Effect of nitric oxide delivery via cardiopulmonary bypass circuit on postoperative oxygenation in adults undergoing cardiac surgery (NOCARD trial): a randomised controlled trial.

BACKGROUND: Cardiac surgery involving cardiopulmonary bypass induces a significant systemic inflammatory response, contributing to various postoperative complications, including pulmonary dysfunction, myocardial and kidney injuries. OBJECTIVE: To investigate the effect of Nitric Oxide delivery via the cardiopulmonary bypass circuit on various postoperative outcomes. DESIGN: A prospective, single-centre, double-blinded, randomised controlled trial. SETTING: Rabin Medical Centre, Beilinson Hospital, Israel. PATIENTS: Adult patients scheduled for elective cardiac surgery were randomly allocated to one of the study groups. INTERVENTIONS: For the treatment group, 40 ppm of nitric oxide was delivered via the cardiopulmonary bypass circuit. For the control group, nitric oxide was not delivered. OUTCOME MEASURES: The primary outcome was the incidence of hypoxaemia, defined as a p a O2 /FiO 2 ratio less than 300 within 24 h postoperatively. The secondary outcomes were the incidences of low cardiac output syndrome and acute kidney injury within 72 h postoperatively. RESULTS: Ninety-eight patients were included in the final analysis, with 47 patients allocated to the control group and 51 to the Nitric Oxide group. The Nitric Oxide group exhibited significantly lower hypoxaemia rates at admission to the cardiothoracic intensive care unit (47.1 vs. 68.1%), P  = 0.043. This effect, however, varied in patients with or without baseline hypoxaemia. Patients with baseline hypoxaemia who received nitric oxide exhibited significantly lower hypoxaemia rates (61.1 vs. 93.8%), P  = 0.042, and higher p a O2 /FiO 2 ratios at all time points, F (1,30) = 6.08, P  = 0.019. Conversely, this benefit was not observed in patients without baseline hypoxaemia. No significant differences were observed in the incidence of low cardiac output syndrome or acute kidney injury. No substantial safety concerns were noted, and toxic methaemoglobin levels were not observed. CONCLUSIONS: Patients with baseline hypoxaemia undergoing cardiac surgery and receiving nitric oxide exhibited lower hypoxaemia rates and higher p a O2 /FiO 2 ratios. No significant differences were found regarding postoperative pulmonary complications and overall outcomes. TRIAL REGISTRATION: NCT04807413.

Spontaneous Flares of Chronic Hepatitis B Virus in Hepatitis Be Antigen Negative Carriers Who Subsequently Clear Hepatitis B Surface Antigen.

BACKGROUND: Acute exacerbations of chronic hepatitis B virus (HBV) infections can occur in HBV-infected, hepatitis e antigen (HBeAg)-negative patients in the absence of recent withdrawal of antiviral or immunosuppressive therapies. Whether these spontaneous "flares" predict subsequent loss of hepatitis B surface antigen (HBsAg) has yet to be determined. OBJECTIVES: To document the percent of patients who experience spontaneous HBV flares and severity of the flares in chronic HBeAg-negative carriers. METHODS: A retrospective review of an HBV database identified and followed HBeAg-negative patients for biochemical evidence of flares (ALT > 5× normal) and subsequent HBsAg status. Patients that subsequently cleared HBsAg were matched 1:1 with those who remained HBsAg positive. RESULTS: Of 1299 HBeAg-negative patients followed for 10.2 ± 6.1 years, 88 (6.8%) developed spontaneous HBV flares. Flares occurred in 14/115 (12.2%) patients who subsequently cleared HBsAg and 4/111 (3.6%) matched patients who remained HBsAg positive (p = 0.025). The severity of flares was similar in the two study cohorts. Following multivariate analyses, only low HBV-DNA levels at baseline identified patients likely to subsequently clear HBsAg. CONCLUSIONS: Although more common in patients who subsequently clear HBsAg, spontaneous HBV flares do not predict subsequent HBsAg clearance.

The relative expression of hepatocellular and cholestatic liver enzymes in adult patients with liver disease.

INTRODUCTION AND OBJECTIVES: Hepatocellular liver injury is characterized by elevations in serum alanine (ALT) and aspartate (AST) aminotransferases while cholestasis is associated with elevated serum alkaline phosphatase (ALP) levels. When both sets of enzymes are elevated, distinguishing between the two patterns of liver disease can be difficult. The aim of this study was to document the predicted ranges of serum ALP values in patients with hepatocellular liver injury and ALT or AST values in patients with cholestasis. MATERIALS AND METHODS: Liver enzyme levels were documented in adult patients with various types and degrees of hepatocellular (non-alcoholic fatty liver disease, hepatitis B and C, alcohol and autoimmune hepatitis) and cholestatic (primary biliary cholangitis and primary sclerosing cholangitis) disease. RESULTS: In 5167 hepatocellular disease patients with ALT (or AST) values that were normal, 1-5×, 5-10× or >10× elevated, median (95% CI) serum ALP levels were 0.64 (0.62-0.66), 0.72 (0.71-0.73), 0.80 (0.77-0.82) and 1.15 (1.0-1.22) fold elevated respectively. In 252 cholestatic patients with ALP values that were normal, 1-5× or >5× elevated, serum ALT (or AST) values were 1.13 (0.93-1.63), 2.47 (2.13-2.70) and 4.57 (3.27-5.63) fold elevated respectively. In 56 patients with concurrent diseases, ALP levels were beyond predicted values for their hepatitis in 38 (68%) and ALT (or AST) values beyond predicted values for their cholestatic disorder in 24 (43%). CONCLUSIONS: These data provide health care providers with predicted ranges of liver enzymes in patients with hepatocellular or cholestatic liver disease and may thereby help to identify patients with concurrent forms of liver disease.

Conversion to general anesthesia and intravenous supplementation during intrapartum cesarean delivery with an indwelling epidural catheter: a retrospective study.

BACKGROUND: Intraoperative pain during cesarean delivery with or without conversion to general anesthesia has been shown to negatively impact maternal and perinatal morbidity. Efforts to reduce these adverse events are a recent focus of obstetric anesthesia care. We aimed to assess rates of and risk factors for conversion to general anesthesia and intraoperative pain during intrapartum cesarean delivery with an indwelling epidural catheter in our academic center. METHODS: In this retrospective cohort study, all women undergoing cesarean delivery with an indwelling epidural catheter between January 2017 and June 2022 were included. Labor epidural analgesia was provided according to a standardized protocol, and conversion to epidural anesthesia was achieved in the operating room before surgery. We determined the conversion rate to general anesthesia and associated risk factors. Second, we examined the rate of administration of analgesics/sedatives and related risk factors in cesarean cases that were not converted to general anesthesia. RESULTS: Among the 1192 women undergoing intrapartum cesarean delivery with epidural anesthesia, there were 97 cases with conversion to general anesthesia (8.1%), of which 87 (89.7%) were due to a failed epidural. Higher age, higher weight, and higher gestational age were associated with decreased odds of conversion to general anesthesia. Higher gravidity and longer surgical time were associated with increased odds. An emergent indication was not associated with conversion to general anesthesia. Intravenous analgesic/sedative supplementation occurred in 141 cases (12.9%). Higher age was associated with decreased odds of supplementation, and longer surgical time was associated with increased odds. CONCLUSION: In our tertiary academic center, the rate of intraoperative conversion to general anesthesia and administration of analgesic/sedative medication among women undergoing intrapartum cesarean delivery with epidural anesthesia was relatively high. Emergency cesarean delivery was not associated with either of the above endpoints.

The relationship between postpartum pain and mother-infant bonding: A prospective observational study.

INTRODUCTION: Postpartum pain is associated with impaired maternal recovery and may influence mother-infant bonding. METHODS: Participants who underwent a vaginal or cesarean delivery were assessed 24 h postpartum. Postpartum pain intensity was measured using the Verbal Numeric Score (VNS) (0-10) and classified as non-severe (<8) or severe pain (≥8). Maternal-infant bonding was evaluated using the Post-Partum Bonding Questionnaire (PBQ; 0-125), with a score > 5 defining impaired bonding. Demographic data included age, BMI, parity, education level, economic status, partnership, prior history of depression, familial history of depression, desire to breastfeed, epidural analgesia during labor, rooming in, and Edinburgh Postnatal Depression Scale (EPDS). Data were analyzed using 2 separate multivariable logistic regression models for vaginal and cesarean deliveries, where maximum postpartum pain was the independent variable and impaired postpartum bonding was the dependent variable and controlled for the other factors collected. RESULTS: Severe postpartum pain (VNS ≥ 8) showed no significant relationship with impaired bonding when controlling for confounding variables. In vaginal deliveries, there was an association between a history of depression and impaired bonding (Odds Ratio 2.2 [1.07-4.65], p = 0.04) and EPDS > 10 and impaired bonding (OR 11.5 [3.2-73.6], p < 0.001). For cesarean deliveries, rooming in with the baby had a protective effect (OR 11.5 [3.2-73.6], p < 0.001). CONCLUSIONS: Contrary to expectations, severe postpartum pain did not influence maternal-infant binding in the cohort of patients with vaginal and cesarean deliveries. Instead, factors such as maternal mental health and rooming-in practices appeared to exert more significant influence. CLINICAL TRIAL REGISTRATION: NCT05206552.

Additive value of superficial parasternal intercostal plane block and serratus anterior plane block in lung transplantation surgery: a retrospective exploratory study.

BACKGROUND: Adequate pain control following lung transplantation (LTx) surgery is paramount. Thoracic epidural analgesia (TEA) is the gold standard; however, the potential use of extracorporeal membrane oxygenation (ECMO) and consequent anticoagulation therapy raises safety concerns, prompting clinicians to seek safer alternatives. The utility of thoracic wall blocks in general thoracic surgery is well established; however, their role in the context of LTx has been poorly investigated. METHODS: In this retrospective exploratory study, we assessed the effect of adding a superficial parasternal intercostal plane (sPIP) block and serratus anterior plane (SAP) block to standard anesthetic and analgesic care on tracheal extubation rates, pain scores and opioid consumption until 72 hours postoperatively in LTx. RESULTS: Sixty patients were included in the analysis; 35 received the standard anesthetic and analgesic care (control group), and 25 received sPIP and SAP blocks in addition to the standard anesthetic and analgesic care (intervention group). We observed higher tracheal extubation rates in the intervention group at 8 hours postoperatively (16.0% vs 0.0%, p=0.03). This was also shown after adjusting for known prognostic factors (OR 1.18; 95% CI 1.04 to 1.33, p=0.02). Furthermore, we noted a lower opioid consumption measured by morphine milligram equivalents at 24 hours in the intervention group (median 405 (IQR 300-490) vs 266 (IQR 168-366), p=0.02). This was also found after adjusting for known prognostic factors (ß -118; 95% CI -221 to 14, p=0.03). CONCLUSION: sPIP and SAP blocks are safe regional analgesic techniques in LTx involving ECMO and clamshell incision. They are associated with faster tracheal extubation and lower opioid consumption. These techniques should be considered when TEA is not appropriate. Further high-quality studies are warranted to confirm these findings.

The impact of primary biliary cholangitis on non-alcoholic fatty liver disease.

BACKGROUND: The impact of chronic cholestatic liver diseases such as primary biliary cholangitis (PBC) on non-alcoholic fatty liver disease (NAFLD) has yet to be described. OBJECTIVES: To document and compare the severity and course of liver disease in patients with NAFLD/PBC versus NAFLD alone. METHODS: In this retrospective, case-control study 68 adult NAFLD/PBC patients were matched 1:2 for age and sex with 136 NAFLD alone patients. Disease activity and severity were documented by serum aminotransferases, albumin, bilirubin and international normalized ratio (INR) values and hepatic fibrosis by Fib-4 and aspartate aminotransferase/platelet ratio indices (APRI). RESULTS: On presentation (baseline), NAFLD/PBC patients had similar serum aminotransferase, albumin and bilirubin levels but lower INR values than NAFLD alone patients. Fib-4 and APRI levels were similar. Despite longer follow-up (favouring more advanced disease) in NAFLD/PBC patients, serum aminotransferases and bilirubin values were similar but albumin and INR levels significantly lower in NAFLD/PBC versus NAFLD alone patients at the end of follow-up. NAFLD/PBC patients also had significantly lower and less worsening of Fib-4 values at the end of follow-up. Transition from intermediate Fib-4 levels to those compatible with no or limited fibrosis was higher in NAFLD/PBC patients. CONCLUSION: These findings suggest PBC does not adversely affect the severity or course of NAFLD.

Low serum alkaline phosphatase levels in patients with chronic liver diseases: Possible contributions to disease pathogenesis.

OBJECTIVES: A low serum alkaline phosphatase (ALP) level is an uncommon finding in patients with chronic liver disease (CLD). The prevalence of this finding and whether low ALP expression influences CLD remain to be determined. The objectives of this study were: (1) to document the prevalence of low serum ALP levels in adult CLD patients and (2) compare features of CLD in patients with low versus normal or elevated serum ALP levels. METHODS: An adult, outpatient liver disease database was searched for patients with low serum ALP levels (<40 IU/L). Hepatic inflammation, function, fibrosis and disease severity were determined by serum aminotransferases, albumin, bilirubin and INR levels, Fib-4 calculations and MELD scores respectively. RESULTS: Of 19,037 patients entered into the database, 47 (0.25%) had consistently low serum ALP levels, 51 (0.27%) low levels on the majority and 469 (2.44%) on the minority of determinations. Patients with consistently low levels were matched (1:2) by age, gender and nature of the underlying liver disease to patients with normal or elevated serum ALP levels. Matched patients with consistently low ALP levels had significantly lower serum aminotransferase and bilirubin levels at their initial visit and throughout the follow-up period (p < 0.05 respectively) while Fib-4 levels and MELD scores were similar at the initial and last follow-up visit. CONCLUSIONS: These results establish the prevalence of low serum ALP levels in adult CLD patients and describe a hitherto unreported association between low serum ALP levels and less biochemical evidence of active disease.

Liver disease referrals to an urban, hospital-based hepatology outpatient clinic over the past 25 years.

BACKGROUND: Additional hepatologists are required to manage the rapidly increasing number of patients with liver disease. One disincentive to trainees considering a career in hepatology is the longstanding perception that outpatient hepatology consists largely of managing patients with alcohol-induced liver disease (ALD). OBJECTIVES: To document the types of liver diseases and changes in liver disease referrals to an urban outpatient liver disease clinic over the past 25 years. METHODS: The nature of the liver disorder, age, gender, and socioeconomic status of patients referred to an urban, hospital-based, liver diseases outpatient program were documented from 1992 to 2017. Joinpoint analysis was performed to identify significant trends in referral prevalence rates of various disorders. RESULTS: In 1992/1993, hepatitis C virus (HCV), followed by hepatitis B virus (HBV), "other", non-alcoholic fatty liver disease (NAFLD), and primary biliary cholangitis (PBC) were the most common underlying liver diseases in referred patients (39, 36, 12, 4.5, and 3.5% respectively), whereas in 2016/2017, NAFLD, HBV, HCV, "other," and ALD were most common (60, 15, 12, 8.7, and 3.3%, respectively). Aside from NAFLD referrals, which consistently increased over the 25-year period, the prevalence of all other liver disease referrals fluctuated but generally declined. Recently referred patients were significantly older (38 ± 13 years in 1992/1993 and 49 ± 15 years in 2016/2017, P < 0.0001), while gender and socioeconomic status have not changed. CONCLUSIONS: Hepatology is a diverse, dynamic subspecialty where ALD continues to constitute less than 5% of all patient referrals.

Seasonal variability in the activity of common chronic liver diseases.

BACKGROUND: Seasonal variations in flu-like illnesses and vaccinations, vitamin D levels, alcohol intake, and sedentary lifestyles raise the possibility that seasonal variations exist in the severity of immune-mediated, alcohol, and obesity- or dyslipidemia-related chronic liver diseases, respectively. METHODS: We documented months-seasons in which biochemical evidence of disease activity is greatest in adult patients with common liver disorders. Months-seasons associated with peak liver enzyme levels in patients with largely immune-mediated disorders (autoimmune hepatitis, primary biliary cholangitis [PBC], and primary sclerosing cholangitis), alcoholic liver disease, and non-alcoholic fatty liver disease were documented from a hospital-based, liver diseases outpatient clinic database. RESULTS: Aside from a spike in the severity of PBC during July (p < .005), no significant associations were found between months-seasons and peak liver enzyme activities in any of these liver disorders. CONCLUSIONS: These findings suggest that seasonal illnesses or immunizations and vitamin D depletion, alcohol intake, and sedentary lifestyle do not significantly exacerbate common underlying immune-mediated, alcohol, or metabolic liver disorders, respectively.