CRISPRi-induced transcriptional regulation of IAH1 gene and its influence on volatile compounds profile in Kluyveromyces marxianus DU3.

Mezcal is a traditional Mexican distilled beverage, known for its marked organoleptic profile, which is influenced by several factors, such as the fermentation process, where a wide variety of microorganisms are present. Kluyveromyces marxianus is one of the main yeasts isolated from mezcal fermentations and has been associated with ester synthesis, contributing to the flavors and aromas of the beverage. In this study, we employed CRISPR interference (CRISPRi) technology, using dCas9 fused to the Mxi1 repressor factor domain, to down-regulate the expression of the IAH1 gene, encoding for an isoamyl acetate-hydrolyzing esterase, in K. marxianus strain DU3. The constructed CRISPRi plasmid successfully targeted the IAH1 gene, allowing for specific gene expression modulation. Through gene expression analysis, we assessed the impact of IAH1 down-regulation on the metabolic profile of volatile compounds. We also measured the expression of other genes involved in volatile compound biosynthesis, including ATF1, EAT1, ADH1, and ZWF1 by RT-qPCR. Results demonstrated successful down-regulation of IAH1 expression in K. marxianus strain DU3 using the CRISPRi system. The modulation of IAH1 gene expression resulted in alterations in the production of volatile compounds, specifically ethyl acetate, which are important contributors to the beverage's aroma. Changes in the expression levels of other genes involved in ester biosynthesis, suggesting that the knockdown of IAH1 may generate intracellular alterations in the balance of these metabolites, triggering a regulatory response. The application of CRISPRi technology in K. marxianus opens the possibility of targeted modulation of gene expression, metabolic engineering strategies, and synthetic biology in this yeast strain.

Experimental pharmacological approaches to reverse impaired awareness of hypoglycemia-a review.

The colossal global burden of diabetes management is compounded by the serious complication of hypoglycemia. Protective physiologic hormonal and neurogenic counterregulatory responses to hypoglycemia are essential to preserve glucose homeostasis and avert serious morbidity. With recurrent exposure to hypoglycemic episodes over time, these counterregulatory responses to hypoglycemia can diminish, resulting in an impaired awareness of hypoglycemia (IAH). IAH is characterized by sudden neuroglycopenia rather than preceding cautionary autonomic symptoms. IAH increases the risk of subsequent sudden and severe hypoglycemic episodes in patients with diabetes. The postulated causative mechanisms behind IAH are complex and varied. It is therefore challenging to identify a single effective therapeutic strategy. In this review, we closely examine the efficacy and feasibility of a myriad of pharmaceutical interventions in preventing and treating IAH as described in clinical and preclinical studies. Pharmaceutical agents outlined include N-acetyl cysteine, GABA A receptor blockers, opioid receptor antagonists, AMP activated protein kinase agonists, potassium channel openers, dehydroepiandrosterone, metoclopramide, antiadrenergic agents, antidiabetic agents and glucagon.

A nomogram for predicting the risk of intra-abdominal hypertension in critically ill patients based on ultrasound and clinical data.

Background: Intra-abdominal hypertension (IAH) is a common complication in critically ill patients. This study aimed to identify independent risk factors for IAH and generate a nomogram to distinguish IAH from non-IAH in these patients. Methods: We retrospectively analyzed 89 critically ill patients and divided them into an IAH group [intra-abdominal pressure (IAP) ≥12 mmHg] and a non-IAH group (IAP <12 mmHg) based on the IAP measured from their bladders. Ultrasound and clinical data were also measured. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for IAH. The correlation between IAP and independent risk factors was also assessed. Results: Of these 89 patients, 45 (51%) were diagnosed with IAH. Univariate analysis showed there were significant differences in the right renal resistance index (RRRI) of the interlobar artery, the right diaphragm thickening rate (RDTR), and lactic acid (Lac) between IAH and non-IAH groups (P<0.001). Multivariate logistic regression analysis revealed that increasing RRRI, RDTR, and Lactic acid (Lac) were independent risk factors for IAH (P=0.001, P=0.001, and P=0.039, respectively). IAP was significantly correlated with RRRI, RDTR, and Lac (r=0.741, r=-0.774, and r=0.396, respectively; P<0.001). The prediction model based on regression analysis results was expressed as follows: predictive score = -17.274 + 31.125 × RRRI - 29.074 × RDTR + 0.621 × Lac. Meanwhile, the IAH nomogram prediction model was established with an area under the receiver operating characteristic (ROC) curve of 0.956 (95% confidence interval: 0.909-1.000). The nomogram showed good calibration for IAH with the Hosmer-Lemeshow test (P=0.864) and was found to be applicable within a wide threshold probability range, especially that higher than 0.40. Conclusions: The noninvasive nomogram based on ultrasound and clinical data has good diagnostic efficiency and can predict the risk of IAH. This nomogram may provide valuable guidance for clinical interventions to reduce IAH morbidity and mortality in critically ill patients.

Intra-abdominal hypertension in cardiac surgery patients: a multicenter observational sub-study of the Accuryn registry.

Intra-abdominal hypertension (IAH) is frequently present in the critically ill and is associated with increased morbidity and mortality. Conventionally, intermittent 'spot-check' manual measurements of bladder pressure in those perceived as high risk are used as surrogates for intra-abdominal pressure (IAP). True patterns of IAH remain unknown. We explored the incidence of IAH in cardiac surgery patients and describe the intra-and postoperative course of IAP using a novel, high frequency, automated bladder pressure measurement system. Sub-analysis of a prospective, multicenter, observational study (NCT04669548) conducted in three large academic medical centers. Continuous urinary output (CUO) and IAP measurements were observed using the Accuryn Monitoring System (Potrero Medical, Hayward, CA). Data collected included demographics, hemodynamic support, and high-frequency IAP and CUO. One Hundred Thirty-Seven cardiac surgery patients were analyzed intraoperatively and followed 48 h postoperatively in the intensive care unit. Median age was 66.4 [58.3, 72.0] years, and 61% were men. Median Foley catheter dwell time was 56.0 [46.8, 77.5] hours, and median baseline IAP was 6.3 [4.0, 8.1] mmHg. 93% (128/137) of patients were in IAH grade I, 82% (113/137) in grade II, 39% (53/137) in grade III, and 5% (7/137) in grade IV for at least 12 cumulative hours. For maximum consecutive duration of IAH, 84% (115/137) of patients spent at least 12 h in grade I, 62% (85/137) in grade II, 18% (25/137) in grade III, and 2% (3/137) in grade IV IAH. During the first 48 h after cardiac surgery, IAH is common and persistent. Improved and automated monitoring of IAP will increase the detection of IAH-which normally would remain undetected using traditional intermittent monitoring methods.

Abdominal paracentesis drainage improves outcome of acute pancreatitis complicated with intra-abdominal hypertension in early phase.

BACKGROUND: Intra-abdominal hypertension (IAH) is an important risk factor for organ dysfunction, and it occurs in the early phase of severe acute pancreatitis (SAP). We have reported a novel step-up approach and shown the benefit of performing abdominal paracentesis drainage (APD) ahead of percutaneous catheter drainage (PCD) when treating Patients with SAP with fluid collections. This study aimed to evaluate the efficacy of APD in Patients with SAP complicated with IAH in the early phase. METHODS: In the present study, 206 AP patients complicated with IAH in the early phase were enrolled in hospital between June 2017 and December 2020. The patients were divided into two groups: 109 underwent APD (APD group) and 97 were managed without APD (non-APD group). We retrospectively compared the outcomes of the APD and non-APD groups for IAH treatment. The parameters including mortality, infection, organ failure, inflammatory factors, indications for further interventions, and drainage-related complications were observed. RESULTS: The demographic data and severity scores of the two groups were comparable. The mortality rate was lower in the APD group (3.7%) than in the non-APD group (8.2%). Compared with the non-APD group, the intra-abdominal pressure and laboratory parameters of the APD group decreased more rapidly, and the mean number of failed organs was lower. However, there was no significant difference in incidence of infections between the two groups. CONCLUSIONS: Application of APD is beneficial to AP patients. It significantly attenuated inflammation injury, avoided further interventions, and reduced multiple organ failure.

Role of intra-abdominal pressure measurement in patients with acute abdomen requiring exploratory laparotomy.

<b>Introduction:</b> Acute abdomen is one of the most common surgical emergencies faced by a surgeon. Monitoring Intra-Abdominal Pressure (IAP) in patients with acute abdomen referred for exploratory laparotomy may help guide the need for early intervention. </br></br> <b>Aim:</b> This study was performed to determine whether preoperative IAP had any significant association with organ failure as assessed using SOFA score. Furthermore, effect of IAP on patient outcome in terms of hospital stay, mortality was also evaluated. </br></br> <b>Materials and methods:</b> 60 patients above 18 years of age presenting with acute abdomen requiring exploratory laparotomy were included in this prospective observational study from November 2013 until March 2015. IAP and SOFA scores were calculated at the time of admission. The outcome of patients was assessed in terms of hospital stay, morbidity and mortality. The correlation between IAP and SOFA scores was also assessed to determine the risk of organ failure. The inferences were drawn with the use of SPSS v22.0 statistical software. ANOVA, Chi-square and Student's t-test were used in the analysis. </br></br> <b> Results:</b> There was a positive correlation between SOFA score and IAP; and this correlation was found to be statistically significant with Pearson's correlation coefficient being 0.6247 and significance levels being <0.0001. Both hospital stay and mortality positively correlated with the degree of IAP. </br></br> <b> Conclusions:</b> IAP should be routinely measured in patients with acute abdomen requiring exploratory laparotomy. Patients with preoperatively raised IAP should be referred for emergency surgery as soon as possible for better outcome.

Craniofacial morphology in patients with obstructive sleep apnea: cephalometric evaluation / Morfologia craniofacial em pacientes com apneia obstrutiva do sono: avaliação cefalométrica

Abstract Introduction: Obstructive sleep apnea is characterized by a reduced airflow through the upper airways during sleep. Two forms of obstructive sleep apnea are described: the central form and the obstructive form. The obstructive form is related to many factors, such as the craniofacial morphology. Objective: To evaluate the correlation between the morphology of the cranial base, of the mandible and the maxilla, and obstructive sleep apnea severity. Methods: Eighty-four patients, mean age of 50.4 years old; 73 males and 11 females with obstructive sleep apnea were enrolled in the present study. Patients with high body mass index and comorbidities were excluded. Lateral cephalograms and polysomnography were collected for each patient to evaluate the correlation between craniofacial morphology and obstructive sleep apnea severity. A Spearman's rho correlation test between cephalometric measurements and obstructive sleep apnea indexes was computed. Statistical significance was set at p < 0.05. Results: Patients with a severe obstructive sleep apnea presented a reduction of sagittal growth of both effective mandibular length and cranio-basal length. The mandibular length was the only variable with a statistical correlation with apnea-hypopnea index. Vertical dimension showed a weak correlation with the severity of obstructive sleep apnea. No correlation with maxillary sagittal dimension was shown. Conclusion: Obstructive sleep apnea severity may be correlated to mandibular and cranial base growth. Facial vertical dimension had no correlation with obstructive sleep apnea severity.

Resumo Introdução: A apneia obstrutiva do sono é caracterizada por um fluxo de ar reduzido nas vias aéreas superiores durante o sono. Duas formas de apneia são descritas: a forma central e a forma obstrutiva. A forma obstrutiva tem sido relacionada a vários fatores, como a morfologia craniofacial. Objetivo: Avaliar a correlação entre a morfologia da base do crânio, da mandíbula e da maxila e a gravidade da apneia obstrutiva do sono. Método: Foram incluídos no presente estudo 84 pacientes com apneia obstrutiva do sono, com média de 50,4 anos; 73 homens e 11 mulheres. Pacientes com alto índice de massa corpórea e comorbidades foram excluídos. Foram coletados cefalogramas laterais e polissonografia para cada paciente para avaliar a correlação entre a morfologia craniofacial e a gravidade da apneia. Foi computado o coeficiente de correlação de postos de Spearman (rho) entre medidas cefalométricas e índices de apneia obstrutiva do sono. A significância estatística foi estabelecida em p < 0,05. Resultados: Pacientes com apneia obstrutiva do sono grave apresentaram redução do crescimento sagital do comprimento mandibular efetivo e do comprimento crânio-basal. O comprimento mandibular foi a única variável que apresentou correlação estatística com o índice de apneia-hipopneia. A dimensão vertical mostrou uma fraca correlação com a gravidade da apneia. Não foi demonstrada correlação com a dimensão maxilar sagital. Conclusão: A gravidade da apneia obstrutiva do sono pode estar correlacionada ao crescimento da base mandibular e craniana. A dimensão facial vertical não apresentou correlação com a gravidade da apneia.

Automated Intra-abdominal Pressure Monitoring During Orthotopic Heart Transplant Leads to Early Diagnosis and Treatment of Intraoperative Abdominal Compartment Syndrome-A Case Report.

We describe a case of spontaneous retroperitoneal hematoma leading to abdominal compartment syndrome and organ failure during a complicated orthotopic heart transplantation in a patient previously on mechanical circulatory support. After the patient had been weaned of cardiopulmonary bypass, the patient suddenly became hemodynamically unstable despite good LV and RV function. While the patient was resuscitated, high intra-abdominal pressures were noted on a novel monitor measuring real-time intra-abdominal pressures and urinary output. The early detection of high intra-abdominal pressures led to a swift decompressive laparotomy with the detection of retroperitoneal hematoma and subsequent hemodynamic stabilization.

Intra-abdominal hypertension in neonates following congenital diaphragmatic hernia repair: Correlation with early postoperative respiratory and gastrointestinal outcomes.

BACKGROUND: Increased intra-abdominal pressure (IAP) is seen in patients after congenital diaphragmatic hernia (CDH) repair owing to reduction of thoracic contents into the relatively smaller abdominal cavity. In infants, IAP ≥11 mmHg is considered intra-abdominal hypertension (IAH). We aim to determine the incidence of IAH and its relationship with duration of ventilatory support, and gastrointestinal function post CDH repair. METHODS: We prospectively recruited all neonates who had CDH repair in four hospitals in Malaysia from June 2018 to October 2020. Intra vesical pressure was used as a proxy for IAP and was measured for 5 consecutive days post surgery. The daily median value was used for analysis. We categorized IAP as <11 mmHg (no IAH), 11-15 mmHg (IAH), and >15 mmHg (severe IAH). Incidence of IAH, its effects on the duration of ventilatory support, and gastrointestinal function were studied. RESULTS: There were 24 neonates included in this study. They were operated between day 1 and 6 of life (median: 4 days old). IAH was detected within the first 3 days post surgery, with 83% occurring on day one. Those requiring ventilatory support for more than 3 days contributed the largest proportion of IAH (n = 17, 71%). There was strong correlation between days of IAH and duration of ventilation (p < 0.001, r = 0.70). There was moderate correlation between days of IAH and duration taken to achieve full enteral feeding (p < 0.005, r = 0.70). CONCLUSION: IAP measurement is a safe and useful adjunct in post CDH monitoring and in predicting ventilatory support requirements and the time needed to establish feeding.

Intra-abdominal hypertension and abdominal compartment syndrome in critically ill patients: A narrative review of past, present, and future steps.

BACKGROUND AND OBJECTIVE: Intra-abdominal hypertension is frequently present in critically ill patients and is an independent predictor for mortality. In this narrative review, we aim to provide a comprehensive overview of current insights into intra-abdominal pressure monitoring, intra-abdominal hypertension, and abdominal compartment syndrome. The focus of this review is on the pathophysiology, risk factors and outcome of intra-abdominal hypertension and abdominal compartment syndrome, and on therapeutic strategies, such as non-operative management, surgical decompression, and management of the open abdomen. Finally, future steps are discussed, including propositions of what a future guideline should focus on. CONCLUSIONS: Pathological intra-abdominal pressure is a continuum ranging from mild intra-abdominal pressure elevation without clinically significant adverse effects to substantial increase in intra-abdominal pressure with serious consequences to all organ systems. Intra-abdominal pressure monitoring should be performed in all patients at risk of intra-abdominal hypertension. Although continuous intra-abdominal pressure monitoring is feasible, this is currently not standard practice. There are a number of effective non-operative medical interventions that may be performed early in the patient's course to reduce intra-abdominal pressure and decrease the need for surgical decompression. Abdominal decompression can be life-saving when abdominal compartment syndrome is refractory to non-operative treatment and should be performed expeditiously. The objectives of open abdomen management are to prevent fistula and to achieve delayed fascial closure at the earliest possible time. There is still a lot to learn and change. The 2013 World Society of Abdominal Compartment Syndrome guidelines should be updated and multicentre studies should evaluate the effect of intra-abdominal hypertension treatment on patient outcome.

The Beginning of Life Issues: An Islamic Perspective.

Islam gives legal precedence to purity of lineage and known parenthood of all children. In Islam treatment to infertility using IVF is permitted within validity of marriage contract with no genes mixing. The paper shows that the Qur'an, the word of Allah, and science, the deeds of Allah are not in major conflicts in defining the start of human life. The Holy Qur'an provides an elegant description of origin, developmental stages of intra-uterine life. The Hadith explains two positions one that believes human embryo get ensouled at conception and the other after 40 days of conception. The paper aims to find that Islam confers moral respect to human embryo, but it also clarifies the absence of full human rights to a developing foetus. In Islam, human embryonic use is probably permissible for therapeutic and reproductive purpose keeping intact the principles of Shari'ah.

Hypoglycaemia.

In health hypoglycaemia is rare and occurs only in circumstances like extreme sports. Hypoglycaemia in type 1 Diabetes (T1D) and advanced type 2 Diabetes (T2D) are the result of interplay between absolute or relative insulin access and defective glucose counterregulation. The basic mechanism is, failure of decreasing insulin and failure of the compensatory increasing counterregulatory hormones at the background of falling blood glucose. Any person with Diabetes on anti-diabetic medication who behaves oddly in any way whatsoever is hypoglycaemic until proven otherwise. Hypoglycaemia can be a terrifying experience for a patient with Diabetes. By definition, hypoglycaemic symptoms are subjective and vary from person to person and even episode to episode in same person. Fear of iatrogenic hypoglycaemia is a major barrier in achieving optimum glycaemic control and quality of life which limits the reduction of diabetic complications. Diabetes patients with comorbidities especially with chronic renal failure, hepatic dysfunction, major limb amputation, terminal illness, cognitive dysfunction etc. are more vulnerable to hypoglycaemia. In most cases, prompt glucose intake reverts hypoglycaemia. Exogenous insulin in T1D and insulin treated advanced T2D have no control by pancreatic regulation. Moreover, failure of increase of glucagon and attenuated secretion in epinephrine causes the defective glucose counterregulation. In this comprehensive review, I will try to touch all related topics for better understanding of hypoglycaemia.

Intravesical monitoring of intra-abdominal pressure after renal transplantation in children: A safety and feasibility study.

IAH after RTX can threaten graft viability. This study aimed to assess the feasibility and safety of longitudinal IAP measurements as an IAH screening method in children after RTX. A cohort of eight children with a mean ± SD [range] age 9.6 ± 6.2 [2-17] years who underwent RTX and 18 control patients were evaluated between May 2017 and February 2018. We compared longitudinal IAP measurements using a Foley manometer to other clinical monitoring data. In total, 29 IAP measurements were performed in RTX patients and 121 in controls. The mean post-operative IAP was 7.4 ± 4.3 [1-16] mm Hg following RTX and 8.1 ± 3.7 [1-19] mm Hg in controls. We noted IAH in 9 (31%) of 29 IAP measurements after RTX and in 41 (34%) of 121 IAP measurements in controls. No graft dysfunction occurred in RTX patients despite elevated IAP values. The mean ± SD [range] time expenditure for IAP measurement was 2.1 ± 0.4 [0.6-3.2] minutes. No severe complications occurred during the IAP measurements. Analysis of longitudinal IAP measurements demonstrated that IAP measurement is safe and feasible in children recovering from renal transplantation in the PICU.

Management of Insulin Autoimmune Hypoglycaemia: Single-centre experience from Western India with systematic review of world literature.

BACKGROUND: Awareness about Insulin Autoimmune Hypoglycaemia (IAH) and its management remains limited. METHODOLOGY: We describe two cohorts: Cohort 1 (n = 7) included patients with IAH from a tertiary care centre in India and Cohort 2 (n = 294) included systematic review of published English literature from PubMed. They were compared with our insulinoma patients (n = 41). RESULTS: Cohort 1 included seven female patients where two had drugs (carbimazole and thiocolchicoside) as triggering factors. Except for one patient requiring oral prednisolone, others had spontaneous remission. The unique features from our series are being first case series of IAH from India and reporting of second case of thiocolchicoside triggered IAH. Cohort 2 had 294 patients identified from 149 publications. Mean age was 54 ± 19 years. Thirty-five different triggers were identified from 160 cases. Antithyroid drugs were most common triggers in Japanese patients and most common HLA allele was DRB1*0406, while it was alpha-lipoic acid and HLA DRB1*0403 in non-Asians. Serum Insulin >100 µIU/mL and insulin to C-peptide molar ratio (ICMR) >0.25 had specificity of 100% and 97.5%, respectively, for IAH as compared to insulinoma. 56% patients had remission with complex carbohydrate diet and trigger removal while 43% required immunosuppressants. 70% achieved remission within 6 months. CONCLUSIONS: Middle age remains most common age group. Sulfhydryl drugs are most common triggers. Serum Insulin >100 µIU/mL and ICMR > 0.25 in critical sample are good predictors for diagnosis of IAH, which needs to be confirmed by IAA. Conservative management with dietary modification and trigger removal usually suffices in majority. Rests need immunosuppressants.

Intra-abdominal pressure may be elevated in patients with open abdomen after emergent laparotomy.

PURPOSE: To estimate the change in intra-abdominal pressure (IAP) among critically ill patient who were left with open abdomen and temporary abdominal closure after laparotomy, during the first 48 h after admission. METHODS: A cohort study in a single ICU in a tertiary care hospital. All adult patients admitted to the ICU after emergent laparotomy for acute abdomen or trauma, who were left with temporary abdominal closure (TAC), were included. Patients were followed up to 48 h. IAP was routinely measured at 0, 6, 12, 24, and 48 h after admission to ICU. RESULTS: Thirty-nine patients were included, 34 were operated due to acute abdomen and 5 due to abdominal trauma. Seventeen patients were treated with skin closure, 13 with Bogota bag, and 9 with negative pressure wound therapy (NPWT). Eleven patients (28.2%) had IAP of 15 mmHg or above at time 0, (mean pressure 19.0 ± 3.0 mmHg), and it dropped to 12 ± 4 mmHg within 48 h (p < 0.01). Reduction in lactate level (2.4 ± 1.0 to 1.2 ± 0.2 mmol/L, p < 0.01) and increase in PaO2/FiO2 ratio (163 ± 34 to 231 ± 83, p = 0.03) were observed as well after 48 h. CONCLUSIONS: This is the first large report of IAP in open abdomen. Elevated IAP may be measured in open abdomen and may subsequently relieve after 48 h.

The significance of intra-abdominal pressure in neurosurgery and neurological diseases: a narrative review and a conceptual proposal.

Intra-abdominal pressure (IAP) is a physiological parameter that has gained considerable attention during the last few decades. The incidence of complications arising from increased IAP, known as intra-abdominal hypertension (IAH) or abdominal compartment syndrome in critically ill patients, is high and its impact is significant. The effects of IAP in neurological conditions and during surgical procedures are largely unexplored. IAP also appears to be relevant during neurosurgical procedures (spine and brain) in the prone position, and in selected cases, IAH may affect cerebrospinal fluid drainage after a ventriculoperitoneal shunt operation. Furthermore, raised IAP is one of the contributors to intracranial hypertension in patients with morbid obesity. In traumatic brain injury, case reports described how abdominal decompression lowers intracerebral pressure. The anatomical substrate for transmission of the IAP to the brain and venous system of the spine is the extradural neural axis compartment; the first reports of this phenomenon can be found in anatomical studies of the sixteenth century. In this review, we summarize the available knowledge on how IAP impacts the cerebrospinal venous system and the jugular venous system via two pathways, and we discuss the implications for neurosurgical procedures as well as the relevance of IAH in neurological disorders.

Is intra-abdominal hypertension a risk factor for ventilator-associated pneumonia?

In the last years, there has been a significant amount of research about the impact of intra-abdominal hypertension (IAH) on the outcomes of critical care patients. IAH is increasingly recognized as potential complication in intensive care unit (ICU) patients. IAH affects all body systems, most notably the cardiac, respiratory, renal, and neurologic systems. IAH affects blood flow to various organs and plays a significant role in the prognosis of the patients. Recognition of IAH, its risk factors and clinical signs can reduce the morbidity and mortality associated. Moreover, knowledge of the pathophysiology may help rationalize the therapeutic approach. On the other hand, ICU patients present frequently ventilator- associated respiratory infections. Ventilator-associated pneumonia (VAP) is the most common healthcare-associated infection (HAI) in adult critical care units. It is associated with increased ICU stay, patient ventilator days and mortality. This paper reviews the relationship between IAH and VAP. Despite animal experimentation and physiological studies on humans, in favor of the impact of IAH to VAP, there is no definitive clinical data that IAH is associated with VAP. Microaspirations form the gastrointestinal track is a pathophysiological mechanism for VAP. This review provides data suggesting that under IAH conditions bacterial translocation might be an additional responsible mechanism for VAP in those patients that merits further investigation in the future.

Large-volume paracentesis effects plasma disappearance rate of indo-cyanine green in critically ill patients with decompensated liver cirrhosis and intraabdominal hypertension.

BACKGROUND: Ascites is a major complication of decompensated liver cirrhosis. Intraabdominal hypertension and structural alterations of parenchyma involve decisive changes in hepatosplanchnic blood flow. Clearance of indo-cyanine green (ICG) is mainly dependent on hepatic perfusion and hepatocellular function. As a consequence, plasma disappearance rate of ICG (ICG-PDR) is rated as a useful dynamic parameter of liver function. This study primarily evaluates the impact of large-volume paracentesis (LVP) on ICG-PDR in critically ill patients with decompensated cirrhosis. Additionally, it describes influences on intraabdominal pressure (IAP), abdominal perfusion pressure (APP), hepatic blood flow, hemodynamic and respiratory function. METHODS: We analyzed LVP in 22 patients with decompensated liver cirrhosis. ICG-PDR was assessed by using noninvasive LiMON technology (Pulsion® Medical Systems; Maquet Getinge Group), and hepatic blood flow was analyzed by color-coded duplex sonography. RESULTS: Paracentesis of a median volume of 3450 mL ascites evoked significant increases of ICG-PDR from 3.6 (2.8-4.6) to 5.1 (3.9-6.2)%/min (p < 0.001). Concomitantly, we observed a raise in "ICG-Clearance" from 99 (73.5-124.5) to 104 (91-143.5) mL/min/m2 (p = 0.005), while circulating blood volume index was unchanged [2412 (1983-3025) before paracentesis vs. 2409 (1997-2805) mL/m2, p = 0.734]. Sonography revealed a significant impact of paracentesis on hepatic blood flow: Hepatic artery resistance index dropped from 0.74 (0.68-0.75) to 0.68 (0.65-0.71) (p < 0.001) and maximum flow velocity in hepatic vein increased from 24 (17-30) to 30 (22-36) cm/s (p < 0.001). Consistent with previous studies, paracentesis caused significant decreases in IAP from 19.0 (15.0-20.3) to 11.0 (8.8-12.3) mmHg (p < 0.001) and central venous pressure from 22.5 (17.8-29.0) to 17.5 (12.8-24.0) mmHg (p < 0.001) with inverse increases in APP from 63.0 (56.8-69.5) to 71.0 (65.5-78.5) mmHg (p < 0.001). Changes in ICG-PDR were concomitant with changes in IAP (r = - 0.602) and APP (r = 0.576). Moreover, we found a substantial improvement in respiratory function. By contrast, hemodynamic parameters assessed by transpulmonary thermodilution, serum bilirubin and international normalized ratio did not change after paracentesis. CONCLUSION: Critically ill patients with decompensated cirrhosis and elevated IAP showed dramatically impaired ICG-PDR. Paracentesis evoked an improvement in ICG-PDR in parallel with a decreased IAP and an increased APP, while conventional parameters of liver function did not change. This effect on ICG-PDR is mainly referable to a relief of intraabdominal hypertension and changes in hepatosplanchnic blood flow.