Transoral incisionless fundoplication for recurrent symptoms after laparoscopic fundoplication.

BACKGROUND: Revision of a failed laparoscopic fundoplication carries higher risk of complication and lower chance of success compared to the original surgery. Transoral incisionless fundoplication (TIF) may be an endoscopic alternative for select GERD patients without need of a moderate/large hiatal hernia repair. The aim of this study was to assess feasibility, efficacy, and safety of TIF 2.0 after failed laparoscopic Nissen or Toupet fundoplication (TIFFF). METHODS: This is a multicenter retrospective cohort study of patients who underwent TIFFF between September 2017 and December 2020 using TIF 2.0 technique (EsophyX Z/Z+) performed by gastroenterologists and surgeons. Patients were included if they had (1) recurrent GERD symptoms, (2) pathologic reflux based upon pH testing or Grade C/D esophagitis or Barrett's esophagus, and (3) hiatal hernia ≤ 2 cm. The primary outcome was improvement in GERD Health-Related Quality of Life (GERD-HRQL) post-TIFFF. The TIFFF cohort was also compared to a similar surgical re-operative cohort using propensity score matching. RESULTS: Twenty patients underwent TIFFF (median 4.1 years after prior fundoplication) and mean GERD-HRQL score improved from 24.3 ± 22.9 to 14.75 ± 21.6 (p = 0.014); mean Reflux Severity Index (RSI) score improved from 14.1 ± 14.6 to 9.1 ± 8.0 (p = 0.046) with 8/10 (80%) of patients with normal RSI (< 13) post-TIF. Esophagitis healed in 78% of patients. PPI use decreased from 85 to 55% with 8/20 (45%) patients off of PPI. Importantly, mean acid exposure time decreased from 12% ± 17.8 to 0.8% ± 1.1 (p = 0.028) with 9/9 (100%) of patients with normalized pH post-TIF. There were no statistically significant differences in clinical efficacy outcomes between TIFFF and surgical revision, but TIFFF had significantly fewer late adverse events. CONCLUSION: Endoscopic rescue with TIF is a safe and efficacious alternative to redo laparoscopic surgery in symptomatic patients with appropriate anatomy and objective evidence of persistent or recurrent reflux.

Bone Turnover Markers Including Undercarboxylated Osteocalcin Are Associated With Mortality Risk in Older Men.

Osteocalcin in its undercarboxylated form (ucOC) may influence diabetes risk; however, its relationship with all-cause and cause-specific mortality is unclear. Whether other bone turnover markers (BTMs) are associated with mortality risk differently from ucOC also remains uncertain. Our aim was to determine associations of serum ucOC with all-cause and cause-specific mortality and compare these with the corresponding associations of serum total osteocalcin (TOC), procollagen type I N-propeptide (PINP), and collagen type 1 C-terminal cross-linked telopeptide (CTX) in older men. We conducted a prospective cohort study of 3871 community-dwelling men, aged 77.0 ± 3.6 years at baseline, followed for a median of 12.3 years. Exposure variables were ucOC, TOC, PINP, and CTX concentrations assayed in serum. Outcomes were incidence of all deaths and deaths due to cardiovascular disease (CVD) or cancer, ascertained using death registry data. Cox regression analyses adjusted for cardiovascular risk factors and prevalent CVD and for prevalent cancer in analyses of cancer-related mortality. Higher concentrations of ucOC, PINP, and CTX were associated with all-cause mortality (hazard ratio [HR] per 1 standard deviation increase: ucOC 1.12, 95% confidence interval [CI] 1.06-1.18, p < 0.001; PINP HR = 1.06, 95% CI 1.01-1.11, p = 0.009; CTX HR = 1.13, 95% CI 1.08-1.19, p < 0.001), but TOC was not associated. Similar results were found after excluding men with an incident fracture during follow-up. Higher ucOC and CTX were associated with CVD mortality (ucOC HR per 1 SD increase 1.13, 95% CI 1.05-1.22, p = 0.001; CTX HR = 1.12, 95% CI 1.04-1.20, p = 0.003), but this result was not significant in competing risks analysis. Higher CTX was also associated with cancer mortality (HR = 1.12, 95% CI 1.01-1.23, p = 0.024). In conclusion, in older men, higher bone turnover, assessed by BTMs including ucOC, is a biomarker for all-cause mortality risk. Undercarboxylated osteocalcin was a more informative biomarker for this outcome than TOC. Higher CTX was associated with all-cause and cancer-related mortality. Further evaluation of causality and potential underlying mechanisms is warranted. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Gastrointestinal Bleeding in Patients With Coronavirus Disease 2019: A Matched Case-Control Study.

INTRODUCTION: Although current literature has addressed gastrointestinal presentations including nausea, vomiting, diarrhea, abnormal liver chemistries, and hyperlipasemia as possible coronavirus disease 2019 (COVID-19) manifestations, the risk and type of gastrointestinal bleeding (GIB) in this population is not well characterized. METHODS: This is a matched case-control (1:2) study with 41 cases of GIB (31 upper and 10 lower) in patients with COVID-19 and 82 matched controls of patients with COVID-19 without GIB. The primary objective was to characterize bleeding etiologies, and our secondary aim was to discuss outcomes and therapeutic approaches. RESULTS: There was no difference in the presenting symptoms of the cases and controls, and no difference in severity of COVID-19 manifestations (P > 0.05) was observed. Ten (32%) patients with upper GIB underwent esophagogastroduodenoscopy and 5 (50%) patients with lower GIBs underwent flexible sigmoidoscopy or colonoscopy. The most common upper and lower GIB etiologies were gastric or duodenal ulcers (80%) and rectal ulcers related to rectal tubes (60%), respectively. Four of the esophagogastroduodenoscopies resulted in therapeutic interventions, and the 3 patients with rectal ulcers were referred to colorectal surgery for rectal packing. Successful hemostasis was achieved in all 7 cases that required interventions. Transfusion requirements between patients who underwent endoscopic therapy and those who were conservatively managed were not significantly different. Anticoagulation and rectal tube usage trended toward being a risk factor for GIB, although it did not reach statistical significance. DISCUSSION: In COVID-19 patients with GIB, compared with matched controls of COVID-19 patients without GIB, there seemed to be no difference in initial presenting symptoms. Of those with upper and lower GIB, the most common etiology was peptic ulcer disease and rectal ulcers from rectal tubes, respectively. Conservative management seems to be a reasonable initial approach in managing these complex cases, but larger studies are needed to guide management.

Risk of Early Colorectal Cancers Needs to Be Considered in Inflammatory Bowel Disease Care.

BACKGROUND: Current guidelines recommend starting colorectal cancer (CRC) surveillance 8-10 years after inflammatory bowel disease (IBD) onset. Recent studies report that the incidence of CRC within 8-10 years of IBD onset (i.e., early CRC) ranges from 12 to 42%. AIMS: To describe the current prevalence of early CRC in a tertiary care center IBD cohort with CRC and to identify associated risk factors. METHODS: We performed a single-center observational study of IBD patients diagnosed with CRC from 2005 to 2015. We compared characteristics of patients with early CRC (diagnosis of CRC within 8 years of initial IBD onset) to those with CRC diagnosed later in their IBD course. RESULTS: Ninety-three patients met inclusion criteria. Eleven (11.8%) patients developed CRC within 8 years of initial IBD onset. On multivariable logistic regression, age greater than 28 at IBD onset (adjusted OR 12.0; 95% CI 2.30, 62.75) and tobacco use (adjusted OR 8.52; 95% CI 1.38, 52.82) were significant predictors of early CRC. A validation cohort confirmed calibration and discrimination of the model. CONCLUSIONS: One out of every eight IBD patients with CRC developed their malignancy prior to the currently recommended timeframe for the initiation of surveillance colonoscopy. IBD onset at 28 years or older and tobacco use were identified as predictors of early CRC. Early CRC should be considered in discussions of cancer surveillance in this population. Prospective cohort studies are necessary to further analyze the impact of early CRC in IBD.

Protein PEGylation for cancer therapy: bench to bedside.

PEGylation is a biochemical modification process of bioactive molecules with polyethylene glycol (PEG), which lends several desirable properties to proteins/peptides, antibodies, and vesicles considered to be used for therapy or genetic modification of cells. However, PEGylation of proteins is a complex process and can be carried out using more than one strategy that depends on the nature of the protein and the desired application. Proteins of interest are covalently conjugated or non-covalently complexed with inert PEG strings. Purification of PEGylated protein is another critical step, which is mainly carried out based on electrostatic interactions or molecular sizes using chromatography. Several PEGylated drugs are being used for diseases like anemia, kidney disease, multiple sclerosis, hemophilia and cancers. With the advancement and increased specificity of the PEGylation process, the world of drug therapy, and specifically cancer therapy could benefit by utilizing this technique to create more stable and non-immunogenic therapies. In this article we describe the structure and functions of PEGylation and how this chemistry helps in drug discovery. Moreover, special emphasis has been given to CCN-family proteins that can be targeted or used as therapy to prevent or block cancer progression through PEGylation technology.

Performance of Non-Cemented, Hemispherical, Rim-Fit, Hydroxyapatite Coated Acetabular Component.

The purpose of this study was to assess the durability of a non-cemented, hemispherical rim-fit, hydroxyapatite coated cup with a highly cross-linked polyethylene in 223 total hip arthroplasties. At 6-years follow-up (range, 5-9), there were no cup revisions for osteolysis or loosening. Radiologic evidence of osseointegration was based on presence of Stress Induced Reactive Cancellous Bone and radial trabeculae, seen in 47% and 93% of cups, respectively; both were most prevalent in Zone 1. There was no interference demarcation in any zones. Two cups were revised (0.9%): one for dislocation and another for infection. The Kaplan-Meier survivorship for cup revision for any failure (infection, dislocation) was 99% and for mechanical failure (osteolysis, loosening) was 100%. This design has excellent safety, efficacy and durability.

Alterations in serum lipid profile patterns in oral squamous cell carcinoma patients.

AIM: Altered lipid profile patterns have been associated with malignancies because lipids play a pivotal role in the maintenance of cell integrity. The present study evaluated alterations in serum lipid profile in oral squamous cell carcinoma patients as well as its association with the habit of tobacco consumption. MATERIALS AND METHODS: The study included 30 oral squamous cell carcinoma patients, 20 patients with the habit of tobacco consumption and 20 controls. Serum lipids, including (i) total cholesterol, (ii) LDL cholesterol (LDLC), (iii) HDL cholesterol (HDLC), (iv) VLDL cholesterol (VLDLC) and (v) triglycerides, were analyzed by spectrophotometric kits. RESULTS: A significant decrease in serum total cholesterol (TC) levels, triglyceride levels (p = 0.007, p = 0.029 respectively) were observed in oral squamous cell carcinoma patients as compared to the healthy control group. The mean serum HDLC levels (p = 0.003) were significantly lowered in the tobacco habituates when compared to the healthy controls. The mean serum total cholesterol levels were significantly lower in subjects with oral squamous cell carcinoma (p = 0.000) as compared to the tobacco habituates. Likewise, LDLC levels and TC:HDLC ratios (p = 0.000 and p = 0.000 respectively) were significantly decreased in oral squamous cell carcinoma patients as compared to the tobacco habituates. Our data strengthens the evidence of an inverse relationship between serum lipid levels and oral squamous cell carcinoma. CONCLUSION: The lower level of serum cholesterol and other lipid constituents in the patients is thought to be due to their increased usage by tumor cells for new membrane biogenesis. CLINICAL SIGNIFICANCE: The lower serum lipid profile status serves as a useful indicator for gauging initial changes occurring in tumor cells. A detailed study of the cholesterol carrying lipoprotein transport mechanisms helps in better understanding of the underlying mechanisms of the regulation of serum cholesterol concentrations in cancer.