Impact of the COVID-19 pandemic on delivery of prostate cancer care in Australia: An interrupted time series analysis.

The COVID-19 pandemic led to a major disruption to health services across the world. The aim of this population-based study was to assess the downstream effects of the pandemic on diagnostic tests and treatment activities related to prostate cancer (PC). The Australian Government Department of Health Medicare Benefits Schedule and the Pharmaceutical Benefits Scheme databases were queried from January 2010 to June 2022. Two interrupted time series were performed Pre-COVID (January 2010 to February 2020) and peri-COVID (March 2020 to June 2022). Temporal modeling was performed to account for seasonal variation. Pre-COVID-19, monthly prostate-specific antigen (PSA) testing showed a declining trend and testing decreased by 81 tests per 100 000 annually. A single-month 38% drop in PSA testing was observed in April 2020; this corresponded to Australia's first wave. No change was observed in the rate of prostate biopsies. Peri-COVID-19 outbreaks, there was a slight shift toward the use of long-acting androgen deprivation therapy (ADT) at 4% with a predilection still for short-acting agents. with no registered change in the overall volume of radiotherapy or surgery. There were no deficits in the number of diagnostic and treatment activities for men with PC. Aside from a slight shift toward long-acting ADT use during the pandemic, no other patterns were observed. The longer-term impact such as missed diagnosis or late presentation affecting chances of survival due to COVID-19 is yet to be ascertained.

Systematic review and network meta-analysis of re-intervention rates of new surgical interventions for benign prostatic hyperplasia.

OBJECTIVE: To assess the re-intervention rates of new surgical benign prostatic hyperplasia (BPH) interventions, as the clinical durability of new surgical interventions for BPH is not widely known. METHODS: A critical review of new surgical BPH therapies namely 'UroLift®', 'Aquablation', 'Rezum', 'prostatic artery embolisation (PAE)' and 'temporary implantable nitinol device (iTIND)' was performed on PubMed, the Cochrane Library, and Embase databases between May 2010 and December 2022 according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. All relevant articles were reviewed, and the risk of bias was evaluated using the Cochrane risk assessment tool and Newcastle-Ottawa Scale. RESULTS: Of the 32 studies included, there were 10 randomised controlled trials and 22 prospective observational cohorts. A total of 2400 participants were studied with a median patient age of 66 years, a median prostate volume of 51.9 mL, and a median International Prostate Symptom Score of 22. The lowest re-intervention rate at 12 months was for Aquablation at 0.01%, followed by Rezum at 0.02%, iTIND at 0.03%, and PAE at 0.05%. Network meta-analysis (NMA) showed that the best-ranked treatment at 12 months was transurethral resection of the prostate (TURP), followed by Aquablation, iTIND, Rezum, and UroLift. Re-intervention rates with these new BPH interventions are comparable, although some interventions reported better outcomes than TURP in the shorter term. CONCLUSIONS: While this systematic review and NMA showed that the re-intervention rate with these new surgical BPH interventions appears to be comparable to TURP in the short term, further studies are required to directly compare these various BPH procedures.

Use of the Hypotension Prediction Index During Cardiac Surgery.

OBJECTIVE: The hypotension prediction index (HPI) is a novel parameter developed by Edwards Lifesciences (Irvine, CA) that is obtained through an algorithm based on arterial pressure waveform characteristics. Past studies have demonstrated its accuracy in predicting hypotensive events in noncardiac surgeries. The authors aimed to evaluate the use of the HPI in cardiac surgeries requiring cardiopulmonary bypass (CPB). DESIGN: Prospective cohort feasibility study. SETTING: Single university medical center. PARTICIPANTS: Sequential adult patients undergoing elective cardiac surgeries requiring CPB between October 1, 2018, and December 31, 2018. INTERVENTIONS: HPI monitor was connected to the patient's arterial pressure transducer. Anesthesiologists and surgeons were blinded to the monitor output. MEASUREMENTS AND MAIN RESULTS: HPI values and hypotensive events were recorded before and after CPB. The primary outcomes were the area under the curve (AUC) of the receiver operating characteristic curve, sensitivity, and specificity of HPI predicting hypotension. The AUC, sensitivity, and specificity for HPI lead time to hypotension five minutes before the event were 0.90 (95% confidence interval [CI]: 0.853-0.949), 84% (95% CI: 77.7-90.5), and 84% (95% CI: 70.9-96.8), respectively. Ten minutes before the event AUC, sensitivity, and specificity for HPI lead time to hypotension were 0.83 (95% CI: 0.750-0.905), 79% (95% CI: 69.8-88.1), and 74% (95% CI: 58.8-89.6), respectively. Fifteen minutes before the hypotensive event AUC, sensitivity, and specificity for HPI lead time to hypotension were 0.83 (95% CI: 0.746-0.911), 79% (95% CI: 68.4-89.0), and 74% (95% CI: 58.8-89.6), respectively. CONCLUSION: HPI predicted hypotensive episodes during cardiac surgeries with a high degree of sensitivity and specificity.

The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer.

Most susceptibility to colorectal cancer (CRC) is not accounted for by known risk factors. Because MLH1, MSH2 and MSH6 mutations underlie high-penetrance CRC susceptibility in hereditary nonpolyposis colon cancer (HNPCC), we hypothesized that attenuated alleles might also underlie susceptibility to sporadic CRC. We looked for gene variants associated with HNPCC in Israeli probands with familial CRC unstratified with respect to the microsatellite instability (MSI) phenotype. Association studies identified a new MLH1 variant (415G-->C, resulting in the amino acid substitution D132H) in approximately 1.3% of Israeli individuals with CRC self-described as Jewish, Christian and Muslim. MLH1 415C confers clinically significant susceptibility to CRC. In contrast to classic HNPCC, CRCs associated with MLH1 415C usually do not have the MSI defect, which is important for clinical mutation screening. Structural and functional analyses showed that the normal ATPase function of MLH1 is attenuated, but not eliminated, by the MLH1 415G-->C mutation. The new MLH1 variant confers a high risk of CRC and identifies a previously unrecognized mechanism in microsatellite-stable tumors. These studies suggest that variants of mismatch repair proteins with attenuated function may account for a higher proportion of susceptibility to sporadic microsatellite-stable CRC than previously assumed.

A review of the objective cognitive function measurements in males receiving hormonal therapy for prostate cancer.

PURPOSE: Prostate cancer (PC) is more common in the older population and the use of hormonal therapy in PC can increase medical frailty and cognitive decline. This narrative review examines the impact of androgen deprivation therapies (ADTs) and next-generational hormonal therapies (NGHT) on cognitive function outcomes amongst patients with hormone-sensitive or castrate-resistant PC. MATERIALS AND METHODS: Six electronic databases were searched from January 2000 to June 2022 for quantitative studies to evaluate the impacts of hormonal therapies (ADT, combined androgen blockade, and NGHT) on cognitive functions in men with PC. RESULTS: Of the 36 studies identified, 20 studies reported no effect of hormonal therapies on any cognitive domain while 16 studies found possible declines in at least one domain. The domains assessed were highly variable and objective assessment measurements were not standardized or widely adopted. While the results have been inconsistent, a relationship between declining androgen levels and poorer performances in the visuospatial and visual memory domains has been highlighted. It was not possible to distinguish the degree of cognitive parameter changes between the populations of hormone-sensitive and castrate-resistant PC. CONCLUSIONS: While the exact impact of ADT and NGHT on cognitive function in men with PC remains controversial, appropriate care should be undertaken especially in older and frail individuals, specifically in those with progressive or established visuospatial or visual memory deficits.

Symptomatic scrotal-inguino-retroperitoneal lymphocele in a kidney transplant patient-to drain but how to drain?

Scrotal-inguino-retroperitoneal (SIR) lymphocele is a rare complication following kidney transplant. This entity is characterized by a tract originating in the retroperitoneal space, through the inguinal canal and scrotum following lymph hydrodissection. Systematic review investigating SIR lymphocele yielded cases with open fenestration of the sac into the peritoneum as treatment. We described a case report of a male in his 60s with a functioning kidney transplant and SIR lymphocele, which was successfully managed in the short term with percutaneous drainage of the collection. However, the collection recurred and computed tomography scan showed a multiloculated collection that prompted surgical management. Intraoperatively, the encapsulated fluid-filled tract was excised and a drain was placed, which was removed 48 h later. The patient wore a hernia belt for 6 weeks as support. He had no recurrence of his lymphocele following serial reviews for 9 months now.

Aortic valve leaflet disruption techniques in transcatheter aortic valve replacement.

With continued technological advancement and technical improvement of transcatheter aortic valve replacement (TAVR), it has become a desirable treatment option for aortic valve stenosis. Its minimally invasive approach compared to surgical aortic valve replacement offers the treatment to a broader patient population, mainly non-surgical candidates. A feared complication of TAVR is the occlusion of coronary artery ostium by the native aortic valve leaflet due to its displacement by the expanded transcatheter valve. Bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction (BASILICA) is a technique developed to mitigate this risk by creating a lengthwise laceration of the left and/or right aortic valve leaflets prior to TAVR. Patient outcomes following TAVR with BASILICA have been promising. Meticulous preoperative examination, patient selection, and hemodynamic management are imperative. With continued refinement, BASILICA may further expand the application of TAVR to patients at high risk for coronary occlusion associated with the procedure.

Can malleable penile prosthesis implantation improve voiding dysfunction in men with concurrent erectile dysfunction and buried penis?

PURPOSE: A buried penis causes voiding dysfunction and limits penetrative sexual intercourse. This pilot study evaluates the urinary outcomes in men with buried penis following insertion of malleable penile implants. MATERIALS AND METHODS: Men with buried penis and co-existing urinary problems and erectile dysfunction underwent malleable penile prosthesis implantation were reviewed in a prospective ethics approved database. Patient demographics, flow rate (Qmax), International Prostate Symptom Score (IPSS), Patient Global Impression of Improvement (PGI-I) score, International Index of Erectile Function (IIEF)-5 score, Sexual Encounter Profile (SEP) and overall satisfaction score (on a 5-point scale) were recorded. RESULTS: A total of 12 men (age 55 to 72 years) were reviewed, and the average gain in penile length post-implant, as measured from the pubis to the tip of the glans penis, was 6.8 (3 to 8) cm. There was a significant improvement in IIEF-5 score (8.2 vs. 22.5; p=0.029) post-implant, and more than half of patients were able to resume normal sexual intercourse and positive SEP-2 and SEP-4 were reported in 9 (75%) and 8 (67%) patients. There were no significant intraoperative or postoperative complication. Significant improvement in Qmax (8.4 ml/s vs. 18.6 ml/s; p=0.042) and IPSS (24.5±5.5 vs 15.5±3.5; p=0.038) were observed. More than two-thirds (83%) reported PGI-I score at 1 or 2, while 9 (75%) patients scored a 5/5 in overall satisfaction rate. CONCLUSIONS: Malleable penile implants increases penile length and improves urinary function in a highly select group of men with a buried penis and erectile dysfunction.

Transanal total mesorectal excision the Gold Coast experience: learning curve and comparison to traditional technique.

BACKGROUND: Laparoscopic and open techniques in rectal cancer are well-published, however, technical challenges remain for mid to low rectal cancer resections in the narrow pelvis. Transanal total mesorectal excision (taTME) has been pioneered to potentially circumvent these challenges. The aims of this study were to evaluate the learning curve associated with our first cases of taTME as well as compare outcomes to that of conventionally performed rectal resections. METHODS: This was a single-centre retrospective study with data collated from all elective resections by the colorectal unit from 2015 to 2017. Primary outcome was completeness of total mesorectal excision and secondary outcomes were intra- and post-operative morbidity and mortality. RESULTS: A total of 43 patients were identified. Of which, 20 underwent taTME. Mesorectal completeness was obtained in only 47.4% in the taTME group compared to 78.3% in the anterior resection group (p = 0.115). 5.9% of patients in our taTME group had positive circumferential resection margin compared to nil in the anterior resection. Conversion rates were greater in the taTME group (15% versus 0%; 0.028). Operative time, length of stay and clavien IV and V complications were greater in the taTME group. CONCLUSION: This study highlights the difficulty in introducing a novel technique given the learning curve. Our results would expect to improve with increased caseload.

In Vitro Sonothrombolysis Enhancement by Transiently Stable Microbubbles Produced by a Flow-Focusing Microfluidic Device.

Therapeutic approaches that enhance thrombolysis by combining recombinant tissue plasminogen activator (rtPA), ultrasound, and/or microbubbles (MBs) are known as sonothrombolysis techniques. To date, sonothrombolysis approaches have primarily utilized commercially available MB formulations (or derivatives thereof) with diameters in the range 1-4 µm and circulation lifetimes between 5 and 15 min. The present study evaluated the in vitro sonothrombolysis efficacy of large diameter MBs (d MB ≥ 10 µm) with much shorter lifetimes that were produced on demand and in close proximity to the blood clot using a flow-focusing microfluidic device. MBs with a N2 gas core and a non-crosslinked bovine serum albumin shell were produced with diameters between 10 and 20 µm at rates between 50 and 950 × 103 per second. Use of these large MBs resulted in approximately 4.0-8.8 fold increases in thrombolysis rates compared to a clinical rtPA dose and approximately 2.1-4.2 fold increases in thrombolysis rates compared to sonothrombolysis techniques using conventional MBs. The results of this study indicate that the large diameter microbubbles with transient stability are capable of significantly enhanced in vitro sonothrombolysis rates when delivered directly to the clot immediately following production by a flow focusing microfluidic device placed essentially in situ adjacent to the clot.

Do Illuminated Foot Pedals Improve the Speed and Accuracy of Pedal Activation During Endoscopic Procedures?

PURPOSE: Endourologic procedures such as percutaneous nephrolithotomy (PCNL) employ the use of foot pedals in low-light operating room (OR) settings. These pedals can be especially difficult to locate or distinguish when several pedals are present during a single operation. Improper instrument activation in the OR has led to serious complications ranging from unintentional electrocautery to patient burns and even an intraoperative explosion. This study evaluates the impact of color-coded illumination on speed and efficiency of foot pedal activation. MATERIALS AND METHODS: During a simulated PCNL procedure, the foot pedals for a C-arm, laser, and ultrasonic lithotripter (USL) were placed in random positions. Ten participants performed pedal activation in a randomized sequence. Objective outcomes included time to instrument activation, number of attempted pedal presses, number of incomplete pedal presses, and number of incorrect pedal presses. Subjective preferences for pedal illumination were also determined. Data were analyzed using Mann-Whitney U, Wilcoxon signed-rank, and Chi-square tests with p < 0.05 indicating statistical significance. RESULTS: Illuminated foot pedals were associated with decreases in the average activation time for all instruments collectively (3.95 seconds vs 6.49 seconds; p = 0.017) and individually (C-arm: 3.07 seconds vs 4.21 seconds; p = 0.006; laser: 13.04 seconds vs 15.18 seconds; p < 0.001; USL: 3.28 seconds vs 4.91 seconds; p < 0.001) compared with nonilluminated pedals. Illuminated pedals were associated with fewer attempted pedal presses (33.5 vs 39.5; p = 0.007) and incomplete pedal presses (1.5 vs 8.5; p = 0.002). The number of incorrect pedal presses decreased with illumination, but this did not reach statistical significance (0 vs 0.5; p = 0.08). Participants reported that illumination simplified pedal activation and recommended its use (p < 0.01). CONCLUSION: Color-coded illumination improved the speed and efficiency of foot pedal activation during simulated PCNL. Participants subjectively preferred using illuminated foot pedals for endourologic procedures and felt that they improved safety and efficiency.

The forkhead box F1 transcription factor is expressed in brain and head mesenchyme during mouse embryonic development.

The forkhead box f1 (Foxf1) transcription factor is expressed in septum transversum mesenchyme and splanchnic (visceral) mesoderm, which give rise to mesenchymal cells of gut-derived organs such as liver, gall bladder, lung, stomach, and intestine. Foxf1 -/- embryos die in utero and haploinsufficiency of the Foxf1 gene resulted in a variety of developmental abnormalities of the lung, gall bladder, esophagus, and trachea and caused defects in liver and lung repair. In this study, we used Foxf1 +/- mouse embryos containing the beta-Galactosidase (beta-Gal) gene knocked into the Foxf1 locus to examine whether Foxf1 is expressed in the developing brain and head region. In addition to previously reported Foxf1 expression patterns, beta-Gal staining was also found in the mesenchyme of developing pituitary gland, eye, pancreas, heart, notochord, genital tubercle, Meckel's cartilage, and cartilage primordia of nasal septum and vertebral bodies. In adult Foxf1 +/- mice, beta-Gal staining was detected in anterior and posterior pituitary gland, astrocytes of the cerebellum and cerebral cortex, lens and retina of the eye, tracheal cartilage, parathyroid, cortical layer of thymus, capsule of the spleen, coronary arteries, and pancreatic blood vessels.

Battle against RNA oxidation: molecular mechanisms for reducing oxidized RNA to protect cells.

Oxidation is probably the most common type of damage that occurs in cellular RNA. Oxidized RNA may be dysfunctional and is implicated in the pathogenesis of age-related human diseases. Cellular mechanisms controlling oxidized RNA have begun to be revealed. Currently, a number of ribonucleases and RNA-binding proteins have been shown to reduce oxidized RNA and to protect cells under oxidative stress. Although information about how these factors work is still very limited, we suggest several mechanisms that can be used to minimize oxidized RNA in various organisms.

Comparing ERCC1 protein expression, mRNA levels, and genotype in squamous cell carcinomas of the head and neck treated with concurrent chemoradiation stratified by HPV status.

BACKGROUND: Previous studies examining excision repair cross-complementation group 1 (ERCC1) in squamous cell carcinoma of the head and neck (SCCHN) have not compared methods of ERCC1 testing nor been stratified by human papillomavirus (HPV) status. METHODS: ERCC1 protein expression, mRNA, and genotype were retrospectively evaluated from pretreatment biopsies in 55 patients with SCCHN treated with chemoradiation. RESULTS: In all, 50% of patients had high ERCC1 protein expression, 28.2% had low mRNA levels, and genotype frequencies were C/C = 17.1%, C/T = 43.9%, and T/T = 39.0%. No correlations were found among protein expression, mRNA, or genotype. With a median follow-up of 54 months, the 5-year overall survival was 57.7%. After adjusting for known prognostic factors, ERCC1 protein level and genotype resulted in hazard ratios indicating an increased risk of death of 4.4-fold (p = .004) and 4.2-fold (p = .044), respectively. An exploratory analysis suggested a differential prognostic effect in HPV-negative SCCHN. CONCLUSIONS: ERCC1 protein expression using the FL297 antibody warrants further study as a potential prognostic marker in SCCHN.

Validation of lysyl oxidase as a prognostic marker for metastasis and survival in head and neck squamous cell carcinoma: Radiation Therapy Oncology Group trial 90-03.

PURPOSE: To validate lysyl oxidase (LOX), a hypoxia-related protein, as a marker for metastasis in an independent head and neck cancer (HNC) patient group enrolled onto a prospective trial. PATIENTS AND METHODS: We performed traditional immunohistochemical (IHC) staining and automated quantitative analysis (AQUA) for LOX expression in 66 HNC patients from one institution. We also performed AQUA staining for LOX in 306 of 1,113 patients treated on a phase III trial comparing four radiation fractionation schedules in locally advanced HNC (RTOG 90-03). Pretreatment characteristics and outcome were similar between patients with and without LOX assessment. We correlated AQUA LOX expression with time to metastasis (TTM), time to progression (TTP), and overall survival (OS). RESULTS: LOX expression from both staining methods predicted for TTM in the first 66 patients. Multivariate analysis, controlling for significant parameters including nodal stage and performance status, revealed tumor LOX expression, as a continuous variable, was an independent predictor for TTM (hazard ratio [HR], 1.21; 95% CI, 1.10 to 1.33; P = .0001), TTP (HR, 1.06; 95% CI, 1.02 to 1.10; P = .0069), and OS (HR, 1.04; 95% CI, 1.00 to 1.07; P = .0311) in RTOG 90-03 patients. This translates into a 259% increase in metastatic risk for a patient at the 75th percentile of LOX compared with one at the 25th percentile. CONCLUSION: AQUA LOX expression was strongly associated with increased metastasis, progression, and death in RTOG 90-03 patients. This study validates that LOX is a marker for metastasis and survival in HNC.

Low allele frequency of MLH1 D132H in American colorectal and endometrial cancer patients.

PURPOSE: Hereditary nonpolyposis colon cancer is caused by mutations in DNA mismatch repair genes, predominantly MLH1 and MSH2. Classic MLH1 mutations cause an approximately 20-fold increase in colorectal cancer susceptibility. Recently, we identified a hypomorphic allele, MLH1 D132H , which impairs, but does not completely eliminate the function of MLH1 in tumor suppression. MLH1 D132H confers an approximately fivefold increase in colorectal cancer susceptibility and was first described in a cohort of Israeli colorectal cancer patients, with an estimated allele frequency of 1.3 percent. Because MLH1 D132H has only recently been described, the ethnic distribution of this risk allele is not well understood. This study was undertaken to determine both the frequencies of this risk allele in ethnic groups outside of Israel and whether families harboring this mutation have susceptibility to extracolonic cancers in the hereditary nonpolyposis colon cancer spectrum. METHODS: We genotyped two independent cohorts: 629 population-based colorectal cancer patients ascertained from clinics in Orange, Imperial, and San Diego Counties, and 515 endometrial cancer patients ascertained from gynecologic oncology clinics in the Midwestern United States. RESULTS: MLH1 D132H was not detected in either study cohort, which together totaled more than 1,100 American colorectal cancer and endometrial cancer patients. CONCLUSIONS: The MLH1 D132H risk variant has significantly lower allele frequency in American compared with Israeli cancer patients and, alone, is unlikely to explain significant amounts of American sporadic colorectal cancer or uterine cancer susceptibility. Genetic testing for the MLH1 D132H allele exclusively is therefore unlikely to be cost effective for genetic risk assessment in American population-based and clinic-based colorectal cancer and endometrial cancer patients.

Haploinsufficiency of the mouse Forkhead Box f1 gene causes defects in gall bladder development.

The forkhead box f1 (Foxf1) transcription factor is expressed in the visceral (splanchnic) mesoderm, which is involved in mesenchymal-epithelial signaling required for development of organs derived from foregut endoderm such as lung, liver, gall bladder, and pancreas. Our previous studies demonstrated that haploinsufficiency of the Foxf1 gene caused pulmonary abnormalities with perinatal lethality from lung hemorrhage in a subset of Foxf1+/- newborn mice. During mouse embryonic development, the liver and biliary primordium emerges from the foregut endoderm, invades the septum transversum mesenchyme, and receives inductive signaling originating from both the septum transversum and cardiac mesenchyme. In this study, we show that Foxf1 is expressed in embryonic septum transversum and gall bladder mesenchyme. Foxf1+/- gall bladders were significantly smaller and had severe structural abnormalities characterized by a deficient external smooth muscle cell layer, reduction in mesenchymal cell number, and in some cases, lack of a discernible biliary epithelial cell layer. This Foxf1+/- phenotype correlates with decreased expression of vascular cell adhesion molecule-1 (VCAM-1), alpha(5) integrin, platelet-derived growth factor receptor alpha (PDGFRalpha) and hepatocyte growth factor (HGF) genes, all of which are critical for cell adhesion, migration, and mesenchymal cell differentiation.

Foxf1 +/- mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injury.

Previous studies have shown that haploinsufficiency of the splanchnic and septum transversum mesoderm Forkhead Box (Fox) f1 transcriptional factor caused defects in lung and gallbladder development and that Foxf1 heterozygous (+/-) mice exhibited defective lung repair in response to injury. In this study, we show that Foxf1 is expressed in hepatic stellate cells in developing and adult liver, suggesting that a subset of stellate cells originates from septum transversum mesenchyme during mouse embryonic development. Because liver regeneration requires a transient differentiation of stellate cells into myofibroblasts, which secrete type I collagen into the extracellular matrix, we examined Foxf1 +/- liver repair following carbon tetrachloride injury, a known model for stellate cell activation. We found that regenerating Foxf1 +/- liver exhibited defective stellate cell activation following CCl(4) liver injury, which was associated with diminished induction of type I collagen, alpha-smooth muscle actin, and Notch-2 protein and resulted in severe hepatic apoptosis despite normal cellular proliferation rates. Furthermore, regenerating Foxf1 +/- livers exhibited decreased levels of interferon-inducible protein 10 (IP-10), delayed induction of monocyte chemoattractant protein 1 (MCP-1) levels, and aberrantly elevated expression of transforming growth factor beta1. In conclusion, Foxf1 +/- mice exhibited abnormal liver repair, diminished activation of hepatic stellate cells, and increased pericentral hepatic apoptosis following CCl(4) injury.