Pulmonary hypertension and valvular heart disease.

Pulmonary hypertension (PH) is an important contributor to morbidity and mortality in patients with left-sided heart disease, including valvular heart disease. In this context, elevated left atrial pressure primarily leads to the development of post-capillary PH. Despite the fact that repair of left-sided valvular heart disease by surgical or interventional approaches will improve PH, recent studies have highlighted that PH (pre- or post-interventional) remains an important predictor of long-term outcome. Here, we review the current knowledge on PH in valvular heart disease taking into account new hemodynamic PH definitions, and the distinction between post- and pre-capillary components of PH. A specific focus is on the precise characterization of hemodynamics and cardiopulmonary interaction, and on potential strategies for the management of residual PH after mitral or aortic valve interventions. In addition, we highlight the clinical significance of tricuspid regurgitation, which may occur as a primary condition or as a consequence of PH and right heart dilatation (functional). In this context, proper patient selection for potential tricuspid valve interventions is crucial. Finally, the article highlights gaps in evidence, and points toward future perspectives.

[Exercise Testing in Respiratory Medicine - DGP Recommendations]. / Belastungsuntersuchungen in der Pneumologie ­ Empfehlungen der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V.

This document replaces the DGP recommendations published in 1998 and 2013. Based on recent studies and a consensus conference, the indications, choice and performance of the adequate exercise testing method and its necessary technical and staffing setting are discussed. Detailed recommendations are provided: for blood gas analysis and right heart catheterization during exercise, walk tests, spiroergometry, and stress echocardiography. The correct use of different exercise tests is discussed for specific situations in respiratory medicine: exercise induced asthma, obesity, monitoring of rehabilitation or therapeutical interventions, preoperative risk stratification, and evaluation in occupational medicine.

[Clinical classification and initial diagnosis of pulmonary hypertension: recommendations of the Cologne Consensus Conference 2016]. / Klinische Klassifikation der pulmonalen Hypertonie und initiale Diagnostik: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the clinical classification and diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the clinical classification and initial diagnosis of PH. This article summarizes the results and recommendations of this working group.

Characterization and Detection of ϵ-Berge-Zhukovskii Equilibria.

The Berge-Zhukovskii equilibrium is an alternate solution concept in non-cooperative game theory that formalizes cooperation in a noncooperative setting. In this paper, the ϵ-Berge-Zhukovskii equilibrium is introduced and characterized by using a generative relation. The generative relation also provides a solution to the problem of computing the ϵ-Berge-Zhukovskii equilibrium for large games, by using evolutionary algorithms. Numerical examples illustrate the approach and provide a possible application for this equilibrium concept.

Oesophageal stenosis dilatation through retrograde trans-gastrostomal approach in a patient with systemic scleroderma.

AIM: The paper presents the surgical solving of an oesophageal stenosis, using a device of pneumatic dilatation with trans-gastrostomal approach, in a patient with multiple disabling handicaps, secondary severe malnutrition and previously diagnosed with scleroderma. MATERIALS AND METHOD: The patient was admitted with severe cachexia (37 kg, 170 cm), characteristic byzantine face with microstomy, distal phalanges resorption in both superior limbs and complete dysphagia, with limitation of mouth opening.The Barium swallow test revealed distal oesophageal stenosis,with an important dilation of the oesophagus above. RESULTS: A gastrostoma was placed to allow nutrition (Gavriliu procedure), under general anaesthesia with trans-tracheostomal intubation. After 3 years, with her metabolic status improved(59 kg), the patient returned to our clinic asking for a solution for natural feeding. The technical difficulties in solving this case were determined by the limited mouth opening, which made anterograde oro-oesophageal balloon dilatation or bougienage impossible, as well as oro-tracheal intubation.Making use of the presence of the gastrostomal orifice,knowing von Hacker's mechanical dilation procedure and using the metallic Key Med kit with balls offered the possibility of the tactics and strategy of guiding a metallic guidewire introduced via the gastrostoma, then trans-stenotic and pulled out through the oral orifice. A modified Foley catheter (personal procedure) was attached to the initial catheter. The trans-stenotic retrograde traction of the Foley balloon was the pneumatic dilator factor that later allowed easy dilatation with the metallic dilator of the Key Med, to the maximum size. The follow-up showed good results, the patient returned to natural nutrition. CONCLUSIONS: The device of oesophageal pneumatic dilatation allows, using the presented surgical technique, a gentle plasty done under radiological supervision and lowers the frequency of accidents. The dilation permits the following use of Key Med kit. The novelty consists in adapting a well-known technique to a new patented device of pneumatic dilation with bidirectional approach under radiological control, for solving this atypical case.

A strategic interaction model of punishment favoring contagion of honest behavior.

The punishment effect on social behavior is analyzed within the strategic interaction framework of Cellular Automata and computational Evolutionary Game Theory. A new game, called Social Honesty (SH), is proposed. The SH game is analyzed in spatial configurations. Probabilistic punishment is used as a dishonesty deterrence mechanism. In order to capture the intrinsic uncertainty of social environments, payoffs are described as random variables. New dynamics, with a new relation between punishment probability and punishment severity, are revealed. Punishment probability proves to be more important than punishment severity in guiding convergence towards honesty as predominant behavior. This result is confirmed by empirical evidence and reported experiments. Critical values and transition intervals for punishment probability and severity are identified and analyzed. Clusters of honest or dishonest players emerge spontaneously from the very first rounds of interaction and are determinant for the future dynamics and outcomes.

Post-surgery morbidity and mortality in colorectal cancer in elderly subjects.

AIM: Surgical procedures with curative or palliative intention in colo-rectal neoplasm in subjects aged over 80 represent a surgical challenge due to the issue they raise: benefits versus increased morbidity. In Romania, according to demographic predictions, the population over the age of 65 will double in the next half century. This, correlated with the increased incidence of colo-rectal cancer in subjects pertaining to the 60- 69 age period and higher, determined us to identify the factors that can influence the occurrence of complications and post-surgery deaths in subjects over 80 years of age that were operated on for colo-rectal cancer. METHODS: This paper includes a retrospective analysis of patients aged over 80, diagnosed and treated for colo-rectal cancer in the 4th Surgery Department of the University Emergency Hospital in Bucharest, in the period 2000 - 2011, following the type of surgery, morbidity and postoperative mortality. Out of a total of 297 cases of patients operated on for colo-rectal cancer, 36 were identified with the age over 80, age average being 83 years (80-91). RESULTS: Out of the total 36 patients aged over 80 years, 22 were subject to surgical procedures with curative intention (in 16 of these subjects a right hemicolectomy was performed and in 6 a left hemicolectomy), the remaining 14 subjects receiving palliative surgical treatment. The factors that negatively influenced post-surgery evolution were diabetes, pre-existing cardiac pathology, evolutionary stage of cancer and the urgency character. In the group with resections, we found a 27.2% (6 cases) morbidity rate and a 18.2% (4 cases) mortality rate. In patients undergoing palliative surgery, the morbidity rate was 28.5% (4 cases) with a mortality rate of 14.3% (2 cases). CONCLUSIONS: Between the 2 groups of patients postoperative morbidity and mortality appeared to be equal. Most often, they were caused by pre-existing cardio-pulmonary pathology and by the urgency character of the surgery, that did not allow a proper rebalancing, and in a lesser extent by the type of surgery. During those 12 years, the percentage of patients aged over 80 years diagnosed annually with colorectal cancer remained constant. Despite advanced age and associated comorbidities, we consider the postoperative evolution to be satisfactory, although postoperative morbidity and mortality were higher than in the general population, according to the literature. Preoperative compensation of associated comorbidities, a surgical procedure performed by experienced teams, together with the ensuring of adequate intensive therapies are required to reduce postoperative risks.

[Clinical case--voluminous diaphragmatic hernia--surgically acute abdomen: diagnostic and therapeutical challenges]. / Caz clinic--hernie diafragmatica voluminoasa--abdomen acut chirurgical: dificultati diagnostice si terapeutice.

We present the case of a 58-year old male patient admitted in the surgery section of the University Emergency Hospital of Bucharest and diagnosed with acute abdomen. The minimal clinical-paraclinical investigation (i.e., thorax-pulmonary Xray, biological probes) raises questions as to the differentiated diagnosis and other associated diseases, also suggesting the existence of voluminous diaphragmatic hernia. The CT thorax-abdomen examination confirms the diaphragmatic hernia suspicion, with intra-thorax ascent of the colon up to the anterior C4 level, but does not explain the abdominal suffering; thus we suspected a biliary ileus or acute appendicitis. Medial laparotomy was imperative. Intrasurgically peritonitis was noticed located by gangrenous acute apendicitis, perforated, with coprolite, for which apendictomy and lavage-drainage pf the peritoneal cavity was performed. Post-surgical status: favourable to recovery.

[70-year-old woman with cardiac hypertrophy and severe pulmonary hypertension: pre- or postcapillary?]. / 70-jährige Patientin mit Myokardhypertrophie und schwerer pulmonaler Hypertonie: Prä- oder postkapillär?

HISTORY AND ADMISSION FINDINGS: A 70-year-old female patient was admitted with progressive dyspnea and peripheral edema. The patient had a medical history of myocardial hypertrophy, diastolic dysfunction and concomitant pulmonary hypertension (PH). INVESTIGATIONS: The physical exam was suggestive of cardiac decompensation. Echocardiography showed myocardial hypertrophy, an enlarged left atrium as well as enlarged right-sided heart chambers. A prominent tricuspid regurgitation jet was present, and the estimated systolic right ventricular pressure was 65 mmHg. Invasive hemodynamic measurements showed a marked pressure elevation in the pulmonary circulation (mean PAP 51 mmHg), combined with an elevated left ventricular end-diastolic pressure (LVEDP) of 30 mmHg and a profound increase in the transpulmonary gradient (TPG, 21 mmHg). TREATMENT AND COURSE: The synopsis of these findings led to the diagnosis of postcapillary PH with a prominent precapillary involvement and cardiac decompensation. Due to signs of volume overload, an adequate diuretic therapy was initiated. The patient was recompensated and lost 7 kg of weight, which was associated with substantial clinical improvement. At invasive follow-up hemodynamic measurement, the patient's PAP was substantially decreased and almost reached normal values. The previously diagnosed precapillary involvement had disappeared. CONCLUSION: PH is a frequent phenomenon in patients with systolic and diastolic heart failure, and might initially appear as a combination of pre- and postcapillary involvement. The patients' volume status has a major influence on pulmonary hemodynamics. An adequate therapy of the underlying heart failure, especially an adequate diuresis, may have marked beneficial effects on pulmonary hemodynamics. Hemodynamic measurements should always be performed in compensated status.

[Clinical and morphological features in a case of recent gastric carcinoma (the signet ring cell carcinoma type)]. / Particularitati clinico-morfologice într-un caz de carcinom gastric incipient (tipul de carcinom în inel cu pecete).

The article presents the case of a male patient, hospitalized due to severe pain in the upper abdomen area, nausea, and vomiting. The patient was diagnosed with surgical acute abdomen, for which emergency surgery is performed. Upon penetration into the peritoneal cavity, stomach inspection shows at the medio-gastric level, on the greater curvature, a callous gastric ulcer, with a central perforation. A large excision is decided up to the healthy (normal) gastric tissue, and the resulting pieces are sent to the pathological anatomy laboratory. The histopathological exam reveals signet ring cell recent gastric carcinoma. The biopsy performed 1 month after surgery, prelevated from the antropyloric zone, reveals antropyloric gastritis with moderate activity and Helicobacter pylori positive. Due to the fact that such cases when this gastric cancer type is diagnosed in recent stages are extremely rare, we considered it useful to present it and look into its macroscopic and microscopic aspects, as well as into the differentiating diagnosis.

Hill-Climbing search and diversification within an evolutionary approach to protein structure prediction.

Proteins are complex structures made of amino acids having a fundamental role in the correct functioning of living cells. The structure of a protein is the result of the protein folding process. However, the general principles that govern the folding of natural proteins into a native structure are unknown. The problem of predicting a protein structure with minimum-energy starting from the unfolded amino acid sequence is a highly complex and important task in molecular and computational biology. Protein structure prediction has important applications in fields such as drug design and disease prediction. The protein structure prediction problem is NP-hard even in simplified lattice protein models. An evolutionary model based on hill-climbing genetic operators is proposed for protein structure prediction in the hydrophobic - polar (HP) model. Problem-specific search operators are implemented and applied using a steepest-ascent hill-climbing approach. Furthermore, the proposed model enforces an explicit diversification stage during the evolution in order to avoid local optimum. The main features of the resulting evolutionary algorithm - hill-climbing mechanism and diversification strategy - are evaluated in a set of numerical experiments for the protein structure prediction problem to assess their impact to the efficiency of the search process. Furthermore, the emerging consolidated model is compared to relevant algorithms from the literature for a set of difficult bidimensional instances from lattice protein models. The results obtained by the proposed algorithm are promising and competitive with those of related methods.

Diagnosis and treatment protocols of cutaneous melanoma: latest approach 2010.

Cutaneous melanoma is the most aggressive skin malignancies with increasing rate of incidence in the latest decades. New imaging technique plays an important role in melanoma management: dermoscopy and computer dermoscopy, ultrasound, MRI, CT, PET and PET/CT. Due to the dermoscopy and lesion diagnosis in early stages the increasing number of curative melanoma are registered. Sentinel lymph node biopsy became a compulsory phase for patients with tumor thickness > 1 mm. Serological biomarkers proved to be a necessary investigation for melanoma diagnosis, follow-up and treatment response. Current TNM melanoma staging is based on AJCC classification since 2001 witch includes new elements like histopathologic ulceration in stage I and II and lymph node micro- and macrometastases in stage III. Treatment protocols include surgical tumor excision with only 1-2 cm safety margins and radical lymphadenectomy is performed after positive sentinel lymph node biopsy. The adjuvant treatment in advanced stages including chemotherapy, unspecific immunotherapy and interferon offers poor results regarding free disease terms rate of survival. The advanced therapeutic procedure like golden nanospheres and gene therapy are recently studied and represent an alternative for future treatment of melanoma. Follow-up protocols have a great importance for detection of the melanoma recurrences and include clinical, serological and imaging evaluation. Despite all new knowledge and technological support the advanced stage melanoma management still remain an unsolved problem.

[Non-invasive diagnosis of pulmonary hypertension: ESC/ERS Guidelines with commentary of the Cologne Consensus Conference 2010]. / Nicht-invasive Diagnostik der pulmonalen Hypertonie: ESC/ERS-Leitlinien mit Kommentierung der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the diagnosis of pulmonary hypertension. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update y appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to non-invasive diagnosis of PH. This commentary summarizes the results and recommendations of the working group on treatment of PAH.

[Amyand's hernia--a clinical case]. / Hernia Amyand--caz clinic.

Amyand's hernia, a rare entity in the surgical pathology, presupposes the presence of the vermiform appendix inside a inguinal hernia sac (1). The hernia sac peritonitis by appendix swelling is even more rare, very few cases being presented in the surgical literature (1). The preoperatory diagnosis of Amyand's hernia is therefore very difficult. We herein present the case of a 71-year old male patient, operated on an emergency basis for hernia, which eventually turned out to be Amyand's hernia, a case which determined us to research the literature dedicated to this topic.

[Update: Current clinical developments in pulmonary hypertension]. / Update: Aktuelle klinische Entwicklungen bei pulmonaler Hypertonie.

During the last years, therapeutic options for the treatment of pulmonary arterial hypertension (PAH) have significantly improved. However, the therapeutic concept depends on the etiology of the disease, so that an exact classification is mandatory. Currently, three substance classes are approved for the treatment of PAH (Group I of the Venice Classification): Endothelin receptor antagonists, phosphodiesterase type-5 inhibitors, and prostanoids. After the World Conference in Dana Point (2008), recent changes in therapeutic strategies comprise the early treatment of the disease, as well as the increased importance of an early use of combination therapy if treatment goals are not met. Several new substances are currently evaluated in clinical trials. The soluble guanylate cyclase (sGC) stimulators achieve potent, NO-independent vasodilation. Another promising pathophysiological approach is currently evaluated by the use of tyrosine kinase inhibitors - anti-proliferative drugs which inhibit or even may reverse the pulmonary vascular remodeling process. Serotonin receptor antagonists are also reported to have anti-proliferative, anti-thrombotic and anti-fibrotic effects. Other forms of pulmonary hypertension (Groups II-V) are strictly separated from PAH. Evidence on treatment with PAH specific agents is strongly needed for these groups. Patients with non-PAH pulmonary hypertension should be referred to PAH expert centers, and preferably treated in controlled studies.

[Clinical characteristics of depressive disorders in hypertensive patients]. / Particularitati clinico-evolutive ale tulburarilor depresive la pacientii hipertensivi.

UNLABELLED: There is an interrelation between the psychic and the somatic affectation in the case of the patients suffering of essential high blood pressure that associates the depressive disorder. OBJECTIVES: Our study aims to compare two groups of patients in regard to the level of depression and anxiety, and to underline the clinical and the evolutional characteristics of the depressive disorder in the case of patients suffering from essential high blood pressure. MATERIAL AND METHODS: The study has been realized on 200 patients divided in 100 patients suffering of depression and 100 patients suffering of depression and HBP. There has been used the anamnesis, the HAMD and the HAMA. RESULTS: We have noticed that the level of depression is significantly increased in the group with depression and HBP by comparison with the group of those without HBP (t = -4.539, p = 0.000 < 0.05). The clinical manifestations and the evolution of the depressive syndrome, for the HBP, are polymorph and presents a nucleus around which are associated series of affective, vegetative and organic states. CONCLUSION: The progression of the HBP leads to the intensification of the neuropsychical disorders and backwards--the negative evolution of depression can lead to the increase of the blood pressure values, frequently causing hypertensive crises.

[The role of cardiopulmonary exercise testing in the assessment of pulmonary hypertension]. / Bedeutung der Spiroergometrie in der Diagnostik der pulmonalen Hypertonie.

Cardiopulmonary exercise testing (CPET) is an important diagnostic instrument for early detection, differential diagnosis and follow-up evaluation in pulmonary hypertension (PH). A pulmonary vasculopathy as the underlying cause for pulmonary arterial hypertension (PAH) can be detected in early stages by measuring gas exchange during exercise. There are characteristic patterns which are typically seen in patients with PAH. Regarding follow-up assessments, CPET can quantify cardiopulmonary exercise capacity in a more differentiated way than global exercise tests like the 6-minute walking distance. Different pathophysiological mechanisms accounting for pulmonary hypertension can be separately evaluated by CPET. Although tremendous progress has been made regarding sensor technology and data processing, CPET is still a method that is technically challenging. In order to obtain reliable results, strict quality control is of crucial importance. Additionally, standardization of result display, independent of equipment manufacturers or institutions, is desirable, in order to ensure a uniform interpretation of results.