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Acute mountain sickness (AMS) causes serious illness for many individuals ascending to high altitude (HA), although preventable with appropriate acclimatisation. AMS is a clinical diagnosis, with symptom severity evaluated using the Lake Louise Score (LLS). Reliable methods of predicting which individuals will develop AMS have not been developed. This systematic review evaluates whether a predictive relationship exists between oxygen saturation and subsequent development of AMS. PubMed, PubMed Central, MEDLINE, Semantic Scholar, Cochrane Library, University of Birmingham Library and clinicaltrials.gov databases were systematically searched from inception to 15 June 2023. Human studies involving collection of peripheral blood oxygen saturation (SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$) from healthy lowlanders during ascent to HA that evaluated any relationship between SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ and AMS severity were considered for eligibility. Risk of bias was assessed using a modified Newcastle–Ottawa Tool for cohort studies (PROPSPERO CRD42023423542). Seven of 980 total identified studies were ultimately included for data extraction. These studies evaluated SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ and AMS (via LLS) in 1406 individuals during ascent to HA (3952–6300 m). Risk of bias was 'low' for six and 'moderate' for one of the included studies. Ascent profiles and SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ measurement methodology varied widely, as did the statistical methods for AMS prediction. Decreasing oxygen saturation measured with pulse oximetry during ascent shows a positive predictive relationship for individuals who develop AMS. Studies have high heterogeneity in ascent profile and oximetry measurement protocols. Further studies with homogeneous methodology are required to enable statistical analysis for more definitive evaluation of AMS predictability by pulse oximetry. What is the central question of this study?Is there a predictive relationship between oxygen saturation and subsequent development of AMS?What is the main finding and its importance?A systematic review of the literature revealed there is a positive predictive trend between pulse oximetry measurements obtained around 3500 m during ascent and the development of acute mountain sickness at higher camps; however, further research is required to develop more robust prediction models. [ABSTRACT FROM AUTHOR]

Acute mountain sickness (AMS) is a well‐studied illness defined by clinical features (e.g., headache and nausea), as assessed by the Lake Louise score (LLS). Although obvious in its severe form, early stages of AMS are poorly defined and easily confused with common travel‐related conditions. Measurement of hypoxaemia, the cause of AMS, should be helpful, yet to date its utility for identifying AMS susceptibility remains unclear. This study quantified altitude‐induced hypoxaemia in individuals during an ascent to 4800 m to determine the utility of nocturnal pulse oximetry measurements for prediction of AMS. Eighteen individuals (36 ± 16 years of age) ascended to 4800 m over 12 days. Symptomology of AMS was assessed each morning via LLS criteria, with participants categorized as either AMS‐positive (LLS ≥ 3 with headache) or AMS‐negative. Overnight peripheral oxygen saturations (ov‐SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$) were recorded continuously (1 Hz) using portable oximeters. Derivatives of these recordings were compared between AMS‐positive and ‐negative subjects (Mann–Whitney U‐test). Exploratory analyses (Pearson's) were conducted to investigate relationships between overnight parameters and AMS severity. Overnight derivatives, including ov‐SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$, heart rate/ov‐SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$, variance, oxygen desaturation index, hypoxic burden and total sleep time at <80% SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$, all differed significantly between AMS‐positive and ‐negative subjects (all P < 0.01), with cumulative/relative frequency plots highlighting these differences visually. Exploratory analysis revealed that ov‐SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$ from 3850 m was correlated with peak LLS at 4800 m (r = 0.58–0.61). The findings highlight the potential for overnight oximetry to predict AMS susceptibility during ascent to high altitude. Further investigation is required to develop, evaluate and optimize predictive models to improve AMS management and prevention. What is the central question of this study?Early stages of acute mountain sickness are poorly defined, with existing assessment methods for the illness being highly ineffective. Can overnight pulse oximetry be used as a detection and prediction tool for deterioration in acute mountain sickness?What is the main finding and its importance?Overnight oximetry measurements from 3850 m were significantly correlated with acute mountain sickness severity at 4800 m (3 days later), whereas Lake Louise scores from the same time points were unrelated. These findings highlight the potential for pulse oximetry recorded from lower camps to be predictive of acute mountain sickness severity at higher altitude. [ABSTRACT FROM AUTHOR]

SAP is selectively concentrated in amyloid deposits by its avid binding to all amyloid fibril types (2,3). SAP binding stabilizes amyloid fibrils, protects them from proteolysis in vitro (5) and [...], Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries (1). Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present (1). There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation (1). Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous (1). There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP) (2,3). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-D-proline compound CPHPC4, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis.

Proteinuria is a transient physiological phenomenon that occurs with a range of physical activities and during ascent to altitude. Exercise intensity appears to dictate the magnitude of postexercise proteinuria; however, evidence also indicates the possible contributions from exercise-induced hypoxemia or reoxygenation. Using an environmental hypoxic chamber, this cross over designed study aimed to evaluate urinary alpha-1 acid glycoprotein (α1-AGP) excretion pre/postexercise performed in hypoxia (HYP) and normoxia (NOR). Sixteen individuals underwent experimental sessions in normoxia (NOR, 20.9% O2) and hypoxia (HYP, 12.0% O2). Sessions began with α 2-h priming period before completing a graded maximal exercise test (GXT) on a cycle ergometer, which was followed by continuation of exposure for an additional 2 h. Physiological responses (i.e., blood pressure, heart rate, and peripheral oxygenation), Lake Louise Scores (LLSs), and urine specimens (analyzed for albumin and α1-AGP) were collected pre- and postexercise (after 30, 60, and 120 min). Peak power output was significantly reduced in HYP (193 ± 45 W) compared with NOR (249 ± 59 W, P < 0.01). Postexercise urinary α1-AGP was greater in NOR (20.04 ± 14.84 mg·min-1 ) than in HYP (15.08 ± 13.46 mg·min-1 ), albeit the difference was not significant (P > 0.05). Changes in urinary α1-AGP from pre- to post-30 min were not related to physiological responses or performance outcomes observed during GXT in NOR or HYP. Despite profound systemic hypoxemia with maximal exercise in hypoxia, postexercise α1-AGP excretion was not elevated above the levels observed following normoxic exercise. [ABSTRACT FROM AUTHOR]

Abstract Background HevyLite™ is a new, recently developed method that facilitates separate quantification of the kappa- and lambda-bounded amounts of a given immunoglobulin (Ig). Using this method, we measured intact immunoglobulin (heavy/light chain; HLC) IgG-kappa, IgG-lambda, IgA-kappa, IgA-lambda individually, as well as their deriving ratios (HLCR) in a series of IgG or IgA multiple myeloma (MM) patients, to investigate and assess the contribution of these tests to disease evaluation. Patients and methods HevyLite™ assays were used in sera from 130 healthy individuals (HI) and 103 MM patients, at time of diagnosis. In patients, the level of paraprotein was IgG in 78 (52 IgG-kappa, 26 IgG-lambda) and IgΑ in 25 (13 IgΑ-kappa, 12 IgΑ-lambda). Durie-Salmon and International Staging System stages were evenly distributed. Symptomatic patients (n = 77) received treatment while asymptomatic ones (n = 26) were followed. Patients' median follow-up was at 32.6 months. HLCR was calculated with the involved Ig (either G or A) as numerator. Results In HI, median IgG-kappa was 6.85, IgG-lambda 3.81, IgA-kappa 1.19 and IgA-lambda 0.98 g/L. The corresponding median involving HLC values in MM patients were 25.8, 23.45, 28.9 and 36.4 g/L. HLC-IgG related to anemia, high serum free light chain ratio and extensive bone marrow infiltration, while high HLCR correlated with the same plus increased β2-microglobulin. In addition, increased HLCR and the presence of immunoparesis correlated with time to treatment. Patients with high HLCR had a significantly shorter survival (p = 0.022); HLCR retained its prognostic value in multivariate analysis. Conclusions HLC and HLCR quantify the precise amount of the involved immunoglobulin more accurately than other methods; moreover, they carry prognostic information regarding survival in MM patients.

Abstract Background Monoclonal free light chains (FLCs) frequently cause rapidly progressive renal failure in patients with multiple myeloma. Immunoassays which provide quantitative measurement of FLCs in serum, have now been adopted into screening algorithms for multiple myeloma and other lymphoproliferative disorders. The assays indicate monoclonal FLC production by the presence of an abnormal κ to λ FLC ratio (reference range 0.26–1.65). Previous work, however, has demonstrated that in patients with renal failure the FLC ratio can be increased above normal with no other evidence of monoclonal proteins suggesting that in this population the range should be extended (reference range 0.37–3.1). This study evaluated the diagnostic sensitivity and specificity of the immunoassays in patients with severe renal failure. Methods Sera from 142 patients with new dialysis-dependent renal failure were assessed by serum protein electrophoresis (SPE), FLC immunoassays and immunofixation electrophoresis. The sensitivity and specificity of the FLC ratio's published reference range was compared with the modified renal reference range for identifying patients with multiple myeloma; by receiver operating characteristic curve analysis. Results Forty one patients had a clinical diagnosis of multiple myeloma; all of these patients had abnormal serum FLC ratios. The modified FLC ratio range increased the specificity of the assays (from 93% to 99%), with no loss of sensitivity. Monoclonal FLCs were identified in the urine from 23 of 24 patients assessed. Conclusion Measurement of serum FLC concentrations and calculation of the serum κ/λ ratio is a convenient, sensitive and specific method for identifying monoclonal FLC production in patients with multiple myeloma and acute renal failure. Rapid diagnosis in these patients will allow early initiation of disease specific treatment, such as chemotherapy plus or minus therapies for direct removal of FLCs.