Low skeletal muscle mass and treatment outcomes among adults with haematologic malignancies: A systematic review and meta‐analysis

Abstract Background Low skeletal muscle mass (LSMM) and/or, function associated with an increased risk of treatment‐related toxicities and inferior overall survival (OS) among adults with solid malignancies. However, the association between LSMM and treatment‐related toxicities among adults with haematologic malignancies remains unclear. Methods Using a pre‐published protocol (CRD42020197814), we searched seven bibliographic databases from inception to 08/2021 for studies reporting the impact of LSMM among adults ≥18 years with a known haematologic malignancy. The primary outcome of interest was OS, and secondary outcomes included progression free survival (PFS) and non‐relapse mortality (NRM). These effect sizes were quantified in terms of hazards ratio (HR) along with 95% confidence interval (CI) and pooled across studies using a DerSimonian–Laird random‐effects model. Heterogeneity was assessed using the Cochran's Q and the I2 statistic. All hypothesis testing was two‐sided with an alpha of 0.05. Results Of 3791 studies screened, we identified 20 studies involving 3468 patients with a mean age of 60 years; 44% were female and the most common malignancy was diffuse large B‐cell lymphoma (42%). Most studies measured muscle mass using single slice computed tomography imaging at the L3 level. The presence of LSMM was associated with worse OS (pooled HR = 1.81, 95% CI = 1.48–2.22, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 60.4%), PFS (pooled HR = 1.61, 95% CI = 1.28–2.02, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 66.0%). Similarly, LSMM was associated with worse NRM (HR = 1.72, 95% CI = 1.34–2.22, P < 0.001) with little evidence of heterogeneity (Cochran's Q, I2 = 0.0%). Conclusions LSMM is associated with worse survival outcomes among adults with haematologic malignancies. Further research into understanding the underlying mechanism of this association and mitigating the negative effects of LSMM among adults with haematologic malignancies is needed

History of posttraumatic stress disorder and outcomes after kidney transplantation.

A history of posttraumatic stress disorder (PTSD), if uncontrolled, represents a contraindication for kidney transplantation. However, no previous large study has assessed the association between pretransplant history of PTSD and posttransplantation outcomes. We examined 4479 US veterans who had undergone transplantation. The diagnosis of history of PTSD was based on a validated algorithm. Measured covariates were used to create a matched cohort (n&nbsp;=&nbsp;560). Associations between pretransplant PTSD and death with functioning graft, all-cause death, and graft loss were examined in survival models. Posttransplant medication nonadherence was assessed using proportion of days covered (PDC). From among 4479 veterans, 282 (6.3%) had a history of PTSD. The mean age&nbsp;±&nbsp;standard deviation (SD) of the cohort at baseline was 61&nbsp;±&nbsp;11&nbsp;years, 91% were male, and 66% and 28% of patients were white and African American, respectively. Compared to patients without a history of PTSD, patients with a history of PTSD had a similar risk of death with a functioning graft (subhazard ratio [SHR] 0.97, 95% confidence interval [CI] 0.61-1.54), all-cause death (1.05, 0.69-1.58), and graft loss (1.09, 0.53-2.26). Moreover, there was no difference in immunosuppressive drug PDC in patients with and without a history of PTSD (PDC: 98&nbsp;±&nbsp;4% vs 99&nbsp;±&nbsp;3%, P&nbsp;=&nbsp;.733 for tacrolimus; PDC: 99&nbsp;±&nbsp;4% vs 98&nbsp;±&nbsp;7%, P&nbsp;=&nbsp;.369 for mycophenolic acid). A history of PTSD in US veterans with end-stage renal disease should not on its own preclude a veteran from being considered for transplantation

History of posttraumatic stress disorder and outcomes after kidney transplantation.

A history of posttraumatic stress disorder (PTSD), if uncontrolled, represents a contraindication for kidney transplantation. However, no previous large study has assessed the association between pretransplant history of PTSD and posttransplantation outcomes. We examined 4479 US veterans who had undergone transplantation. The diagnosis of history of PTSD was based on a validated algorithm. Measured covariates were used to create a matched cohort (n&nbsp;=&nbsp;560). Associations between pretransplant PTSD and death with functioning graft, all-cause death, and graft loss were examined in survival models. Posttransplant medication nonadherence was assessed using proportion of days covered (PDC). From among 4479 veterans, 282 (6.3%) had a history of PTSD. The mean age&nbsp;±&nbsp;standard deviation (SD) of the cohort at baseline was 61&nbsp;±&nbsp;11&nbsp;years, 91% were male, and 66% and 28% of patients were white and African American, respectively. Compared to patients without a history of PTSD, patients with a history of PTSD had a similar risk of death with a functioning graft (subhazard ratio [SHR] 0.97, 95% confidence interval [CI] 0.61-1.54), all-cause death (1.05, 0.69-1.58), and graft loss (1.09, 0.53-2.26). Moreover, there was no difference in immunosuppressive drug PDC in patients with and without a history of PTSD (PDC: 98&nbsp;±&nbsp;4% vs 99&nbsp;±&nbsp;3%, P&nbsp;=&nbsp;.733 for tacrolimus; PDC: 99&nbsp;±&nbsp;4% vs 98&nbsp;±&nbsp;7%, P&nbsp;=&nbsp;.369 for mycophenolic acid). A history of PTSD in US veterans with end-stage renal disease should not on its own preclude a veteran from being considered for transplantation

A Prospective Epidemiological Study of Acute Mountain Sickness in Nepalese Pilgrims Ascending to High Altitude (4380 m)

<div><p>Background</p><p>Each year, thousands of pilgrims travel to the Janai Purnima festival in Gosainkunda, Nepal (4380 m), ascending rapidly and often without the aid of pharmaceutical prophylaxis.</p><p>Methods</p><p>During the 2012 Janai Purnima festival, 538 subjects were recruited in Dhunche (1950 m) before ascending to Gosainkunda. Through interviews, subjects provided demographic information, ratings of AMS symptoms (Lake Louise Scores; LLS), ascent profiles, and strategies for prophylaxis.</p><p>Results</p><p>In the 491 subjects (91% follow-up rate) who were assessed upon arrival at Gosainkunda, the incidence of AMS was 34.0%. AMS was more common in females than in males (RR = 1.57; 95% CI = 1.23, 2.00), and the AMS incidence was greater in subjects >35 years compared to subjects ≤35 years (RR = 1.63; 95% CI = 1.36, 1.95). There was a greater incidence of AMS in subjects who chose to use garlic as a prophylactic compared to those who did not (RR = 1.69; 95% CI = 1.26, 2.28). Although the LLS of brothers had a moderate correlation (intraclass correlation = 0.40, p = 0.023), sibling AMS status was a weak predictor of AMS.</p><p>Conclusions</p><p>The incidence of AMS upon reaching 4380 m was 34% in a large population of Nepalese pilgrims. Sex, age, and ascent rate were significant factors in the development of AMS, and traditional Nepalese remedies were ineffective in the prevention of AMS.</p></div

The ascent profile from Dhunche (1950 m) to Gosainkunda (4380 m).

<p>All subjects ascended to Gosainkunda via this route in 1, 2, or 3 days. The average grade of the ascent was approximately 12%.</p

Characteristics of Nepalese pilgrims assessed upon arrival to Gosainkunda (4380 m).

<p>Data are presented as mean (standard deviation) or as a percent.</p

The results of multiple binary logistic regression for the individual predictors of AMS in Nepalese pilgrims upon arrival to Gosainkunda (4380 m).

†<p>Males, subjects ≤35 years, and the 2-day ascent group were used as the reference categories for the calculation of odds ratios.</p>*<p>This result is significant (<i>i.e.</i>, p<0.05).</p

The frequency of Lake Louise Scores in Nepalese pilgrims (n = 491) upon arrival to Gosainkunda (4380 m).

<p>The frequency of Lake Louise Scores in Nepalese pilgrims (n = 491) upon arrival to Gosainkunda (4380 m).</p

Statistical relationships between dichotomous variables and the incidence of acute mountain sickness (AMS) in Nepalese pilgrims upon arrival to Gosainkunda (4380 m).

†<p>The age indicator was missing 3 values due to incomplete data forms.</p>‡<p>The 3-day ascent group was removed from the analysis of ascent rate data (see text).</p>*<p>This result is statistically significant (<i>i.e.</i>, p<0.05).</p