F. Castagna

Preoperative Proteinuria and Reduced Glomerular Filtration Rate Predicts Renal Replacement Therapy in Patients Supported With Continuous-Flow Left Ventricular Assist DevicesCLINICAL PERSPECTIVE

Background—Renal failure requiring renal replacement therapy (RRT) has detrimental effects on quality of life and survival of patients with continuous-flow left ventricular assist devices (CF-LVADs). Current guidelines do not offer a decision-making algorithm for CF-LVAD candidates with poor baseline renal function. Objective of this study was to identify risk factors associated with RRT after CF-LVAD implantation. Methods and Results—Three hundred and eighty-nine consecutive patients underwent contemporary CF-LVAD implantation at the Columbia University Medical Center between January 2004 and August 2015. Baseline demographics, comorbid conditions, clinical risk scores, and renal function were analyzed in patients with or without RRT after CF-LVAD implantation. Time-dependent receiver-operating characteristic curve analysis was performed to define optimal cutoffs for continuous risk factors. Forty-four patients (11.6%) required RRT during a median follow-up of 9.9 months. Patients requiring RRT had significantly worse renal function, lower hemoglobin, and increased proteinuria at baseline. Low estimated glomerular filtration rate (<40 mL/min/1.73 m2) and proteinuria (urine protein to creatinine ratio ≥0.55 mg/mg) were significant predictors of RRT after CF-LVAD support. Dipstick proteinuria was also a significant predictor of RRT after CF-LVAD implantation. Patients with both low estimated glomerular filtration rate and proteinuria had highest risk of RRT (63.6%) compared with those with either low estimated glomerular filtration rate or proteinuria (18.7%) and those with neither of these risk factors (2.7%) at 1-year follow-up (log-rank P<0.001). Conclusions—Estimated glomerular filtration rate and proteinuria are predictors RRT after CF-LVAD implantation and should be routinely assessed in CF-LVAD candidates to guide decision making.

At the origin of medical semeiotics: Charles J. B. Williams and tactile vocal fremitus

The year 2016 has marked the bicentennial of the invention of the stethoscope by the French physician René Laennec (1781–1826). This tool has significantly contributed to the development of medical semeiotics, and to the birth of modern medicine and clinical method. Actually, the auscultation by stethoscope is not the only nineteenth-century discovery in semeiotics that deserves to be remembered and celebrated. Indeed, a few years after Laennec’s studies, some clinicians developed and perfected another semeiotic manoeuver: tactile vocal fremitus. When a person speaks, the vocal cords create vibrations (vocal fremitus) in the trachea, bronchi and through the lungs and chest wall, where they can be felt (tactile fremitus). Fremitus can be detected by placing the palms of the hands firmly against either side of the chest, while the patient speaks. This is repeated until the entire posterior thorax has been covered. If the patient has a consolidation in the lungs (pneumonia, fibrosis, or bronchiectasis), vibrations will be stronger and the fremitus will be louder, since sounds travel faster through materials that are denser than air. If the patient suffers from a pleural effusion, the physician will feel a decrease in vibration. Other common causes of decreased fremitus are atelectasis, obstructed bronchus, pneumothorax, oedema, and emphysema. The origin of Tactile Vocal Fremitus dated back to the first part of the nineteenth century. In his ‘‘De l’auscultation médiate’’ (1819), Laennec described what may be learned from listening to the patient’s spoken voice with the stethoscope placed over the chest [1]. In particular, he recognized some pathological signs that could evidence lung consolidation: bronchophony, egophony and pectoriloquy. These signs are based on a similar mechanism: lung consolidation transmits the sound of the voice to the periphery of the lungs, where it is usually not heard. The French physician described the different sounds that come from patient’s lungs, and stated that the quality of the resulting sound was influenced by pronouncing more or less clear and distinct words (lorsque le malade parle lentement et par mots entrecoupés) and using a trembling voice (voix chevrotante) [1]. Laennec’s work inspired other physicians to investigate the chest sounds while the patient speaks, in particular, the English doctor Charles J. B. Williams (1805-1889), who spent a year (1825–1826) in France working with him [2]. In 1828, Williams first described the phenomenon of vocal tactile fremitus, defining as ‘‘a slight vibratory fremitus or thrill that may likewise be felt on the application of the hand to the parietes during the exercise of the voice’’. [3] In ‘‘Lectures on the physiology and diseases of the chest’’, (1839) Williams provided more details: ‘‘[the voice] may be transmitted across the tissue to the parietes in merely an obscure diffused fremitus. This I call the pectoral fremitus. It may be also felt by the hand applied on the chest’’ [4]. He also explained the pathological value of the alteration of this sign: ‘‘the absence of the vocal fremitus is sometimes a valuable sign. [...] Liquid in the pleura will generally, more or less, destroy this fremitus, and the difference that it produces is often a very valuable sign of the presence of liquid. & Michele Augusto Riva michele.riva@unimib.it

Pope Innocent XI’s renal stones: an example of medical correspondence

It is a common practice to ask for advice from colleagues. Laboratory and imaging data are often part of information exchange between physicians. Thanks to modern computer systems, the transmission of material is much easier today compared to the past, but it would be a mistake to consider that solely a modern phenomenon. Indeed, physicians also used to circulate medical opinions in ancient times. The correspondence between Giovanni Maria Lancisi (1654–1720) and Antonio Vallisneri (1661–1730) about the renal stones found during the autopsy of Pope Innocent XI (1611–1689) is a good example of this wide topic. Furthermore, we would like to demonstrate the importance of medical correspondence in the development of Modern Medicine. Born Benedetto Odescalchi, Innocent XI started his ecclesiastic career as the bishop of Como (northern Italy) to become later cardinal in Ferrara and papal legate in Novara, near Turin [1]. Similar to other kings and noblemen of that period, Odescalchi suffered from gout, probably due to genetic predispositions and diet. After his election as Pope in 1676, this disease and its clinical manifestation (podagra), often complicated by erysipelas, forced Innocent XI to celebrate only Sunday Mass, without attending other public functions and meetings [1]. From 1682, he spent most of his time in bed, until his death on 12 August 1689, after 2 months of acute fever [1]. The surgeon Ippolito Magnani performed the necroscopy of Innocent XI, under the supervision of the papal physician Giovanni Maria Lancisi, who was one of the most appreciated and renowned physicians in Rome and the personal physician of several popes. During the autopsy, Lancisi and Magnani found several cysts in the Pope’s kidneys and two huge renal stones, a 9-ounce stone in the left kidney and a 7-ounce in the right kidney. During Odescalchi’s papacy, the association between uric acid and kidney stones was not known. In 1679, Antoni van Leeuwenhoek (1632–1723) discovered, for the first time, urate crystals using his microscope, but only several years later did the English physician Sir Alfred Baring Garrod (1819–1907) affirm that urate was “the cause of gouty inflammation” [2]. The kidney stones of Pope Odescalchi impressed Lancisi to the point that he decided to send a sketch of the large calyceal staghorns (Fig. 1) to Antonio Vallisneri [3], a member of the Galilean school of experimental scientists and a well-known physician. Vallisneri, fascinated by the sketch, returned a letter to Lancisi with his comments and descriptions of the stones. The exchange of letters between Lancisi and Vallisneri demonstrates that scientific correspondence between physicians and scientists was already a common practice during the seventeenth century. It was not a mere description of medical curiosities, but a way to share hypotheses of pathophysiologic mechanisms of diseases. Indeed, as mentioned by the Florentine physician Tommaso Alghisi (1669–1713), the correspondence with Vallisneri allowed Lancisi to hypothesize that only the renal cortex produces the urine, since the stones did not deform and damage this part of the Pope’s kidneys [4]. As nowadays, images were essential in ancient medical correspondence, so letters often contained drawings made by the physicians themselves. Lancisi, with his letters, proved to be a good artist, as doctors were at that time. Furthermore, the image of Innocent XI’s renal stones represents one of the first illustrations of staghorn in history. Finally, ancient medical correspondence can provide modern historians with valuable information on state-of-art of medical knowledge in past periods. In detail, the analyzed letters * Michele Augusto Riva michele.riva@unimib.it