Translation into Brazilian Portuguese and transcultural adaptation and validation of the treatment specific questionnaire Home Parenteral Nutrition- Quality of Life (HPN-QOL©).

BACKGROUND & AIMS: Home Parenteral Nutrition (HPN) is the main treatment for patients with chronic intestinal failure. It is commonly prescribed for nutritional recovery, survival increase and, whenever possible, improvement of quality of life. As there are no validated instruments in Brazilian Portuguese to be used in these patients, the objective of this study was to carry out the transcultural adaptation and validation of Home Parenteral Nutrition - Quality of life (HPN-QOL©) into Brazilian Portuguese. METHODS: This observational and cross-sectional study was conducted at the multidisciplinary short-bowel syndrome clinic (AMULSIC) of the Hospital das Clínicas of the University of São Paulo Medical School (HC-FMUSP). A five-stage protocol was adopted for the transcultural adaptation: initial translation; synthesis; reverse translation; experts committee and pre-test. The adapted questionnaire was applied to a convenience (representative) sample (n = 16) and Cronbach's Alpha Coefficient, Intraclass Correlation Coefficient (ICC), and Bland-Altman Test were submitted for the analysis of the internal consistency and intraobserver and interobserver reproducibility. RESULTS: The transcultural adaptation was considered excellent (Content Validity Index = 100%). The internal consistency was satisfactory for most of the scales (16/19), and α > 0.70 was 84.21%. ICC values revealed high intraobserver and interobserver reproducibility in most of the scales. No significant difference was observed between intraobservers and interobservers in any of the questions (p > 0.05). CONCLUSIONS: The questionnaire was shown as adapted and valid for use in Brazil. Future trials with a higher sample are yet to be developed to shed light on specific scales that were inconsistent. It's expected that this would contribute for the usual quality of life assessment for individuals treated with HPN in Brazil.

Treating short bowel syndrome with pharmacotherapy.

INTRODUCTION: Short bowel syndrome (SBS) has traditionally been regarded as a rapidly fatal medical catastrophe. The advent of pharmacological options directly targeting disease pathophysiology justified this review. AREAS COVERED: Since the 1970s, home parenteral nutrition has reduced mortality, converting SBS into a chronic and disabling compensated and occasionally curable illness. Off-label antidiarrheal drugs and related products, though having minimal scientific evidence of efficacy, represent the standard-of-care and are here reviewed. Trophic intestinal hormones, including GLP-2 and its analogs, have great promise for alleviating malabsorption, the most important symptom within a nonsurgical, routine outpatient framework. Current indications involve adults with massive intestinal losses (fecal wet weight >1500 g/day). Surgical options such as intestinal lengthening or transplantation are also addressed although these options are considerably more aggressive and have stricter indications. EXPERT OPINION: GLP-2 analogs are the first candidates from a pioneering pharmacotherapic family within the SBS framework, namely disease-modifying, absorption-restoring agents. This family of drugs, potentially applicable in all contexts of severe intestinal loss, could become the therapeutic benchmark of the near future.

Intravenous supplementation type and volume are associated with 1-year outcome and major complications in patients with chronic intestinal failure.

BACKGROUND AND AIM: No marker to categorise the severity of chronic intestinal failure (CIF) has been developed. A 1-year international survey was carried out to investigate whether the European Society for Clinical Nutrition and Metabolism clinical classification of CIF, based on the type and volume of the intravenous supplementation (IVS), could be an indicator of CIF severity. METHODS: At baseline, participating home parenteral nutrition (HPN) centres enrolled all adults with ongoing CIF due to non-malignant disease; demographic data, body mass index, CIF mechanism, underlying disease, HPN duration and IVS category were recorded for each patient. The type of IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorised as <1, 1-2, 2-3 and >3 L/day. The severity of CIF was determined by patient outcome (still on HPN, weaned from HPN, deceased) and the occurrence of major HPN/CIF-related complications: intestinal failure-associated liver disease (IFALD), catheter-related venous thrombosis and catheter-related bloodstream infection (CRBSI). RESULTS: Fifty-one HPN centres included 2194 patients. The analysis showed that both IVS type and volume were independently associated with the odds of weaning from HPN (significantly higher for PN <1 L/day than for FE and all PN >1 L/day), patients' death (lower for FE, p=0.079), presence of IFALD cholestasis/liver failure and occurrence of CRBSI (significantly higher for PN 2-3 and PN >3 L/day). CONCLUSIONS: The type and volume of IVS required by patients with CIF could be indicators to categorise the severity of CIF in both clinical practice and research protocols.

Transplante multivisceral em suínos: modelo de pesquisa e treinamento / Multivisceral transplantation in pigs: a model for research and training

Objective: To present a model for research and training in multivisceral transplantation in pigs. Methods: Eight Large White pigs (four donors and four recipients) were operated. The multivisceral transplant with stomach, duodenum, pancreas, liver and intestine was performed similarly to transplantation in humans with a few differences, described below. Anastomoses were performed as follows: end-to-end from the supra-hepatic vena cava of the graft to the recipient juxta diaphragmatic vena cava; end-to-end from the infra-hepatic vena cava of the graft to the inferior (suprarenal) vena cava of the recipient; and endto- side patch of the aorta of the graft to the infrarenal aorta of the recipient plus digestive reconstruction. Results: The performance of the multivisceral transplantion was possible in all four animals. Reperfusions of the multivisceral graft led to a severe ischemia-reperfusion syndrome, despite flushing of the graft. The animals presented with hypotension and the need for high doses of vasoactive drugs, and all of them were sacrificed after discontinuing these drugs. Conclusion: Some alternatives to minimize the ischemia-reperfusion syndrome, such as the use of another vasoactive drug, use of a third pig merely for blood transfusion, presence of an anesthesia team in the operating room, and reduction of the graft, will be the next steps to enable experimental studies.

Objetivo: Apresentar um modelo de pesquisa e treinamento em transplante multivisceral em suínos. Métodos: Oito porcos da raça Large White (quatro doadores e quatro receptores) foram operados. O transplante multivisceral com estômago, duodeno, pâncreas, fígado e intestino foi realizado a semelhança do transplante em seres humanoscom algumas diferenças descritas a seguir. Foram realizadas as anastomoses de veia cava supra-hepática do enxerto com a veia cava do receptor justa diafragmática término-terminal, veia cava infrahepática do enxerto com a veia cava inferior (suprarrenal) do receptor término-terminal e patch da aorta do enxerto com a aorta infrarrenal do receptor término-lateral e reconstrução digestiva. Resultados: Foi possível a realização do transplante multivisceral nos quatro animais. A reperfusão do enxerto multivisceral levou a uma grave síndrome de isquemia-reperfusão, apesar do flush do enxerto. Os animais apresentaram hipotensão com necessidade de drogas vasoativas em altas doses, sendo todos sacrificados com a retirada dessas drogas. Conclusão: Alternativas para minimizar a síndrome de isquemiareperfusão, como o uso de mais de uma droga vasoativa, uso de um terceiro porco apenas para transfusão sanguínea, presença de umaequipe de anestesia na sala de cirurgia e redução do enxerto, serão os próximos passos para possibilitar estudos experimentais.

Multivisceral transplantation in pigs: a model for research and training.

OBJECTIVE: To present a model for research and training in multivisceral transplantation in pigs. METHODS: Eight Large White pigs (four donors and four recipients) were operated. The multivisceral transplant with stomach, duodenum, pancreas, liver and intestine was performed similarly to transplantation in humans with a few differences, described below. Anastomoses were performed as follows: end-to-end from the supra-hepatic vena cava of the graft to the recipient juxta diaphragmatic vena cava; end-to-end from the infra-hepatic vena cava of the graft to the inferior (suprarenal) vena cava of the recipient; and end-to-side patch of the aorta of the graft to the infrarenal aorta of the recipient plus digestive reconstruction. RESULTS: The performance of the multivisceral transplantion was possible in all four animals. Reperfusions of the multivisceral graft led to a severe ischemia-reperfusion syndrome, despite flushing of the graft. The animals presented with hypotension and the need for high doses of vasoactive drugs, and all of them were sacrificed after discontinuing these drugs. CONCLUSION: Some alternatives to minimize the ischemia-reperfusion syndrome, such as the use of another vasoactive drug, use of a third pig merely for blood transfusion, presence of an anesthesia team in the operating room, and reduction of the graft, will be the next steps to enable experimental studies.

[Cytokine participation in the acute rejection of intestinal transplantation in rats]. / Participação de citocinas na rejeição aguda do transplante intestinal em ratos.

BACKGROUND: Intestinal transplantation is a possible treatment for patients with short bowel syndrome, aiming the reintroduction of oral diet. However, the major obstacle in this procedure is the strong rejection. Delay in rejection diagnosis may be irreversible and lethal. AIM: To define method for early diagnosis of rejection based on the presence of interleucin-6 (IL-6) e interferon- gamma (IFN-gamma) from intestinal allograft. MATERIAL AND METHODS: Isogenic rats Brown-Norway (BN) and Lewis (LEW) were submitted to intestinal heterotopic allotransplantation and divided in two groups: LEW donor to LEW recipient isograft group (C) and BN donor to LEW recipient allograft group (Tx). According to the day of sacrifice, Tx group were subdivided in three subgroups with eight animals each as follow: Tx3--sacrificed at third postoperative day (POD), Tx5--sacrificed at fifth POD and Tx7--sacrificed at seventh POD. Eight animals from control group were subdivided in three moments according to the time of biopsy from the graft as follow: C3--biopsy at third POD; C5--biopsy at fifth POD and C7--biopsy at seventh POD. All animals from control group were sacrificed at seventh POD. Rejection parameters were compared between the control groups (C3 vs C5, C3 vs C7 and C5 vs C7, and allograft group (Tx3 vs Tx5, Tx3 vs Tx7 and Tx5 vs Tx7). The same parameters were analyzed between the control group and allograft groups (C3 vs Tx3, C5 vs Tx5 and C7 vs Tx7). RESULTS: In C group no statistical significant difference regarding the immunoexpression of the cytokines, while in Tx group, immunoexpression of IL-6 and IFN-gamma were remarkable since the fifth postoperative day.

Participação da apoptose na rejeição aguda do transplante intestinal em ratos / Apoptosis participation in the acute rejection of intestinal transplantation in rats

RACIONAL: O transplante de intestino delgado é procedimento cirúrgico em estudo visando sua aplicação no tratamento dos pacientes portadores da síndrome do intestino curto, com vistas à reabilitação oral. A grande barreira, porém, se deve à rejeição pela grande quantidade de tecido linfóide presente no intestino delgado. OBJETIVO: Estudo da apoptose em alotransplante heterotópico intestinal. MATERIAL E MÉTODOS: Realizaram-se 24 alotransplantes intestinais em ratos da raça Brown-Norway (doador) para Lewis (receptor), sendo subdivididos em três subgrupos de oito animais, sacrificados respectivamente no terceiro dia de pós-operatório (Tx(3)), no quinto dia de pós-operatório (Tx(5)) e no sétimo dia de pós-operatório (Tx(7)) para coleta das biopsias dos enxertos intestinais. Compararam-se os resultados com o grupo isotransplante (C) que envolveu oito animais da raça Lewis (doador) para Lewis (receptor), porém neste grupo realizaram-se biopsias seriadas no mesmo animal, sendo subdivididos em três momentos: biopsia no terceiro dia de pós-operatório (C(3)), no quinto dia de pós-operatório (C(5)) e sacrificados no sétimo dia de pós-operatório (C(7)) para coleta da biopsia. Realizou-se, inicialmente, análise intragrupo entre os momentos C(3), C(5) e C(7) para todos os parâmetros de rejeição citados anteriormente, como também para os três subgrupos Tx(3), Tx(5) e Tx(7). Posteriormente, realizou-se a análise intergrupo de forma transversal e pareada comparando-se o grupo isotransplante com o grupo alotransplante. (C(3) com Tx(3); C(5) com Tx(5) e C(7) com Tx(7)). No grupo isotransplante não houve expressão estatística quanto aos marcadores analisados. Porém, no grupo alotransplante observou-se que alterações da apoptose foram marcantes a partir do terceiro dia de pós-operatório.

Estudo das alterações das citocinas inflamatórias na rejeição aguda do transplante intestinal em ratos / Cytokine participation in the acute rejection of intestinal transplantation in rats

RACIONAL: O transplante de intestino delgado é procedimento cirúrgico em estudo visando sua aplicação no tratamento dos pacientes portadores da síndrome do intestino curto, com vistas à reabilitação oral. Porém a grande barreira se deve à "rejeição" pela grande quantidade de tecido linfóide presente no intestino delgado. OBJETIVO: Avaliar a atuação das citocinas, interleucina-6 e interferon-gama em alotransplante heterotópico intestinal. MATERIAL E MÉTODOS: Realizaram-se 24 alotransplantes intestinais em ratos da raça Brown-Norway (doador) para Lewis (receptor), sendo subdivididos em três subgrupos de oito animais, sacrificados respectivamente no terceiro dia de pós-operatório (Tx(3)), no quinto dia de pós-operatório (Tx(5)) e no sétimo dia de pós-operatório (Tx(7)) para coleta das biopsias dos enxertos intestinais. Enquanto que no grupo isotransplante (C) envolveu oito animais da raça Lewis (doador) para Lewis (receptor), porém neste grupo realizaram-se biopsias seriadas no mesmo animal, sendo subdivididos em três momentos: biopsia no terceiro dia de pós-operatório (C(3)), no quinto dia de pós-operatório (C(5)) e sacrificados no sétimo dia de pós-operatório (C(7)) para coleta da biopsia. Realizou-se inicialmente análise intragrupo entre os momentos C(3), C(5) e C(7) para todos os parâmetros de rejeição citados anteriormente, como também para os três subgrupos Tx(3), Tx(5) e Tx(7). Posteriormente, realizou-se a análise intergrupo de forma transversal e pareada comparando-se o grupo isotransplante com o grupo alotransplante (C(3) com Tx(3); C(5) com Tx(5) e C(7) com Tx(7)). RESULTADOS: No grupo isotransplante não houve diferença estatisticamente significante quanto à imunoexpressão das citocinas estudadas, todavia no grupo alotransplante observou-se que alterações da interleucina-6 e de interferon-gama ocorreram a partir do quinto dia de pós-operatório.

[Apoptosis participation in the acute rejection of intestinal transplantation in rats]. / Participação da apoptose na rejeição aguda do transplante intestinal em ratos.

BACKGROUND: Intestinal transplantation is a possible treatment for patients with short bowel syndrome, aiming the reintroduction of oral diet. However, the major obstacle in this procedure is the strong rejection. Delay in rejection diagnosis may be irreversible and lethal. AIM: To define method for early diagnosis of rejection based on the apoptosis from intestinal allograft. MATERIAL AND METHODS: Isogenic rats Brown-Norway (BN) and Lewis (LEW) were submitted to intestinal heterotopic allotransplantation and divided in two groups: LEW donor to LEW recipient isograft group C and BN donor to LEW recipient allograft group (Tx). According to the day of sacrifice, Tx group were subdivided in three subgroups with eight animals each as follow: Tx3-- sacrificed at third postoperative day (POD), Tx5 -- sacrificed at fifth POD and Tx7 -- sacrificed at seventh POD. Eight animals from control group were subdivided in three moments according to the time of biopsy from the graft as follow: C3 -- biopsy at third POD; C5 -- biopsy at fifth POD and C7 -- biopsy at seventh POD. All animals from control group were sacrificed at seventh POD. Rejection parameters were compared between the control groups (C3 vs C5, C3 vs C7 and C5 vs C7, and allograft group (Tx3 vs Tx5, Tx3 vs Tx7 and Tx5 vs Tx7). The same parameters were analyzed between the control group and allograft groups ( C3 vs Tx3, C5 vs Tx5 and C7 vs Tx7). In C group no statistical significant difference regarding the expression of the apoptotic cells were detected, while in Tx group, the presence of apoptotic cells were remarkable since the third postoperative day.

Study of morbidity in orthotopic small intestine transplantation with Wistar rats. Experimental study.

BACKGROUND: Transplantation of the small intestine is a surgical procedure currently under investigation for its possible application in the treatment of patients with short bowel syndrome, aiming at the reintroduction of an oral diet. AIM: To define the morbidity and mortality of intestinal transplantation in small animals using microsurgery. Intra and postoperative morbidity and mortality were studied in Wistar rats submitted to orthotopic intestinal allotransplantation. MATERIAL AND METHOD: The animals were divided into three groups: group A (37 donor animals), group B (37 recipient animals), and group C (10 control animals). Group B was divided into three subgroups according to survival time. Subgroup TI consisted of animals that died during surgery or due to causes directly related to surgical intervention, subgroup T2 consisted of animals that died between the 4th and 29th postoperative day, and subgroup T3 consisted of animals that survived after 30 days. Transplanted animals were evaluated in terms of surgical technique used (vascular and intestinal anastomosis), graft quality, surgical time, and clinical parameters. The animals that died by the 29th postoperative day were submitted to autopsy and the remaining ones were sacrificed after 30 days. RESULT: There was a high rate of complication of a surgical nature. Early mortality rate, i.e., mortality up to the third postoperative day, was 54% with vascular anastomosis being the major cause of death. Surgical time was evaluated in a restricted and homogeneous group and showed a strong prognostic value in terms of successful transplantation. Clinical parameters such as weight loss, reduction of ingestion, reduction of motor activity and diarrhea were directly correlated with acute rejection. CONCLUSION: The experimented intestinal transplant is a procedure companied by considerable morbidity and mortality due to surgical complications in postoperative period, vascular anastomosis and total surgical time.

Study of morbidity in orthotopic small intestine transplantation with wistar rats: experimental study

Transplantation of the small intestine is a surgical procedure currently under investigation for its possible application in the treatment of patients with short bowel syndrome, aiming at the reintroduction of an oral diet. AIM: To define the morbidity and mortality of intestinal transplantation in small animals using microsurgery. Intra and postoperative morbidity and mortality were studied in Wistar rats submitted to orthotopic intestinal allotransplantation. MATERIAL AND METHOD: The animals were divided into three groups: group A (37 donor animals), group B (37 recipient animals), and group C (10 control animals). Group B was divided into three subgroups according to survival time. Subgroup TI consisted of animals that died during surgery or due to causes directly related to surgical intervention, subgroup T2 consisted of animals that died between the 4th and 29th postoperative day, and subgroup T3 consisted of animals that survived after 30 days. Transplanted animals were evaluated in terms of surgical technique used (vascular and intestinal anastomosis), graft quality, surgical time, and clinical parameters. The animals that died by the 29th postoperative day were submitted to autopsy and the remaining ones were sacrificed after 30 days. RESULT: There was a high rate of complication of a surgical nature. Early mortality rate, i.e., mortality up to the third postoperative day, was 54% with vascular anastomosis being the major cause of death. Surgical time was evaluated in a restricted and homogeneous group and showed a strong prognostic value in terms of successful transplantation. Clinical parameters such as weight loss, reduction of ingestion, reduction of motor activity and diarrhea were directly correlated with acute rejection. CONCLUSION: The experimented intestinal transplant is a procedure companied by considerable morbidity and mortality due to surgical complications in postoperative period, vascular anastomosis and total surgical time

Resultado da toracotomia precoce no tratamento dos nódulos solitários näo calcificados do pulmäo: análise de 19 casos / Results of early thoracotomy in the treatment of non-calcified solitary pulmonary nodules: analysis of 19 cases

Apresentamos 19 pacientes que foram submetidos a toracotomia e ressecçäo de nódulos näo calcificados do pulmäo desde 1980 (7 anos), com o objetivo de verificar se a toracotomia precoce nestes doentes foi conduta válida. A idade média foi de 50 anos, o mais jovem com dez e o mais idoso com 73 anos. Quanto ao sexo, seis eram do feminino e 13 do masculino, todos assintomáticos. Constatamos que nove (47,3%) dos nódulos eram carcinomas do pulmäo, com maior incidência em doentes acima de 50 anos (54,5%). Näo houve morte no pósoperatório imediato e ocorreram complicaçöes em apenas três doentes (15,7%). O seguimento ambulatorial foi realizado em todos os doentes e o tempo de evoluçäo mínima foi de um e o máximo de sete anos. Os portadores de nódulos benignos estäo todos bem. De nove casos com câncer pulmonar, dois morreram após três anos e seis meses e cinco anos, respectivamente. Considerando que o diagnóstico da natureza do nódulo no pré-operatório, isto é, se benigno ou maligno, nem sempre pode ser obtido e que é alta a incidência de cânceres de pequeno tamanho seräo adequadamente tratados e o prognóstico será melhor do que os dos que já ultrapassaram a fase de nódulo solitário