Clinical efficacy and safety of multipotent adult progenitor cells (invimestrocel) for acute respiratory distress syndrome (ARDS) caused by pneumonia: a randomized, open-label, standard therapy-controlled, phase 2 multicenter study (ONE-BRIDGE).

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory lung injury with high mortality; no approved medication exists. Efficacy and safety of bone marrow-derived, allogeneic, multipotent adult progenitor cells (invimestrocel) plus standard treatment in patients with ARDS caused by pneumonia was evaluated. METHODS: A randomized, open-label, standard therapy-controlled, phase 2 study (January 2019-September 2021) conducted in 29 centers in Japan. Patients with ARDS caused by pneumonia, with extensive early fibroproliferation on high-resolution computed tomography and low risk of systemic organ failure identified by an Acute Physiology and Chronic Health Evaluation (APACHE II) score were included. Patients were randomized 2:1 to receive a single intravenous infusion of 9.0 × 108 cells of invimestrocel (administered at a rate of up to 10 mL/min over 30-60 min by free flow) plus standard treatment (N = 20) or standard treatment (N = 10) consistent with the clinical practice guidelines of the Japanese Respiratory Society for the management of ARDS. Primary endpoint was ventilator-free days (VFDs) through day 28 after study treatment. Analysis of covariance was performed with treatment group, age, partial pressure arterial oxygen/fraction of inspired oxygen ratio, and APACHE II score as covariates. RESULTS: Median (interquartile range) number of VFDs was numerically higher in the invimestrocel group versus standard group (20.0 [0.0-24.0] vs 11.0 [0.0-14.0]) but was not statistically significantly different (least square [LS] means [95% confidence interval (CI)]: invimestrocel group, 11.6 [6.9-16.3]; standard group, 6.2 [- 0.4 to 12.8]; LS mean difference [95% CI], 5.4 [- 1.9 to 12.8]; p = 0.1397). Ventilator weaning rate at day 28 was 65% (13/20) versus 30% (3/10), and mortality rate was 21% (4/19) versus 29% (2/7) at day 28 and 26% (5/19 patients) versus 43% (3/7 patients) at day 180, for the invimestrocel and standard groups, respectively. No allergic or serious adverse reactions were associated with invimestrocel. CONCLUSIONS: In Japanese patients with ARDS caused by pneumonia, invimestrocel plus standard treatment resulted in no significant difference in the number of VFDs but may result in improved survival compared with standard treatment. Invimestrocel was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03807804; January 8, 2019; https://clinicaltrials.gov/ct2/show/NCT03807804 .

Acute Respiratory Failure of Unknown Etiology After Charcoal-Burning Suicide Attempt: Suspected Hypersensitivity Pneumonitis.

We report a case of a 25-year-old man who presented to the emergency department with respiratory distress after attempting suicide using burning charcoal briquettes. Charcoal briquette suicide is a method of suicide by carbon monoxide poisoning through inhalation of carbon monoxide produced when charcoal briquettes are burned. The patient had a history of childhood asthma, but he was not on any scheduled treatment regimen. Upon admission, he had an elevated respiratory rate, hypoxic respiratory failure, and bilateral respiratory wheezing. Computed tomography showed significant mottled and infiltrated shadows in the upper lobes of both lungs, and hypersensitivity pneumonitis was suspected. Sputum culture, autoantibodies such as antinuclear antibodies, and other diagnostic tests ruled out other conditions. The patient was treated with antibacterial agents and steroids. Imaging tests showed improvement over time. He was discharged on the seventh day. Charcoal briquette is a rare antigen that can potentially trigger hypersensitivity pneumonitis. Physicians should consider hypersensitivity pneumonitis as the differential diagnosis of respiratory failure after a charcoal-burning suicide attempt.

Fatal Asphyxia Potentially Caused by COVID-19-Induced Exacerbation of Pre-existing Tracheal Stenosis.

We report a case of cardiac arrest due to asphyxia caused by coronavirus disease 2019 (COVID-19) in a patient with no history of tracheal intubation but with a history of subglottic stenosis. A 54-year-old man suffered a cardiac arrest at home. The patient had tracheal stenosis; therefore, it was difficult to intubate. The patient had COVID-19, which was presumed to have aggravated the existing tracheal stenosis and caused asphyxiation. The patient died seven days later. This is, to our knowledge, the first report of a patient with subglottic stenosis potentially aggravated by COVID-19, resulting in asphyxia-related cardiopulmonary arrest. The patient could not be saved, but emergency physicians should be aware that airway obstruction can be caused by viral infections, including severe acute respiratory syndrome coronavirus 2 infections. Physicians should consider the difficulty in performing oral intubation and cricothyrotomy and be aware of alternative methods to secure the airway.

Pneumatosis Intestinalis With Abdominal Wall Emphysema in Hypothermia.

In this report, we present a case in which intestinal and abdominal wall emphysema was observed, but the patient was unconscious due to hypothermia, making it difficult to determine the indication for surgery. Pneumatosis intestinalis (PI) is a pathological condition characterized by the presence of gas within the walls of the small or large intestine and is considered a surgical emergency when accompanied by manifestations of peritonitis on abdominal examination, metabolic acidosis, and lactic acid levels above 2.0 mmol/L. In this specific case, the patient's blood draw results indicated the requirement for an emergency laparotomy; however, the patient's unconscious state became a challenge to make decision on informed consenting. The case illustrates the difficulties encountered in making treatment decisions in critically ill patients and the necessity for thorough assessments and close monitoring of vital signs in such patients.

Three Cases of Lactic Acidosis Caused by Biguanides.

Biguanides may cause lactic acidosis (LA) in elderly patients. We report three cases of LA after the administration of biguanides. Case 1 was an 85-year-old man with no hepatic dysfunction who was discharged, case 2 was a 67-year-old man with no hepatic dysfunction who was discharged, and case 3 was a 77-year-old woman with hepatic dysfunction who died. Therefore, caution should be exercised in administering biguanides to elderly patients with hepatic dysfunction.

Ventilator-associated events: prevalence and mortality in Japan.

BACKGROUND: In 2013, the Centers for Disease Control and Prevention (CDC) issued the concept of the ventilator-associated events (VAEs) as a quality indicator (QI) in the intensive care unit (ICU). A number of studies have been conducted in the United States and other Western countries to evaluate its practicality. However, information on VAEs in non-Western countries is scarce. The purpose of this preliminary study was to illuminate the incidence and associated mortality rate of VAEs in Japan, as a first step in the effort to determine its practicality. METHODS: We conducted a multi-center, retrospective review of patient medical record using VAEs surveillance algorithm. We analyzed 785 patients with ≥2 days of mechanical ventilator (MV), admitted to the ICU at seven urban hospital in Japan. The prevalence of VAEs, including its three subtypes, and in-ICU mortality were researched. RESULTS: Forty-nine VAEs were identified, affecting 5.7% of patients requiring MV for ≥2 days and 6.4 per 1,000 MV days. Mortality in those who developed VAEs was 42.9%, significantly higher than the rest of the cohort (vs. 15.4%, P<0.001). The overall equivalent distribution of the three VAEs subtype incidences was evaluated: the incidences of VAC only, IVAC only and PVAP were 2.20, 1.90 and 2.29 per 1,000 MV days respectively (P=0.933). However, VAE etiology and mortality was facility dependent. ICUs with a large proportion of surgical patients and more severe cases tended to have increased VAE incidence, with a converse decrease in closed ICUs. CONCLUSIONS: The prevalence of VAEs appears low in Japanese ICUs. Nonetheless, mortality was substantially higher in patients who developed VAEs. Although some potential indices of VAEs are suggested to serve as QIs, additional studies to elaborate its practicality would further be required.

Steroids Improve Hemodynamics in Infants With Adrenal Insufficiency After Cardiac Surgery.

OBJECTIVE: To investigate whether steroid replacement therapy improved hemodynamics in infants after surgery for congenital heart disease only when they develop adrenal insufficiency. The authors retrospectively investigated adrenal function and evaluated hemodynamic responses to steroid replacement therapy in infants after surgery for congenital heart disease. DESIGN: Retrospective, cohort study. SETTING: Intensive care unit in the National Cerebral and Cardiovascular Center Hospital in Japan. PATIENTS: Thirty-two neonates and infants<3 months old who underwent cardiovascular surgery. INTERVENTIONS: The patients were divided into 2 groups based on corticotropin stimulation test results: group AI with adrenal insufficiency (baseline cortisol<15 µg/dL or incremental increase after testing of<9 µg/dL, with baseline cortisol of 15-34 µg/dL); and group N with normal adrenal function. The corticotropin stimulation test was performed by injecting 3.5 µg/kg of tetracosactide acetate. Hydrocortisone (1 mg/kg) was administered every 6 hours, and hemodynamics were compared before and after steroid administration between the groups. MEASUREMENTS AND MAIN RESULTS: Seven patients were classified into group AI, and demonstrated a mean blood pressure increase from 53±8 mmHg before treatment to 68±9 mmHg 18 hours after steroid administration (p<0.01). Urine output also increased, from 2.7±1.0 mL/kg/h to 4.8±1.9 mL/kg/h (p<0.05). In group N, neither mean blood pressure nor urine output increased after steroid administration. CONCLUSIONS: After surgery for congenital heart disease, one-fifth of infants developed adrenal insufficiency. Steroid replacement therapy improved hemodynamics only in the subgroup with adrenal insufficiency.

Neurally adjusted ventilatory assist improves patient-ventilator synchrony in a patient with tetanus and unstable diaphragmatic electrical activity.

A 79-y-old man with generalized tetanus was admitted to the ICU. A left-forearm wound was surgically debrided, and the wound was closed. On postoperative day 1, after the patient experienced opisthotonos and convulsions, endotracheal intubation was performed. Propofol and diazepam were infused but failed to stop the convulsions. Morphine, midazolam, dantrolene, and rocuronium were used to ameliorate the muscle spasms. Magnesium sulfate was also infused. On postoperative day 15, patient-ventilator asynchrony was apparent. The patient showed recurrent tachypnea and bradypnea, which seemed typical of Cheyne-Stokes respiration. A neurally adjusted ventilatory assist (NAVA) catheter was inserted transnasally, and electrical activity of the diaphragm (Edi) was monitored. Readings showed regular attempts to breathe at 40-50 breaths/min with periodic changes in Edi amplitude. NAVA mode improved patient-ventilator synchrony. Periodic breathing continued for 2 weeks. We stopped monitoring Edi on postoperative day 39. He began respiratory rehabilitation and was transferred to a hospital for rehabilitation on postoperative day 80. We encountered periodic respiration in a patient with tetanus. Edi monitoring revealed periodic amplitude change. The cause of the periodic breathing pattern in this patient could not be determined but may be attributable to side effects of the pharmacologic interventions or the natural history of the disease itself. NAVA mode improved patient-ventilator synchrony.

Hyperoxemia in mechanically ventilated, critically ill subjects: incidence and related factors.

BACKGROUND: Excessive supplemental oxygen causes injurious hyperoxemia. Before establishing the best P(aO2) targets for mechanically ventilated patients, it is important to understand the incidence of hyperoxemia and related factors. We investigated oxygenation in mechanically ventilated subjects in our ICU and evaluated factors related to hyperoxemia (P(aO2) > 120 mm Hg) at 48 h after initiation of mechanical ventilation. METHODS: We retrospectively reviewed the medical records of patients admitted to our ICU from January 2010 to May 2013. Inclusion criteria were 15 y of age or older and administration of mechanical ventilation for > 48 h. Patients at risk of imminent death on admission or who had received noninvasive ventilation were excluded. We collected subject demographics, reasons for mechanical ventilation, and during mechanical ventilation, we collected arterial blood gas data and ventilator settings on the first day of intubation (T1), 48 h after initiation of mechanical ventilation (T2), and on the day of extubation (T3). Multivariable logistic regression analysis was performed to clarify independent variables related to hyperoxemia at T2. RESULTS: For the study period, data for 328 subjects were analyzed. P(aO2) statistically significantly increased over time to 90 (interquartile range of 74-109) mm Hg at T1, 105 (89-120) mm Hg at T2, and 103 (91-119) mm Hg at T3 (P < .001), coincident with decreases in F(IO2) of 0.4 (0.3-0.5) at T1, 0.3 (0.3-0.4) at T2, and 0.3 (0.3-0.35) at T3 (P < .001). Hyperoxemia occurred in 15.6% (T1), 25.3% (T2), and 22.4% (T3) of subjects. Multivariable logistic regression analysis revealed that hyperoxemia was independently associated with age of < 40 y (odds ratio 2.6, 95% CI 1.1-6.0), Acute Physiology and Chronic Health Evaluation II scores of ≥ 30 (odds ratio 0.53, 95% CI 0.3-1.0), and decompensated heart failure (odds ratio 1.9, 95% CI 1.1 to 3.5). CONCLUSIONS: During mechanical ventilation of critically ill subjects, P(aO2) increased, and F(IO2) decreased. One in 4 subjects were hyperoxemic at T2, and hyperoxemia persisted until T3.

Changes in endotracheal tube cuff pressure in mechanically ventilated adult patients.

During mechanical ventilation, endotracheal tube cuff pressure should be maintained within proper range. We investigated the effect of frequent adjustment on cuff pressure in 27 mechanically ventilated patients. Cuff pressure was recorded every 2 h and was adjusted to 24 cmH2O each time. We found that cuff pressure was decreased by 4.9 ± 2.9 cmH2O from the target value. Cuff pressure decreased to less than 20 cmH2O in 45% of measurement occasions 2 h after adjusting it to 24 cmH2O.

Complete bronchial obstruction by granuloma in a paediatric patient with translaryngeal endotracheal tube: a case report.

INTRODUCTION: Although continuous or frequent stimuli in tracheostomized patients may cause tracheal granulomas, little is known about management of patients with translaryngeal intubation. CASE PRESENTATION: A 1-month-old Japanese boy, weighing 3.5kg, was admitted to our hospital owing to cardiac failure caused by an atrial septal defect and intractable arrhythmia. To treat his unstable cardiovascular status, surgery was performed to close his atrial septal defect. After the operation, stenosis was detected by auscultation and flow limitation worsened. A bronchoscopy revealed granulomas completely obstructing his right bronchus and partially obstructing his left bronchus. Dexamethasone infusion partially reduced the mass, after which removal by yttrium aluminium garnet laser was tried. The airway obstruction was not resolved, however, because of granuloma reproliferation. Budesonide (aerosol liquid) inhalation was started, and tissue was reduced using an yttrium aluminium garnet laser and physically removed using forceps. After continued budesonide inhalation, he was successfully liberated from the ventilator. CONCLUSIONS: Life-threatening airway obstruction by granulomas developed in a translaryngeally intubated paediatric patient. The granuloma was detected after a couple of weeks of intubation. A bronchial granuloma is rare in paediatric patients. It should be suspected with evidence of bronchial obstruction. Treatment with corticosteroids and surgery using a laser maybe indicated.

Successful use of extracorporeal membrane oxygenation in the reversal of cardiorespiratory failure induced by atonic uterine bleeding: a case report.

INTRODUCTION: Although extracorporeal membrane oxygenation has made sufficient progress to be considered for the management of life-threatening cardiac and respiratory failure, the risk of hemorrhagic complications may outweigh the benefits for patients with bleeding tendencies. We report, to the best of our knowledge, the first case of successful treatment by extracorporeal membrane oxygenation, without any hemorrhagic complications, of postpartum cardiorespiratory failure after massive uterine bleeding. CASE PRESENTATION: A 25-year-old Japanese woman experienced massive atonic bleeding after delivering her second baby. Recovery from hemorrhagic shock was managed by conservative treatments, but she developed decompensated heart failure and refractory hypoxia. Because we could not obtain hemodynamic stability and proper oxygenation even with high doses of catecholamines and maximal ventilator settings, we administered venoarterial extracorporeal membrane oxygenation, whereupon her hemodynamic status immediately stabilized. After 72 hours of support without major bleeding, extracorporeal membrane oxygenation was successfully withdrawn. CONCLUSION: Even in cases of obstetric bleeding, if clotting status is stringently monitored, extracorporeal membrane oxygenation can be considered as an ultimate means of life support.

Humidification performance of two high-flow nasal cannula devices: a bench study.

INTRODUCTION: Delivering heated and humidified medical gas at 20-60 L/min, high-flow nasal cannula (HFNC) creates low levels of PEEP and ameliorates respiratory mechanics. It has become a common therapy for patients with respiratory failure. However, independent measurement of heat and humidity during HFNC and comparison of HFNC devices are lacking. METHODS: We evaluated 2 HFNC (Airvo 2 and Optiflow system) devices. Each HFNC was connected to simulated external nares using the manufacturer's standard circuit. The Airvo 2 outlet-chamber temperature was set at 37°C. The Optiflow system incorporated an O2/air blender and a heated humidifier, which was set at 40°C/3. For both systems, HFNC flow was tested at 20, 40, and 50 L/min. Simulating spontaneous breathing using a mechanical ventilator and TTL test lung, we tested tidal volumes (VT) of 300, 500, and 700 mL, and breathing frequencies of 10 and 20 breaths/min. The TTL was connected to the simulated external nares with a standard ventilator circuit. To prevent condensation, the circuit was placed in an incubator maintained at 37°C. Small, medium, and large nasal prongs were tested. Absolute humidity (AH) of inspired gas was measured at the simulated external nares. RESULTS: At 20, 40, and 50 L/min of flow, respective AH values for the Airvo 2 were 35.3 ± 2.0, 37.1 ± 2.2, and 37.6 ± 2.1 mg/L, and for the Optiflow system, 33.1 ± 1.5, 35.9 ± 1.7, and 36.2 ± 1.8 mg/L. AH was lower at 20 L/min of HFNC flow than at 40 and 50 L/min (P < .01). While AH remained constant at 40 and 50 L/min, at 20 L/min of HFNC flow, AH decreased as VT increased for both devices. CONCLUSIONS: During bench use of HFNC, AH increased with increasing HFNC flow. When the inspiratory flow of spontaneous breathing exceeded the HFNC flow, AH was influenced by VT. At all experimental settings, AH remained > 30 mg/L.

Decrease in cuff pressure during the measurement procedure: an experimental study.

BACKGROUND: To prevent endotracheal tube (ETT)-related complications during mechanical ventilation, ETT cuff pressure should be kept within proper range. In clinical settings, cuff pressure often decreases from target values. METHODS: We performed an experimental study to investigate the effects of measuring devices and endotracheal tubes on change in cuff pressure. We continuously measured cuff pressure by inserting a three-way stopcock in the middle of an ETT pilot balloon system. After adjusting the cuff pressure to 24 cmH2O, we disconnected and reconnected each cuff inflator to the inflation valve of the ETT and measured the changes in the cuff pressure. We measured the change in cuff pressure with different ETT sizes, cuff shapes, brands of cuff inflator, and with and without added extension tubes. RESULTS: The cuff pressure decreased, on average, by 6.6 cmH2O (standard deviation 1.9), when connecting the cuff inflator to the pilot balloon. The measured cuff pressure was less than 20 cmH2O in 67% of the tests. The cuff pressure decreased more when an extension tube was used. The brand of cuff inflator made no difference to the pressure loss. The cuff pressure decreased more with ETTs of smaller size and with ETTs with pyriform cuffs. CONCLUSIONS: Procedures to connect cuff inflators to inflation valves resulted in the loss of cuff pressure by 6.6 cmH2O on average.

Hygrometric properties of inspired gas and oral dryness in patients with acute respiratory failure during noninvasive ventilation.

BACKGROUND: Because noninvasive ventilation (NIV) delivers medical gas at high flow, inadequate humidification may cause oral dryness and patient discomfort. Heated humidification can be used during NIV, but little has been reported about the effects on the hygrometric conditions inside an oronasal mask and oral dryness during 24 hours on NIV. METHODS: We measured absolute humidity (AH) inside oronasal masks on subjects with acute respiratory failure during 24 hours on NIV. A single-limb turbine ventilator and oronasal mask with an exhalation port were used for NIV. Oral moistness was evaluated using an oral moisture-checking device, and 3 times during the 24 hours the subjects subjectively scored the feeling of dryness on a 0-10 scale in which 10 was the most severe dryness. RESULTS: Sixteen subjects were enrolled. The mean ± SD AH inside the mask was 30.0 ± 2.6 mg H2O/L (range 23.1-33.3 mg H2O/L). The median oral moistness was 19.2% (IQR 4.4-24.0%), and the median oral dryness score was 5.5 (IQR 4-7). AH and inspired gas leak correlated inversely, both within the subjects (r = -0.56, P < .001) and between the subjects (r = -0.58, P = .02). AH and oral moistness correlated within the subjects (r = 0.39, P = .04). Oral breathing was associated with reduced oral moistness (P = .001) and increased oral dryness score (P = .002). CONCLUSIONS: AH varied among the subjects, and some complained of oral dryness even with heated humidifier. Oral breathing decreased oral moistness and worsened the feeling of dryness.

Effect of high-flow nasal cannula on thoraco-abdominal synchrony in adult critically ill patients.

BACKGROUND: High-flow nasal cannula (HFNC) creates positive oropharyngeal airway pressure and improves oxygenation. It remains unclear, however, whether HFNC improves thoraco-abdominal synchrony in patients with mild to moderate respiratory failure. Using respiratory inductive plethysmography, we investigated the effects of HFNC on thoraco-abdominal synchrony. METHODS: We studied 40 adult subjects requiring oxygen therapy in the ICU. Low-flow oxygen (up to 8 L/min) was administered via oronasal mask for 30 min, followed by HFNC at 30-50 L/min. Respiratory inductive plethysmography transducer bands were circumferentially placed: one around the rib cage, and one around the abdomen. We measured the movement of the rib-cage and abdomen, and used the sum signal to represent tidal volume (V(T)) during mask breathing, and at 30 min during HFNC. We calculated the ratio of maximum compartmental amplitude (MCA) to V(T), and the phase angle. We assessed arterial blood gas and vital signs at each period, and mouth status during HFNC. We used multiple regression analysis to identify factors associated with improvement in thoraco-abdominal synchrony. RESULTS: During HFNC, breathing frequency significantly decreased from 25 breaths/min (IQR 22-27 breaths/min) to 21 breaths/min (IQR 18-24 breaths/min) (P < .001), and MCA/VT (P < .001) and phase angle (P = .047) significantly improved. CONCLUSIONS: HFNC improved thoraco-abdominal synchrony in adult subjects with mild to moderate respiratory failure.

[Delayed discharge from the intensive care unit].

BACKGROUND: Delayed discharge from ICU to the general ward can exert an adverse effect. We researched whether patients are discharged smoothly from our ICU to the general ward. METHODS: We defined that patients were eligible for discharge if they are without administration of catecholamine, being assisted by mechanical ventilation and having blood purification therapy. RESULTS: Average time from actual discharge to the time patient was considered eligible for discharge was fifteen hours. This study was retrospective. CONCLUSIONS: We need to investigate further the reasons why delayed discharge occurred. It is im portant that patients are discharged from the ICU to the general ward properly. Delayed discharge can delay the recovery and expose the patient to multi-resistant microorganisms. We studied whether patients are discharged smoothly from the ICU to the general ward.

A novel method of post-pyloric feeding tube placement at bedside.

PURPOSE: Post-pyloric feeding tube placement is often difficult, and special equipment or peristalsis agents are used to aid insertion. Although several reports have described blind techniques for post-pyloric feeding-tube placement, no general consensus about method preference has been achieved. MATERIALS AND METHODS: The technique is performed as follows: via the nostril, a stylet-tipped feeding tube is advanced about 70 cm; to confirm tip location to the right of the epigastric area, towards the right hypochondriac region, 5 mL shots of air are injected to enable touch detection of bubbling; finally, the tube is advanced to a length of 100 cm, during which the strength of bubbling seems to diminish under palpation. RESULTS: We prospectively enrolled consecutive patients whose oral intake was expected to be difficult for 48 hours in the intensive care unit. Forty-one patients were enrolled and the rate of successful placement at first attempt was 95.1%. Mean duration for successful placement was 15 minutes. CONCLUSIONS: With a novel technique, from the bedside, without special tools or drugs, we successfully placed post-pyloric feeding tubes. Essential points when inserting the tube are confirmation of the location of the tube tip by palpation of injected air, and to avoid deflection and looping.

Incidence of bacterial contamination in infusion set needles.

We examined the incidence and types of bacterial contamination in 265 infusion set needles in adult critically ill patients. Bacterial contamination was detected in 15 samples (5.7%), and a total of 17 organisms were isolated. Ten were coagulase-negative staphylococci (CNS) and Staphylococcus aureus, and the remainder were α-Streptococcus, Corynebacterium, and gram-negative rods. Although the contamination was not directly related to catheter-related bloodstream infections exchanging infusion bottles can cause intraluminal contamination and is a possible route of these infections.