Decreased oxygen availability at high altitude requires physiological adjustments allowing for adequate tissue oxygenation. One such mechanism is a slow increase in the hemoglobin concentration ([Hb]) resulting in elevated [Hb] in high-altitude residents. Diagnosis of anemia at different altitudes requires reference values for [Hb]. Our aim was to establish such values based on published data of residents living at different altitudes by applying meta-analysis and multiple regressions. Results show that [Hb]is increased in all high-altitude residents. However, the magnitude of increase varies among the regions analyzed and among ethnic groups within a region. The highest increase was found in residents of the Andes (1 g/dL/1000 m), but this increment was smaller in all other regions of the world (0.6 g/dL/1000 m). While sufficient data exist for adult males and females showing that sex differences in [Hb] persist with altitude, data for infants, children, and pregnant women are incomplete preventing such analyses. Because WHO reference values were originally based on [Hb] of South American people, we conclude that individual reference values have to be defined for ethnic groups to reliably diagnose anemia and erythrocytosis in high-altitude residents. Future studies need to test their applicability for children of different ages and pregnant women.

Background Cutibacterium species are common pathogens in periprosthetic joint infections (PJI). These infections are often treated with β-lactams or clindamycin as monotherapy, or in combination with rifampin. Clinical evidence supporting the value of adding rifampin for treatment of Cutibacterium PJI is lacking. Materials/methods In this multicenter retrospective study, we evaluated patients with Cutibacterium PJI. The primary endpoint was clinical success, defined by the absence of infection relapse or new infection within a minimal follow-up of 12 months. We used Fisher’s exact tests and Cox proportional hazards models to analyze the effect of rifampin and other factors on clinical success after PJI. Results We included 187 patients (72.2% male, median age 67 years) with a median follow-up of 36 months. The surgical intervention was two-stage exchange in 95 (50.8%), one-stage exchange in 51 (27.3%), debridement and implant retention (DAIR) in 34 (18.2%), and explantation without reimplantation in 7 (3.7%). Rifampin was included in the antibiotic regimen in 81 (43.3%) cases. Infection relapse occurred in 28 (15.0%), and new infection in 13 (7.0%) cases. In the time-to-event analysis, DAIR (adjusted HR=2.15, p=0.03) and antibiotic treatment over 6 weeks (adjusted HR=0.29, p=0.0002) significantly influenced treatment failure. We observed a tentative evidence for a beneficial effect of adding rifampin to the antibiotic treatment – though not statistically significant for treatment failure (adjusted HR=0.5, p=0.07) and not for relapses (adjusted HR=0.5, p=0.10). Conclusions We conclude that a rifampin combination is not markedly superior in Cutibacterium PJI but a dedicated prospective multicenter study is needed.

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The developing human fetus is able to cope with the physiological reduction in oxygen supply occurring in utero. However, it is not known if microvascularization of the fetus is augmented when pregnancy occurs at high altitude. Fifty-three healthy term newborns in Puno, Peru (3,840 m) were compared with sea-level controls. Pre- and postductal arterial oxygen saturation (SpO2) was determined. Cerebral and calf muscle regional tissue oxygenation was measured using near infrared spectroscopy (NIRS). Skin microcirculation was noninvasively measured using incident dark field imaging. Pre- and postductal SpO2 in Peruvian babies was 88.1 and 88.4%, respectively, which was 10.4 and 9.7% lower than in newborns at sea level (P < 0.001). Cerebral and regional oxygen saturation was significantly lower in the Peruvian newborns (cerebral: 71.0 vs. 74.9%; regional: 68.5 vs. 76.0%, P < 0.001). Transcutaneously measured total vessel density in the Peruvian newborns was 14% higher than that in the newborns born at sea level (29.7 vs. 26.0 mm/mm(2); P ≤ 0.001). This study demonstrates that microvascular vessel density in neonates born to mothers living at high altitude is higher than that in neonates born at sea level.

SummaryWe have studied prospectively the clinical course and serum concentrations of thromboxane B 2 (TxB 2 ) and leukotriene B 4 (LTB 4 ) in patients developing adult respiratory distress syndrome (ARDS) after oesophagectomy. The clinical course was assessed according to a validated ARDS score, and intra-and postoperative measurements of TxB 2 and LTB 4 in pre-and post-pulmonary blood were performed in 18 patients undergoing oesophagectomy for oesophageal carcinoma and 11 control patients undergoing thoracotomy and pulmonary resection. Six of 18 patients undergoing oesophagectomy, but no control patient, developed ARDS. The ARDS score was highest on day 8 after operation. Only patients with ARDS had a significant postoperative increase in postpulmonary, but not pre-pulmonary, TxB 2 concentrations (P : 0.05 vs patients without ARDS).This study provides evidence that TxA 2 , originating from the lungs, was associated with the development of ARDS after oesophageal resection. In view of the high incidence of ARDS after oesophagectomy (10-30%), prophylactic treatment of patients undergoing oesophageal resection with clinically applicable thromboxane synthetase inhibitors may be warranted. (Br. J. Anaesth. 1998; 80: 36-40) Keywords: lung adult respiratory distress syndrome; complications, adult respiratory distress syndrome; surgery, gastrointestinal; hormones, thromboxane; hormones, leukotrienes Adult respiratory distress syndrome (ARDS) is one of the primary contributors to mortality in ICU patients. 1 A wide variety of clinical conditions such as sepsis, burns, trauma 2-4 and major surgery, and oesophageal resections in particular, 5 6 predispose to the development of ARDS. In a meta-analysis of more than 60 000 patients undergoing oesophagectomy, 27% developed ARDS after transthoracic resection and 13% after transhiatal resection. 7 The following factors appear to increase the risk of postoperative ARDS in patients with oesophageal carcinoma: smoking and chronic obstructive pulmonary disease (COPD), transthoracic mobilization of the oesophagus with contusion of the lung during extensive surgery and postoperative (silent) aspiration. 8 Because of the heterogenity of sepsis or trauma patients, it is difficult to acquire comparable study populations for clinical studies of ARDS. In these patients, the triggering insult for ARDS is seldom predictable and it varies greatly in intensity; also, patient conditions such as age, immune and nutritional status and coexisting medical conditions vary widely. Patients undergoing oesophageal resection for oesophageal carcinoma, however, are a homogenous group, with 1-3 of 10 patients developing ARDS. 7 They are usually aged 50-70 yr, the majority have a history of smoking and preoperative weight loss, they are suffering from the same underlying disease, and the duration and magnitude of the insult triggering ARDS (i.e. oesophageal resection) is uniform. In addition, these patients are unique in that they are exposed to a planned triggering factor (i.e. oesophageal resection) ...

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An increase in pulmonary artery pressure is a common observation in adult mammals exposed to global alveolar hypoxia. It is considered a maladaptive response that places an increased workload on the right ventricle. The mechanisms initiating and maintaining the elevated pressure are of considerable interest in understanding pulmonary vascular homeostasis. There is an expectation that identifying the key molecules in the integrated vascular response to hypoxia will inform potential drug targets. One strategy is to take advantage of experiments of nature, specifically, to understand the genetic basis for the inter-individual variation in the pulmonary vascular response to acute and chronic hypoxia. To date, detailed phenotyping of highlanders has focused on haematocrit and oxygen saturation rather than cardiovascular phenotypes. This review explores what we can learn from those studies with respect to the pulmonary circulation. K E Y W O R D S genetics, high-altitude, hypoxia-inducible factor, hypoxiainducible factor prolyl hydroxylase 2, oxygen sensing, pulmonary vasoconstriction, vascular remodelling 1 | INTRODUCTION Under physiological conditions, the adult pulmonary circulation is maintained as a high-flow, low-pressure, and low-resistance system through which the entire cardiac output (CO) must pass. Exposure to hypoxia leads to the constriction of small resistance arteries in the lung, referred to as hypoxic pulmonary vasoconstriction (HPV)

Introduction Physical fitness benefits health. However, there is a research gap on how physical fitness, particularly aerobic endurance capacity and muscle power, is influenced by residential altitude, blood parameters, weight, and other cofactors in a population living at low to moderate altitudes (300–2100 masl). Materials and Methods We explored how endurance and muscle power performance changes with residential altitude, Body Mass Index (BMI), hemoglobin and creatinine levels among 108,677 Swiss men aged 18–22 years (covering >90% of Swiss birth cohorts) conscripted to the Swiss Armed Forces between 2007 and 2012. The test battery included a blood test of about 65%, a physical evaluation of about 85%, and the BMI of all conscripts. Results Residential altitude was significantly associated with endurance ( p < 0.001) but not with muscle power performance ( p = 0.858) after adjusting for all available cofactors. Higher BMI showed the greatest negative association with both endurance and muscle power performance. For muscle power performance, the association with creatinine levels was significant. Elevated C-reactive protein (CRP) and hemoglobin levels were stronger contributors in explaining endurance than muscle power performance. Conclusion We found a significant association between low to moderate residential altitude and aerobic endurance capacity even after adjustment for hemoglobin, creatinine, BMI and sociodemographic factors. Non-assessed factors such as vitamin D levels, air pollution, and lifestyle aspects may explain the presented remaining association partially and could also be associated with residential altitude. Monitoring the health and fitness of young people and their determinants is important and of practical concern for disease prevention and public health implications.