Refeeding syndrome as described in 1507 by Antonio Benivieni in Florence.

In 1981, Weinsier and Krumdieck described death resulting from overzealous total parenteral nutrition in two chronically malnourished, but stable, patients given aggressive total parenteral nutrition. This was the birth of what is now called the refeeding syndrome, a nutrition-related disorder associated with severe electrolyte disturbances. The purpose of this work is to demonstrate that refeeding syndrome was first described medically in Florence by Antonio Benivieni in 1507 in his book On Some Hidden and Remarkable Causes of Diseases and Cures. What we now know as refeeding syndrome was described in Report No. LVII of that book. The condition occurred as a result of the famine that affected Florence in 1496. The report documents (i) death due to starvation, (ii) death due to ingestion of deteriorated/toxic foods (inevitable in times of famine when healthy food is scarce), (iii) death caused by excessive food ingestion after forced, prolonged abstinence from food in adults, (iv) the death of breast-fed children and of their starved mothers eating to satiety and (v) the more favourable clinical outcome of those admitted to hospitals. It is possible that Benivieni was inspired by the description of the deaths of starved deserters in the book The Jewish War (70 AD) by the Romano-Jewish historian Flavius Josephus. Nevertheless, Benivieni wrote the first medical account of the central clinical features of refeeding syndrome. The main, broad clinical aspects of refeeding syndrome, described by Weinsier and Krumdieck in 1981, had been documented in medical literature four centuries earlier by Benivieni.

Legislative proposal in Italy to facilitate contacts between deceased organ donor families and transplant recipients.

Contacts between organ donors and recipients might be possible in the near future in Italy. As suggested by The Italian Committee of Bioethics "anonymity is requested by the Italian National Transplant Centre" before transplantation anonymity shall be strict in order to grant privacy, gratuity, justice, solidarity and benefits and avoids organ trafficking. Following a period that is ethically correct and justifiable, organ donor families and recipients can meet after signing a valid declaration of consent, expressed on a template valid for the whole country. A third party within the body of the National Health Systems shall control the validity of the consent. The opinion stresses that contacts are not a right but a possibility justifiable on ethical grounds if the procedure is followed appropriately. A legislative proposal has been presented before the Chamber of deputies incorporating all suggestions made by the National Committee of Bioethics. The agreement between parties might be signed a year after transplantation. This is a long enough period of time for the recipients to fully appreciate the benefits of the procedure and for the donor families to see the effects of their decision (the opinion and the Law proposal hit the Zeitgeist, and keep Italy in the regulation of European Union).

Safety of low intensity oral anticoagulant therapy in patients with bileaflet mechanical aortic valve prosthesis: A propensity weighted study.

BACKGROUND: Scarce data are available on the long-term outcomes of different regimens of oral anticoagulation in an all comer population of patients undergoing aortic valve replacement with a bileaflet mechanical heart valve. METHODS: Outcomes of 88 patients discharged with a target INR of 2.0 (LOW-INR) were compared to 147 contemporary patients who have been recommended a target INR of 2.5 (CONV). Primary outcome was the composite of any thromboembolic or haemorrhagic events. Secondary outcomes were the individual components of the primary outcome, cardiovascular mortality and stroke. To reduce selection bias, a propensity weighted analysis was performed. RESULTS: After inverse probability of treatment weighting, the primary endpoint occurred in 0.7% of patient in the LOW-INR group and in 7.0% in the CONV group (p = .0255). Linearized event rate were significantly lower in the LOW-INR group (primary endpoint: rate difference - 12.0 per 1000 patient/years, p = .0052; haemorrhage: -5.8 per 1000 patient/years, p = .0330; neurological events: -7.6 per 1000 patient/years, p = .0140). Conventional target INR was associated with an increased hazard of the composite endpoint (HR 11.193, 95% CI 1.424-88.003, p = .0217). CONCLUSIONS: Lowering the intensity of oral anticoagulation resulted in a relevant clinical benefit of reduced rates of haemorrhagic and neurological adverse events in the mid-term follow-up. This report confirms the safety profile of the low INR regimen in an all comer population undergoing aortic valve replacement with an Abbott mechanical valve.

[Laws regulating transplantation should express the contemporaneity. Questions to the constitutionalist Francesco Paolo Casavola and to the philosophers Remo Bodei and Aldo Masullo about the possibility deciding the destiny of one's own organs at the time one decides on how to die and on contacts between donor families and recipients.]

Transplantation represents modernity thus the laws regulating the procedure should be continuously renovated and remodeled in order to take full advantage of progress. The debate is about Law no. 219, December 22, 2017 and on Law no. 222, April 1, 1999. The quests are a) about the possibility to modify the first so that people deciding on how they want to die, may also decide about their willingness to allow the removal of their organs for transplantation and b) the possibility for donor families and recipients to have contacts after transplantation in the case both sides agree. Questions were emailed to the constitutionalist Francesco Paolo Casavola, immediate Past President of the National Committee for Bioethics, and to the philosophers Remo Bodei and Aldo Masullo. Their answers received by September 16, support the idea a) to include in the Law no. 219, 2017 the possibility to decide not only on the modality one wants to die but also on the possibility to allow his own organs to be removed for transplantation and b) to liberalize contacts between donor families and recipients when both side agree. For both changes there is enough evidence of their feasibility-necessity. The answers related to contacts between donor families and recipients support the decision of the National Committee for Bioethics on September 27, 2018. Professor Casavola also suggests that contacts should organized and supervised by the ethical committees of the hospitals where the transplantation procedure is accomplished.

Antonino D'Antona (1842-1913) was the first in describing the crush syndrome with renal failure following the Messina earthquake of December 28, 1908.

There is confusion about the first description of the association between crush syndrome and renal failure. It has been traditionally attributed to Bywaters and Beall. The present study aims to analyze the problem by analyzing medical reports on the Messina-Reggio Calabria earth-quake of December 28, 1908 by using documents heretofore unknown. It demonstrates that first description of rabdomyolysis with renal failure is attributed to Antonino DAntona (1842- 1913). DAntona, professor of surgery at the University of Naples, coordinated the health net organized in Naples to assist persons wounded during the quake. Many of them in shock were transferred to Naples by ships. Franz von Colmers (1875-1960) was the chief surgeon of the German Mission of the Red Cross after the quake. Because his late arrival, he did not treat patients with shock. He described rabdomyolysis. The third medical report is that of Rocco Caminiti (1868-1946), collaborator of DAntona at the University of Naples, and chief of surgery at the Loreto Hospital. He directed a rescue group in Villa San Giovanni and Reggio Calabria. In 1910, he reported on rabdomyolysis in patients treated in the place of the disaster. Therefore the present study indicates that Antonino DAntona holds the priority for description of rabdomyolysis and kidney injury. There is no longer a place for the eponym Bywaters syndrome.

[The Italian Places of Nicholas Green 20 years after his assassination]. / I luoghi italiani di Nicholas Green venti anni dopo il suo assassinio

Twenty years ago, Nicholas Green, a 7- year-old American boy was shot, while on vacation, on the Autostrada (motorway) Salerno to Reggio Calabria in Italy. His organs, with the consent of his parents, Reg and Maggie, were removed and 7 persons had their lives changed. In Italy in these last 20 years, organ donation has increased powerfully from 6.2 to 18.2 per million population with a peak at 20 in 2006. Reg and Maggie Green, after Nicholas death, started campaigning for organ donation by making full use of the media. Italian justice was efficient and the criminals were imprisoned quickly. With popular enthusiasm, a total of 103 places were dedicated to Nicholas (schools, halls, squares, streets, parks, gardens, private collections), a proof of great appreciation. Teaching organ donation to children, nurses and medical students is a powerful tool to convey the message of organ donation. To prevent opposition to organ removal when brain death occurs as Professor Francesco Casavola says signing for organ donation should be a family decision and laws for organ donation should be updated frequently in order to meet the progress of modernity.

Pattern of resolution of pulmonary hypertension, long-term allograft right ventricular function, and exercise capacity in high-risk heart transplant recipients listed under oral sildenafil.

Unresponsive pulmonary hypertension (PH) implies poor posttransplant outcomes. Data on late adaptation of the right ventricle (RV) are still few. This study evaluated three-yr RV function and remodeling, exercise capacity, and hemodynamic data in a selected group of patients initially disqualified because of PH. Between May 2005 and December 2009, 31 consecutive patients were qualified for oral sildenafil because of unresponsive PH at baseline right heart catheterization (RHC). After a 12-wk trial, RHC disclosed PH reversibility (mean PVR: 5.41 ± 3 Wood units, mean TPG 14.5 ± 5.6 mmHg, and mean systolic PAP 68.9 ± 15.1 mmHg), allowing listing even though as high-risk procedures. All patients underwent heart transplantation. RV failure developed in three patients (9.6%), and hospital mortality was 3.2%. Protocol RHC disclosed pulmonary hemodynamic profile normalization within the third postoperative month, allowing weaning from sildenafil in the 30 hospital survivors. One- and three-yr RHCs confirmed stable PH reversal (n = 26, all three-yr survivors). Parameters of late RV function and remodeling proved satisfactory. Parameters of functional capacity (Vo2 peak 19.7 ± 3.6 mL/kg/min and slope VE/Vco2 34.8 ± 2.7) proved homogeneous to those measured in transplant recipients with normal preoperative pulmonary artery pressure. Oral sildenafil is effective in allowing candidacy, safe transplantation, and long-term survival in PH recipients initially disqualified.

Early cell changes and TGFß pathway alterations in the aortopathy associated with bicuspid aortic valve stenosis.

Previous studies on BAV (bicuspid aortic valve)-related aortopathy, whose aetiology is still debated, have focused mainly on severe dilatations. In the present study, we aimed to detect earlier signs of aortopathy. Specimens were collected from the 'concavity' (lesser curvature) and the 'convexity' (greater curvature) of mildly dilated AAs (ascending aortas; diameter ≤4 cm) with stenotic TAV (tricuspid aortic valve) or BAV and from donor normal aortas. Specimens were submitted to morphometry, immunohistochemistry and differential gene-expression analysis, focusing on SMC (smooth muscle cell) phenotype, remodelling, MF (myofibroblast) differentiation and TGFß (transforming growth factor ß) pathway. Smoothelin and myocardin mRNAs decreased in all the samples from patients, with the exception of those from BAV convexity, where a change in orientation of smoothelin-positive SMCs and an increase of α-SMA (α-smooth muscle actin) mRNA occurred. Dilated aortas from BAV and TAV patients showed both shared and distinct alterations concerning the TGFß pathway, including an increased TGFß and TGFßR2 (TGFß receptor 2) expression in both groups and a decreased TGFßR1 expression in BAV samples only. Despite a decrease of the mRNA coding for the ED-A (extra domain-A) isoform of FN (fibronectin) in the BAV convexity, the onset of the expression of the corresponding protein in the media was observed in dilated aortas, whereas the normal media from donors was negative for this isoform. This discrepancy could be related to modifications in the intima, normally expressing ED-A FN and showing an altered structure in mild aortic dilatations in comparison with donor aorta. Our results suggest that changes in SMC phenotype and, likely, MF differentiation, occur early in the aortopathy associated with valve stenosis. The defective expression of TGFßR1 in BAV might be a constitutive feature, while other changes we reported could be influenced by haemodynamics.

Hemostatic modifications of the Bentall procedure: imbricated proximal suture and fibrin sealant reduce postoperative morbidity and mortality rates.

Bleeding is an important predictor of morbidity and mortality rates after the Bentall operation. This study reports our recent experience with composite aortic root replacement via a slightly modified button-Bentall operation. Fifty-six consecutive patients underwent a Bentall operation on an elective basis from January 2008 through December 2009. In all cases, we used 2 modifications: we imbricated the pledgeted 2-0 polyester interrupted U stitches of the proximal suture line, and at that same suture line we sealed with fibrin glue the possible sources of oozing. The series featured high proportions of associated procedures (25%) and reoperations (23%). The mean cardiopulmonary bypass and aortic cross-clamp times were 166 ± 50 and 113 ± 27 min, respectively. No case of operative or hospital (30-day) death was observed. Postoperative drainage amounted to 705 mL (median) on the first postoperative day and 377 mL (mean) on the second. Surgical re-exploration for bleeding was needed in only 1 patient (1.8%). Postoperative acute kidney injury was observed in 5 patients, neurologic complications in 3, and respiratory insufficiency requiring prolonged mechanical ventilation in another 3. Both respiratory and renal complications were significantly associated with greater consumption of blood products (P=0.03 and P=0.001, respectively). We conclude that the combined use of imbricated proximal suture-line stitches and subsequent fibrin-sealant spraying were associated with no deaths and with low rates of bleeding and other adverse postoperative sequelae in our 2-year experience with the Bentall operation in an elective series of patients characterized by a difficult mixture of prognoses.

The need for a specific risk prediction system in native valve infective endocarditis surgery.

The need for a specific risk score system for infective endocarditis (IE) surgery has been previously claimed. In a single-center pilot study, preliminary to future multicentric development and validation, bivariate and multivariate (logistic regression) analysis of early postoperative mortality predictors in 440 native valve IE patients were performed. Mathematical procedures assigned scores to the independent predictors emerged (AUC of the ROC curve: 0.88). Overall mortality was 9.1%. Six predictors were identified and assigned scores, including age (5-13 points), renal failure (5), NYHA class IV (9), critical preoperative state (11), lack of preoperative attainment of blood culture negativity (5), perivalvular involvement (5). Four risk classes were drawn ranging from "very low risk" (≤5 points, mean predicted mortality 1%), and to "very high risk" (≥20 points, 43% mortality). IE-specific risk stratification models are both needed, as disease-specific factors (e.g., cultures, abscess), beside the generic ones (e.g., age, renal impairment) affect mortality, and feasible.

Mechanical aortic valve replacement in young women planning on pregnancy: maternal and fetal outcomes under low oral anticoagulation, a pilot observational study on a comprehensive pre-operative counseling protocol.

OBJECTIVES: This pilot prospective observational study aimed to evaluate the maternal and fetal outcomes of pregnancies under low-dose oral anticoagulation therapy after aortic mechanical replacement. BACKGROUND: Need for valve replacement is still an issue for young women with native valve disease who are planning on future pregnancy. Choice of replacement device is a challenging clinical task. METHODS: A comprehensive pre-operative counseling protocol to guide choice of replacement device was developed. The pre-operative anticoagulation trial to determine the warfarin daily dosage needed to reach target international normalized ratio (INR) represented the main stem of such protocol. Pregnancies on low-dose anticoagulation therapy (target INR: 1.5 to 2.5) were allowed in a highly selected subset of mechanical aortic valve recipients. RESULTS: Twenty-two patients of 40 originally referred for native valve disease surgery requiring valve replacement, safely underwent the pre-operative anticoagulation challenge. No maternal or fetal complications were detected in 16 pregnancies under low oral anticoagulation. Patterns of warfarin daily dosage and induced INRs were characterized during pregnancy. CONCLUSIONS: In this small sample observational study, a pre-operative anticoagulation therapy trial helped young women scheduled for valve replacement to acquire complete information as to the choice of prosthetic device. In selected third-generation mechanical aortic prosthesis recipients, low-dose anticoagulation therapy seems safe and feasible for both mother and fetus. Further studies are needed to validate this approach.

Aortic erosion during negative pressure therapy in a pediatric heart transplant recipient.

A happy-ending "series of unfortunate events" is reported of the successful emergency treatment of an erosion of the ascending aorta during negative pressure sternal wound therapy for a relapse of Berlin Heart driveline infection in a pediatric transplant recipient. Several key issues related to assist device-related infections and negative pressure complications are discussed in this peculiar setting.

Biomechanical implications of the congenital bicuspid aortic valve: a finite element study of aortic root function from in vivo data.

OBJECTIVE: Congenital bicuspid aortic valves frequently cause aortic stenosis or regurgitation. Improved understanding of valve and root biomechanics is needed to achieve advancements in surgical repair techniques. By using imaging-derived data, finite element models were developed to quantify aortic valve and root biomechanical alterations associated with bicuspid geometry. METHODS: A dynamic 3-dimensional finite element model of the aortic root with a bicuspid aortic valve (type 1 right/left) was developed. The model's geometry was based on measurements from 2-dimensional magnetic resonance images acquired in 8 normotensive and otherwise healthy subjects with echocardiographically normal function of their bicuspid aortic valves. Numeric results were compared with those obtained from our previous model representing the normal root with a tricuspid aortic valve. The effects of raphe thickening on valve kinematics and stresses were also evaluated. RESULTS: During systole, the bicuspid valve opened asymmetrically compared with the normal valve, resulting in an elliptic shape of its orifice. During diastole, the conjoint cusp occluded a larger proportion of the valve orifice and leaflet bending was altered, although competence was preserved. The bicuspid model presented higher stresses compared with the tricuspid model, particularly in the central basal region of the conjoint cusp (+800%). The presence of a raphe partially reduced stress in this region but increased stress in the other cusp. CONCLUSIONS: Aortic valve function is altered in clinically normally functioning bicuspid aortic valves. Bicuspid geometry per se entails abnormal leaflet stress. The stress location suggests that leaflet stress may play a role in tissue remodeling at the raphe region and in early leaflet degeneration.

Noninvasive positive-pressure ventilation for extubation failure after cardiac surgery: Pilot safety evaluation.

OBJECTIVE: Extubation failure is a serious complication after cardiac surgery. The role of noninvasive positive-pressure ventilation for acute respiratory failure in patients undergoing cardiac surgery is unknown. This study aimed to assess the safety of implementing noninvasive positive-pressure ventilation in this setting and its impact on lung function and operative outcomes. METHODS: In a 6-month pilot prospective survey, the study population comprised 43 patients (32 were male with a mean age of 65.73 +/- 9 years; 3 heart transplantations, 18 coronary artery bypass grafts, 5 aortic dissections, and 17 valvular procedures; 34 active smokers, 25 with medically treated chronic obstructive pulmonary disease, 21 emergency/urgency procedures) who required noninvasive positive-pressure ventilation for acute respiratory failure after initial weaning from a respirator. The cause of acute respiratory failure (classified as post-cardiopulmonary bypass lung injury in 48.8% [21 patients], cardiogenic edema in 30.2% [13 patients], and pneumonia in 21% [9 patients]), length of noninvasive positive-pressure ventilation support, respiratory ratios (arterial oxygen tension/fraction of inspired oxygen assessed immediately before noninvasive positive-pressure ventilation, and every 6 hours after institution of pressure ventilation), and need for reintubation along with a set of predefined safety parameters were recorded. RESULTS: The mean length of noninvasive positive-pressure ventilation support was 33.8 +/- 24.04 hours. Plotting respiratory ratios with length of noninvasive positive-pressure ventilation supports a significant improvement was already evident within the first 6-hour frame (133.6 +/- 39.5 vs 205 +/- 65.7; P < .001) for all causes. Noninvasive positive-pressure ventilation prevented intubation in 74.4% of the patients, with satisfactory recovery for post-cardiopulmonary bypass lung injury and cardiogenic dysfunction (90.5% and 69.2%, respectively) and poor results (55% reintubated) in those treated for pneumonia. Noninvasive positive-pressure ventilation safety approached 97.7%. CONCLUSION: In appropriate candidates, noninvasive positive-pressure ventilation exerts favorable effects on lung function, preventing reintubation. The cost-effectiveness of its systematic use in this setting should be assessed.