The non-invasive mechanical ventilation: the experience of the department of Internal Medicine and Critical Area of the Polyclinic Hospital of Modena

Acute respiratory failure (ARF) is a deficiency of the respiratory system that causes an alteration of normal levels of oxygen and/or carbon dioxide in the blood. ARF may be due to alterations in gaseous diffusion in alveolar-capillary level (type “1” acute respiratory failure), or to alterations in the functioning of the respiratory pump (type “2” acute respiratory failure) or to an association of the above causes. ARF specific etiological treatment must be associated to oxygen administration, through ventilation, which may be spontaneous or mechanical (non-invasive or invasive). The actual study describes experience about non-invasive mechanical ventilation in the department of Internal Medicine and Critical Area of the Polyclinic Hospital of Modena, from 2010 to 2014, examining clinical parameters and outcomes. Respiratory failure is a condition in which the respiratory system is not able to adequately carry out its gas exchange functions, such as oxygenation of the arterial blood and/or elimination of carbon dioxide from the venous blood. Conventionally, (1),(2),(3) respiratory failure is defined in case of: Partial pressure of arterial oxygen (PaO2) <60 mmHg; Partial pressure of carbon dioxide in the arterial blood (PCO2)> 45 mmHg; Association of both previous. You can distinguish two types of acute respiratory failure(4)(ARF): ARF type “1”, with gas exchange impairment and hypoxemia (associated with hypo/normocapnia). The pathophysiological mechanism behind is an important intrapulmonary shunt with changes in ventilation/perfusion ratio. Generally diseases responsible for this condition are acute pulmonary edema, ARDS, severe pneumonia and pulmonary embolism. ARF type “2”, with hypoventilation and hypercapnia. It is caused by a reduction of the ventilation volume/minute or by an increase of physiologic dead space. Among the most common diseases there are neuromuscular diseases, myopathies, chronic obstructive pulmonary disease (COPD), bronchial asthma and restrictive lung disease. The two types of respiratory failure are closely connected and can evolve into one another. The ARF therapy can be divided into: Etiological therapy: it is directed to the treatment of the specific cause that induced ARF, it can be delivered with inotropic agents, antibiotics, bronchodilators, steroids etc. Supportive therapy (or symptomatic): aimed at correcting hypoxemia and respiratory acidosis, is indicated in all respiratory insufficiencies and it is based on the administration of O2 and postural therapy. Ventilation can be spontaneous (delivered by low or high flow systems) or mechanical. Mechanical ventilation is classifiable under invasive ventilation (IMV) or non-invasive (NIV). The IMV provides the invasion of the patient’s airways to put them in communication with the respiratory system. It can be through tracheal intubation or tracheotomy and it’s a relevant method adopted by resuscitation intensive departments and partly by respiratory diseases departments. The NIV despite is a method that requires training and experience to be used optimally, it has the advantage to be used in emergency medicine departments and in other departments from specialists who are not resuscitators or pulmonologists. Moreover, compared to the IMV, the NIV offers the following advantages: reduction in the respiratory work, absence of complications related to prosthesis, possibility of avoiding sedation required for the IMV, conservation of laryngeal functions and cost reduction.(5) The NIV techniques most used in emergency medicine departments are CPAP (Continuous positive airway pressure) and BiPAP (or BiLevel - BiLevel positive airway pressure) CPAP provides a predetermined positive pressure, greater than atmospheric, which is maintained constant throughout the respiratory cycle, and it improves oxygenation by increasing the functional residual capacity, favouring the recruitment and the patency of the alveoli excluded from the ventilation and improving the relationship between ventilation and perfusion. The main indications for CPAP are acute cardiogenic pulmonary edema (ACPE), hypoxic and not hypercapnic ARF, obstructive sleep apnea syndrome (OSAS); atelectasis. (8),(9),(10) BiPAP provides two different levels of positive pressure, which are an inspiratory positive airway pressure (IPAP) and an expiratory positive airway pressure (EPAP). BiPAP facilitates the removal of air exhaled and prevents cases of re-breathing of CO2. It also reduces the patient's work of breathing. The main indications to BiPAP are hypercapnic ARF, chronic obstructive pulmonary disease (COPD) exacerbation, pneumonia, neuromuscular disorders, dysfunction of the respiratory center (sedation/intoxication), shock (cardiovascular/septic). (11), (12)Acute respiratory failure (ARF) is a deficiency of the respiratory system that causes an alteration of normal levels of oxygen and/or carbon dioxide in the blood. ARF may be due to alterations in gaseous diffusion in alveolar-capillary level (type “1” acute respiratory failure), or to alterations in the functioning of the respiratory pump (type “2” acute respiratory failure) or to an association of the above causes. ARF specific etiological treatment must be associated to oxygen administration, through ventilation, which may be spontaneous or mechanical (non-invasive or invasive). The actual study describes experience about non-invasive mechanical ventilation in the department of Internal Medicine and Critical Area of the Polyclinic Hospital of Modena, from 2010 to 2014, examining clinical parameters and outcomes. Respiratory failure is a condition in which the respiratory system is not able to adequately carry out its gas exchange functions, such as oxygenation of the arterial blood and/or elimination of carbon dioxide from the venous blood. Conventionally, (1),(2),(3) respiratory failure is defined in case of: Partial pressure of arterial oxygen (PaO2) <60 mmHg; Partial pressure of carbon dioxide in the arterial blood (PCO2)> 45 mmHg; Association of both previous. You can distinguish two types of acute respiratory failure(4)(ARF): ARF type “1”, with gas exchange impairment and hypoxemia (associated with hypo/normocapnia). The pathophysiological mechanism behind is an important intrapulmonary shunt with changes in ventilation/perfusion ratio. Generally diseases responsible for this condition are acute pulmonary edema, ARDS, severe pneumonia and pulmonary embolism. ARF type “2”, with hypoventilation and hypercapnia. It is caused by a reduction of the ventilation volume/minute or by an increase of physiologic dead space. Among the most common diseases there are neuromuscular diseases, myopathies, chronic obstructive pulmonary disease (COPD), bronchial asthma and restrictive lung disease. The two types of respiratory failure are closely connected and can evolve into one another. The ARF therapy can be divided into: Etiological therapy: it is directed to the treatment of the specific cause that induced ARF, it can be delivered with inotropic agents, antibiotics, bronchodilators, steroids etc. Supportive therapy (or symptomatic): aimed at correcting hypoxemia and respiratory acidosis, is indicated in all respiratory insufficiencies and it is based on the administration of O2 and postural therapy. Ventilation can be spontaneous (delivered by low or high flow systems) or mechanical. Mechanical ventilation is classifiable under invasive ventilation (IMV) or non-invasive (NIV). The IMV provides the invasion of the patient’s airways to put them in communication with the respiratory system. It can be through tracheal intubation or tracheotomy and it’s a relevant method adopted by resuscitation intensive departments and partly by respiratory diseases departments. The NIV despite is a method that requires training and experience to be used optimally, it has the advantage to be used in emergency medicine departments and in other departments from specialists who are not resuscitators or pulmonologists. Moreover, compared to the IMV, the NIV offers the following advantages: reduction in the respiratory work, absence of complications related to prosthesis, possibility of avoiding sedation required for the IMV, conservation of laryngeal functions and cost reduction.(5) The NIV techniques most used in emergency medicine departments are CPAP (Continuous positive airway pressure) and BiPAP (or BiLevel - BiLevel positive airway pressure) CPAP provides a predetermined positive pressure, greater than atmospheric, which is maintained constant throughout the respiratory cycle, and it improves oxygenation by increasing the functional residual capacity, favouring the recruitment and the patency of the alveoli excluded from the ventilation and improving the relationship between ventilation and perfusion. The main indications for CPAP are acute cardiogenic pulmonary edema (ACPE), hypoxic and not hypercapnic ARF, obstructive sleep apnea syndrome (OSAS); atelectasis. (8),(9),(10) BiPAP provides two different levels of positive pressure, which are an inspiratory positive airway pressure (IPAP) and an expiratory positive airway pressure (EPAP). BiPAP facilitates the removal of air exhaled and prevents cases of re-breathing of CO2. It also reduces the patient's work of breathing. The main indications to BiPAP are hypercapnic ARF, chronic obstructive pulmonary disease (COPD) exacerbation, pneumonia, neuromuscular disorders, dysfunction of the respiratory center (sedation/intoxication), shock (cardiovascular/septic). (11), (12

Th Inducing POZ-Kruppel Factor (ThPOK) Is a Key Regulator of the Immune Response since the Early Steps of Colorectal Carcinogenesis

We purposed to evaluate the role of Th inducing POZ-Kruppel Factor (ThPOK), a transcriptional regulator of T cell fate, in tumour-induced immune system plasticity in colorectal carcinogenesis. The amounts of CD4+, CD8+ and CD56+ and ThPOK+ cells infiltrate in normal colorectal mucosa (NM), in dysplastic aberrant crypt foci (microadenomas, MA), the earliest detectable lesions in colorectal carcinogenesis, and in colorectal carcinomas (CRC), were measured, and the colocalization of ThPOK with the above-mentioned markers of immune cells was evaluated using confocal microscopy. Interestingly, ThPOK showed a prominent increase since MA. A strong colocalization of ThPOK with CD4 both in NM and in MA was observed, weaker in carcinomas. Surprisingly, there was a peak in the colocalization levels of ThPOK with CD8 in MA, which was evident, although to a lesser extent, in carcinomas, too. In conclusion, according to the data of the present study, ThPOK may be considered a central regulator of the earliest events in the immune system during colorectal cancer development, decreasing the immune response against cancer cells

A founder MLH1 mutation in families from the districts of Modena and Reggio-Emilia in northern Italy with hereditary non-polyposis colorectal cancer associated with protein elongation and instability.

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Th Inducing POZ-Kruppel Factor (ThPOK) Is a Key Regulator of the Immune Response since the Early Steps of Colorectal Carcinogenesis

We purposed to evaluate the role of Th inducing POZ-Kruppel Factor (ThPOK), a transcriptional regulator of T cell fate, in tumour-induced immune system plasticity in colorectal carcinogenesis. The amounts of CD4+, CD8+ and CD56+ and ThPOK+ cells infiltrate in normal colorectal mucosa (NM), in dysplastic aberrant crypt foci (microadenomas, MA), the earliest detectable lesions in colorectal carcinogenesis, and in colorectal carcinomas (CRC), were measured, and the colocalization of ThPOK with the above-mentioned markers of immune cells was evaluated using confocal microscopy. Interestingly, ThPOK showed a prominent increase since MA. A strong colocalization of ThPOK with CD4 both in NM and in MA was observed, weaker in carcinomas. Surprisingly, there was a peak in the colocalization levels of ThPOK with CD8 in MA, which was evident, although to a lesser extent, in carcinomas, too. In conclusion, according to the data of the present study, ThPOK may be considered a central regulator of the earliest events in the immune system during colorectal cancer development, decreasing the immune response against cancer cells

CANCER OCCURRENCE IN THE FOLLOW-UP OF 25 FAMILIES WITH HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER (HNPCC)

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Inheritance and susceptibility to tumours of the large bowel: A new classification of colorectal malignancies

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GENETIC EPIDEMIOLOGY OF HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER

Lynch syndrome or Hereditary non-polyposis colorectal cancer (HNPCC) has recently received considerable attention either for its clinical implication or for the characterization of the molecular basis. HNPCC is an autosomal dominant disorder featured by the development of early onset colorectal malignancies frequently localized in the proximal colon, synchronous and metachronous lesions of the large bowel, and association with tumors of other organs, especially endometrium, stomach and urinary tract. In typical cases the clinical diagnosis may be relatively easy, but in many other instancies small size of families, possible low penetrance, variable expressivity, and frequency of phenocopies may render the identification of Lynch syndrome extremely complex. Molecular biology will be of considerable help in diagnosis HNPCC, since at least four genes have recently been identified whose mutations are closely associated with the development of this phenotype. Various studies in different races and continents seem to indicate that the frequency of Lynch syndrome is in the order of 1 to 5% of all colorectal malignancies. In most of these investigations the clinical guideline for the definition of HNPCC were the so-called ''Amsterdam Criteria'', proposed by the International Collaborative group on HNPCC. In some of these series, gene mutation were found in 50-70% of the families. However, the problem is much more complex owing to the existence - in a given population - of ''suspected'' HNPCC families and juvenile cases that might represent possible first mutations of a HNPCC kindred. Molecular studies should make clear how many of these families are true HNPCC and how many represent spurious aggregates of cancer. Finally, segregation analysis repetedly showed that the autosomal dominant model was the most plausible type of transmission in HNPCC families, though more complex models (i.e., codominant) cannot be excluded and deserve further investigations

IDENTIFICATION OF HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER IN THE GENERAL-POPULATION - THE 6-YEAR EXPERIENCE OF A POPULATION-BASED REGISTRY

Background. Hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) is an autosomal dominant disease characterized by early-onset intestinal neoplasms, localization of tumors in the proximal colon, and frequent association with cancers at other sites, especially the endometrium, skin, and stomach. The identification of HNPCC is often difficult, owing to the lack of biomarkers and the extreme frequency of sporadic colorectal cancer in the Western World. Methods. The authors reviewed the clinical data and the family trees of all patients (n = 817) with colorectal malignancies registered in the local health district between 1984-1989 with the following objectives: (1) to identify families with HNPCC and (2) to establish the frequency of the syndrome in northern Italy. Six clinical criteria were defined (vertical transmission, familial aggregation, early age at onset, right colon localization, multiple tumors, and mucinous carcinoma), all indicative of an increased possibility of HNPCC. Results. The registered families were divided into various subgroups according to the presence (in the nuclear pedigree) of four or more criteria (41 families, 5.0% of total), three criteria (58 families, 7%), two criteria (73, 8.9%), or less than two criteria (203 families, 24.8%). The remaining 380 case families did not show criteria suggesting a genetic component. One hundred thirty-three genealogic trees were extended further to gather information on second-degree and third-degree relatives. The expanded pedigrees were further analyzed to ascertain if they met the recently proposed requisites for HNPCC. Nineteen of 37 (51%) families with four criteria met the minimum requisites and could therefore be considered HNPCC. Similarly, HNPCC was diagnosed in six extended pedigrees of the three-criteria (16.6%) and in three families (8.5%) of the two-criteria subgroups. The difference in the detection of HNPCC among various subgroups was statistically significant (P < 0.001). From the observed findings, the frequency of HNPCC in this population can be estimated to be between 3.4-4.5% of all cases of colorectal cancer. Conclusions. HNPCC can be identified in the general population through the data of a colorectal cancer registry if the nuclear pedigrees of all incident cases are traced and a proportion of them selectively expanded. The observed frequency of HNPCC was rather consistent with previous estimates in other populations

RISK OF CANCER REVEALED BY FOLLOW-UP OF FAMILIES WITH HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER - REPLY

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