Apoptosis is associated with CD36/fatty acid translocase upregulation in non‐alcoholic steatohepatitis

Background & aims: Hepatocyte apoptosis is a key event in non‐alcoholic steatohepatitis (NASH). We studied the effect of obesity on free fatty acid (FFA) levels, fatty acid transport proteins (FATPs) and on extrinsic and intrinsic activation of apoptosis in the liver. Methods: Liver biopsies were harvested from 52 morbidly obese patients [body mass index (BMI): 53.82±1.41; age: 45±10.50; 15 males/37 females] undergoing bariatric surgery, and were scored for NASH, evaluated for fibrosis, and investigated for intrahepatic expression of FATPs, death receptors and cytosolic apoptosis‐related molecules. Findings were correlated with serum FFA levels and the degrees of intrahepatic (terminal dUTP nick end labelling) and systemic (M30) apoptosis. Results: In patients' liver sections, FATPs as well as select parameters of extrinsic and intrinsic apoptosis were found to be upregulated (CD36/FAT: × 11.56; FATP‐5: × 1.33; CD95/Fas: × 3.18; NOXA: × 2.79). These findings correlated with significantly elevated serum FFAs (control: 14.72±2.32 mg/dl vs. patients: 23.03±1.24 mg/dl) and M30 levels (control: 83.12±7.46 U/L vs. patients: 212.61±22.16 U/L). We found correlations between FATPs and apoptosis mediators as well as with histological criteria of NASH and fibrosis. Conclusions: Increased FFA and FATPs are associated with extrinsically and intrinsically induced apoptosis, liver damage and fibrosis in obese patients. Thus, FATPs may offer an interesting new approach to understand and potentially intervene NASH pathogenesis.     

Sources of anticipatory distress among breast surgery patients

Surgical consultation concerning the possibility of breast cancer is a distressing experience, and having to take the next step of breast surgery even more so for many women. However, the sources of variability in such presurgical distress are not well understood. Sixty-one women (mean age = 51) were recruited immediately following surgical consultation in which a recommendation of breast surgery (excisional biopsy/lumpectomy); was made. Patients completed measures of distress, worry about cancer and surgery, trait anxiety, optimism and pessimism prior to surgery. Surprisingly, results revealed no effect of surgeon-provided information concerning preliminary diagnosis on patient distress. Rather, worry about what the surgeon might find concerning the breast mass during surgery, worry about having to go through the operative procedures, and patient optimism were the only factors that uniquely contributed to patient distress (p's < 0.05). This study provides a foundation for future clinical interventions to reduce presurgery distress.     

Disrupted sleep the night before breast surgery is associated with increased postoperative pain

Despite the best available clinical care, pain after surgery is a virtually universal patient experience that can have pervasive negative consequences. Given the large variability among patients in postoperative pain levels, research on novel modifiable risk factors is needed. One such factor suggested by recent experimental studies indicates that disruption of even a single night's sleep can increase subsequent pain in healthy volunteers. In this preliminary clinical study, we tested the hypothesis that poor sleep the night before surgery would predict heightened postoperative pain. Patients (n=24) scheduled for routine breast-conserving surgical procedures for the diagnosis or treatment of cancer were recruited and wore an actigraphy device providing objective, validated measures of sleep duration and disruption (low sleep efficiency). Pain severity and interference with daily activities for the week after surgery was assessed with the Brief Pain Inventory. As hypothesized, multiple regression analyses revealed that lower sleep efficiency was a significant predictor of greater pain severity and interference, controlling for age, race, and perioperative analgesics as appropriate. Sleep efficiency was not significantly related to measures of depressed mood, emotional upset, or relaxation assessed on the morning of surgery. Patients with sleep efficiency in the lowest tertile had clinically higher levels of pain (>2 points) compared with patients in the highest sleep efficiency tertile. Sleep duration had no significant effects. This preliminary clinical study supports the possibility that sleep disruption on the night before surgery may increase patients' experience of pain after surgery. Research to investigate the mechanisms underlying these effects and to explore the possible clinical benefits of interventions to improve patients' sleep before surgery is now warranted.     

Poor clinical and virological outcome of nucleos(t)ide analogue monotherapy in HBV/HDV co-infected patients

Co-infection of Hepatitis B (HBV) and Delta viruses (HDV) represent the most severe form of viral hepatitis. While treatment with pegylated Interferon alpha (PEG-IFNα) is well established, therapy with nucleoside or nucleotide analogues (NA) has been a matter of debate. We aimed to investigate the role of NA treatment in a well-defined single centre cohort.In a retrospective approach, we observed 53 HDV RNA positive and/or anti-HDV-positive patients recruited at a German referral centre between 2000 and 2019. Patients were followed for at least 3 months (mean time of follow up: 4.6 years; range: 0.2–14.1 years). Patients who had liver transplantation or hepatocellular carcinoma at the time of presentation were excluded. 43% (n = 23) were treated with NA, 43% (n = 23) received IFNα-based therapies and 13% (n = 7) were untreated.Liver cirrhosis was already present in 53% (28/53) of patients at first presentation. During follow-up, liver-related endpoints developed in 44% of all patients (n = 23). NA-treatment was associated with a significantly worse clinical outcome (P = .01; odds ratio [OR] = 4.92; CI = 1.51–16.01) compared to both, untreated (P = .38; OR = 0.46; CI = 0.80–2.61) and IFNα-based-treated patients (P = .04; OR = 0.29; CI = 0.89–0.94) in univariate logistic regression analysis. HBsAg levels declined by more than 50% during NA-based therapy in only 7 cases (7/23; mean time: 3.6 years; range: 0.8–8.5 years) and during IFNα-based therapy in 14 cases (14/23; mean time: 2.8 years, range 0.7–8.5 years). HDV RNA became undetectable during follow up in 30% of patients receiving NA alone (7/23; mean time: 5.0 years; range: 0.6–13.5 years), in 35% of patients receiving IFNα-based therapy (8/23; mean time: 2.9 years, range: 0.3–7.6 years).The effect of NA in patients with HBV/HDV co-infection is limited. Treatment with NA was associated with a higher likelihood of clinical disease progression. Interferon alpha therapy was beneficial in reducing liver complications and improves long-term outcome.     

Radiation-associated extraskeletal osteosarcoma of the chest wall

Radiation-associated sarcoma is a rare but potential complication of radiation therapy. Most reported cases of osteosarcoma of the chest wall following radiation therapy for breast cancer arise from the chest wall skeletal structures. In contrast, few cases of extraskeletal osteosarcomas have been reported. We report a rare example of an extraskeletal osteosarcoma involving the pectoralis major muscle occurring after radiation therapy for breast cancer. Extraskeletal osteosarcomas are rare soft tissue tumors with a high rate of local recurrence and a poor prognosis.