ECG Dilemma

"Case: A 31-year-old man with an unremarkable past medical history presented with substernal chest pressure without radiation of two-hours duration. The patient's vitals remained stable and an ECG was obtained. What is the diagnosis? ... Answer: D) Destrocardia."Zachary Oman (1), Leni Abraham (2), Piotr J. Horbal (1), Jad Raffoul (2), Tarek Helmy (2) ; 1. Department of Internal Medicine, Saint Louis University School of Medicine. 2. The Center for Comprehensive Cardiovascular Care, Saint Louis University School of Medicine.Includes bibliographical reference

Microwave Treatment of Prostate Cancer and Hyperplasia

Microwave ablation in the form of microwave energy applied to a heart muscle by a coaxial catheter inserted in a vein in the groin area can be used to heat and kill diseased heart cells. A microwave catheter has been developed to provide deep myocardial ablation to treat ventricular tachycardia by restoring appropriate electrical activity within the heart and eliminating irregular heartbeats. The resulting microwave catheter design, which is now being developed for commercial use in treating ventricular tachycardia, can be modified to treat prostate cancer and benign prostatic hyperplasia (BPH). Inasmuch as the occurrence of BPH is increasing currently 350,000 operations per year are performed in the United States alone to treat this condition this microwave catheter has significant commercial potential

Facial Fat Grafting (FFG): Worth the Risk? A Systematic Review of Complications and Critical Appraisal

Introduction: Autologous fat is ideal soft tissue filler. It is easily accessible, biocompatible, cheap, and it provides both volume augmentation and skin quality improvement. Fat grafting has been used since 1893, but it has only gained widespread popularity since the development of modern liposuction by Colemann and Illouz in the 1980s. Every year more than half a million facial fat grafting procedures are carried out worldwide and the trend is rapidly increasing. Overall, general complications associated with facial fat grafting are assumed to be around 2%. Is that true? Material and Methods: Until July 2021, a systematic search of the literature was performed interrogating PubMed search engines. The following algorithm was used for the research: (fat graft OR lipofilling) AND face AND complications. Exclusion criteria applied hierarchically were review articles, not reporting recipient site complications; not in English and paediatric population. Abstracts were manually screened by LS, GS, JM and PDS separately and subsequently matched for accuracy. Pertinent full-text articles were retrieved and analysed and data were extracted from the database. The flow chart of article selection is described following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: In total, 462 papers were identified by PubMed search. A total of 359 were excluded: 38 papers were not in English, 41 were review articles, 279 articles did not report recipient site complications and 1 was not on human subjects. Average complication rate ranged from 1.5% to 81.4%. A total of 298 adverse events were identified: 40 (13.4%) intravascular injections, 13 (4.3%) asymmetry, 57 (19.1%) irregularities, 22 (7.4%) graft hypertrophy, 21 (7%) fat necrosis, 73 (24.5%) prolonged oedema, 1 (0.3%) infection, 6 (2%) prolonged erythema, 15 (5%) telangiectasia and 50 (16.8%) cases of acne activation. Conclusions: FFG related side effects could be resumed in three categories: severe, moderate, and minor. Severe (13.4%) side effects such as intravascular injection or migration require neurological or neurosurgical management and often lead to permanent disability or death. Moderate (38.3%) side effects such as fat hypertrophy, necrosis, cyst formation, irregularities and asymmetries require a retouch operation. Minor (48.3%) side effects such as prolonged oedema or erythema require no surgical management. Despite the fact that the overall general complication rate of facial fat grafting is assumed to be around 2%, the real complication rate of facial fat grafting is unknown due to a lack of reporting and the absence of consensus on side effect definition and identification. More RCTs are necessary to further determine the real complication rate of this procedure

Genistein inhibits radiation-induced activation of NF-κB in prostate cancer cells promoting apoptosis and G\u3csub\u3e2\u3c/sub\u3e/M cell cycle arrest

Abstract Background New cancer therapeutic strategies must be investigated that enhance prostate cancer treatment while minimizing associated toxicities. We have previously shown that genistein, the major isoflavone found in soy, enhanced prostate cancer radiotherapy in vitro and in vivo. In this study, we investigated the cellular and molecular interaction between genistein and radiation using PC-3 human prostate cancer cells. Methods Tumor cell survival and progression was determined by clonogenic analysis, flow cytometry, EMSA analysis of NF-κB, and western blot analysis of cyclin B1, p21WAF1/Cip1, and cleaved PARP protein. Results Genistein combined with radiation caused greater inhibition in PC-3 colony formation compared to genistein or radiation alone. Treatment sequence of genistein followed by radiation and continuous exposure to genistein showed optimal effect. Cell cycle analysis demonstrated a significant dose- and time-dependent G2/M arrest induced by genistein and radiation that correlated with increased p21WAF1/Cip1 and decreased cyclin B1 expression. NF-κB activity was significantly decreased by genistein, yet increased by radiation. Radiation-induced activation of NF-κB activity was strongly inhibited by genistein pre-treatment. A significant and striking increase in cleaved PARP protein was measured following combined genistein and radiation treatment, indicating increased apoptosis. Conclusion A mechanism of increased cell death by genistein and radiation is proposed to occur via inhibition of NF-κB, leading to altered expression of regulatory cell cycle proteins such as cyclin B and/or p21WAF1/Cip1, thus promoting G2/M arrest and increased radiosensitivity. These findings support the important and novel strategy of combining genistein with radiation for the treatment of prostate cancer

Impact of etiology leading to abdominoperineal resection with anterolateral thigh flap reconstruction: A retrospective cohort study.

Large and deep perineal defects following abdominal perineal resection (APR) are a challenge for reconstructive surgeons. Even if generally performed for oncological reasons, APR can be indicated as well in extended infection-related debridement for Hidradenitis suppurativa, Fournier's gangrene, or Crohn's disease. We aimed to compare the outcomes of two groups of patients with different indications for APR (infectious vs. oncological) after pedicled anterolateral thigh (ALT) flap coverage RESULTS: Forty-four consecutive pedicled ALT flap used for coverage after APR in 40 patients were analyzed. Twenty-seven patients (67.5%) underwent APR for oncological reasons and 13 patients (32.5%) for infectious reasons. The overall postoperative complications rate was significantly higher for infectious cases (76.5% vs. 40.7%, p = 0.0304). Major complications occurred in 52.9% of infectious cases versus 11.1% of oncological cases (p = 0.0045). Obesity and infectious etiology were independent risk factors for overall and major complications, respectively. Patients undergoing APR for acute or chronic infections had significantly more overall and major complications than patients having oncological APR. Modified care might be considered, especially in obese patients, in terms of surgical debridement, antibiotic treatment modalities, and postoperative management

Efficient decellularization of equine tendon with preserved biomechanical properties and cytocompatibility for human tendon surgery indications.

Chronic and acute tendon injuries are frequent afflictions, for which treatment is often long and unsatisfactory. When facing extended injuries, matrices and scaffolds with sufficient biomechanical properties are required for surgical repair and could additionally serve as supports for cellular therapies to improve healing. In this study, protocols of either commonly used detergents only (SDS 1%, Triton 1%, TBP 1%, and Tween-20 1%) or a combination of freeze/thaw (F/T) cycles with decellularization agents (NaCl 1M, ddH <sub>2</sub> O) were evaluated for the decellularization of horse equine superficial digital flexor tendon (SDFT) for hand flexor or extensor tendon reconstruction. Decellularization efficiency was assessed microscopically by histological staining (HE, DAPI) and DNA quantification. Macroscopical structure and biomechanical integrity of the tendon matrices were further assessed by gross observation, histological staining (SR), and mechanical testing (ultimate strain and stress, Young's modulus, energy to failure) for select protocols. Decellularization with hypertonic NaCl 1M in association with F/T cycles produced the most robust tendon matrices, which were nontoxic after 10 days for subsequent recellularization with human fetal progenitor tendon cells (hFPTs). This standardized protocol uses a less aggressive decellularization agent than current practice, which allows subsequent reseeding with allogenic cells, therefore making them very suitable and bioengineered tendon matrices for human tendon reconstruction in the clinic

Bio-Enhanced Neoligaments Graft Bearing FE002 Primary Progenitor Tenocytes: Allogeneic Tissue Engineering & Surgical Proofs-of-Concept for Hand Ligament Regenerative Medicine.

Hand tendon/ligament structural ruptures (tears, lacerations) often require surgical reconstruction and grafting, for the restauration of finger mechanical functions. Clinical-grade human primary progenitor tenocytes (FE002 cryopreserved progenitor cell source) have been previously proposed for diversified therapeutic uses within allogeneic tissue engineering and regenerative medicine applications. The aim of this study was to establish bioengineering and surgical proofs-of-concept for an artificial graft (Neoligaments Infinity-Lock 3 device) bearing cultured and viable FE002 primary progenitor tenocytes. Technical optimization and in vitro validation work showed that the combined preparations could be rapidly obtained (dynamic cell seeding of 10 <sup>5</sup> cells/cm of scaffold, 7 days of co-culture). The studied standardized transplants presented homogeneous cellular colonization in vitro (cellular alignment/coating along the scaffold fibers) and other critical functional attributes (tendon extracellular matrix component such as collagen I and aggrecan synthesis/deposition along the scaffold fibers). Notably, major safety- and functionality-related parameters/attributes of the FE002 cells/finished combination products were compiled and set forth (telomerase activity, adhesion and biological coating potentials). A two-part human cadaveric study enabled to establish clinical protocols for hand ligament cell-assisted surgery (ligamento-suspension plasty after trapeziectomy, thumb metacarpo-phalangeal ulnar collateral ligamentoplasty). Importantly, the aggregated experimental results clearly confirmed that functional and clinically usable allogeneic cell-scaffold combination products could be rapidly and robustly prepared for bio-enhanced hand ligament reconstruction. Major advantages of the considered bioengineered graft were discussed in light of existing clinical protocols based on autologous tenocyte transplantation. Overall, this study established proofs-of-concept for the translational development of a functional tissue engineering protocol in allogeneic musculoskeletal regenerative medicine, in view of a pilot clinical trial

Imbalanced Base Excision Repair in Response to Folate Deficiency Is Accelerated by Polymerase β Haploinsufficiency

The mechanism by which folate deficiency influences carcinogenesis is not well established, but a phenotype of DNA strand breaks, mutations, and chromosomal instability suggests an inability to repair DNA damage. To elucidate the mechanism by which folate deficiency influences carcinogenicity, we have analyzed the effect of folate deficiency on base excision repair (BER), the pathway responsible for repairing uracil in DNA. We observe an up-regulation in initiation of BER in liver of the folate-deficient mice, as evidenced by an increase in uracil DNA glycosylase protein (30%, p < 0.01) and activity (31%, p < 0.05). However, no up-regulation in either BER or its rate-determining enzyme, DNA polymerase beta (beta-pol) is observed in response to folate deficiency. Accordingly, an accumulation of repair intermediates in the form of DNA single strand breaks (37% increase, p < 0.03) is observed. These data indicate that folate deficiency alters the balance and coordination of BER by stimulating initiation without subsequently stimulating the completion of repair, resulting in a functional BER deficiency. In directly establishing that the inability to induce beta-pol and mount a BER response when folate is deficient is causative in the accumulation of toxic repair intermediates, beta-pol-haploinsufficient mice subjected to folate deficiency displayed additional increases in DNA single strand breaks (52% increase, p < 0.05) as well as accumulation in aldehydic DNA lesions (38% increase, p < 0.01). Since young beta-polhaploinsufficient mice do not spontaneously exhibit increased levels of these repair intermediates, these data demonstrate that folate deficiency and beta-pol haploinsufficiency interact to increase the accumulation of DNA damage. In addition to establishing a direct role for beta-pol in the phenotype expressed by folate deficiency, these data are also consistent with the concept that repair of uracil and abasic sites is more efficient than repair of oxidized bases

Apurinic/Apyrimidinic Endonuclease (APE/REF-1) Haploinsufficient Mice Display Tissue-specific Differences in DNA Polymerase β-Dependent Base Excision Repair

Apurinic/apyrimidinic (AP) endonuclease (APE) is a multifunctional protein possessing both DNA repair and redox regulatory activities. In base excision repair (BER), APE is responsible for processing spontaneous, chemical, or monofunctional DNA glycosylase-initiated AP sites via its 5'-endonuclease activity and 3'-"end-trimming" activity when processing residues produced as a consequence of bifunctional DNA glycosylases. In this study, we have fully characterized a mammalian model of APE haploinsufficiency by using a mouse containing a heterozygous gene-targeted deletion of the APE gene (Apex(+/-)). Our data indicate that Apex(+/-) mice are indeed APE-haploinsufficient, as exhibited by a 40-50% reduction (p < 0.05) in APE mRNA, protein, and 5'-endonuclease activity in all tissues studied. Based on gene dosage, we expected to see a concomitant reduction in BER activity; however, by using an in vitro G:U mismatch BER assay, we observed tissue-specific alterations in monofunctional glycosylase-initiated BER activity, e.g. liver (35% decrease, p < 0.05), testes (55% increase, p < 0.05), and brain (no significant difference). The observed changes in BER activity correlated tightly with changes in DNA polymerase beta and AP site DNA binding levels. We propose a mechanism of BER that may be influenced by the redox regulatory activity of APE, and we suggest that reduced APE may render a cell/tissue more susceptible to dysregulation of the polymerase beta-dependent BER response to cellular stress

Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

BACKGROUND: We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC) model established in our laboratory. METHODS: The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs. RESULTS: In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer. CONCLUSION: Our studies in both RCC and prostate tumor models demonstrate that the combination of genistein with primary tumor irradiation is a more effective and safer therapeutic approach as the tumor growth and progression are inhibited both in the primary and metastatic sites