The effect of thyroid hormone therapy on muscle function, strength and mass in older adults with subclinical hypothyroidism-an ancillary study within two randomized placebo controlled trials.

BACKGROUND: loss of skeletal muscle function, strength and mass is common in older adults, with important socioeconomic impacts. Subclinical hypothyroidism is common with increasing age and has been associated with reduced muscle strength. Yet, no randomized placebo-controlled trial (RCT) has investigated whether treatment of subclinical hypothyroidism affects muscle function and mass. METHODS: this is an ancillary study within two RCTs conducted among adults aged ≥65 years with persistent subclinical hypothyroidism (thyrotropin (TSH) 4.60-19.99 mIU/l, normal free thyroxine). Participants received daily levothyroxine with TSH-guided dose adjustment or placebo and mock titration. Primary outcome was gait speed at final visit (median 18 months). Secondary outcomes were handgrip strength at 1-year follow-up and yearly change in muscle mass. RESULTS: we included 267 participants from Switzerland and the Netherlands. Mean age was 77.5 years (range 65.1-97.1), 129 (48.3%) were women, and their mean baseline TSH was 6.36 mIU/l (standard deviation [SD] 1.9). At final visit, mean TSH was 3.8 mIU/l (SD 2.3) in the levothyroxine group and 5.1 mIU/l (SD 1.8, P < 0.05) in the placebo group. Compared to placebo, participants in the levothyroxine group had similar gait speed at final visit (adjusted between-group mean difference [MD] 0.01 m/s, 95% confidence interval [CI] -0.06 to 0.09), similar handgrip strength at one year (MD -1.22 kg, 95% CI -2.60 to 0.15) and similar yearly change in muscle mass (MD -0.15 m2, 95% CI -0.49 to 0.18). CONCLUSIONS: in this ancillary analysis of two RCTs, treatment of subclinical hypothyroidism did not affect muscle function, strength and mass in individuals 65 years and older.

Prevalence and assessment of frailty in interstitial lung disease - a systematic review and meta-analysis.

BACKGROUND: Frailty is a multisystem dysregulation that challenges homeostasis and increases vulnerability towards stressors. In patients with interstitial lung diseases (ILD) frailty is associated with poorer lung function, greater physical impairment, and higher symptom burden. Our understanding of the prevalence of frailty in ILD and consequently its impact on the ILD population is limited. OBJECTIVE AND METHODS: We aimed to systematically review frailty assessment tools and to determine frailty prevalence across different ILD cohorts. Meta-analyses were used to calculate the pooled prevalence of frailty in the ILD population. RESULTS: We identified 26 studies (15 full-texts, 11 conference abstracts) including a total of 4614 patients with ILD. The most commonly used frailty assessment tools were the Fried Frailty Phenotype (FFP), the Short Physical Performance Battery (SPPB), and the cumulative Frailty Index (FI). Data allowed for meta-analyses of FFP and SPPB prevalence. The pooled prevalence of frailty was 35% (95% CI 25%-45%) by FFP, and 19% (95% CI 12%-28%) by SPPB. CONCLUSIONS: Frailty is common in ILD, with considerable variability of frailty prevalence depending on the frailty assessment tool used. These findings highlight the importance of frailty in ILD and the need for a standardized approach to frailty assessment in this population.

Autochthonous Case of Pulmonary Histoplasmosis, Switzerland.

In Europe, pulmonary histoplasmosis is rarely diagnosed except in travelers. We report a probable autochthonous case of severe chronic pulmonary histoplasmosis in an immunocompetent man in Switzerland without travel history outside of Europe. Diagnosis was achieved by histopathology, fungal culture, and serology, but the source of the infection remains speculative.

Impact on survival through consolidation radiotherapy for diffuse large B-cell lymphoma: a comprehensive meta-analysis.

Rituximab has improved response rates and overall survival in B-cell lymphoma (DLBCL). Radiotherapy is an effective treatment modality for lymphomas, but there is uncertainty on its use as consolidation after chemo-immunotherapy mainly in advanced stages. We evaluated its efficacy with a comprehensive meta-analysis and a systematic search of Pubmed, Embase, Cochrane, and abstracts from ASCO, ASH, ESMO and ASTRO published from June 1966 and December 2018. We identified 11 trials that evaluated consolidation radiotherapy following chemotherapy in a randomized fashion in 4'584 patients. The primary endpoint of this meta-analysis was PFS. As three of the eleven trials were retracted, this data is based on 2414 patients. For the primary endpoint (PFS), we found a hazard ratio (HR) of 0.77 (0.51 to 1.17, pooled (tau2: 0.25; I2: 85%), and a HR of 0.80 (0.53 to 1.21, pooled (bivariate meta-analysis). For overall survival, the HR is 0.93 (0.61 to 1.40; pooled (tau2: 0.25; I2: 74%) and 0.86 (0.58 to 1.27) in a bivariate meta-analysis. The lack of benefit did not change over time (p-value: 0.95 (tau2: 0.32; I2: 88%), and was also absent for PFS when stratifying for chemotherapy, the use of Rituximab, age, the dose of radiotherapy, application to patients in complete remission and with bulky disease. None of the trials used a PET-guided approach. This meta-analysis revealed no survival benefit when consolidation radiotherapy is given to unselected DLBCL patients following chemotherapy. These results need to be considered in future trials in the PET-CT era.

Cardiac Implantable Electronic Device-Related Infection Due to Granulicatella adiacens.

Cardiac implantable electronic device-related infection is clinically challenging. Curative treatment commonly includes system removal. A case caused by Granulicatella adiacens occurred in a 32-year-old woman. Clinical course, literature review, and biofilm investigations enabled successful antibiotic management without system removal.