Larger spleens and greater splenic contraction during exercise may be an adaptive characteristic of Nepali Sherpa at high-altitude.

OBJECTIVES: The Sherpa ethnic group living at altitude in Nepal may have experienced natural selection in response to chronic hypoxia. We have previously shown that Sherpa in Kathmandu (1400 m) possess larger spleens and a greater apnea-induced splenic contraction compared to lowland Nepalis. This may be significant for exercise capacity at altitude as the human spleen responds to stress-induced catecholamine secretion by an immediate contraction, which results in transiently elevated hemoglobin concentration ([Hb]). METHODS: To investigate splenic contraction in response to exercise at high-altitude (4300 m; Pb = ~450 Torr), we recruited 63 acclimatized Sherpa (29F) and 14 Nepali non-Sherpa (7F). Spleen volume was measured before and after maximal exercise on a cycle ergometer by ultrasonography, along with [Hb] and oxygen saturation (SpO2). RESULTS: Resting spleen volume was larger in the Sherpa compared with Nepali non-Sherpa (237 ± 62 vs. 165 ± 34 mL, p < .001), as was the exercise-induced splenic contraction (Δspleen volume, 91 ± 40 vs. 38 ± 32 mL, p < .001). From rest to exercise, [Hb] increased (1.2 to 1.4 g.dl-1), SpO2 decreased (~9%) and calculated arterial oxygen content (CaO2) remained stable, but there were no significant differences between groups. In Sherpa, both resting spleen volume and the Δspleen volume were modest positive predictors of the change (Δ) in [Hb] and CaO2 with exercise (p-values from .026 to .037 and R2 values from 0.059 to 0.067 for the predictor variable). CONCLUSIONS: Larger spleens and greater splenic contraction may be an adaptive characteristic of Nepali Sherpa to increase CaO2 during exercise at altitude, but the direct link between spleen size/function and hypoxia tolerance remains unclear.

Differential splenic responses to hyperoxic breathing at high altitude in Sherpa and lowlanders.

The human spleen contracts in response to stress-induced catecholamine secretion, resulting in a temporary rise in haemoglobin concentration ([Hb]). Recent findings highlighted enhanced splenic response to exercise at high altitude in Sherpa, possibly due to a blunted splenic response to hypoxia. To explore the potential blunted splenic contraction in Sherpas at high altitude, we examined changes in spleen volume during hyperoxic breathing, comparing acclimatized Sherpa with acclimatized individuals of lowland ancestry. Our study included 14 non-Sherpa (7 female) residing at altitude for a mean continuous duration of 3 months and 46 Sherpa (24 female) with an average of 4 years altitude exposure. Participants underwent a hyperoxic breathing test at altitude (4300 m; barrometric pressure = âˆ¼430 torr; P O 2 ${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$  = âˆ¼90 torr). Throughout the test, we measured spleen volume using ultrasonography and monitored oxygen saturation ( S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ). During rest, Sherpa exhibited larger spleens (226 ± 70 mL) compared to non-Sherpa (165 ± 34 mL; P < 0.001; effect size (ES) = 0.95, 95% CI: 0.3-1.6). In response to hyperoxia, non-Sherpa demonstrated 22 ± 12% increase in spleen size (35 ± 17 mL, 95% CI: 20.7-48.9; P < 0.001; ES = 1.8, 95% CI: 0.93-2.66), while spleen size remained unchanged in Sherpa (-2 ± 13 mL, 95% CI: -2.4 to 7.3; P = 0.640; ES = 0.18, 95% CI: -0.10 to 0.47). Our findings suggest that Sherpa and non-Sherpas of lowland ancestry exhibit distinct variations in spleen volume during hyperoxia at high altitude, potentially indicating two distinct splenic functions. In Sherpa, this phenomenon may signify a diminished splenic response to altitude-related hypoxia at rest, potentially contributing to enhanced splenic contractions during physical stress. Conversely, non-Sherpa experienced a transient increase in spleen size during hyperoxia, indicating an active tonic contraction, which may influence early altitude acclimatization in lowlanders by raising [Hb].

Comparison of the Efficacy and Safety of Left Atrial Appendage Closure and Direct Oral Anticoagulants for Atrial Fibrillation: A Meta-Analysis of Randomized Control Trials and Observational Studies.

The aim of this study was to compare the efficacy and safety of left atrial appendage closure (LAAC) and direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF). This meta-analysis was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. Two investigators performed an online database search on PubMed, Web of Science, and Scopus databases from inception to October 31, 2023, without any language or time restrictions. Outcomes assessed in this meta-analysis included all-cause mortality, cardiovascular mortality, stroke, and major bleeding events. Eight studies were included in this meta-analysis, enrolling 7,629 participants with AF (4,287 in the DOAC group and 3,342 in the LAAC group). The pooled analysis showed that the risk of all-cause mortality was significantly higher in patients in the DOAC group compared to LAAC (relative risk (RR): 1.87, 95% confidence interval (CI): 1.50 to 2.34). The risk of cardiovascular mortality was 1.60 times higher in patients receiving DOACs compared to those receiving LAAC (RR: 1.60, 95% CI: 1.12 to 2.28). The risk of stroke was not significantly different between the two groups (RR: 1.15, 95% CI: 0.95 to 1.41). In conclusion, LAAC for AF patients proves to be safe and effective for stroke prevention, exhibiting a superior profile in terms of all-cause mortality, cardiovascular events, and major bleeding compared to oral anticoagulation (OAC). These findings prompt consideration of LAAC as a preferred treatment for cardiovascular event prevention in high-bleeding-risk patients.

Palliative Care: The Emerging Field in Bhutan.

The rise in noncommunicable diseases and initiation of cancer treatment in Bhutan, combined with a global recognition of the need for palliative care, led the country's Ministry of Health to identify the need for palliative care. A team of nurses at Jigme Dorji Wangchuck National Referral Hospital in Thimphu were recruited to launch the country's first homecare palliative program. The Bhutan Cancer Society contributed financially to this effort, and other nongovernment organizations and faculty at the Khesar Gyalpo University of Medical Sciences of Bhutan School of Nursing contributed on the academia front.