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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.

Background and Aims The history of popes is an untapped treasure for historian of medicine for many reasons including i. number, ii. richness of documents available on their lives, iii. gender homogeneity, iiii. Long lasting lives, v. their affluence, vi. number of archiaters and personal physicians and surgeon of high professional level, viii. lived for many years in the same environment (Rome). Taking into consideration the availability of documents from 1100 onward (10 centuries of European history), popes represent good models to study a. the diseases of popes, b. social medicine, c. history of European universities and beyond, d. the history of hospitals, e. the history of archiaters, and f. the diseases of power. We are studying renal stone disease in popes from St Peter to John Paul II (34-2005). Preliminary results on gouty popes have been presented at ERA-EDTA Congress in Budapest and Milan pointing that out 20 gouty pontiffs 12 were stone formers or died because of its complications and 6 popes died because of non-gouty renal stones. The goal of this study is to provide an historical outline on renal stone disease in gouty and not gouty popes reigning in the years 537-1830 (from Vigilius―the 1st stone former pope―to Pius VIII, the last gouty pope). Methods We have studied history of popes on many books including those authored by von Ranke, von Pastor, de Novaes, Henrion, Paravicini Bagliani, Reardon, Rendina, Ceccarelli and Cosmacini. We have also studied the histories of archiaters of Platina and Marini. Results 25 out 193 popes were found gouty. Their mean age at start of pontiff was 64.6 and 70.6 at death, that nearly correspond to the time-course decline of age-related uric acid excretion. Thirteen of these popes had histories, signs, symptoms, and /or postmortem examination compatible with a diagnosis of renal stone disease. Six of them died with uremia, 4 were hydropics, 6 died because of stroke. In addition we have also outlined the narratives of 14 non gouty popes who had renal stone disease. The last pope affected by renal stone disease was Pius VI (1775-1779) , the last gouty popes was Pius VIII (1829-1830). Conclusion We have excluded from gouty popes Alexander VII erroneously defined gouty by Giuseppe De Novaes in 1815 and also excluded John IX since his gout―hypothesized by Wendy J Reardon in 1971―is not supported by documents. There are a few available specific data on the topic. A fundamental contribution was published by Lorenzo Gualino in 1934. He reported on 19 gouty popes, 12 of whom with histories or signs, or symptoms, and/or postmortem examination confirming renal stone diseaase. He also reported on 8 non gouty popes suffering from or died of renal stone disease. The findings should be matched also with those of Giovanni Ceccarelli (2001) who reported on 11 gouty popes 6 presenting with signs of stones and five dying anuric and/or hydropic. This paper includes on all popes with renal stone disease. Stroke and heart failure in gouty popes are a priority. In the last 2 centuries renal stone disease was no more a papal disease.

Background and Aims Pope Gregory I (Magnus)―born c.540 AD, Pope 580-604 AD―in a letter to Bishop Venanzio ofLuni (later venerated as a saint) wrote “I have been confined to bed for the last eleven months, because of pain and malaise and suffer because of goutand my life has been turned into a penitence for my sins thus I am waiting death as a physician who will give me health”. He was the first Pope to suffer of gout and opens a list including in the years 20 pontiffs that includes Sisinnius, (b.650, pope 21 day in 708); Boniface VI (b. 806, Pope 15 days in 886), Honorius IV (b.1210, Pope 1285-1287); Boniface VIII (b. 1230, Pope 1294-1303); Clement VI (b.1281,Pope 1342-1352), Nicholas V (b.1387, Pope 1447-1455); Pius II( b. 1405, Pope 1458-1464); Sixtus IV (b. 1414, Pope 1471-1474); Pius III (b.1440, Pope 26 days in 1503); Pius IV (b. 1499, Pope 1559-1565); Julius II (b. 1443, Pope 1503-1516); Julius III (b.1481, Pope 1550-1555); Clement VIII (b. 1536, Pope 1592- 1605); Clement X (b.1581, Pope 1670-1676); Innocent XI (b.1681, Pope 1676-1689); Innocent XII (b.1649, Pope 1676-2692); Innocent XIII (b.1655, Pope 1721-1724); Benedict XIV (b. 1765, Pope 1740-1758), and Pius VIII (b.1761, Pope 1829-1830). Their mean age at death was 69.4 years, the youngest being Sisinnius (59 years), the oldest being Clement X (96 years). Results Some popes were strong eaters like Boniface VIII. He was chronically affected by gout and renal stone disease and by the fear for death, and the search for therapies capable to prolong life. Cosmacini says “podagroso e gottoso”… the Pope is affected by arthritis and renal disease due to overalimentation very rich (straricca) in meat”. He enrolled various archiaters among them Taddeo Alderotti (1223-1295), Pietro da Abano (1257-1315), Anselmo da Bergamo (artisphysicae professor), Simone of Genova (author of Clavissanationis), Accursino from Pistoia, Manzia from Fabriano, Gugliemo da Brescia, Angelo da Camerino and Campano da Novara (Magister Campanus), the naturalist he too affected by renal stone disease. Julius III too was a strong eater (he loved fatty foods seasoned with garlic) as was Pius IV, the hard worker who everyday used to take a nap after lunch and a long walk later in the day. By contrast Nicholas V (his Pontiff saw in 1453 the Fall of Costantinople and the end of the Hundred Years War) was a sober eater and drinker as were Pius II who made use of simple common foods, little wine and slept up to 5-6 hours. Probably Nicholas V died uremic since his pale natural color switched into yellowish-brown (itaque ex naturali et subcandido in croceumsubcinericiumque color suusconversusest). Pius III “was a sober eater and drinker and used to dine every two days. Some of the above popes were patrons of universities (Boniface VIII, Nicholas V, Pius II), some were patrons of arts and science (Nicholas V, Sixtus IV). Boniface VIII is remembered for the Bulla detestandeferitatis (against dismemberment and evisceration of cadavers), issued on September 27, 1299). For thatBulla, during the subsequent centuries he was wrongly accused even by Herman Boerhaave and Albrecht von Haller to have retarded the advancement of medicine by impeding anatomical dissections. By contrast Sixtus IV is remembered not only for modernizing Rome and embelling it, but for the 1482 Breve to the University of Tubingen allowing―for teaching purposes ―dissection of dead bodies of people sentenced to death.