A Perspective on the Surgical Management of Congestive Heart Failure

Surgical treatment of patients with congestive heart failure (CHF) has steadily advanced from rescue procedures such as aneurysmectomy, rupture repair, ventricular assist devices (VADs), and transplantation to procedures that can prevent or delay the progression of cardiac dysfunction and failure. The latter include operations such as coronary artery bypass grafting (CABG) and mitral valve repair for patients with ischemic cardiomyopathy (ICMP) and mitral annular dilatation, ventricular restoration and remodeling, and cardiac resynchronization therapy. As the number of heart transplants reported worldwide continues to decline over the past decade (by over 30%), newer surgical therapies have emerged. A need arises for clinical registries such as the NIH-sponsored LVAD registry and registries for biventricular pacing and AICD implantation, for total artificial heart implants, and for mitral valve repair in patients with ICMP. Prospective trials comparing sole ventricular restoration therapy (SVR) to SVR with concomitant CABG/MVR, coronary sinus versus epicardial LV pacing for ventricular resynchronization therapy, trials comparing LVAD as destination therapy to AICD implants, mitral valve repair versus chordal-sparing valve replacement for ischemic and valvular cardiomyopathy, and off-pump versus on-pump CABG for patients with ICMP are urgently needed. Future research should also be directed toward drugs targeting “B-cell mediated” humeral vascular rejection—the Achilles heel of cardiac transplantation, xenotransplantation, permanently implantable VADs, gene therapy, and myocardial cell regeneration therapy.     

Seminal factor VII and factor VIIa: supporting evidence for the presence of an active tissue factor-dependent coagulation pathway in human semen

Human semen spontaneously coagulates into a semisolid mass and then wholly liquefies in a process that may have some similarity to that of normal blood. This well described phenomenon is referred to as coagulation and liquefaction of semen. Besides other active components of the haemostatic system, semen contains a significant amount of functional tissue factor (TF). However, TF needs factor (F)VII in order to exert it actions. In this study, we assessed human semen for the presence of FVII and FVIIa, and related their levels to conventional fertility parameters. Using a functional, one stage, clotting assay based upon the prolongation of the prothrombin clotting time, using the ACL 300R analyser and an Imubind FVIIa ELISA assay, FVII and FVIIa levels were measured in 97 semen specimens obtained from sub-fertile (sperm counts <20 x 10(6)/mL), normally fertile (sperm counts >or=20 x 10(6) but <60 x 10(6)/mL), fertile sperm donors (sperm counts >or=60 x 10(6)/mL), vasectomized subjects and in a pooled normal semen parameters group (categorization into groups was based on the World Health Organization guidelines on fertility criteria). In addition, conventional semen parameters were analysed on all semen samples. Both FVII and FVIIa were quantifiable in human semen. The mean levels of FVII and FVIIa were 4.4 IU/dL and 12 ng/mL respectively. Despite the observed variations of FVIIa levels in the studied groups they did not meet statistical significance when the groups were tested against each other. However, seminal FVIIa levels showed a significant positive association with semen liquefaction time, sperm motility and semen volume. The anti-sperm antibodies and sperm-agglutination groups were also associated with raised seminal FVIIa levels. We observed no significant relationship between FVIIa levels and total sperm concentration, sperm count per mL (sperm density), sperm progression and days of sexual abstinence. This study demonstrates that human semen contains appreciable amounts of FVII and FVIIa. It is possible to quantify these using commercially available assays. There also appears to be a direct correlation between the levels of these factors and certain seminal parameters. This finding reinforces the concept of an active clotting system in human semen, by establishing the missing link in the activation of a TF-dependent pathway.     

Therapeutic nipple-sparing mastectomy: trends based on a national cancer database

Background

Current reports on nipple-sparing mastectomy (NSM) are limited to single-institution series. We use the National Cancer Institute's Surveillance, Epidemiology, and End Results database to report on the national experience with NSM.

Methods

Population-level deidentified data were extracted from the Surveillance, Epidemiology, and End Results database. All female breast cancer patients treated with NSM from 2005 to 2009 were included. Case analysis was performed with respect to demographic and oncologic characteristics.

Results

Four hundred forty-nine patients underwent therapeutic NSM; this number increased from 66 patients in 2005 to 133 in 2009. Patients were distributed across 16 regions, although nearly 50% were from a region of California. Tumor diameter was <2 cm in 224 patients (50%). Lymph nodes were positive in 59 patients (13%), while radiation was delivered to 74 patients (16%).

Conclusions

NSM use has been increasing over the past several years. A majority of patients have tumor size <2 cm, although the number of patients with tumor size ≥2 cm has increased over time. Further population-based studies of NSM may benefit from collection of oncologic data such as tumor-to-nipple distance and tumor location.     

Subcutaneous hyalohyphomycosis caused by Fusarium in a kidney transplant recipient

Fusarium is a filamentous opportunistic pathogenic fungus responsible for superficial as well as invasive infection in immunocompromized hosts. Net state of immunosuppression and cytomegalovirus (CMV) infection appear to predispose to this disease which is life-threatening when disseminated. Though infections with Fusarium have been widely described in hematological malignancies and hematopoietic stem cell transplant cases, they have been reported to be rare in solid organ transplant recipients, are often localized and carry a favorable prognosis. We here describe a rare case of subcutaneous non-invasive infection with Fusarium in a renal allograft recipient two and half years after transplantation. Patient had a previous history of CMV infection along with multiple other recurrent co-infections. Diagnosis was based on culture of tissue specimens yielding Fusarium species. The infection had a protracted course with persistence of lesions after treatment with voriconazole alone, requiring a combination of complete surgical excision and therapy with the anti-fungal drug.     

Sexual activity and function in women with and without pelvic floor disorders

Introduction and hypothesis

We describe differences in sexual activity and function in women with and without pelvic floor disorders (PFDs).

Methods

Heterosexual women ≥40 years of age who presented to either urogynecology or general gynecology clinics at 11 clinical sites were recruited. Women were asked if they were sexually active with a male partner. Validated questionnaires and Pelvic Organ Prolapse Quantification (POP-Q) examinations assessed urinary incontinence (UI), fecal incontinence (FI), and/or pelvic organ prolapse (POP). Sexual activity and function was measured by the Female Sexual Function Index (FSFI). Student’s t test was used to assess continuous variables; categorical variables were assessed with Fisher’s exact test and logistic regression. Univariate and multivariate analyses were used to assess the impact of pelvic floor disorders (PFDs) on FSFI total and domain scores.

Results

Five hundred and five women met eligibility requirements and gave consent for participation. Women with and without PFDs did not differ in race, body mass index (BMI), comorbid medical conditions, or hormone use. Women with PFDs were slightly older than women without PFDs (55.6?+?10.8 vs. 51.6?+?8.3 years, P <0.001); all analyses were controlled for age. Women with PFDs were as likely to be sexually active as women without PFDs (61.6 vs. 75.5 %, P?=?0.09). There was no difference in total FSFI scores between cohorts (23.2?+?8.5 vs. 24.4?+?9.2, P?=?0.23) or FSFI domain scores (all P?=?NS).

Conclusion

Rates of sexual activity and function are not different between women with and without PFDs.     

Analysis of youtube as a source of information for peripheral neuropathy

Introduction: YouTube is an important resource for patients. No study has evaluated the information on peripheral neuropathy disseminated by YouTube videos. In this study, our aim was to perform a systematic review of information on YouTube regarding peripheral neuropathy. Methods: The Web site ( www.youtube.com ) was searched between September 19 and 21, 2014, for the terms “neuropathy,” “peripheral neuropathy,” “diabetic neuropathy,” “neuropathy causes,” and “neuropathy treatment.” Results: Two hundred videos met the inclusion criteria. Healthcare professionals accounted for almost half of the treatment videos (41 of 92; 44.6%), and most came from chiropractors (18 of 41; 43.9%). Alternative medicine was cited most frequently among the treatment discussions (54 of 145, 37.2%), followed by devices (38 of 145, 26.2%), and pharmacological treatments (23 of 145, 15.9%). Conclusions: Approximately half of the treatment options discussed in the videos were not evidence‐based. Caution should be exercised when YouTube videos are used as a patient resource. Muscle Nerve 53 : 27–31, 2016     

How deceased donor transplantation is impacting a decline in commercial transplantation-the Tamil Nadu experience

India with a population of 1.2 billion has a renal transplantation rate of 3.25 per million population. The major cause of chronic kidney disease is hypertension and diabetes. The crude and age-adjusted incidence rates of end-stage renal disease are estimated to be 151 and 232 per million population, respectively, in India. There was a remarkable lack of knowledge in the public about deceased organ donation until a decade ago. However, the role played by the media and nongovernmental organizations in partnership with the government has emphasized and implemented deceased donor transplantation in certain states in India-to mention particularly, the Tamil Nadu model. In the last 2 years, deceased organ donation has reached 1.3 per million population in Tamil Nadu, thereby effectively eliminating commercial transplantation. There is no religious bar for organ donation. A central transplant coordinator appointed by the government oversees legitimate and transparent allocation of deceased organs both in the public and private facilities as per the transplant waiting list. This model also takes care of the poor sections of society by conducting donation and transplantation through government-run public facilities free of cost. In the last 2 years, deceased donor transplantation has been performed through this network procuring organs such as the heart, heart valves, lung, liver, kidneys, cornea, and skin. The infrastructural lack of immunological surveillance-including donor-specific antibody monitoring, human leukocyte antigen typing, and panel reactive antibody except in a few tertiary care centers-prevents allocation according to the immunological status of the recipient. This private-public partnership promoting deceased donor transplantation has effectively eliminated commercialization in transplantation in the state of Tamil Nadu with a population of 72 million which is a model for other regions of South Asia and developing countries.     

Limb lengthening over plate

Background:

The limb lengthening over plate eliminates the associated risk of infection with limb lengthening over intramedullary nail. We present our experience of limb lengthening in 15 patients with a plate fixed on the proximal segment, followed by corticotomy and application of external fixator.

Materials and Methods:

15 patients (7 females, 8 males) were included in this consecutive series. The average age was 18.1 years (range 8–35 years). Fifteen tibiae and one femur were lengthened in 15 patients. Lengthening was achieved at 1 mm/day followed by distal segment fixation with three or four screws on reaching the target length.

Results:

The preoperative target length was successfully achieved in all patients at a mean of 4.1 cm (range 1.8–6.5 cm). The mean duration of external fixation was 75.3 days (range 33–116 days) with the mean external fixation index at 19.2 days/cm (range 10.0–38.3 days/cm). One patient suffered deep infection up to the plate, three patients had mild procurvatum deformities, and one patient developed mild tendo achilles contracture.

Conclusion:

Lengthening over a plate allows early removal of external fixator and eliminates the risk of creating deep intramedullary infection as with lengthening over nail. Lengthening over plate is also applicable to children with open physis.     

GABAergic Interneurons at Supraspinal and Spinal Levels Differentially Modulate the Antinociceptive Effect of Nitrous Oxide in Fischer Rats

Background: The study hypothesizes that nitrous oxide (N2O) releases opioid peptide in the brain stem, which results in inhibition of [gamma]-aminobutyric acid-mediated (GABAergic) neurons that tonically inhibit the descending noradrenergic inhibitory neurons (DNIN), resulting in activation of DNIN. In the spinal cord, activation of DNIN leads to the release of norepinephrine, which inhibits nociceptive processing through direct activation of [alpha]2 adrenoceptor and indirect activation of GABAergic neurons through [alpha]1 adrenoceptor. Arising from this hypothesis, it follows that GABAergic neurons will modulate the antinociceptive effect of N2O in diametrically opposite directions at supraspinal and spinal levels. The authors have tested this tenet and further examined the effect of midazolam, a GABA-mimetic agent, on N2O-induced antinociceptive effect.

Methods: Adult male Fischer rats were administered muscimol (GABAA receptor agonist) intracerebroventricularly (icv), gabazine (GABAA receptor antagonist) intrathecally (intrathecal), or midazolam intraperitoneally (intraperitoneal). Fifteen minutes later, they were exposed to air or 75% N2O and were subjected to the plantar test after 30 min of gas exposure. In some animals administered with midazolam, gas exposure was continued for 90 min, and the brain and spinal cord were examined immunohistochemically.

Results: The N2O-induced antinociceptive effect, which was attenuated by icv muscimol, intrathecal gabazine, and intraperitoneal midazolam. Midazolam inhibited N2O-induced c-Fos expression (a marker of neuronal activation) in the pontine A7 and spinal cord.     

Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes

BACKGROUND: Myocardial infarction results in the death of cardiomyocytes, which are replaced by scar tissue. Cardiomyocytes cannot regenerate because they are terminally differentiated. Mesenchymal cells are pluripotent cells, which have the potential to differentiate to specialized tissues under appropriate stimuli. The aim of this study was to direct differentiation of the adult mesenchymal stem cells isolated from fatty tissue into cardiomyocytes using 5-azacytidine. METHODS: Adult mesenchymal stem cells were isolated from the fatty tissue of New Zealand White rabbits and cultured in RPMI medium. Second-passaged mesenchymal cells were treated with various concentrations of 5-azacytidine and incubated for different intervals of time. The cells were plated in six-well dishes at 500, 5,000, and 50,000 cells/well. These cells were treated with 1-, 3-, 6-, 9-, and 12-micromol/L concentrations of 5-azacytidine and incubated for 12, 24, 48, and 72 hours. Later, the medium was replaced with fresh medium and incubated in a CO2 incubator. The medium was changed once at 3 to 4 days. At 2 months, the cells were fixed with 0.4% glutaraldehyde for 2 hours and later washed with phosphate-buffered saline. The transformed cells were subjected to immunostaining for the myosin heavy chain, alpha actinin, and troponin-I. RESULTS: After treatment with 5-azacytidine, the adult mesenchymal stem cells were transformed into cardiomyocytes. At 1 week, some cells showed binucleation and extended cytoplasmic processes with adjacent cells. At 2 weeks, 20% to 30% of the cells increased in size and formed a ball-like appearance. At 3 weeks, these cells began to beat spontaneously in culture when observed under phase contrast microscope. Immunostaining of the transformed cells for myosin heavy chain, alpha actinin, and troponin-I was positive. The differentiated cells maintained the phenotype and did not dedifferentiate up to 2 months after treatment with 5-azacytidine. CONCLUSIONS: These observations confirm that adult mesenchymal stem cells isolated from fatty tissue can be chemically transformed into cardiomyocytes. This can potentially be a source of autologous cells for myocardial repair.