Causes, management, and prognosis of severe gastrointestinal bleedings in critically ill patients with pancreatic cancer: A retrospective multicenter study.

BACKGROUND: Gastrointestinal (GI) bleeding is a leading cause of intensive care unit (ICU) admission in pancreatic cancer patients. AIMS: To analyze causes, ICU mortality and hemostatic treatment success rates of GI bleeding in pancreatic cancer patients requiring ICU admission. METHODS: Retrospective multicenter cohort study between 2009 and 2021. Patients with a recent pancreatic resection surgery were excluded. RESULTS: Ninety-five patients were included (62 % males, 67 years-old). Fifty-one percent presented hemorrhagic shock, 41 % required mechanical ventilation. Main GI bleeding causes were gastroduodenal tumor invasion (32 %), gastroesophageal varices (21 %) and arterial aneurysm (12 %). Arterial aneurysms were more frequent in patients with previous pancreatic resection (36 % vs 2 %, p < 0.001). Hemostatic procedures included gastroduodenal endoscopy in 81 % patients and arterial embolization in 28 % patients. ICU mortality was 19 %. Multivariate analysis identified four variables associated with mortality: performance status >2 (OR 9.34, p = 0.026), mechanical ventilation (OR 14.14, p = 0.003), treatment success (OR 0.09, p = 0.010), hemorrhagic shock (OR 11.24, p = 0.010). Treatment success was 46 % and was associated with aneurysmal bleeding (OR 29.89, p = 0.005), ongoing chemotherapy (OR 0.22, p = 0.016), and prothrombin time ratio (OR 1.05, p = 0.001). CONCLUSION: In pancreatic cancer patients with severe GI bleeding, early identification of aneurysmal bleeding (particularly in case of previous resection surgery) and coagulopathy management may increase the treatment success and reduce mortality.

Clinical features and outcomes of patients with pancreatic cancer requiring unplanned medical ICU admission: A retrospective multicenter study.

BACKGROUND: We sought to describe the reasons for intensive care unit (ICU) admission and outcomes of patients with pancreatic cancer requiring unplanned medical ICU admission. PATIENTS AND METHODS: Retrospective cohort study in five ICUs from 2009 to 2020. All patients with pancreatic cancer admitted to the ICU were included. Patients having undergone recent surgery were excluded (< 4 weeks). RESULTS: 269 patients were included. Tumors were mainly adenocarcinoma (90%). Main reason for admission was sepsis/septic shock (32%) with a biliary tract infection in 44 (51%) patients. Second reason for admission was gastrointestinal bleeding (28%). ICU and 3-month mortality rates were 26% and 59% respectively. Performance status 3-4 (odds ratio OR 3.58), disease status (responsive/stable -ref-, newly diagnosed OR 3.25, progressive OR 5.99), mechanical ventilation (OR 8.03), vasopressors (OR 4.19), SAPS 2 (OR 1.69) and pH (OR 0.02) were independently associated with ICU mortality. Performance status 3-4 (Hazard ratio HR 1.96) and disease status (responsive/stable -ref-, newly diagnosed HR 2.67, progressive HR 4.14) were associated with 3-month mortality. CONCLUSION: Reasons for ICU admissions of pancreatic cancer patients differ from those observed in other solid cancer. Short- and medium-term mortality are strongly influenced by performance status and disease status at ICU admission.

Clinical characteristics of and outcomes for patients with COVID-19 and comorbid lung diseases primarily hospitalized in a conventional pulmonology unit: A retrospective study.

BACKGROUND: Scant data are currently available about a potential link between comorbid chronic lung diseases (CLD) and the risk and severity of the coronavirus disease 2019 (COVID-19) infection. METHODS: To describe the clinical characteristics of and outcomes for patients with COVID-19 infection, including patients with comorbid respiratory diseases, who have been primarily hospitalized in the pulmonology department of Strasbourg University Hospital, France. In this retrospective, single-center study, we included all confirmed cases of COVID-19 from March 3 to April 15, 2020. We then compared the symptoms, biological and radiological findings, and outcomes for patients with and without CLD. RESULTS: Of the 124 patients that were enrolled, the median age was 62 years, and 75 patients (60%) were male. Overall, 40% of patients (n=50) had preexisting CLD, including chronic obstructive pulmonary disease (COPD) (n=15, 12%) and asthma (n=19, 15%). Twenty-eight patients were transferred to the intensive care unit (ICU), and six patients died in our unit. CLD were not predictive of ICU hospitalization, but a significantly higher total mortality was observed (17.6% vs. 5.5%, P<0.05) in these patients. CONCLUSIONS: Our results suggest the lack of an over-representation of CLD in COVID-19, representing 40% of patients in this cohort and even within a pulmonology department. CLD were not a risk factor for ICU management. However, a tendency to higher global mortality was observed in COVID-19 patients with CLD. Further studies are warranted to determine the risk of COVID-19 for patients with comorbid CLD.

[Membranous microparticles and respiratory disease]. / Microparticules membranaires et maladies respiratoires.

Microparticles (MP) are plasmic membrane fragments released from cells after physiological stimulation or stress conditions like inflammation or infection. Their production is correlated to the rate of cell apoptosis. All types of cells can produce MP but they are produced mainly by platelets, endothelial cells, and leukocytes. They carry many bio-active molecules on their surface, specific to the parental cell, giving them the ability to be biomarkers and bio-effectors. MP are present in circulating blood, tissues and many biological fluids. Circulating MP levels can change during the course of many diseases. They have been the subject of many studies in the fields of cardiovascular disease and oncology. In the lungs, they are present in circulating blood and in the airways. They seem to have a role in pulmonary homeostasis in physiological situations and also in the expression of several disease processes. In this review of the literature, we were interested in the quantitative and qualitative variations in MP and their impact in airway diseases like chronic obstructive pulmonary disease (COPD) and asthma, pulmonary fibrosis and pulmonary hypertension.

Successful lung retransplantation in a patient with acute fibrinous and organizing pneumonia: a case report.

Acute fibrinous and organizing pneumonia (AFOP) is an unusual histopathologic pattern characterized by the formation of intra-alveolar plugs of fibrin deposition and associated organizing pneumonia. AFOP is considered to be a form of rejection and portends a dismal prognosis. Here, we present the case of a young male patient who initially underwent a double lung transplantation for cystic fibrosis. After 42 months of regular follow-up, he experienced rapidly progressive respiratory failure. Acute rejection and opportunistic lung infections were suspected. The clinical conditions rapidly deteriorated despite treatment with broad-spectrum antibiotics and high-dose steroids. Therefore, AFOP was suspected owing to: 1) acute clinical presentation; 2) pulmonary computerized tomographic data; 3) typical histopathologic findings on transbronchial biopsieseconds, and 4) lack of response to different treatments. The patient required an emergency bilateral lung retransplantation 44 months after the initial transplantation. The histopathologic analysis of the explanted lungs confirmed the diagnosis of AFOP. Two years after the 2nd transplant, the patient is alive and well. To the best of our knowledge, this is the 1st case of a patient experiencing AFOP following lung transplantation who was successfully rescued by a 2nd bilateral lung retransplantation.

Myostatin inactivation induces a similar muscle molecular signature in double-muscled cattle as in mice.

Myostatin (MSTN), a member of the TGF-ß superfamily, is a negative regulator of skeletal muscle mass. We have previously shown that the cell survival/apoptosis pathway is a downstream target of MSTN loss-of-function in mice through the regulation of the expression or abundance of many survival and apoptotic factors. In this study, we used western-blot and quantitative PCR (qPCR) analyses to validate these novel downstream targets of MSTN in double-muscled (DM) cattle v. their controls including 260-day-old foetuses and adult cows from the INRA95 strain. MSTN loss-of-function in DM foetuses and DM cows resulted in a glycolytic shift of the muscles (e.g. upregulation of H-MyBP, PGM1 and SNTA1 and downregulation of H-FABP), activation of cell survival pathway through regulation of some components of the PI3K/Akt pathway (e.g. upregulation of DJ-1 and Gsk-3ßser9/Gsk-3ßtotal ratio and downregulation of PTEN) and upregulation of cell survival factors translationally controlled tumour protein (14-3-3E, Pink1). We also found a lower abundance of pro-apoptotic transcripts and/or proteins (Caspase-3, caspase-8, caspase-9, BID, ID2 and Daxx) and a higher expression of anti-apoptotic transcripts (Traf2 and Bcl2l2) in DM muscles. All together, these results are in favour of activation of the cell survival pathway and loss of apoptosis pathway within the muscles of DM animals. Alteration of both pathways may increase myonuclear or satellite cell survival, which is crucial for protein synthesis. This could contribute to muscle hypertrophy in DM foetuses and DM cows.

Is hepatitis C virus NS3 protease quasispecies heterogeneity predictive of progression from cirrhosis to hepatocellular carcinoma?

We investigated whether an HCV NS3 protease quasispecies heterogeneity was associated with progression from viral cirrhosis to hepatocellular carcinoma (HCC). The NS3 protease quasispecies structure of 10 HCV-1b cirrhotic patients (controls) was compared with that of 10 paired HCV-1b cirrhotic patients who displayed progression to HCC (cases). NS3 protease genetic complexity and diversity did not differ significantly between cases and controls. Amino acid substitutions were detected at 20 (11%) and 25 (14%) sites in at least two variants of the NS3 protease in cases and controls, respectively. Significant differences in the percentage of substituted clones were observed for 10 NS3 sites. Mutations Y56F, I71V, T72I, Q86P, P89S, S101G/D, R117H, S122G/T/N, V132I and V170I were more frequently observed in the NS3 protease sequences of controls than in those of cases. Residue V107 was substituted in NS3 cases but not in controls. However, these differences did not allow the definition of a specific NS3 profile related to HCC occurrence. The NS3 secondary structure B1-1 previously identified as potentially predictive of HCC was identified with a higher frequency in cases quasispecies (84.2%) than in controls (55.9%; P < 0.05). Our results suggest that there may be a relationship to fibrosis progression when diversity parameters are considered together with secondary structure profiles. Further investigations are required to determine the cellular interactions of HCV NS3 protease in the context of carcinogenesis.

Centrifugation-based isolation of myosin for measurement of its synthesis rate in small muscle samples.

Myosin is involved in muscle mobility which is particularly affected in many pathophysiological situations. It is composed of heavy (MHC) and light (MLC) chains and measurements of its specific fractional synthesis rate (FSR) are scarce, mostly because of difficulties in isolating this protein. Our aim was to isolate pure myosin from small rat gastrocnemius skeletal muscle samples by setting up a procedure compatible with determination of stable isotope incorporation into myosin using mass spectrometry detection, allowing calculation of its FSR. A centrifugation method was compared to a validated but time-consuming elution gel electrophoresis method. Statistical analysis by the Bland and Altman test revealed a tight relationship between both methods (r2 >0.97, p <0.0001). The purity of the myosin fractions using the two procedures was verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In addition, the centrifugation procedure allowed simultaneous purification of MLC and MHC, whereas the elution gel electrophoresis technique resulted only in MHC isolation. Finally, the FSRs of myosin and MHC were found to be 0.114+/-0.026 and 0.140+/-0.029%/h, respectively (p not significant). In conclusion, the centrifugation method is a useful and reproducible procedure that results in sufficient amounts of pure myosin for reliable determinations of its own synthesis rate in vivo.

Surveillance network for herpes simplex virus resistance to antiviral drugs: 3-year follow-up.

Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains. We have formed a network of 15 virology laboratories which have isolated and identified, between May 1999 and April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The sensitivity of each isolate to ACV was evaluated by a colorimetric test (C. Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217, 2002). During this study, 3900 isolated strains among 3357 patients were collected; 55% of the patients were immunocompetent. Only six immunocompetent patients excreted ACV-resistant HSV strains (0.32%), including one female patient not treated with ACV who was infected primary by an ACV-resistant strain. Among the 54 immunocompromised patients from whom ACV-resistant HSV strains were isolated (3.5%), the bone marrow transplantation patients showed the highest prevalence of resistance (10.9%), whereas among patients infected by human immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the patients who excreted the ACV-resistant strains were treated with foscarnet (PFA), and 61% of them developed resistance to PFA. The collection of a large number of isolates enabled an evaluation of the prevalence of resistance of HSV strains to antiviral drugs to be made. This prevalence has remained stable over the last 10 years, as much among immunocompetent patients as among immunocompromised patients.

Coronavirus-related nosocomial viral respiratory infections in a neonatal and paediatric intensive care unit: a prospective study.

The incidence of nosocomial viral respiratory infections (NVRI) in neonates and children hospitalized in paediatric and neonatal intensive care units (PNICU) is unknown. Human coronaviruses (HCoV) have been implicated in NVRI in hospitalized preterm neonates. The objectives of this study were to determine the incidence of HCoV-related NVRI in neonates and children hospitalized in a PNICU and the prevalence of viral respiratory tract infections in staff. All neonates (age< or =28 days) and children (age>28 days) hospitalized between November 1997 and April 1998 were included. Nasal samples were obtained by cytological brush at admission and weekly thereafter. Nasal samples were taken monthly from staff. Virological studies were performed, using indirect immunofluorescence, for HCoV strains 229E and OC43, respiratory syncytial virus (RSV), influenza virus types A and B, paramyxoviruses types 1, 2 and 3 and adenovirus. A total of 120 patients were enrolled (64 neonates and 56 children). Twenty-two samples from 20 patients were positive (incidence 16.7%). In neonates, seven positive samples, all for HCoV, were detected (incidence 11%). Risk factors for NVRI in neonates were: duration of hospitalization, antibiotic treatment and duration of parenteral nutrition (P<0.01). Monthly prevalence of viral infections in staff was between 0% and 10.5%, mainly with HCoV. In children, 15 samples were positive in 13 children at admission (seven RSV, five influenza and three adenovirus) but no NVRI were observed. In spite of a high rate of community-acquired infection in hospitalized children, the incidence of NVRI with common respiratory viruses appears low in neonates, HCoV being the most important pathogen of NRVI in neonates during this study period. Further research is needed to evaluate the long-term impact on pulmonary function.

Reduced whole-body fat oxidation in women and in the elderly.

OBJECTIVE: To test the hypothesis that the increase in fat mass observed with aging might be related to a decrease in whole-body fat oxidation. SUBJECTS AND MEASUREMENTS: Forty volunteers had measurements of sleeping and 24 h substrate oxidation in calorimetric chambers, body composition with the (18)O dilution technique, VO(2)max, and fiber composition analysis from a biopsy of vastus lateralis. They were divided into 10 young women, 10 young men, 10 elderly women and 10 elderly men. RESULTS: Sleeping fat oxidation and 24 h fat oxidation were lower in women than in men and in elderly than in young participants. Sleeping fat oxidation was correlated to fat-free mass and energy balance (multivariate analysis). Twenty four hour fat oxidation was correlated to total energy expenditure and energy balance (multivariate analysis). After adjustment for differences in these factors, sleeping and 24 h fat oxidation were no longer different between age and sex groups. None of the parameters of macronutrient metabolism was correlated with muscle fiber composition. CONCLUSION: Our data suggest that fat oxidation is lower in elderly subjects. This difference could favour fat mass gain if fat intake is not adequately reduced. Differences in fat-free mass and in total energy expenditure appear to participate in the reduction in fat oxidation. International Journal of Obesity (2001) 25, 39-44

Antibody response of patients with Helicobacter pylori-related gastric adenocarcinoma: significance of anti-cagA antibodies.

The aim of this study was to search for a specific antibody pattern in sera from patients suffering from Helicobacter pylori-related gastric adenocarcinoma (GAC). The serological response of 22 patients suffering from GAC, 31 patients with gastroduodenal ulcer, and 39 asymptomatic subjects was analyzed using immunoblotting performed with three H. pylori strains: strain ATCC 43579; strain B110, isolated from a patient with ulcers; and strain B225, isolated from a patient with GAC. In addition, the latex agglutination test Pyloriset Dry was used to analyze ambiguous sera. H. pylori seropositivity was 75% in the GAC group, 61.3% in the ulcer group, and 56.4% in the asymptomatic group. Anti-CagA antibodies were found more often in the GAC group (48.8%) and in the ulcer group (47.3%) than in the asymptomatic group (21.2%). These percentages depended on the strain used as an antigen: in the GAC group, the anti-CagA frequencies were 93.3, 40, and 13.3% with strains B225, B110, and ATCC 43579, respectively. Thus the presence of anti-CagA antibodies was increased in patients suffering from H. pylori-related GAC, in particular when the CagA antigen was from a GAC strain. These data suggest the existence of a CagA protein specifically expressed by H. pylori strains isolated from GAC patients.

Changes in the metabolic and contractile characteristics of muscle in male cattle between 10 and 16 months of age.

Samples of semitendinosus muscle from 28 male cattle (18 Salers and 10 Limousins) were taken at 10 months (biopsy) and at 16 months of age (at slaughter). The animals had received the same diet and were slaughtered after the same duration of fattening. The activities of isocitrate dehydrogenase and lactate dehydrogenase were measured in the muscle samples. The five lactate dehydrogenase isoenzymes were separated by electrophoresis under non-denaturing conditions and assayed by densitometry. Fibres were identified by histochemistry by myofibrillar ATPase and succinate dehydrogenase activities as SO (slow oxidative), FOG (fast oxidative glycolytic) or FG (fast glycolytic), and by immunohistochemistry by their reaction to monoclonal antibodies specific to slow and fast myosin heavy chain reactions in I, IIC, IIA, IIAB and IIB type fibres. The isocitrate dehydrogenase activity was not modified between 10 and 16 months of age; the lactate dehydrogenase activity decreased and was correlated with an increase in the proportion of the H isozyme to the detriment of the proportion of the M form. This period was characterized by an increase in fibre size, increased expression of MHC IIa, resulting in more IIA fibres, less IIB fibres, and an increase in the percentage of type IIAB fibres, however the proportions of SO, FOG and FG, when analysed statistically, were not modified between 10 and 16 months of age.

Age-related changes and location of type I, III and IV collagens during skeletal muscle development of double-muscled and normal bovine foetuses.

The aim of this study was to investigate age-related changes in collagen content in muscles of normal and double-muscled (DM) bovine foetuses. Psoas major (PM) and triceps brachii (TB) muscles were collected from foetuses at 110 to 260 days post-conception (p.c.), frozen and powdered. Cyanogen bromide (CNBr) digestion and hydroxyproline measurements were carried out on the powder. CNBr peptides underwent SDS-polyacrylamide gel electrophoresis, and type I and III collagen relative variations were measured by densitometric analysis. Type I and III procollagen mRNA were located by in situ hybridization and types I, III and IV collagen located by indirect immunofluorescence. Although there was no significant difference between normal and DM animals in the amounts of collagen (except in PM muscle at 180 and 230 days p.c.), there was nevertheless a tendency to lower collagen content in muscles of DM animals. Amounts of hydroxyproline in PM and TB muscles from 110 to 230 days p.c. increased two- and threefold to 8.5 micrograms per mg of dry matter (d.m.) and 12 micrograms per mg d.m., respectively, and then decreased up to 260 days p.c., when they were twice as high in TB muscle (9.1 micrograms per mg d.m.) as in PM (4.5 micrograms per mg d.m.). The same difference in hydroxyproline levels was observed between normal adult PM and TB muscles. These variations were explained, mainly, by those of type I. In foetal muscle, in both genotypes and as in adult muscle, perimysium was types I and III, and endomysium type I, III and IV. Procollagen type I and III mRNA were located in perimysium. In conclusion, this study emphasizes that at the end of foetal life, collagen content is representative of what it will be in adult in muscle of both normal and DM animals.

Classification of bovine muscle fibres by different histochemical techniques.

The classification of bovine muscle fibres is of particular interest for the food industry because meat tenderness depends in part on the proportion of the different types of fibres. It is, therefore, important to define reliable methods for classifying fibre types. There are several classification systems. One is based on contractile type alone, as revealed by myofibrillar ATPase activity or with antibodies against myosin heavy chain. Others take both contractile and metabolic types into account. In this study, the classifications of fibres obtained by these three systems were compared on the semitendinosus and longissimus thoracis muscles of 35 Charolais bulls. Only the use of antibodies allowed the identification of a proportion of hybrid fibres containing two isoforms of fast myosin heavy chain (2a and 2b). In addition, the combination of metabolic types showed that the metabolism of these hybrid fibres differed according to the muscle.

Comparison of the foetal development of muscle in normal and double-muscled cattle.

Muscle differentiation was studied in foetal Semitendinosus muscle from normal cattle and those with the 'culard' gene of muscular hypertrophy sampled at 90, 130, 170 and 210 days of foetal life. The different fibre types were characterized by immunohistochemistry with antibodies specific to different isoforms of myosin heavy chains. The isoforms were separated by electrophoresis, identified by immunoblotting and quantified by ELISA. In double-muscled animals, there was a slower rate of differentiation in the first generation of cells, most markedly apparent at 90 days. At 130 days, differentiation was retarded mainly in the second generation, while at 170 days there was no longer any difference between the two animal types in the differentiation of first generation cells, which were totally slow in both. At the same stage however, type IIC fibres in double-muscled animals were much slower in appearing and continued to be so at 210 days, albeit to a lesser extent. These findings show that differentiation of the muscle fibres occurs at a slower rate in double-muscled foetuses particularly during the first two-thirds of foetal life.

Identification and typing of pyogenic streptococci by enzyme electrophoretic polymorphism.

Polyacrylamide-agarose gel electrophoresis was used to study polymorphism of lactate dehydrogenase (LDH), nucleoside phosphorylase (NSP), phosphoglucose isomerase (PGI), hydroxybutyrate dehydrogenase (HBD), adenylate kinase (ADK) and esterases of 44 strains of Streptococcus pyogenes, 25 group G streptococcal strains, 11 "S. equisimilis" strains, seven S. dysgalactiae strains, four S. canis strains, three S. equi strains and seven S. zooepidemicus strains. Analysis of LDH, NSP, PGI, HBD and ADK provided valuable interspecies differentiation, by showing that four groups of strains corresponded to the four known DNA homology groups. Esterases showed greater intraspecies variation than the other enzymes. The combined analysis of the six enzymes indicated 31 zymotypes among S. pyogenes, 14 in group G streptococci and 11 in "S. equisimilis" strains. This was shown to be an effective technique for typing pyogenic streptococci.

Study of the influence of age and weaning on the contractile and metabolic characteristics of bovine muscle.

Weaning is an interesting period for the study of the nutritional regulation of muscle energy metabolism, since during this stage the nature of the substrates supplied to the muscle and their energy balance are profoundly changed. The aim of this study was to determine the effect of these modifications on the contractile and metabolic characteristics of bovine muscle. Two similar groups of 7 male Montbéliard calves were used with the same age and weight, and with the same energy intake. One group consisted of milk-fed calves, the other of weaned animals. The latter were progressively weaned over a period between 107 and 128 d. The average age at slaughter in the 2 groups was 170 d. Biopsy specimens of semitendinosus (ST) muscle were taken at the ages of 66 d, 94 d (before the beginning of weaning) and 136 d (at the end of weaning) to follow the evolution of muscle characteristics. Samples of longissimus thoracis (LT) muscle were taken 24 h after slaughter and used to study the changes in protein and DNA content. The proportion and area of the different types of fiber, I (slow, oxidative), IIA (fast, oxido-glycolytic), IIB (fast, glycolytic) and IIC (fast/slow, oxidoglycolytic) were measured by immunohistochemistry and image analysis. The metabolism of the muscles was determined by studying isocitrate dehydrogenase (ICDH, oxidative) and lactate dehydrogenase (LDH, glycolytic) activity. The results obtained between 2 and 6 months of life showed an overall increase in the area of the fibers (I, IIA, IIB and IIC) and a conversion of type IIA fibers into type IIB accompanied by a shift in the energy metabolism towards a glycolytic type. Weaning caused temporary stress, whose main consequences were to decrease overall muscle fiber area and the percentage of type IIB fibers, and increase the proportion of type IIC fibers in weaned animals. These effects may have been due to the nutritional and behavioral disturbances that accompany weaning, because 42 d after the end of weaning there was no difference in the size of ST and LT fibers between the 2 groups whereas the proportion of type IIA fibers was still higher in weaned animals.