Evaluation of prenatal central nervous system anomalies: obstetric management, fetal outcomes and chromosome abnormalities.

OBJECTIVE: To study the outcomes of fetuses who were diagnosed with central nervous system (CNS) anomalies during prenatal period and to describe the obstetric management of those pregnancies. METHODS: In this retrospective study, fetuses who were detected to have central nervous system anomalies by prenatal ultrasound from January 2010 to December 2019 were recruited. Data regarding prenatal diagnosis and obstetric outcomes were retrieved from maternal and paediatric records. The prognosis of fetuses who were born alive was classified based on their neurodevelopmental outcome within two years of life. RESULTS: There were a total of 365 fetuses with CNS anomalies within the 10-year study period, with a mean gestational age of 24.65±7.37 weeks at diagnosis. Ventriculomegaly (23.36%) was the commonest CNS anomalies seen. 198 (54.20%) of these fetuses had associated extra-CNS anomalies, with cardiovascular being the most common system involved. Fetal karyotyping was performed in 111 pregnancies, with chromosomal aberrations detected in 53 (49.07%) cases and culture failure in 3 cases. Majority of the chromosomal abnormalities were Edward syndrome (trisomy 18) and Patau syndrome (trisomy 13). Fetuses with congenital CNS anomalies and abnormal chromosomal karyotyping were more likely to be diagnosed earlier by prenatal ultrasound and tend to have poorer obstetric and neurocognitive prognosis. Prenatally, 86 (23.56%) of the cases were lost to follow up and likely to deliver elsewhere. Among the 279 cases whom their pregnancy outcomes were available, 139 (49.82%) pregnancies resulted in live births, 105 (37.63%) pregnancies were electively terminated, while the remaining 35 (12.54%) pregnancies ended in spontaneous loss. The decision of termination of pregnancy largely depends on mean diagnostic gestational age, presence of chromosomal aberrations and abnormal amniotic fluid volume in those fetuses. Two years after delivery, only 75 (53.96%) children out of 139 live births were still alive, 43 (30.93%) died and 21 (15.11%) cases were lost to follow-up. 32 (23.02%) children with prenatally diagnosed CNS anomalies had normal neurodevelopmental outcome. The presence of multiple CNS anomalies and involvement of extra-CNS anomalies indicated a poorer neurodevelopmental prognosis. CONCLUSION: Less than 50% of fetuses with prenatally diagnosed CNS anomalies resulted in live births. Even if they survive till delivery, 36.45% of them passed away within 2 years and 62.79% of children who survived till 2 years old had neurodevelopmental disability.

Microfluidic chambers using fluid walls for cell biology.

Many proofs of concept have demonstrated the potential of microfluidics in cell biology. However, the technology remains inaccessible to many biologists, as it often requires complex manufacturing facilities (such as soft lithography) and uses materials foreign to cell biology (such as polydimethylsiloxane). Here, we present a method for creating microfluidic environments by simply reshaping fluids on a substrate. For applications in cell biology, we use cell media on a virgin Petri dish overlaid with an immiscible fluorocarbon. A hydrophobic/fluorophilic stylus then reshapes the media into any pattern by creating liquid walls of fluorocarbon. Microfluidic arrangements suitable for cell culture are made in minutes using materials familiar to biologists. The versatility of the method is demonstrated by creating analogs of a common platform in cell biology, the microtiter plate. Using this vehicle, we demonstrate many manipulations required for cell culture and downstream analysis, including feeding, replating, cloning, cryopreservation, lysis plus RT-PCR, transfection plus genome editing, and fixation plus immunolabeling (when fluid walls are reconfigured during use). We also show that mammalian cells grow and respond to stimuli normally, and worm eggs develop into adults. This simple approach provides biologists with an entrée into microfluidics.

The Effect of Far-Infrared Therapy on the Peritoneal Expression of Glucose Degradation Products in Diabetic Patients on Peritoneal Dialysis.

Peritoneal dialysis (PD) is a treatment modality for end-stage renal disease (ESRD) patients. Dextrose is a common osmotic agent used in PD solutions and its absorption may exacerbate diabetes mellitus, a common complication of ESRD. PD solutions also contain glucose degradation products (GDPs) that may lead to encapsulating peritoneal sclerosis (EPS), a severe complication of PD. A previous study showed that far-infrared (FIR) therapy improved a patient's gastrointestinal symptoms due to EPS. Due to limited literature on the matter, this study aims to investigate dialysate GDPs and peritoneal function in diabetic patients on PD. Thirty-one PD patients were enrolled and underwent 40 min of FIR therapy twice daily for six months. We demonstrated the effect of FIR therapy on the following: (1) decrease of methylglyoxal (p = 0.02), furfural (p = 0.005), and 5-hydroxymethylfurfural (p = 0.03), (2) increase of D/D0 glucose ratio (p = 0.03), and (3) decrease of potassium levels (p = 0.008) in both DM and non-DM patients, as well as (4) maintenance and increase of peritoneal Kt/V in DM and non-DM patients, respectively (p = 0.03). FIR therapy is a non-invasive intervention that can decrease dialysate GDPs in PD patients by improving peritoneal transport rate and solute removal clearance, while also maintaining dialysis adequacy.

Far-infrared therapy improves ankle brachial index in hemodialysis patients with peripheral artery disease.

Ankle brachial index (ABI) is a diagnostic tool for peripheral artery disease (PAD), which is an important issue in hemodialysis (HD) patients. We enrolled 198 maintenance HD patients in this study. PAD is defined as ABI ≤ 0.90. Only PAD patients received far-infrared (FIR) therapy using the WS TY101 FIR emitter for 40 min during each HD session, three times weekly for 6 months. The ABI was measured at the bilateral lower extremities for 4 times [pre-dialytic timing (0 min) and 40 min after the initiation of HD session at both day 0 and 6 months after the FIR therapy]. The primary outcome is the change in ABI. There were 51 out of 198 patients with PAD. In comparison with the period without FIR therapy in the 51 PAD patients, 6 months of FIR therapy significantly improved the ABI of the right/left side for 0 min (from 0.77 ± 0.19 to 0.81 ± 0.20, p = 0.027/0.79 ± 0.20 to 0.81 ± 0.17, p = 0.049), 40 min during HD (from 0.73 ± 0.23 to 0.83 ± 0.19, p < 0.001/from 0.77 ± 0.21 to 0.83 ± 0.18, p < 0.001), and the incremental change between 0 and 40 min (from - 0.04 ± 0.14 to 0.05 ± 0.13, p = 0.007/from - 0.05 ± 0.13 to 0.03 ± 0.11, p = 0.012), respectively. In conclusion, the application of FIR therapy for 40 min, three times weekly for 6 months, has improved the ABI of both lower extremities, thus providing a new strategy of PAD treatment in HD patients.

Yeast GSK-3 kinase regulates astral microtubule function through phosphorylation of the microtubule-stabilizing kinesin Kip2.

The S. cerevisiae kinesin Kip2 stabilises astral microtubules (MTs) and facilitates spindle positioning through transport of MT-associated proteins, such as the yeast CLIP-170 homologue Bik1, dynein and the adenomatous-polyposis-coli-related protein Kar9 to the plus ends of astral MTs. Here, we show that Kip2 associates with its processivity factor Bim1, the yeast homologue of the plus-end-tracking protein EB1. This interaction requires an EB1-binding motif in the N-terminal extension of Kip2 and is negatively regulated by phosphorylation through Mck1, the yeast glycogen synthase kinase 3. In addition, Mck1-dependent phosphorylation decreases the intrinsic MT affinity of Kip2. Reduction in Kip2 phosphorylation leads to stabilisation of astral MTs, and accumulation of Kip2, dynein and Kar9 at MT plus ends, whereas loss of Mck1 function leads to defects in spindle positioning. Furthermore, we provide evidence that a subpopulation of Mck1 at the bud-cortex phosphorylates Kip2. We propose that yeast GSK-3 spatially controls astral MT dynamics and the loading of dynein and Kar9 on astral MT plus ends by regulating Kip2 interactions with Bim1 and MTs.

Prognostic role of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma undergoing liver transplantation.

Vascular endothelial growth factor (VEGF) is pivotal in the development of hepatocellular carcinoma (HCC). Studies have demonstrated the prognostic value of circulating VEGF levels in patients undergoing liver resection or locoregional therapy (LRT) for HCC. We investigated the significance of preoperative plasma VEGF levels in patients with HCC undergoing liver transplantation (LT) at a Western transplant center. Pre-LT plasma VEGF levels were measured with an enzyme-linked immunoassay for 164 patients with HCC undergoing LT. The preoperative plasma VEGF level was correlated with clinicopathological variables and overall and recurrence-free post-LT survival. A higher pre-LT plasma VEGF level was significantly associated with pre-LT LRT (P = 0.01), multiple tumors (P = 0.02), a total tumor diameter ≥ 5 cm (P = 0.01), bilobar tumor distribution (P = 0.03), tumor vascular invasion (VI; P < 0.001), and HCC beyond the Milan criteria (P < 0.001). Patients with a plasma VEGF level > 44 pg/mL had significantly worse overall and disease-free survival than those with VEGF levels ≤ 44 pg/mL (P = 0.04 and P = 0.02, respectively). In a multivariate analysis, a plasma VEGF level > 44 pg/mL was independently associated with tumor VI (P < 0.001) and recurrence-free survival (hazard ratio = 2.12, 95% confidence interval = 1.08-4.14, P = 0.03). In conclusion, in patients with chronic end-stage liver disease and HCC, a pre-LT plasma VEGF level > 44 pg/mL may be a predictor of tumor VI and recurrence-free post-LT survival.

Predictors and Prevalence of Alcohol and Cannabis Co-use Among Filipino Adolescents: Evidence From a School-based Student Health Survey.

OBJECTIVES: This study explored the prevalence and predictors of alcohol and cannabis co-use among 9263 Filipino adolescents, using data from the 2019 Global School-based Student Health Survey (GSHS). METHODS: We conducted a cross-sectional secondary analysis of the GSHS, targeting adolescents aged 13-17 years and excluding cases with incomplete data on alcohol and cannabis use. Our analysis employed the bivariate chi-square test of independence and multivariable logistic regression using Stata version 18 to identify significant predictors of co-use, with a p-value threshold set at 0.05. RESULTS: The weighted prevalence of co-users was 4.2% (95% confidence interval [CI], 3.4 to 5.3). Significant predictors included male sex (adjusted odds ratio [aOR], 4.50; 95% CI, 3.31 to 6.10; p<0.001) and being in a lower academic year, specifically grade 7 (aOR, 4.08; 95% CI, 2.39 to 6.99; p<0.001) and grade 8 (aOR, 2.20; 95% CI, 1.30 to 3.72; p=0.003). Poor sleep quality was also a significant predictor (aOR, 1.77; 95% CI, 1.29 to 2.44; p<0.001), as was a history of attempted suicide (aOR, 5.31; 95% CI, 4.00 to 7.06; p<0.001). Physical inactivity was associated with lower odds of co-use (aOR, 0.45; 95% CI, 0.33 to 0.62; p<0.001). Additionally, non-attendance of physical education classes (aOR, 1.48; 95% CI, 1.06 to 2.05; p=0.021), infrequent unapproved parental checks (aOR, 1.37; 95% CI, 1.04 to 1.80; p=0.024), and lower parental awareness of free-time activities (aOR, 0.63; 95% CI, 0.45 to 0.87; p=0.005) were associated with higher odds of co-use. Factors not significantly linked to co-use included age group, being in grade 9, always feeling lonely, having no close friends, being bullied outside school, and whether a parent or guardian understood the adolescent's worries. CONCLUSIONS: The findings highlight the critical need for comprehensive interventions in the Philippines, addressing not only physical inactivity and parental monitoring but also focusing on sex, academic grade, participation in physical education classes, sleep quality, and suicide attempt history, to effectively reduce alcohol and cannabis co-use among adolescents.

Double Filtration Plasmapheresis with Polyvinyl Alcohol-Based Membrane Lowers Serum Inflammation and Toxins in Patients with Hyperlipidemia.

Hyperlipidemia is increasing in prevalence and is highly correlated with cardiovascular disease (CVD). Lipid-lowering medications prevent CVD but may not be suitable when the side effects are intolerable or hypercholesterolemia is too severe. Double-filtration plasmapheresis (DF) has shown its therapeutic effect on hyperlipidemia, but its side effects are not yet known. We enrolled 45 adults with hyperlipidemia in our study. The sera before and two weeks after DF were evaluated, and we also analyzed perfluorochemicals to see if DF could remove these lipophilic toxins. After DF, all lipid profile components (total cholesterol, triglycerides, high-density lipoprotein [HDL], and low-density lipoprotein [LDL]) had significantly decreased. Leukocyte counts increased while platelet levels decreased, which may have been caused by the puncture wound from DF and consumption of platelets during the process. As for uremic toxins and inflammation, levels of C-reactive protein, uric acid, and alanine transaminase (ALT) all decreased, which may be related to the removal of serum perfluorooctane sulfonate (PFOS) and improvement of renal function. The total cholesterol/HDL ratio and triglycerides were significantly higher in the diabetes mellitus (DM) group at baseline but did not significantly differ after DF. In conclusion, DF showed potential for improving inflammation and removing serum lipids and PFOS in adults with hyperlipidemia.

The Associations between Erythropoietic Response with Inflammation Markers and Perfluorinated Chemicals in Hemodialysis Patients.

Erythropoiesis-stimulating agents (ESA) are used to treat anemia in hemodialysis (HD) patients. We investigated the role of inflammation and accumulation of environmental toxins (perfluorinated chemicals (PFCs), such as perfluorooctanoic acid and perfluorooctane sulfonate) in the erythropoietic response of HD patients who receive a fixed monthly continuous erythropoietin receptor activator (CERA) dosage. Forty-five patients underwent three successive phases of ESA treatment for two months each (phase one: 100 µg CERA once monthly; phase two: 50 µg CERA twice monthly; phase three: 100 µg CERA once monthly). Patient data were collected to determine the association of various factors with erythropoietic response (change in hematocrit). Liquid chromatography-tandem mass spectrometry was used to analyze perfluorinated chemicals. Twenty-eight patients exhibited a poor erythropoietic response that was significantly associated with: age > 80 years, initial hematocrit > 36%, glucose > 200 mg/dL, alanine aminotransferase > 21 U/L, c-reactive protein > 1 mg/dL, interleukin-6 > 10 ng/mL, lactate dehydrogenase ≤ 190 U/L, and chloride ≤ 93 mEq/L. There was also a borderline significant association between inflammation and PFCs, although PFCs failed to show any impact on ESA response. Age, glucose, chloride, liver function, and inflammation may be associated with cost-effective fixed CERA dosage administered at an increased frequency.

Perfluorooctanesulfonate Can Cause Negative Bias in Creatinine Measurement in Hemodialysis Patients Using Polysulfone Dialysis Membranes.

Serum creatinine is an important clinical marker for renal clearance. However, two conventional methods (Jaffe and enzymatic) are prone to interferences with organic compounds as compared to the standard method (isotope dilution-liquid chromatography-mass spectrometry) and can cause a significant negative bias. Perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) are two common perfluorochemicals (PFCs) that can easily be accumulated in humans. We aimed to verify whether this bias is the result of an accumulation of PFCs. The serum creatinine values of 124 hemodialysis patients were analyzed using the three methods. We also aimed to evaluate which biochemical parameters will influence the difference between the conventional methods and the standard method. We found that a significant underestimation occurred when using the conventional methods. Albumin is an independent factor associated with negative bias, but it loses this correlation after dialysis, likely due to the removal of protein-bound uremic toxins. PFOS can cause negative bias when using the enzymatic method. Furthermore, this linear correlation is more significant in patients who used polysulfone-based dialysis membranes, possibly due to the better clearance of other uremic toxins. The serum creatinine of uremic patients can be significantly underestimated when using conventional methods. PFCs, as well the type of dialysis membrane being used, can be influencing factors.

Far-Infrared Therapy Improves Arteriovenous Fistula Patency and Decreases Plasma Asymmetric Dimethylarginine in Patients with Advanced Diabetic Kidney Disease: A Prospective Randomized Controlled Trial.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and plays a significant role in the pathogenesis of arteriovenous fistula (AVF) dysfunction. The aim of this study is to evaluate the effect of far-infrared (FIR) therapy on the maturation and patency of newly-created AVFs in patients with advanced diabetic kidney disease (DKD) as well as the concurrent change in plasma ADMA. The study enrolled 144 participants with advanced DKD where 101 patients were randomly allocated to the FIR therapy group (N = 50) and control group (N = 51). Patients receiving FIR therapy had a decreased AVF failure rate within 12 months (16% versus 35.3%; p = 0.027); decreased incremental change of ADMA concentration at the 3rd and 12th month; increased AVF blood flow at the 1st, 3rd, and 12th month; increased 3-month physiologic maturation rate (88% versus 68.6%; p = 0.034); increased 1-year unassisted AVF patency rate (84% versus 64.7%; p = 0.017); and increased clinical AVF maturation rate within 12 months (84% versus 62.7%; p = 0.029) compared to the control group. The study demonstrates that FIR therapy can reduce the incremental changes in plasma ADMA concentration, which may be associated with the improvement of AVF prognosis in patients with advanced DKD.

Prognostic roles of human equilibrative transporter 1 (hENT-1) and ribonucleoside reductase subunit M1 (RRM1) in resected pancreatic cancer.

BACKGROUND: Pancreatic adenocarcinoma is a malignancy with a dismal prognosis. Previous studies have suggested that in pancreatic cancer, human equilibrative nucleoside transporter 1 (hENT-1) and ribonucleoside reductase subunit M1 (RRM1) expression may have prognostic value as well as predictive value with sensitivity to gemcitabine. This study investigated the prognostic value of hENT-1 and RRM1 expression in resected pancreatic cancer. METHODS: Eighty-four patients who underwent pancreaticoduodenectomy from 2000 to 2005 were included in this study. Patients were followed for a median of 60 months (range, 44-110). Total RNA was isolated from macrodissected paraffin-embedded tumors. hENT-1 and RRM1 expression levels in tumors were evaluated by quantitative reverse transcription-polymerase chain reaction (QRT-PCR), normalized to 2 reference genes, and expressed as ΔCt (low ΔCt means high expression). Univariate and multivariable prognostic factors for overall survival (OS) and progression-free survival (PFS) were identified via Cox proportional hazards analysis. RESULTS: Univariate analysis identified hENT-1, overall stage, lymphovascular invasion, perineural invasion, and adjuvant therapy as prognostic factors for both PFS and OS. Multivariate analysis confirmed the association of low expression of hENT-1 (ΔCt > 0.2027) (P = .007), perineural invasion (P = .021), and lack of adjuvant treatment (P < 0.001) with worse OS. Multivariate analysis also confirmed the association of low expression of hENT-1 (ΔCt > 0.5391) with worse PFS (P = .016) in addition to overall stage (P = .013), perineural invasion (P = .042), and lack of adjuvant treatment (hazard ratio 2.31, P = .029). RRM1 expression was not associated with OS or PFS in the current cohort. CONCLUSIONS: Low expression of hENT-1 was associated with worse OS and PFS in patients with resected pancreatic adenocarcinoma independent of gemcitabine therapy.

What is the indication for sorafenib in hepatocellular carcinoma? A clinical challenge.

The incidence of hepatocellular carcinoma is rising in many countries, including the United States. Approval of sorafenib (Nexavar) as the first targeted therapy for treatment of advanced hepatocellular carcinoma (HCC) represents a milestone in the treatment of this disease. The approval was based on two large randomized phase III trials from the Western and Eastern hemispheres that showed an overall survival benefit compared with placebo in patients with well-preserved liver function. The exact indication for sorafenib is unclear, however. The U.S. Food and Drug Administration (FDA) authorized use of sorafenib for "unresectable HCC", an indication which is very broad, vague, and confusing. Less is known about the effects of sorafenib in patients with decompensated liver disease, or of sorafenib in combination with local therapy or in a transplant setting. Prospective trials are lacking in these areas. We will review current data on use of sorafenib in HCC.

Hemorrhagic pericardial tamponade in a peritoneal dialysis patient.

Uremic pericarditis and pericardial effusion are possible complications among patients with end-stage renal disease. The accumulation of toxic metabolites may contribute to the pathogenesis of uremic pericarditis. Bleeding diathesis in peritoneal dialysis patients raises the risk of hemorrhagic pericardial tamponade, which is a fatal complication of peritoneal dialysis. We report a case of hemorrhagic pericardial tamponade who was nonadherent to peritoneal dialysis with initial presentation of hypotension and syncope. Transthoracic echocardiogram revealed septated, fibrinoid pericardial effusion and right ventricular diastolic compression. A massive bloody pericardial effusion was drained when he underwent the pericardial window procedure. There was a significant improvement both in his clinical condition and in the echocardiogram images after the procedure. Hemorrhagic pericardial tamponade occurs in uremic patients but is rarely seen in those undergoing peritoneal dialysis. Early diagnosis, immediate surgical drainage, and regular follow-up with echocardiography are crucial to achieve better prognoses in future similar clinical scenarios.

Long-term prognosis of vascular access in hemodialysis patients with systemic lupus erythematosus: a retrospective cohort study.

Patients with systemic lupus erythematosus (SLE) have a higher risk of vascular complications. This retrospective cohort study aimed to analyze the differences in the risk of arteriovenous fistula or graft (AVF/AVG) dysfunction in hemodialysis patients with and without SLE from Taiwan's National Health Insurance Database over a 10-year period. AVF/AVG dysfunction is defined as the occurrence of the first episode of intervention after vascular access creation. A total of 1366 HD patients with SLE had higher incidence rates of AVF/AVG dysfunction than 4098 non-SLE HD patients in the following 4 periods: (1) after 1 year (incidence rates = 15.21% and 13.01%, respectively; subdistribution hazard ratio (SHR) = 1.16; P = 0.007), (2) 1st-to-10th-year period (15.36% and 13.25%; SHR = 1.16; P = 0.007), (3) 5th-to-10th-year period (11.91% and 8.1%; SHR = 1.42; P = 0.003), and (4) overall period (23.53% and 21.66%; SHR = 1.09; P = 0.027). In conclusion, there were significantly higher incidence rates of AVF/AVG dysfunction in SLE patients during the long-term follow-up period. Vascular access function should be monitored regularly by clinical examinations, especially after 1 year and during 5 to 10 years, to improve AVF/AVG patency and dialysis adequacy in SLE patients undergoing maintenance hemodialysis.

The Effect of Far-Infrared Therapy on the Peritoneal Membrane Transport Characteristics of Uremic Patients Undergoing Peritoneal Dialysis: An Open-Prospective Proof-of-Concept Study.

Long-term peritoneal dialysis (PD) can lead to detrimental changes in peritoneal membrane function, which may be related to the accumulation of glucose degradation products. A previous study demonstrated that 6 months of far-infrared (FIR) therapy may decrease glucose degradation products in PD dialysate. Due to limited literature on this matter, this study aims to investigate the effect of FIR therapy on the peritoneal membrane transport characteristics of PD patients. Patients were grouped according to baseline peritoneal transport status: lower transporters (low and low-average) and higher transporters (high-average and high). Both groups underwent 40 min of FIR therapy twice daily for 1 year. In lower transporters, FIR therapy increased weekly dialysate creatinine clearance (6.91 L/wk/1.73 m2; p = 0.04) and D/P creatinine (0.05; p = 0.01). In higher transporters, FIR therapy decreased D/P creatinine (-0.05; p = 0.01) and increased D/D0 glucose (0.05; p = 0.006). Fifty percent of high transporter patients shifted to high-average status after FIR therapy. FIR therapy may decrease D/P creatinine for patients in the higher transporter group and cause high transporters to shift to high-average status, which suggests the potential of FIR therapy in improving peritoneal membrane function in PD patients.

Is there a role for adjuvant treatment after hepatic resection for hepatocellular carcinoma?

The only curative treatment option for hepatocellular carcinoma patients is either a surgical resection or liver transplantation. Due to limited supply of donor organs and the stringent selection criteria for liver transplantation, resection is the mainstay of therapy, particularly for patients with preserved liver function and small tumors with no portal hypertension. However, tumor recurrences and subsequent death is common after resection, which has prompted a search for an effective adjuvant therapy to improve patient outcomes. Studies have looked at various adjuvant treatment modalities, including systemic chemotherapy, intra-arterial approaches with or without chemotherapy, and the use of cytokines, but there is still no established role for adjuvant therapy after a curative liver resection. Unfortunately, many of these trials lack adequate sample sizes, and are heterogeneous in the patient populations and study end points, thereby limiting robust conclusions. Based on current available data, the role of adjuvant therapy after liver resection needs to be further investigated. The use of molecular targeted therapy focusing on the vascular endothelial growth factor pathway appears to be a promising step. Clinical trials assessing adjuvant therapies after a curative liver resection are urgently needed. These should ideally be prospective, randomized trials with properly selected patients and appropriate end points.

Safety and feasibility of using sorafenib in recurrent hepatocellular carcinoma after orthotopic liver transplantation.

BACKGROUND AND AIM: The majority of patients who undergo orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) have a very good prognosis if the tumor is within the Milan criteria. However, 10-15% of patients will have reoccurrence after OLT. Currently, sorafenib is available for advanced HCC. The safety and efficacy of sorafenib in this population has not been reported. METHODS: We retrospectively looked at 54 patients who received sorafenib for advanced HCC. Out of 54 patients, we analyzed 9 who received sorafenib after OLT for HCC reoccurrence at Cleveland Clinic. RESULT: The median age at the time treatment with sorafenib was initiated was 59 years (range 46-77). Two patients received prior local therapy. Most of the toxicity was expected side effects from sorafenib except in 1 patient who developed hematological toxicity. Six patients required dose reduction secondary to toxicity. There were no unexpected complications from interaction with immunosuppressive medication. One patient achieved complete radiographic remission. Median survival from the start of sorafenib had not been reached at the time of writing; however, the 4-month survival rate is currently estimated to be 84 ± 15%, and 1 patient with lung reoccurrence has been treated for almost 18 months thus far. CONCLUSION: Sorafenib can be used in patients with recurrent HCC after liver transplantation with tolerable toxicity; however, dose adjustment may be required. A larger prospective study is necessary to determine the efficacy of sorafenib in this group of patients.

To Work at Clinics or at Hospitals? Analysis of Family Physician Recruitment Advertising in Taiwan.

Family physicians act as gatekeepers of the healthcare system and have an indispensable role in providing holistic care in the primary care system. While previous studies had focused on the geographic maldistribution of family physicians, the current study investigated the distribution of job opportunities for family physicians by analyzing recruitment advertisements posted in medical association journals, as an indirect way to observe the marketplace demand for physicians. We collected all the recruitment advertisements for family physicians in the twelve issues of the Taiwan Medical Journal, the official organ of the Taiwan Medical Association, in 2018. In contrast to 124 new trainees annually, 739 advertisements for family physicians were posted within the entire year. After eliminating repeated advertisements, there were 302 distinct advertisements, of which hospitals accounted for 18.9% (n = 57). The job opportunities at hospitals were offered mainly by regional hospitals (n = 26) and community hospitals (n = 29), but only two by medical centers. Family physicians in Taiwan were in great demand not only by primary care clinics but also by hospitals. The role of family physicians in hospitals is worth further study.