Hormonal modifications in patients admitted to an internal intensive care unit for acute hypoxaemic respiratory failure

AbstractTo clarify which endocrine modifications can be observed in acute hypoxaemic respiratory failure, 15 severely ill male patients [PAT; median age: 61 (range: 48 years); median height: 173 (range: 12) cm; median mass: 73 (range 31) kg] were investigated immediately upon admission to an intensive care unit (ICU) for this clinical disorder. Before starting treatment, the blood gases were measured and a number of selected hormones with special relevance for an ICU setting were determined. These are known to be modified by acute hypoxaemia in healthy subjects and to possess glucoregulatory properties, or an influence upon cardiocirculation or the vascular volume regulation: insulin, cortisol, adrenaline, noradrenaline, atrial natriuretic peptide, renin, aldosterone, angiotensin converting enzyme, and endothelin-I (ET). To elucidate whether potential endocrine changes resulted from acute hypoxaemia alone, the underlying disease, or unspecific influences connected with the ICU setting, all measurements were compared to those of a completely healthy reference group (REF) with comparable acute experimental hypoxaemia. The latter state was achieved by having the REF breathe a gas mixture with the oxygen content reduced to 14% (H).In the REF, neither the medians nor the distribution of endocrinologic measurements were modified significantly by acute hypoxaemia. In the PAT, the medians were increased considerably, yet with a slight diminution of ET. The distribution of individual values was considerably broader than in the REF with H.In conclusion, considerable increases in the means of the above hormones, with the exception of ET, can be registered in severely ill patients admitted to ICUs with acute hypoxaemic failure. However, such modifications cannot be considered attributable exclusively to acute arterial hypoxaemia. The underlying clinical disorders, such as septicaemia or an unspecific endocrine epiphenomenon, including severe and not only hypoxaemic stress, seem to be predominant

Early Pliocene Hominid Tooth from Galili, Somali Region, Ethiopia

A fossil hominid tooth was discovered during survey at Galili, Somali region, Ethiopia. The geological and faunal context indicate an Early Pliocene age. The specimen (GLL 33) consists of an almost complete lower right third molar likely representing a male individual of advanced age-at-death. Its comparative metrical, morphological and (micro)structural analysis (supported by a microtomographic record) suggests a tentative taxonomic allocation to Australopithecus cf. A. afarensis

Earliest evidence of dental caries manipulation in the Late Upper Palaeolithic

Prehistoric dental treatments were extremely rare, and the few documented cases are known from the Neolithic, when the adoption of early farming culture caused an increase of carious lesions. Here we report the earliest evidence of dental caries intervention on a Late Upper Palaeolithic modern human specimen (Villabruna) from a burial in Northern Italy. Using Scanning Electron Microscopy we show the presence of striations deriving from the manipulation of a large occlusal carious cavity of the lower right third molar. The striations have a “V”-shaped transverse section and several parallel micro-scratches at their base, as typically displayed by cutmarks on teeth. Based on in vitro experimental replication and a complete functional reconstruction of the Villabruna dental arches, we confirm that the identified striations and the associated extensive enamel chipping on the mesial wall of the cavity were produced ante-mortem by pointed flint tools during scratching and levering activities. The Villabruna specimen is therefore the oldest known evidence of dental caries intervention, suggesting at least some knowledge of disease treatment well before the Neolithic. This study suggests that primitive forms of carious treatment in human evolution entail an adaptation of the well-known toothpicking for levering and scratching rather than drilling practices

Exploring directional and fluctuating asymmetry in the human palate during growth

open24siObjectives: Palate morphology is constantly changing throughout an individual's lifespan, yet its asymmetry during growth is still little understood. In this research, we focus on the study of palate morphology by using 3D geometric morphometric approaches to observe changes at different stages of life, and to quantify the impact of directional and fluctuating asymmetry on different areas at different growth stages. Materials and Methods: The sample consists of 183 individuals (1–72 years) from two identified human skeletal collections of 19th and early 20th Century Italian contexts. A 3D-template of 41 (semi)landmarks was applied on digital palate models to observe morphological variation during growth. Results: Asymmetrical components of the morphological structure appears multidirectional on the entire palate surface in individuals <2 years old and become oriented (opposite bilateral direction) between 2 and 6 years of age. Specifically, directional asymmetry differentially impacts palate morphology at different stages of growth. Both the anterior and posterior palate are affected by mild alterations in the first year of life, while between 2 and 6 years asymmetry is segregated in the anterior area, and moderate asymmetry affects the entire palatal surface up to 12 years of age. Our results show that stability of the masticatory system seems to be reached around 13–35 years first by females and then males. From 36 years on both sexes show similar asymmetry on the anterior area. Regarding fluctuating asymmetry, inter-individual variability is mostly visible up to 12 years of age, after which only directional trends can be clearly observed at a group level. Discussion: Morphological structure appears instable during the first year of life and acquires an opposite asymmetric bilateral direction between 2 and 6 years of age. This condition has been also documented in adults; when paired with vertical alteration, anterior/posterior asymmetry seems to characterize palate morphology, which is probably due to mechanical factors during the lifespan. Fluctuating asymmetry is predominant in the first period of life due to a plausible relationship with the strength of morphological instability of the masticatory system. Directional asymmetry, on the other hand, shows that the patterning of group-level morphological change might be explained as a functional response to differential inputs (physiological forces, nutritive and non-nutritive habits, para-masticatory activity as well as the development of speech) in different growth stages. This research has implications with respect to medical and evolutionary fields. In medicine, palate morphology should be considered when planning orthodontic and surgical procedures as it could affect the outcome. As far as an evolutionary perspective is concerned the dominance of directional asymmetries in the masticatory system could provide information on dietary and cultural habits as well as pathological conditions in our ancestors.embargoed_20220511Oxilia G.; Menghi Sartorio J.C.; Bortolini E.; Zampirolo G.; Papini A.; Boggioni M.; Martini S.; Marciani F.; Arrighi S.; Figus C.; Marciani G.; Romandini M.; Silvestrini S.; Pedrosi M.E.; Mori T.; Riga A.; Kullmer O.; Sarig R.; Fiorenza L.; Giganti M.; Sorrentino R.; Belcastro M.G.; Cecchi J.M.; Benazzi S.Oxilia G.; Menghi Sartorio J.C.; Bortolini E.; Zampirolo G.; Papini A.; Boggioni M.; Martini S.; Marciani F.; Arrighi S.; Figus C.; Marciani G.; Romandini M.; Silvestrini S.; Pedrosi M.E.; Mori T.; Riga A.; Kullmer O.; Sarig R.; Fiorenza L.; Giganti M.; Sorrentino R.; Belcastro M.G.; Cecchi J.M.; Benazzi S

Reconstruction versus conservative treatment after rupture of the anterior cruciate ligament: cost effectiveness analysis

BACKGROUND: The decision whether to treat conservatively or reconstruct surgically a torn anterior cruciate ligament (ACL) is an ongoing subject of debate. The high prevalence and associated public health burden of torn ACL has led to continuous efforts to determine the best therapeutic approach. A critical evaluation of benefits and expenditures of both treatment options as in a cost effectiveness analysis seems well-suited to provide valuable information for treating physicians and healthcare policymakers. METHODS: A literature review identified four of 7410 searched articles providing sufficient outcome probabilities for the two treatment options for modeling. A transformation key based on the expert opinions of 25 orthopedic surgeons was used to derive utilities from available evidence. The cost data for both treatment strategies were based on average figures compiled by Orthopaedic University Hospital Balgrist and reinforced by Swiss national statistics. A decision tree was constructed to derive the cost-effectiveness of each strategy, which was then tested for robustness using Monte Carlo simulation. RESULTS: Decision tree analysis revealed a cost effectiveness of 16,038 USD/0.78 QALY for ACL reconstruction and 15,466 USD/0.66 QALY for conservative treatment, implying an incremental cost effectiveness of 4,890 USD/QALY for ACL reconstruction. Sensitivity analysis of utilities did not change the trend. CONCLUSION: ACL reconstruction for reestablishment of knee stability seems cost effective in the Swiss setting based on currently available evidence. This, however, should be reinforced with randomized controlled trials comparing the two treatment strategies

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences