Clinical examination findings are used in primary care to give an initial diagnosis to patients with low back pain and related leg symptoms. The purpose of this study was to develop best evidence Clinical Diagnostic Rules (CDR] for the identification of the most common patho-anatomical disorders in the lumbar spine; i.e. intervertebral discs, sacroiliac joints, facet joints, bone, muscles, nerve roots, muscles, peripheral nerve tissue, and central nervous system sensitization. A sensitive electronic search strategy using MEDLINE, EMBASE and CINAHL databases was combined with hand searching and citation tracking to identify eligible studies. Criteria for inclusion were: persons with low back pain with or without related leg symptoms, history or physical examination findings suitable for use in primary care, comparison with acceptable reference standards, and statistical reporting permitting calculation of diagnostic value. Quality assessments were made independently by two reviewers using the Quality Assessment of Diagnostic Accuracy Studies tool. Clinical examination findings that were investigated by at least two studies were included and results that met our predefined threshold of positive likelihood ratio ≥ 2 or negative likelihood ratio ≤ 0.5 were considered for the CDR. Sixty-four studies satisfied our eligible criteria. We were able to construct promising CDRs for symptomatic intervertebral disc, sacroiliac joint, spondylolisthesis, disc herniation with nerve root involvement, and spinal stenosis. Single clinical test appear not to be as useful as clusters of tests that are more closely in line with clinical decision making. This is the first comprehensive systematic review of diagnostic accuracy studies that evaluate clinical examination findings for their ability to identify the most common patho-anatomical disorders in the lumbar spine. In some diagnostic categories we have sufficient evidence to recommend a CDR. In others, we have only preliminary evidence that needs testing in future studies. Most findings were tested in secondary or tertiary care. Thus, the accuracy of the findings in a primary care setting has yet to be confirmed.

Immune checkpoint inhibitors (ICIs) have improved cancer outcomes. However, immune-related adverse effects are common. The aim was to investigate the incidence of diarrhea and colitis of ICIs alone and in combination with chemotherapy or tyrosine kinase inhibitors (TKIs), histopathological findings, and management. Two separate studies, including meta-analyses, were performed. Key inclusion criteria were for Study I) phase I-IV trials, and data on diarrhea and/or colitis; for Study II) studies describing histopathologic and endoscopic findings and/or biologic treatment for ICI-induced colitis. The incidence of anti-PD-1/PD-L1 antibody-induced diarrhea and colitis was 10% and 2%, respectively, with no clinically relevant differences between the compounds. The CTLA-4 inhibitor, ipilimumab, induced diarrhea and colitis in 33% and 7% of patients, respectively, whereas the incidence of diarrhea and colitis following ipilimumab combined with nivolumab was 21%-37% and 4%-8%, depending on regimen. The incidence of all-grade diarrhea following ICIs combined with chemotherapy or TKIs was high (17%-56%), whereas only 0.5% of patients developed severe (≥grade 3) colitis. The main patterns of histopathologic presentation after PD-1/CTLA-4 inhibitor mono- or combination therapy were acute and chronic active colitis and microscopic colitis-like. Infliximab and vedolizumab were equally effective against ICI-induced colitis. Expanding treatment options include combinations of ICIs and chemotherapy/TKI with a high incidence of diarrhea and a low incidence of colitis; thus, a potential risk of overtreatment with corticosteroids exists. We suggest a more tailored approach, particularly for the management of low-grade diarrhea. Prospective clinical trials are needed to refine management.

Older patients with cancer are underrepresented in trials investigating the effect of exercise therapy. The aim of this systematic review was to investigate the effect of exercise therapy during medical antineoplastic treatment in older patients (≥ 65 years) with cancer. A systematic review following the Cochrane guidelines was performed. Randomized controlled trials were identified through a systematic literature search in MEDLINE, EMBASE, CENTRAL, and CINAHL up to December 2019. Study selection was performed independently by two reviewers. Four randomized controlled trials published between 2014 and 2019 were included comprising a total of 412 participants. Most participants were diagnosed with breast, prostate or colorectal cancer. The studies were characterized by large differences in design, interventions and outcomes, which prevented meta-analyses. The interventions ranged from 4 weeks to 12 months and involved both supervised and unsupervised exercise programs. Some evidence of beneficial effects from the interventions were documented on physical function, muscle strength, physical activity and cognitive function. No evidence of effects was found for health-related quality of life, aerobic capacity, body composition, cancer-related symptoms and side effects, or for any clinical outcomes. No adverse events were reported. Exercise therapy seems to be safe and feasible in older patients with cancer. However, due to a limited number of studies, small sample sizes and heterogeneity across study design, the effects of exercise in older patients with cancer receiving medical antineoplastic treatment are inconclusive.

Immune checkpoint inhibitors (ICIs) have improved outcomes for various malignancies. However, serious immune-related adverse events (irAEs), including neurologic complications (NAEs), may occur. The aim of this study was to examine the incidence and spectrum of NAEs and evaluate management strategies for reducing their impact. Two studies were conducted: 1) A meta-analysis of phase I-IV clinical trials involving adults with malignancies treated with ICIs, either as monotherapy, in combination with other ICIs, or with chemotherapy. The primary outcome was the incidence of (ir)NAEs, summarized using a meta-analysis with a random-effects model. 2) A systematic review of the literature addressing the clinical manifestations and treatment of irNAEs. The meta-analysis included 657 unique trials with 91,340 participants. For all ICIs, the incidence of all-grade NAEs was 0.24% (95% CI, 0.15-0.32%). Cerebral events, cerebrovascular accidents, were increased post-treatment and accounted for 54% of all grade-5 events in clinical trials. Among 991 reported irNAE cases, 77% of patients improved with treatment; however, 42% experienced unresolved sequelae and the overall mortality rate was 17.1%. Among patients with overlapping myasthenia gravis, myositis, and myocarditis ("Triple M"), the mortality reached 38%; primarily due respiratory failure (50%) or cardiotoxicity (41%). Although the incidence of ICI-related NAEs is low such side effects may lead to severe morbidity and mortality. In patients with Triple M syndrome intensive respiratory function monitoring and support are essential parameters to improve the outcome. PROSPERO Protocol # CRD42023463750.

Reports vary considerably concerning characteristics of patients who will respond to mobilizing exercises or manipulation. The objective of this prospective cohort study was to identify characteristics of patients with a changeable lumbar condition, i.e. presenting with centralization or peripheralization, that were likely to benefit the most from either the McKenzie method or spinal manipulation. 350 patients with chronic low back pain were randomized to either the McKenzie method or manipulation. The possible effect modifiers were age, severity of leg pain, pain-distribution, nerve root involvement, duration of symptoms, and centralization of symptoms. The primary outcome was the number of patients reporting success at two months follow-up. The values of the dichotomized predictors were tested according to the prespecified analysis plan. No predictors were found to produce a statistically significant interaction effect. The McKenzie method was superior to manipulation across all subgroups, thus the probability of success was consistently in favor of this treatment independent of predictor observed. When the two strongest predictors, nerve root involvement and peripheralization, were combined, the chance of success was relative risk 10.5 (95% CI 0.71-155.43) for the McKenzie method and 1.23 (95% CI 1.03-1.46) for manipulation (P = 0.11 for interaction effect). We did not find any baseline variables which were statistically significant effect modifiers in predicting different response to either McKenzie treatment or spinal manipulation when compared to each other. However, we did identify nerve root involvement and peripheralization to produce differences in response to McKenzie treatment compared to manipulation that appear to be clinically important. These findings need testing in larger studies. Clinicaltrials.gov: NCT00939107