Risk stratification in cardiogenic shock: a focus on the available evidence.

Cardiogenic shock is a clinical syndrome which is defined as the presence of primary cardiac disorder that results in hypotension together with signs of organ hypoperfusion in the state of normovolaemia or hypervolaemia. It represents a complex life-threatening condition, characterized by a high mortality rate, that requires urgent diagnostic assessment as well as treatment; therefore, it is of paramount important to advocate for a thorough risk stratification. In fact, the early identification of patients that could benefit the most from more aggressive and invasive approaches could facilitate a more efficient resource allocation. This review attempts to critically analyse the current evidence on prognosis in cardiogenic shock, focusing in particular on clinical, laboratoristic and echocardiographic prognostic parameters. Furthermore, it focuses also on the available prognostic scores, highlighting the strengths and the possible pitfalls. Finally, it provides insights into future direction that could be followed in order to ameliorate risk stratification in this delicate subset of patients.

Embolization of the renal artery before graft nephrectomy: a comparing study to evaluate the possible benefits.

The graft nephrectomy is burdened by immunological and surgical complications. The main surgical complications of graft nephrectomy are hemorrhage, infections, vascular injury and death. The mortality is high, with percentages varying between 1.3 and 38%. Therefore, graft nephrectomy should be recommended only in selected cases. We conducted a retrospective study, comparing the data of 26 patients undergoing an allograft nephrectomy (2009-2013), without embolization of the renal artery (NO EMBO group) with the data of 40 patients undergoing an allograft nephrectomy (2014-2019), with embolization of the renal artery (EMBO group). We included only graft nephrectomies performed at least 6 months after transplantation. The patients included in the study were consecutive because until 2013 we did not perform the embolization of the renal graft artery. Afterwards, from 2014, instead, we routinely carry out embolization to all patients to be subjected to graft nephrectomy. We, therefore, wanted to analyze whether this surgical approach compared to the previous technique can lead to an improvement in morbidity and mortality, reducing the risk of bleeding and operating times. The examination of our data highlights that embolization of renal artery reduces the operating times of the explant, in addition the group subjected to embolization had less changes in hemoglobinemia and less blood loss.

Quantitative shape analysis of chemoresistant colon cancer cells: correlation between morphotype and phenotype.

Morphological, qualitative observations allow pathologists to correlate the shape the cells acquire with the progressive, underlying neoplastic transformation they are experienced. Cell morphology, indeed, roughly scales with malignancy. A quantitative parameter for characterizing complex irregular structures is the Normalized Bending Energy (NBE). NBE provides a global feature for shape characterization correspondent to the amount of energy needed to transform the specific shape under analysis into its lowest energy state. We hypothesized that a chemotherapy resistant cancer cell line would experience a significant change in its shape, and that such a modification might be quantified by means of NBE parameterization. We checked out the usefulness of a mathematical algorithm to distinguish wild and 5-fluorouracil (5-FU)-resistant colon cancer HCT-8 cells (HCT-8FUres). NBE values, as well as cellular and molecular parameters, were recorded in both cell populations. Results demonstrated that acquisition of drug resistance is accompanied by statistically significant morphological changes in cell membrane, as well as in biological parameters. Namely, NBE increased progressively meanwhile cells become more resistant to increasing 5-FU concentrations. These data indicate how tight the relationships between morphology and phenotype is, and they support the idea to follow a cell transition toward a drug-resistant phenotype by means of morphological monitoring.

Two-photon optogenetics.

The use of optogenetics, the technology that combines genetic and optical methods to monitor and control the activity of specific cell populations, is now widely adopted in neuroscience. The development of optogenetic tools, such as natural photosensitive ion channels and pumps or calcium- and voltage-sensitive proteins, has been growing tremendously during the past 10 years, thanks to the improvement of their performances in terms of facilitating light stimulation. To this aim, efficient illumination methods are also needed. The most common way to photostimulate optogenetic tools has been, so far, widefield illumination with visible light. However, the necessity of addressing the complexity of brain architecture has recently imposed switching to the use of two-photon excitation, which provides a better spatial specificity and deeper penetration in scattering tissue. Two-photon excitation is still challenging, due to intrinsic characteristics of optogenetic tools (e.g., the low conductivity of light-sensitive channels), and efficient illumination methods are therefore essential for advancing in this domain. Here, we present a review on the existing two-photon optical approaches for photoactivation of optogenetic tools, and future perspectives for the widespread implementation of these techniques.

Fractal analysis in a systems biology approach to cancer.

Cancer is a highly complex disease due to the disruption of tissue architecture. Thus, tissues, and not individual cells, are the proper level of observation for the study of carcinogenesis. This paradigm shift from a reductionist approach to a systems biology approach is long overdue. Indeed, cell phenotypes are emergent modes arising through collective non-linear interactions among different cellular and microenvironmental components, generally described by "phase space diagrams", where stable states (attractors) are embedded into a landscape model. Within this framework, cell states and cell transitions are generally conceived as mainly specified by gene-regulatory networks. However, the system's dynamics is not reducible to the integrated functioning of the genome-proteome network alone; the epithelia-stroma interacting system must be taken into consideration in order to give a more comprehensive picture. Given that cell shape represents the spatial geometric configuration acquired as a result of the integrated set of cellular and environmental cues, we posit that fractal-shape parameters represent "omics" descriptors of the epithelium-stroma system. Within this framework, function appears to follow form, and not the other way around.

Zebrafish stem cell differentiation stage factors suppress Bcl-xL release and enhance 5-Fu-mediated apoptosis in colon cancer cells.

Stem cell differentiation stage factors (SCDSF), taken from Zebrafish embryos during the stage in which totipotent stem cells are differentiating into pluripotent stem cells, have been shown to inhibit proliferation and induce apoptosis in colon tumors. In order to ascertain if these embryonic factors could synergistically/additively interact with 5-Fluorouracil (5-Fu), whole cell-count, flow-cytometry analysis and apoptotic parameters were recorded in human colon cancer cells (Caco2) treated with Zebrafish stem cell differentiation stage factors (SCDSF 3 µg/ml) in association or not with 5-Fu in the sub-pharmacological therapeutic range (0.01 mg/ml). Cell proliferation was significantly reduced by SCDSF, meanwhile SCDSF+5-Fu leads to an almost complete growth-inhibition. SCDSF produces a significant apoptotic effect, meanwhile the association with 5-FU leads to an enhanced additive apoptotic rate at both 24 and 72 hrs. SCDSF alone and in association with 5-Fu trigger both the extrinsic and the intrinsic apoptotic pathways, activating caspase-8, -3 and -7. SCDSF and 5-Fu alone exerted opposite effects on Bax and Bcl-xL proteins, meanwhile SCDSF+5-Fu induced an almost complete suppression of Bcl-xL release and a dramatic increase in the Bax/Bcl-xL ratio. These data suggest that zebrafish embryo factors could improve chemotherapy efficacy by reducing anti-apoptotic proteins involved in drug-resistance processes.

Embryonic morphogenetic field induces phenotypic reversion in cancer cells. Review article.

Cancer cells introduced into developing embryos can be committed to a complete reversion of their malignant phenotype. It is unlikely that such effects could be ascribed to only few molecular components interacting according to a simple linear-dynamics model, and they claim against the somatic mutation theory of cancer. Some 50 years ago, Needham and Waddington speculated that cancer represents an escape from morphogenetic field like those which guide embryonic development. Indeed, disruption of the morphogenetic field of a tissue can promote the onset as well as the progression of cancer. On the other hand, placing tumor cells into a "normal" morphogenetic field - like that of an embryonic tissue - one can reverse malignant phenotype, "reprogramming" tumor into normal cells. According to the theoretical framework provided by the thermodynamics of dissipative systems, morphogenetic fields could be considered as distinct attractors, to which cell behaviors are converging. Cancer-attractors are likely positioned somewhat close to embryonic-attractors. Indeed, tumors share several morphological and ultra-structural features with embryonic cells. The recovering of an "embryonic-like" cell shape might enable the gene regulatory network to reactivate embryonic programs, and consequently to express antigenic and biochemical embryonic characters. This condition confers to cancer an unusual sensitivity to embryonic regulatory cues. Thus, it is not surprising that cancer cells exposed to specific embryonic morphogenetic fields undergoes significant modifications, eventually leading to a complete phenotypic reversion.

Beyond the oncogene paradigm: understanding complexity in cancerogenesis.

In the past decades, an enormous amount of precious information has been collected about molecular and genetic characteristics of cancer. This knowledge is mainly based on a reductionistic approach, meanwhile cancer is widely recognized to be a 'system biology disease'. The behavior of complex physiological processes cannot be understood simply by knowing how the parts work in isolation. There is not solely a matter how to integrate all available knowledge in such a way that we can still deal with complexity, but we must be aware that a deeply transformation of the currently accepted oncologic paradigm is urgently needed. We have to think in terms of biological networks: understanding of complex functions may in fact be impossible without taking into consideration influences (rules and constraints) outside of the genome. Systems Biology involves connecting experimental unsupervised multivariate data to mathematical and computational approach than can simulate biologic systems for hypothesis testing or that can account for what it is not known from high-throughput data sets. Metabolomics could establish the requested link between genotype and phenotype, providing informations that ensure an integrated understanding of pathogenic mechanisms and metabolic phenotypes and provide a screening tool for new targeted drug.

Euthanasia, assisted suicide and end-of-life care: attitudes of students, residents and attending physicians

BACKGROUND: Attitudes in regard to end-of life issues are evolving in Western societies. We have sought to trace this evolution in the relatively homogeneous cultural setting of Puerto Rico. METHODS: One hundred fifty-two medical students, 62 medical residents and 84 members of three medical faculties were asked whether in terminally ill patients they: 1) would support a request for euthanasia(E); 2) if legalized, would engage in, would oppose or would not be opposed to others engaging physician-assisted suicide(PAS); 3) would consider ethical to prescribe full doses of drugs needed to alleviate pain, even if they knew it would hasten death; 4) would agree to limit certain resources for the terminally ill. Gender and religious affiliation were also requested. RESULTS: Twenty-eight percent of the students, 26of the residents and 31of the faculty supported E. Only 13of the students, 18of the residents and 11of the faculty would engage in PAS. Men were more willing than women to acquiesce to a request for E or PAS. Religious affiliation or its absence did not influence the support or opposition to E and PAS. If it would hasten death, 86of the residents, but only 65of the faculty considered ethical to prescribe the dose of drugs needed to alleviate pain. More than 2/3 of the students, residents and faculty favored the limiting of certain resources for the terminally ill. CONCLUSIONS: In our cultural and medical environment, men are more willing than women to engage in E or PAS. The attitude towards E and PAS is not influenced by religious affiliation. If it hastens death, some still consider unethical to prescribe full doses of drugs needed to alleviate pain in the dying patient.

Polymyositis: rare complication of hepatitis B vaccination. An unusual cause of toxic shock syndrome

Transient weakness of the legs developed in a 17 year-old male high school student three weeks after the initial injection of a hepatitis B vaccine. Seventeen days after the second injection of the vaccine, low-grade fever, a pruritic maculopapular rash appeared and weakness of the legs recurred. This was associated with elevation of the creatinine kinase to 2,406 U/L. The day after admission he became afebrile and in the subsequent four days the rash improved but leg weakness persisted. One-month later, muscle strength had returned; and the creatinine kinase had returned to normal levels. The only case of dermatomyositis associated with hepatitis B vaccination and the findings in the six reported cases of surface antigen-positive hepatitis associated with polyomyositis or dermatomyositis are briefly reviewed. Hepatitis B vaccination should be encouraged, but it is important to be aware that, rarely, dermatomyositis, polymyositis or neurovascular complications may occur. Polymyositis associated with the administration of the hepatitis B vaccine or with hepatitis B virus infection is a rare occurrence. A Medline Search performed from 1960 to January 2002 associating hepatitis B vaccine or hepatitis B virus with myopathy, myositis, polymyositis and dermatomyositis, showed only one case of dermatomyositis related to the hepatitis B vaccine, and six case reports relating polymyositis to hepatitis B virus infection. We present a case where a causal relationship between polymyositis and hepatitis B vaccination appears quite likely

ST. segment elevation: is it a possible infarct?

In patients with acute substernal pain seen at Emergency Departments, ST segment elevations are considered the hallmark of an acute myocardial infarct. Acute substernal pain associated with ST segment elevations is the inclusion criteria for thrombolytic therapy. However, there are other conditions, which may present with ST segment elevation in which thrombolytic therapy is not indicated. Acute pericarditis and ECG variants of normal must also be considered in the differential diagnosis. Three cases are presented that illustrate this ECG presentation. It is of paramount importance, that the Emergency Department physician who does the triage for these patients be able to identify the various causes of ST segment elevation

ST. segment elevation: is it a possible infarct?

In patients with acute substernal pain seen at Emergency Departments, ST segment elevations are considered the hallmark of an acute myocardial infarct. Acute substernal pain associated with ST segment elevations is the inclusion criteria for thrombolytic therapy. However, there are other conditions, which may present with ST segment elevation in which thrombolytic therapy is not indicated. Acute pericarditis and ECG variants of normal must also be considered in the differential diagnosis. Three cases are presented that illustrate this ECG presentation. It is of paramount importance, that the Emergency Department physician who does the triage for these patients be able to identify the various causes of ST segment elevation.

Absence of antihyperglycemic effect of jambolan in experimental and clinical models.

The use of alternative therapies to treat diabetes, including teas prepared with different vegetables, is widespread in Brazil. In Porto Alegre, a southern city of Brazil, the tea prepared from leaves of Syzygium cumini (L.) Skeels or S. jambos (L.) Alst has been report to be used frequently by diabetic patients. We investigated the postulated antihyperglycemic effect of the S. cumini (L.) Skeels in three experiments. In the first, a randomized, parallel, placebo controlled trial, tea prepared from leaves of S. cumini did not present any antihyperglycernic effect in 30 non-diabetic young volunteers submitted to a glucose blood tolerance test. In the animal experiments, we tested the effect of increasing doses of the crude extract prepared from leaves of S. cumini administrated for 2 weeks, on the post-prandial blood glucose level of normal rats and rats with streptozotocin-induced diabetes mellitus. The treatment did not produce any antihyperglycernic effect in both models. These results do not rule out hypoglycemic effects in patients with type 2 diabetes mellitus, but strongly suggest that, for a while, the jambolan can not be recommended as an antihyperglycemic treatment.

Cerebral thrombosis and vasculitis: an uncommon complication of ulcerative colitis.

Cerebral thrombotic disease is a rare and nearly always fatal complication of ulcerative colitis. It is associated with a necrotizing vasculitis. We report a fatal case with a confusing neurologic picture arising from this complication. Autopsy revealed necrosis and hemorrhages affecting both cortical grey and white matter. Microscopic examination showed thrombosis of small and medium size vessels associated with hemorrhages and a necrotizing angiitis. Ulcerations, hemorrhages, pseudopolyps, and cryptic abscesses were found in the rectosigmoid region of the colon compatible with active ulcerative colitis. A sudden neurologic deficit in a patient with ulcerative colitis should direct attention to the consideration of a cerebral thrombotic event and the possibility of an associated cerebral vasculitis. Diagnosis may be strongly suggested by MRI or arteriography, but it may require confirmation by biopsy of the brain parenchyma and leptomeninges. A hypercoagulable state has been associated with the thrombosis. Anticoagulation has yielded successful results in some patients with cerebral thrombosis but the risk of massive intracranial and gastrointestinal bleeding preclude to establish clear indications. Neurologic improvement has been obtained with the use of steroids and cyclophosphamide.

Cerebral thrombosis and vasculitis: an uncommon complication of ulcerative colitis

Cerebral thrombotic disease is a rare and nearly always fatal complication of ulcerative colitis. It is associated with a necrotizing vasculitis. We report a fatal case with a confusing neurologic picture arising from this complication. Autopsy revealed necrosis and hemorrhages affecting both cortical grey and white matter. Microscopic examination showed thrombosis of small and medium size vessels associated with hemorrhages and a necrotizing angiitis. Ulcerations, hemorrhages, pseudopolyps, and cryptic abscesses were found in the rectosigmoid region of the colon compatible with active ulcerative colitis. A sudden neurologic deficit in a patient with ulcerative colitis should direct attention to the consideration of a cerebral thrombotic event and the possibility of an associated cerebral vasculitis. Diagnosis may be strongly suggested by MRI or arteriography, but it may require confirmation by biopsy of the brain parenchyma and leptomeninges. A hypercoagulable state has been associated with the thrombosis. Anticoagulation has yielded successful results in some patients with cerebral thrombosis but the risk of massive intracranial and gastrointestinal bleeding preclude to establish clear indications. Neurologic improvement has been obtained with the use of steroids and cyclophosphamide

Clostridial sepsis: is death avoidable?

Massive intravascular hemolysis is a rare yet often fatal complication of clostridial sepsis. The only chance for survival is an early diagnosis and prompt initiation of treatment. We report a rapidly fatal case who developed electrocardiographic changes of acute myocardial injury. Autopsy showed gas-filled bubbles and cysts in the myocardium partially filled with sporulating bacilli with the morphology of clostridia. Gas filled bubbles were also present in the lungs, liver, kidneys and spleen. The gastric mucosa showed hemorrhagic and necrotizing changes, the probable site of entry of the infection

Prevalence of hepatitis C virus infection at three hemodialysis units in the western region of Puerto Rico

OBJECTIVE: In the United States hepatitis C virus infection (HCV) affects approximately 20 percent of hemodialysis patients but its prevalence in Puerto Rico has not been established. We have sought to determine the prevalence of HCV infection in a homogeneous sample of patients on hemodialysis in the western region of Puerto Rico and to identify its risks factors. METHODS: All patients in the hemodialysis units of Aguadilla, Mayagüez and San Germán, during December 1997 to March 1998, completed a written questionnaire in which they were asked about transfusions, multiple sexual partners, i.v. drugs use, tattooing, occupation, imprisonment, organ transplantation and years on hemodialysis. Serum samples were analysed for HCV antibodies by an enzyme-linked immunoadsorbent assay (ELISA). Sera with positive results for HCV were subjected to a confirmatory test by the polymerase chain reaction (PCR). RESULTS: Thirteen of the 376 (3) subjects had a positive ELISA (one patient died prior the confirmatory test with PCR). Six out of the twelve patients had a positive PCR. Two had been transfused. Three were illicit i.v. drug users and one had received a renal transplant. The liver biopsies in all patients showed chronic hepatitis and in two there was cirrhosis. CONCLUSIONS: Our prevalence was two percent. As reported elsewhere blood transfusion, organ transplantation and illicit i.v. drug abuse were the major risk factors for HCV infection in our patients. Nosocomial factors were irrelevant in the results

Clostridial sepsis: is death avoidable?

Massive intravascular hemolysis is a rare yet often fatal complication of clostridial sepsis. The only chance for survival is an early diagnosis and prompt initiation of treatment. We report a rapidly fatal case who developed electrocardiographic changes of acute myocardial injury. Autopsy showed gas-filled bubbles and cysts in the myocardium partially filled with sporulating bacilli with the morphology of clostridia. Gas filled bubbles were also present in the lungs, liver, kidneys and spleen. The gastric mucosa showed hemorrhagic and necrotizing changes, the probable site of entry of the infection.

Prevalence of hepatitis C virus infection at three hemodialysis units in the western region of Puerto Rico.

OBJECTIVE: In the United States hepatitis C virus infection (HCV) affects approximately 20 percent of hemodialysis patients but its prevalence in Puerto Rico has not been established. We have sought to determine the prevalence of HCV infection in a homogeneous sample of patients on hemodialysis in the western region of Puerto Rico and to identify its risks factors. METHODS: All patients in the hemodialysis units of Aguadilla, Mayagüez and San Germán, during December 1997 to March 1998, completed a written questionnaire in which they were asked about transfusions, multiple sexual partners, i.v. drugs use, tattooing, occupation, imprisonment, organ transplantation and years on hemodialysis. Serum samples were analysed for HCV antibodies by an enzyme-linked immunoadsorbent assay (ELISA). Sera with positive results for HCV were subjected to a confirmatory test by the polymerase chain reaction (PCR). RESULTS: Thirteen of the 376 (3%) subjects had a positive ELISA (one patient died prior the confirmatory test with PCR). Six out of the twelve patients had a positive PCR. Two had been transfused. Three were illicit i.v. drug users and one had received a renal transplant. The liver biopsies in all patients showed chronic hepatitis and in two there was cirrhosis. CONCLUSIONS: Our prevalence was two percent. As reported elsewhere blood transfusion, organ transplantation and illicit i.v. drug abuse were the major risk factors for HCV infection in our patients. Nosocomial factors were irrelevant in the results.

Cardiopulmonary resuscitation personal choices of physicians and nurses.

Nine hundred and twenty-two attending physicians, residents and graduate nurses in five hospitals were requested to state their personal preference to receive either cardiopulmonary resuscitation (CPR) or intubation and mechanical ventilation (MV) when given three estimated outcomes: 1) complete recovery, 2) important loss in mental and physical functions, c) persistent unconsciousness. They also could choose not to accept either procedure. Seventy three percent would accept CPR and 70 percent MV, only if complete recovery was likely. Thirteen percent would accept CPR and MV if important losses of function were likely. Eight percent would accept CPR and 5 percent would accept MV if recovery of consciousness was unlikely. Six percent would not accept CPR and eleven percent would not accept MV under any circumstance. Men and women differed in the choice of outcomes which made resuscitation acceptable to them (p < .001). More women than men would accept CPR and MV if complete recovery was likely and were unwilling to accept CPR or MV under any circumstance at all. Half as many women as men would accept MV if they were likely to remain unconscious. Choices also varied with age and professional training. There are large individual differences as to how physicians and nurses would like their personal cardiopulmonary arrest to be managed. Their choice is appropriately influenced by the expected outcome and seems to be influenced by the local hospital setting.