Secondary amputation after lower extremity free-flap reconstruction.

BACKGROUND: Microsurgical free-tissue transfer is often the definitive reconstructive option for lower extremity limb salvage. Despite an initial successful free-flap reconstruction, some patients ultimately undergo lower extremity amputation. The indications for secondary amputation include non- or malunion, infection, hardware failure, or chronic pain. This study aimed to identify the etiology and outcome of secondary amputation after lower extremity free-flap reconstruction. METHODS: A retrospective cohort study was performed including patients who underwent lower extremity free-flap reconstruction from January 2002 to December 2020. Patients who underwent secondary amputation were identified. A survey based on the PROMIS® Pain Interference Scale and activities of daily living (ADLs) was then conducted to assess patient-reported outcomes. Fifteen (52%) patients who underwent amputation responded to the survey, with a median follow-up time of 4.4 years. RESULTS: Of 410 patients who underwent lower extremity free-flap reconstruction, 40 (9.8%) patients underwent subsequent amputation. Of these, 10 patients had failed free-flap reconstruction and 30 patients had secondary amputation after an initially successful soft tissue coverage. The most common etiology for secondary amputation was infection (68%, n = 27). Eighty percent (n = 12) of survey respondents were able to use a prosthetic limb and ambulate. CONCLUSIONS: The most common etiology of secondary amputation was infection. Most patients who ultimately underwent amputation were able to ambulate with a prosthetic, but the majority of patients reported chronic pain. This study could be used to guide potential free-flap candidates regarding the risks and outcomes of lower extremity free-flap reconstruction.

[Mouse models of diabetic retinopathy: systematic review of the literature]. / Revue systématique de la littérature des modèles murins de rétinopathie diabétique.

INTRODUCTION: Diabetic retinopathy (DR) is a leading cause of vision loss worldwide. A variety of species of animals have been used to investigate the pathogenesis of DR. However, the mouse model of diabetic retinopathy, which is an attractive model due to the genetic modifications which can be carried out, remains underutilized. In order to explain this discrepancy, we performed a review of the literature concerning various mouse models of diabetic retinopathy so as to define their advantages and disadvantages. MATERIAL AND METHODS: We carried out a literature review using PubMed. We selected articles describing models of DR with pericyte loss, retinal capillary abnormalities and hyperglycemia. Articles not meeting these three criteria were excluded. RESULTS: Out of 25 articles, we found seven models of DR. For each of these models, we report the method of induction of DR and the electrophysiological and histopathological features. CONCLUSION: Models obtained through genetic manipulation appear the most interesting, since the diabetes and its complications present early without additional physiologic modifications. However, since these models differ frequently by sex, this is an important parameter that must be taken into account.

Comparison of risk-adjustment models using administrative or clinical data for outcome prediction in patients after myocardial infarction or coronary bypass surgery in Korea.

OBJECTIVE: The objectives of this study were to compare the performance indicators of risk-adjustment models based on administrative and clinical data in Korea, and to assess whether administrative data alone is useful for comparing quality of care. METHODS: Outcome was defined as death within 30 days of discharge. For administrative data, the risk factors were; age, sex, and 11 past histories and two past major procedures, which were retrospectively chased in National Health Insurance database using patient Identification Number. For clinical data, the severity score of the three risk-adjustment measures [MedisGroups, Disease Staging (DS) and Computerized Severity Index (CSI)] was used as the independent predictors of 30-day mortality. Risk-adjustment models were developed by logistic regression analysis for 13,885 Acute Myocardial Infarction (AMI) and 2115 Coronary Artery Bypass Graft (CABG) patients based on administrative data and for 208 AMI patients and 478 CABG patients using clinical data. Performances of models were examined using c-statistic and Hosmer-Lemeshow statistic. RESULTS: The results obtained showed the superiority of the clinical model. For AMI, the c-statistic of the administrative model was 0.696, and those of the CSI, DS and MedisGroups models were 0.772, 0.861 and 0.988 respectively. For CABG, the c-statistic of the administrative model was 0.568, and those of the CSI, DS and MedisGroups models were 0.665, 0.731 and 0.816 respectively. CONCLUSION: Our results indicate that risk-adjustment model only using administrative data are probably not useful for assessing quality of care in Korea.

Vaccination of seronegative volunteers with a human immunodeficiency virus type 1 env/rev DNA vaccine induces antigen-specific proliferation and lymphocyte production of beta-chemokines.

There is a pressing need to test novel vaccine concepts in an effort to develop an effective vaccine for human immunodeficiency virus (HIV) type 1. A phase I clinical study was done to test the immunogenicity of an HIV env/rev DNA vaccine, which was administered intramuscularly to HIV-1-seronegative persons. Subjects received 3 doses of vaccine at a single concentration (100 or 300 microgram) at 0, 4, 8, and 24 weeks. In at least 1 of multiple assays, the 6 subjects who received the 300-microgram dose had DNA vaccine-induced antigen-specific lymphocyte proliferative responses and antigen-specific production of both interferon-gamma and beta-chemokine. Furthermore, 4 of 5 subjects in the 300 microgram-dose group responded to both the rev and env components of the vaccine. The responses did not persist within inoculated individuals and scored in different individuals at different times in the trial. This study supports that HIV-1 DNA vaccine antigens can stimulate multiple immune responses in vaccine-naive individuals, and it warrants additional studies designed to enhance DNA vaccine immunogenicity.

HIV-1 DNA vaccines and chemokines.

DNA vaccines have a demonstrated ability to induce humoral and cellular immune responses in animal models and humans. The technology, although it dates back to the 1950's, has had an insurgence of interest within the past few years following concurrent research papers. The basic technology is being applied broadly to viral, bacterial and parasitic infections. It has also been demonstrated that genes delivered via plasmid expression vectors result in expression of functional proteins in the inoculated host. Further, injection of plasmids encoding cytokine, chemokine or co-stimulatory molecules, also referred to as immunomodulatory plasmids can lead to the further expansion of this technology to include directed immunology. We have been developing DNA technology specifically with a focus as a vaccine against HIV-1 infection. We report that such vaccines can stimulate immune responses in a variety of relevant animal systems including humoral and cellular responses as well as the production of beta-chemokines. We describe that the beta-chemokines can both modulate the immune response induced by DNA vaccines and be modulated by the DNA vaccines in the murine and chimpanzee models as well as in humans.

Age-specific decrease in seroprevalence of schistosomiasis in Puerto Rico.

In our previous work, we reported the first systematic, island-wide, serologic survey for schistosomiasis in Puerto Rico in 40 years. In that study, approximately 3,000 serum samples from the 76 municipalities comprising the island of Puerto Rico were tested for the detection of antibodies to S. mansoni microsomal antigens by the Falcon assay screening test-enzyme-linked immunosorbent assay (FAST-ELISA) and those positive were confirmed by an enzyme-linked immunoelectrotransfer blot (EITB). The highest EITB positivity was found in 17 municipalities, which comprised 48% of all seropositive samples. An additional finding was that 10% of the 215 EITB-positive samples were from individuals 25 years or younger and were for the most part of residents from the high seroprevalence areas. Thus, for this study we focused on 766 individuals 25 years of age or younger (45.5% males and 54.4% females), two-thirds of which were from 10 municipalities with the highest EITB seropositivity, and one-third from the 10 municipalities with the lowest EITB seropositivity found in our previous study. Of all samples, the results showed an overall FAST-ELISA positivity of 11.6%, with males similar to females (12.6 versus 10.7%, respectively). Confirmation by EITB was only 1.8%, with a males three-fold higher than females (3% versus 0.7%). When seropositivity was measured by age in five-year increments, a clear age-specific decrease in seropositivity was observed. Thus, by FAST-ELISA, 16.7% of the 21-25-year-old age group was positive, decreasing to 14.6%, 9.9%, 7.9%, and 9.3% in the 16-20-, 11-15-, 6-10-, and 1-5-year-old age groups, respectively. Confirmatory EITB showed even more impressive results: 4.7%, 2.6%, 1.2%, 0.7%, and 0% in the same age brackets. With regard to the high prevalence municipalities, only four of 10 (11 of 228 = 4.8%) had confirmatory EITB-positive samples and most were from municipalities of the Rio Grande de Loiza River basin and tributaries. The male to female positivity ratio was 4:1. Of the low prevalence municipalities, only single positive cases (by EITB) were found in three disperse municipalities. These results support the concept that there has been little transmission of S. mansoni in Puerto Rico during the first half of the 1990s and confirms anecdotal comments of local physicians who have seen virtually no new infections during the past three years. This makes the documentation of eradication of schistosomiasis from Puerto Rico feasible, a goal that should be set as being before the 100th anniversary of its discovery on the island by Isaac Gonzalez-Martinez in 1904.

Neurocysticercosis in persons with epilepsy in Medellín, Colombia. The Neuroepidemiological Research Group of Antioquia.

PURPOSE: A prospective series of 643 persons with epilepsy attending a reference neurologic center in Medellín, Colombia, was examined by computed tomography (CT scan) or serology or both with the enzyme-linked immunoelectrotransfer blot assay (EITB) to assess the prevalence of Taenia solium cysticercosis. METHODS: All presenting patients were consecutively enrolled in the study. Five hundred forty-six persons underwent cerebral CT scans; 376 of them also had serum EITB performed. RESULTS: Prevalence of neurocysticercosis by CT scan was 13.92%. Overall prevalence of T. solium antibodies with EITB was 9.82%, but for those with late-onset epilepsy (onset after age 30 years), prevalence increased to 17.5% and 19% for those who originated from outside urban Medellín. Seroprevalence in individuals with mixed lesions (cysts and calcifications) was 88.2% and 64.10% in those with live cysts. Conversely, only 2.72% of persons with CT findings not related to neurocysticercosis had positive EITB tests. CONCLUSIONS: Our study shows that an important proportion of individuals with epilepsy have radiologic or serologic evidence of T. solium infection, suggesting that neurocysticercosis is an important etiology for epilepsy in Colombia.

Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens.

Immunization with nucleic acids has been shown to induce both antigen-specific cellular and humoral immune responses in vivo. We hypothesize that immunization with DNA could be enhanced by directing specific immune responses induced by the vaccine based on the differential correlates of protection known for a particular pathogen. Recently we and others reported that specific immune responses generated by DNA vaccine could be modulated by co-delivery of gene expression cassettes encoding for IL-12, granulocyte-macrophage colony-stimulating factor and the co-stimulatory molecule CD86. To further engineer the immune response in vivo, we investigated the induction and regulation of immune responses following the co-delivery of pro-inflammatory cytokine (IL-1 alpha, TNF-alpha, and TNF-beta), Th1 cytokine (IL-2, IL-12, IL-15, and IL-18), and Th2 cytokine (IL-4, IL-5 and IL-10) genes. We observed enhancement of antigen-specific humoral response with the co-delivery of Th2 cytokine genes IL-4, IL-5, and IL-10 as well as those of IL-2 and IL-18. A dramatic increase in antigen-specific T helper cell proliferation was seen with IL-2 and TNF-alpha gene co-injections. In addition, we observed a significant enhancement of the cytotoxic response with the co-administration of TNF-alpha and IL-15 genes with HIV-1 DNA immunogens. These increases in CTL response were both MHC class I restricted and CD8+ T cell dependent. Together with earlier reports on the utility of co-immunizing using immunologically important molecules together with DNA immunogens, we demonstrate the potential of this strategy as an important tool for the development of more rationally designed vaccines.

Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine.

Nucleic acid immunization has been investigated as immunotherapy for infectious diseases as well as for treating specific types of cancers. In this approach, nucleic acid expression cassettes are directly inoculated into the host, whose transfected cells become the production source of novel and possibly immunologically foreign protein. We have developed a DNA vaccine construct which encodes for PSA by cloning a cDNA for PSA into a mammalian expression vector under control of a CMV promoter. We investigated and characterized the immunogenicity of PSA DNA expression cassettes in mice. PSA-specific immune responses induced in vivo by immunization were characterized by enzyme-linked immunosorbent assay (ELISA), T helper proliferation cytotoxic T lymphocyte (CTL), and flow cytometry assays. We observed a strong and persistent antibody response against PSA for at least 180 days following immunization. In addition, a significant T helper cell proliferation was observed against PSA protein. Using synthetic peptides spanning the PSA open frame, we identified four dominant T helper epitopes of PSA. Furthermore, immunization with PSA plasmid induced MHC Class I CD8+ T cell-restricted cytotoxic T lymphocyte response against tumor cell targets expressing PSA. The prostate represents a very specific functional organ critical for reproduction but not for the health and survival of the individual. Understanding the immunogenicity of PSA DNA immunization cassettes offers insight into the possible use of this tumor-associated antigen as a target for immunotherapy. These results demonstrate the ability of the genetic PSA to serve as a specific immune target capable of generating both humoral and cellular immune responses in vivo.

Geographic clustering and seroprevalence of schistosomiasis in Puerto Rico (1995).

A systematic, island-wide survey for schistosomiasis in Puerto Rico has not been conducted for more than 40 years. In 1974, a thorough survey of Boqueron de Las Piedras, a small community, showed a prevalence of 40%. No additional information on prevalence in Puerto Rico has been obtained during the ensuing 21 years. Concern for the public health of residents and visitors prompted the formation of the Bilharzia Commission in 1994 and the systematic serosurvey reported herein. Two thousand nine hundred fifty-five plasma samples from healthy donors were obtained randomly from the Red Cross in March and April 1995. Sex, resident municipalities, and age of the donors were recorded. The donors were from all but three of 79 municipalities in Puerto Rico. No sample was available from the three out island municipalities of Mona, Vieques, and Culebra. Male donors (n = 2,027) outnumbered females (n = 928) by more than 2:1, ages ranged from nine to 76 years with most (85.3%) between 19 and 51 years of age. All samples were tested with the Falcon assay screening test:enzyme-linked immunosorbent assay (FAST:ELISA) with microsomal antigens of Schistosoma mansoni. All FAST:ELISA+ samples were confirmed by enzyme-linked immunoelectrotransfer blot (EITB). Our data showed that 15.4% were FAST:ELISA+, and 10.6% were confirmed by EITB; 13.5% of the males and 4.1% of the females were EITB+. If we exclude those municipalities with fewer than five samples, the prevalence of EITB+ ranged from 0% to 38.5%, with the highest seroprevalence rates (21.1-38.5%) concentrated in 17 municipalities, which accounted for 48% of all seropositive samples. These 17 municipalities, however, contain only 18% of the total population of Puerto Rico. Two areas of high seroprevalence rates center around Jayuya (38.5%) and Naguabo (36.4%). The previously surveyed area of Boqueron is located in Las Piedras (35.3%), adjacent to Naguabo. In addition, we found 10% (21) of our total 215 donors less than 25 years of age to be EITB+ and all but two are residents of the high prevalence districts. These data strongly support the contention that schistosomiasis has been transmitted in a focal fashion during the past approximately 20 years.

[Prevalence of neurocysticercosis in individuals affected by epilepsy]. / Prevalencia de neurocisticercosis en individuos afectados de epilepsia.

INTRODUCTION: In this investigations, was carried out a neurocysticercosis (NC) prevalence study during seven months in the Instituto Neurológico de Antioquia with the purpose of known neurocysticercosis frequency as cause of epilepsy in patients older than ten years that we attended in our institute. MATERIAL AND METHODS: Computerized tomographies (CT) were made to 503 patients, with epilepsy, 24.7% of them were CT positive for NC. Cysticercosis enzyme linked immunoelectrotransfer blot (EITB) and enzyme linked immunoabsorbent assay (ELISA) test were made to 178 patients, 19.6% were EITB positive for NC and 5% ELISA positive for NC. Results. From this result it is possible to infer that about 8% of the 503 patients with epilepsy had cysticercosis, according to EITB that is the golden assay for NC. The CT and ELISA test had 94.3% and 27.7% sensitivity, respectively, according to EITB. The specificity of the CT for NC was 49.2% and specificity for ELISA test was 100% as compared to EITB. The multivariate analysis with logistic regression allowed to establish association of positive EITB with factors such as male sex, eating pork, headaches and multiple lesions in CT. CONCLUSIONS: Prevention and education actions are necessary for the interruption of the neurocysticercosis transmission chain in order to diminish the high prevalence of epilepsy in the country and its complication and consequences.

Biomechanical performance of laser-drilled and channel taper point needles.

The purpose of this study is to evaluate the biomechanical performance of laser-drilled and channel needle swages. The laser-drilled swages have a more uniform circumference that encounters lower drag forces than the channel needle swages. In addition, the length of the laser-drilled hole is shorter than that of the channel needles, allowing the physician to grasp the laser-drilled needle close (3 mm) to the needle end without deformation. These benefits of laser-drilled swages indicate that they should replace all channel needles.

Scavenging high-voltage copper wire, a hazardous petty larceny.

With the current emphasis on recycling and the establishment of markets for sale of used copper wire, scavenging of copper wire from old buildings and equipment has become common. Although scavenging without permission constitutes theft, a more significant risk to the perpetrator is the potential for electrical burn injury in attempting to remove "hot" wire. A severe high-voltage electrical burn injury sustained while attempting to scavenge wire from an old house is reported. The circumstances surrounding the injury, the clinical management of the case, and the long-term consequences to the patient are presented and discussed.