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Background: Postoperative pneumonia (POP) is a life-threatening complication of lung resection. The incidence, causative bacteria, predisposing factors, and outcome are poorly understood. Design: Prospective observational study. Methods: A prospective study of all patients undergoing major lung resections for noninfectious disease was performed over a 6-mo period. Culture of intraoperative bronchial aspirates was systematically performed. All patients with suspicion of pneumonia underwent bronchoscopic sampling and culture before antibiotherapy. Results: One hundred and sixty-eight patients were included in the study. Bronchial colonization was identified in 31 of 136 patients (22.8%) on analysis of intraoperative samples. The incidence of POP was 25% (42 of 168). Microbiologically documented and nondocumented pneumonias were recorded in 24 and 18 cases, respectively. Haemophilus species, Streptococcus species, and, to a much lesser extent, Pseudomonas and Serratia species were the most frequently identified pathogens. Among colonized and noncolonized patients, POP occurred in 15 of 31 and 20 of 105 cases, respectively (p = 0.0010; relative risk, 2.54). Death occurred in 8 of 42 patients who developed POP and in 3 of 126 of patients who did not (p = 0.0012). Patients with POP required noninvasive ventilation or reintubation more frequently than patients who did not develop POP (p < 0.0000001 and p = 0.00075, respectively). POP was associated with longer intensive care unit and hospital stay (p < 0.0000001 and p = 0.0000005, respectively). Multivariate analysis showed that chronic obstructive pulmonary disease, extent of resection, presence of intraoperative bronchial colonization, and male sex were independent risk factors for POP. Conclusions: Pneumonia acquired in-hospital represents a relatively frequent complication of lung resections, associated with an important percentage of postoperative morbidity and mortality. [ABSTRACT FROM AUTHOR]

Generating hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) has been a long-lasting quest in the field of hematopoiesis. Previous studies suggested that enforced expression of BCR-ABL, the unique oncogenic driver of chronic myelogeneous leukemia (CML), in embryonic stem cells (ESCs)-derived hematopoietic cells is sufficient to confer long-term in vivo repopulating potential. To precisely uncover the molecular events regulated by the tyrosine kinase activity of BCR-ABL1 (p210) during the course of hematopoietic differentiation, we engineered a Tet-ON inducible system to modulate its expression in murine ESCs (mESCs). We showed in unique site-directed knock-in ESC model that BCR-ABL expression tightly regulated by doxycycline (dox) controls the formation and the maintenance of immature hematopoietic progenitors. Interestingly, these progenitors can be expanded in vitro for several passages in the presence of dox. Our analysis of cell surface markers and transcriptome compared with wild-type fetal and adult HSCs unraveled a similar molecular signature. Long-term culture initiating cell (LTC-IC) assay confirmed their self-renewal capacities albeit with a differentiation bias toward erythroid and myeloid cells. Collectively, our novel Tet-ON system represents a unique in vitro model to shed lights on ESC-derived hematopoiesis, CML initiation, and maintenance., Competing Interests: Conflict of Interest Disclosure The authors declare no competing financial interests., (Copyright © 2023. Published by Elsevier Inc.)

Chronic myeloid leukemia (CML) is a clonal hematopoietic malignancy driven by the BCR-ABL1 fusion oncoprotein. The development of tyrosine kinase inhibitors (TKIs) has deeply increased long-term survival of CML patients. Nonetheless, one patient out of four will switch TKI off owing either to drug intolerance or resistance partly due to amplification or mutations of BCR-ABL1 oncogene and alteration in ATP-binding cassette (ABC) transporters. Increasing evidence suggests the involvement of the microRNA miR-495-3p in cancer-associated chemoresistance through multidrug resistance 1 (MDR1) gene, which encodes an ATP-dependent efflux pump. Our study aimed at investigating the potential role of miR-495-3p in CML TKI chemo-sensitivity and determining the underlying molecular circuitry involved. We first observed that miR-495-3p expression was lower in BCR-ABL1-expressing cellular models in vitro. Notably, loss-of-function experiments showed increased proliferation associated with a decreased number of nondividing cells (G0/G1) and resistance to Imatinib. Conversely, our data showed that miR-495-3p overexpression hindered leukemic cell growth and TKI resistance in Imatinib-resistant T315I-mutant cells, as well as drug efflux activity through MDR1 regulation. Further investigating the role of miR-495-3p in CML patients, we found that predicted miR-495-3p targets were upregulated in patients in blast crisis that were involved in protein phosphorylation and associated with the worst prognosis. Taken together, our results demonstrate that downregulation of miR-495-3p expression is important in the malignant phenotype of CML and TKI resistance mechanisms and could be a useful biomarker and a potential therapeutic target to eradicate CML., Competing Interests: Conflict of Interest Disclosure The authors have no competing interests to declare in relation to this work., (Copyright © 2022 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

Objective: Successful treatment of osteomyelitis is more likely with accurate diagnosis and identification of the causative pathogens. This typically requires obtaining a specimen of bone, usually by image-guided biopsy. We sought to develop a simpler bedside method for definitively diagnosing osteomyelitis., Research Design and Methods: Over 2 years, we enrolled consecutive patients presenting to our diabetic foot clinic with a foot ulcer and clinically suspected osteomyelitis but without soft tissue infection. Each underwent hybrid (67)Ga single-photon emission computed tomography and X-ray computed tomography (SPECT/CT) imaging; those with a positive scan underwent bedside percutaneous bone puncture. Patients with a positive bone culture received culture-guided antibiotic therapy. Patients with negative (67)Ga SPECT/CT imaging or with positive imaging but negative bone culture were not treated with antibiotics. All patients were followed up for ≥ 1 year., Results: Among 55 patients who underwent (67)Ga SPECT/CT imaging, 13 had negative results and all of their foot ulcers resolved without antibiotic therapy. Among 42 with positive imaging, 2 were excluded (for recent antibiotic therapy) and 40 had bone punctures (3 punctured twice): 19 had negative results, 3 of which were likely false negatives, and 24 had positive results (all gram-positive cocci). At follow-up, 3 patients had died, 3 had undergone amputation, and 47 had no evidence of foot infection. The sensitivity and specificity of this combined method were 88.0 and 93.6%, respectively, and the positive and negative predictive values were 91.7 and 90.7%, respectively., Conclusions: Coupling of (67)Ga SPECT/CT imaging and bedside percutaneous bone puncture appears to be accurate and safe for diagnosing diabetic foot osteomyelitis in patients without signs of soft tissue infection, obviating the need for antibiotic treatment in 55% of suspected cases.

Due to the differences in the management of Mycobacterium kansasii disease and tuberculosis, an accurate diagnosis is required. This report, which describes what we believe to be the first documented case of M. kansasii infection in a patient suffering from anorexia nervosa, sheds light on the possible occurrence of a non-tuberculous mycobacterial infection that can mimic tuberculosis, on the risk of a misleading interpretation of interferon-gamma release assays, and on the temporal response to these tests.

The incidence of invasive streptococcal pyogenic infections has been on a worldwide increase. The most frequent clinical manifestations start with cutaneous septicemias. We report an unusual case of Streptococcus pyogenes-based septicemia, secondary to appendicitis with rapidly evolving peritonitis.

Background: The recommended antibiotic prophylaxis by second-generation cephalosporins reduces the incidence of wound infection and empyema, but its effectiveness on postoperative pneumonias (POPs) after major lung resection lacks demonstration. We investigated risk factors and characteristics of POPs occurring when antibiotic prophylaxis by second-generation cephalosporin or an alternative prophylaxis targeting organisms responsible for bronchial colonization was used., Methods: An 18-month prospective study on all patients undergoing lung resections for noninfectious disease was performed. Prophylaxis by cefamandole (3 g/24 h, over 48 hours) was used during the first 6 months, whereas amoxicillin-clavulanate (6 g/24 h, over 24 hours) was used during the subsequent 12 months. Intraoperative bronchial aspirates were systematically cultured. Patients with suspicion of pneumonia underwent bronchoscopic sampling for culture., Results: Included were 168 patients in the first period and 277 patients in the second period. The incidence of POP decreased by 45% during the second period (P = 0.0027). A significant reduction in antibiotic therapy requirement for postoperative infections (P = 0.0044) was also observed. Thirty-day mortality decreased from 6.5% to 2.9% (P = 0.06). Multivariate analysis showed that type of resection, intraoperative colonization, chronic obstructive pulmonary disease, gender, body mass index, and type of prophylaxis were independent risk factors of POP. A case control-study that matched patients of the two periods according to these risk factors (except for antibiotic prophylaxis) confirmed that the incidence of POP was lowered during the second period., Conclusions: Targeted antibiotic prophylaxis may decrease the rate of POPs after lung resection and improve outcome.

Three clinical isolates of Salmonella enterica recovered between 2000 and 2003 in France and Senegal were found to produce extended-spectrum beta-lactamase CTX-M-15. The two isolates from Senegal were recovered from stool of a hospitalized patient with gastroenteritis in 2000 and from an urine specimen of an out-patient with urinary tract infection in 2001. These S. enterica isolates belonged to serotype Kentucky and were clonally related as determined by pulsed-field gel electrophoresis and automated ribotyping. The third isolate of serotype Typhimurium was recovered from a patient hospitalized in France for an acute gastroenteritis acquired in Lebanon. The bla(CTX-M-15) gene was located on two different transferable plasmids, one of which also carried bla(TEM-1), bla(OXA-30), aminoglycoside-, tetracycline-, and sulfamethoxazole-trimethoprim resistance genes. ISEcp1 element was found to be located upstream of bla(CTX-M-15) in the same position as reported previously in CTX-M-15-producing Escherichia coli from India and Turkey. This is the first report of bla(CTX-M-15) in the genus Salmonella.

Objective: The aim of this retrospective study was to assess the incidence of nutritional status on the development of nosocomial pneumonia in patients with chronic obstructive pulmonary disease (COPD) suffering an acute episode of respiratory failure requiring ventilatory assistance., Patients and Methods: The study included 48 patients with COPD who were hospitalized in an intensive care unit for acute respiratory failure requiring ventilatory assistance. Nutritional status was assessed within 24 hours of admission to the intensive care unit. Body weight, tricipital skin fold, brachial muscle circumference, creatinuria-waist index, plasma levels of albumin, transferrin, transthyretin and retinol-binding protein, the Multitest and lymphocyte counts were recorded. The diagnosis of nosocomial pneumonia was based on recognized criteria: occurrence more than 48 hours after admission, Andrews' criteria for bacterial pneumonia and bacteriological proof., Results: Nineteen of the 48 patients developed nosocomial pneumonia. The nutritional parameters at admission to intensive care were not significantly different between patients who developed nosocomial pneumonia and those who remained free of lung infection. The duration of ventilatory assistance and total stay in the intensive care unit were significantly longer in patients who developed nosocomial pneumonia., Conclusion: This study showed that in patients with COPD who undergo ventilatory assistance for acute decompensation, the development of nosocomial pneumonia was not correlated with nutritional status admission.

Two immunocompromised children, aged 3 years and 1 1/2 month, developed an hospital-acquired Legionnaire's disease. In one case, Legionella pneumophila serotype 1 was identified by culture in pleural fluid; LP1 was isolated in all the warm water samples in the hospital. Clinical, epidemiological data and laboratory findings are discussed.

Two hundred children and their mothers were examined when they were 10 months, 2 years and 4 years of age. Anti-cytomegalovirus, anti-Herpesvirus hominis and anti-rubella virus antibodies were titered. The evolution of antibody titers showed that primary infections with cytomegalovirus and Herpesvirus are especially frequent during the first months of life, and that mothers are the principal source of infection. In the group studied, it appeared that country of origin of the parents was the most important socio-economic factor influencing the frequency of infections in children, based upon the large variations of the serum positivity in mothers.

The authors have performed 28 ankle fusions for septic causes. There were 23 cases of septic arthritis and 5 severely comminuted compound fractures treated by primary fusion. Arthrodesis was made after wide excision and stabilization by external fixator. In 23 cases secondary bone grafting was done. Only in 13 cases was a satisfactory contact between the bony surfaces obtained. There was no contact at all in 9 cases. The authors have had good experience with the A.L.J. model of external fixator. On 7 occasions, secondary grafting was made using a cortico-cancellous graft with 3 failures. On 6 occasions, the Papineau technique was used with success but healing was slow. Out of 24 patients, the final result was good in 18 with 4 failures of fusion and 3 persistent sinuses. The importance of a wide excision is emphasised leading to the need for the use of external fixation. In cases of skin loss in recent comminuted fractures, the Papineau method is indicated as a primary procedure.

This series comprises 74 post-operative infections of fractures of the upper end of the femur, 47 associated with internal fixation and 27 with prostheses. The organisms were different in the 13 men, with a predominance of gram-positive cocci, from those in the 61 women in which the significantly high proportion of gram-negative organisms seemed to be due frequent to soiling of urinary origin. In the 47 internal fixations, local wound toilet gave 29 successful results with union in the normal time. Two patients were not able to be operated on again and died before they could be treated. Sixteen failures, including seven deaths, were due to septic arthritis of the hip. The diagnosis of septic arthritis was difficult, which explains why resection of the head and neck of femur was only made in six cases, five of them successfully. In the 27 prostheses, the best results were obtained by deep wound toilet retaining the prosthesis, with nine successes in ten cases. An acceptable functional result was compatible with a persistent grumbling infection.

Two types of pre-operative skin preparation were compared in a prospective randomized study conducted on 100 patients undergoing elective surgery: 51 patients were shaven (group I) and 49 were prepared with a depilatory agent. In all cases skin preparation was performed on the eve of the operation. Bacterial density, measured immediately before surgery by application of a contact agar preparation was 493 +/- 928 CFU in group I and 386 +/- 670 CFU in group II (NS). Bacterial density was less than 25 CFU in a significantly greater number of group II patients (P less than 0.01). On the second postoperative day, the number of scars without any sign of sepsis was significantly greater in group II patients (P less than 0.05). In addition, the depilatory agent proved bactericidal against 3 pathogenic strains (S. aureus, Pseudomonas aeruginosa and E. coli). Depilation with a chemical agent seems to be a satisfactory method of pre-operative skin preparation. It is more rapid than shaving, it can be applied to areas not easily accessible to razors, and it can often be carried out by the patient himself.

Eight instances of septic arthritis of the hip were treated in 6 paraplegics. On each occasion the hip had been infected through a nearby ulcer. In 2 cases the diagnosis was only made at operation because signs of a severe infection are not obvious in paraplegics. The radiographs were often misleading, the joint space being either normal or narrowed even before the onset of sepsis. The treatment combined antibiotic therapy with resection of the head and neck stabilized by external fixation for 45 days. The procedure was only successful in 5 cases out of 8 as far as infection was concerned. The resection did not impair ability to sit in this type of patient.