CONCLUSIONS: The SORG nomogram accurately estimated 3- and 12-months survival for operable spine metastatic disease, and is therefore, useful in clinical practice.

Prospective non-interventional multicentre observational trial of first-line anti-cancer treatment in patients with metastatic renal cell cancer in Belgium.

OBJECTIVES: Renal cell carcinoma (RCC) accounts for 2·4% of all new cancers in Belgium. Over the past decade, the armamentarium for systemic therapy of metastatic RCC (mRCC) has undergone important changes with implementation of targeted therapies directed against pathways involved in the pathogenesis of RCC. We describe first-line treatment choice of a group of patients in 9 Belgian oncology centres between October 2009 and November 2012. METHODS: A clinical report form was established to assess patient characteristics, Karnofsky performance score, Memorial Sloan-Kettering Cancer Center risk criteria (MSKCC) and first-line therapy of mRCC patients. Choice of therapy and starting dose was analyzed before and after reimbursement of pazopanib in Belgium. RESULTS: Ninety-six patients were eligible for the study. Non-smokers accounted for 53% of the patients. Seventy-three per cent of the patients had 0 or 1 MSKCC criteria in the group of patients that started treatment more than 1 year after initial diagnosis. In the group of patients that started therapy less than 1 year after diagnosis, 85% had 2 or more MSKCC criteria. This difference was statistically significant (P<0·0001). Overall distribution of the first-line therapies consisted of 43% sunitinib, 33% pazopanib, 14% temsirolimus, 7% everolimus and 3% sorafenib. Seventeen (18%) out of 96 patients started at a reduced dose level. CONCLUSION: This report shows that the guidelines for the start of first-line treatment in mRCC in 9 centres in Belgium were applied most of the time: a tyrosine kinase inhibitor was the first treatment choice for most patients while temsirolimus was an option for poor prognosis patients. In the majority of patients standard dose levels were initiated, although in some patients adaptation of dosage/treatment schedule was recorded.

Osteoporosis and radial head fractures in female patients: a case-control study.

BACKGROUND: Identifying radial head fractures as fragility fractures may improve case-findings for osteoporosis and thus be an indicator other fragility fractures. MATERIALS AND METHODS: Thirty-five women aged ≥ 50 years with a radial head fracture and 57 controls were retrospectively selected and matched for age in strata of 5 years. Peripheral bone mineral density (BMD) measurement was performed at the calcaneus. A T score of less than -2.7 was considered osteoporosis. If the T value was between -1.4 and -2.7, an additional dual energy X-ray (DXA) scan was performed. RESULTS: The patients were a median age of 60 years compared with 58 years for the control patients (P = .33). The mean T score of the patients was -1.8 (standard deviation [SD], 1.0; range, -2.2 to -0.3) compared with -1.2 (SD, 1.2; range, -4.0 to 1.3) for the control patients (P = .04). Osteoporosis was diagnosed in 11 patients and in 5 control patients. The patients had an increased risk of osteoporosis compared with the control patients (odds ratio, 3.4; P = .027). CONCLUSIONS: This study confirms that radial head fractures in women aged ≥ 50 years are potentially osteoporotic fractures. Offering these patients a BMD measurement may prevent future osteoporotic fractures, such as hip and spine fractures.