胰肾联合移植的排斥反应

目的探讨胰肾联合移植术后的排斥反应。方法对我院施行的3例胰肾联合移植的病人，采用FK506 MMF Perid Zenapax四联免疫治疗方案，通过床边彩超及Cr、BUN、血糖等来监测移植物的排斥反应。对排斥反应采用激素冲击疗法，对激素不敏感者采用OKT3治疗。结果3例患者中有2例出现排斥反应，其发生率达66％；在出现排斥反应时，首先表现为低热、全身不适，尿量减少，血Cr、BUN升高，彩超示移植物血流阻抗升高，之后才是血糖升高。结论胰肾联合移植中，排斥反应与多种因素有关，移植肾对移植胰具有保护作用，肾脏可以作为监测胰腺排异的窗口，彩超检查可以作为筛选移植物排异反应的手段。     

胰肾联合移植中供体切取和修整的技巧

目的:总结胰肾一期联合移植中供体胰十二指肠及肾脏切取及修整的经验。方法:回顾性分析19例胰肾联合移植术中供体胰十二指肠及肾脏切取的方法与移植物的修整技巧。结果:无1例发生移植物损伤。联合移植术后9 d之内18例完全停用外源性胰岛素,空腹血糖正常，尿糖≤（+）。术后2～4 d，血肌酐和尿素氮降至正常。3例出现移植肾脏急性排斥反应，2例发生移植胰腺急性排斥反应，给予甲泼尼龙冲击治疗后恢复正常。1例术后因移植物加速排斥反应，术后11 d切除移植胰、肾。结论:胰肾联合移植手术中，供体胰十二指肠及肾脏的切取及修整是手术成功的重要因素之一。     

胰肾联合移植术后排斥反应分析

目的 探讨预防和逆转胰肾联合移植术后排斥反应的方法。方法 回顾性分析1999年9月～2003年9月17例同种异体胰肾联合移植手术患者的临床资料。全部病例采用口服免疫抑制剂：环孢素A、霉酚酸酯或硫唑嘌呤、激素三联用药。其中2例术前及术后第5天应用抗IL-2R单克隆抗体,3例应用OKT3进行免疫诱导。结果 17例患者中1例发生移植胰腺、肾脏加速性排斥反应．经保守治疗无效,切除移植物;8例发生急性排斥反应,其中单纯肾脏排斥反应6例,同时累及胰腺、肾脏的排斥反应2例,经甲泼尼龙或OKT3治疗后均逆转。结论 胰肾联合移植术后合理应用免疫抑制剂。术前采用综合措施降低高危受者的致敏性,是预防和治疗排斥反应的有效方法。     

胰肾联合移植53例术后长期存活的临床观察

目的 分析53例胰肾联合移植长期存活情况及其影响因素.方法 回顾性分析2000年1月至2009年6月间施行的53例胰肾联合移植受者和移植物长期存活情况,分析受者死亡原因和移植物功能丧失原因.结果 3、5和8年受者存活率分别为90.1％、89.1％和80.0％,3、5和8年移植胰腺存活率分别为84.9％、84.8％和60.0％,3、5和8年移植肾存活率分别为83.0％、82.6％和53.3％.受者死亡原因分别为感染(4例)、移植肾功能丧失(2例)、心血管急症(1例)和脑卒中(1例).移植胰腺功能丧失的主要原因为带功能受者死亡、排斥反应和外科并发症.移植肾功能丧失的主要原因为排斥反应和带功能受者死亡.结论 胰肾联合移植治疗终末期糖尿病肾病远期效果良好,感染、排斥反应和外科并发症是受者死亡和移植物功能丧失的主要原因.     

胰腺和肾脏在联合移植中排斥反应的比较

目的:比较胰腺和肾脏在联合移植中的排斥反应.方法:以大鼠同种异体胰肾联合移植为基础,对来自同一供体的联合移植的胰腺和肾脏排斥反应进行比较分析.结果:1.肾脏间质排斥反应出现较胰腺早.程度也较胰腺重,且以早期标本为著;2.胰肾血管排斥反应分级分布相似,无显著差异;3.胰肾间质排斥反应均早于血管出现,程度也较重     

胰肾联合移植治疗肝移植后糖尿病合并肾功能衰竭二例

目的 总结肝移植后再行胰肾联合移植治疗糖尿病合并肾功能衰竭的临床处理经验.方法 2例肝移植受者术前合并有2型糖尿病,分别于肝移植后7年余和4年余发生肾功能衰竭,遂行胰肾联合移植,2例的移植肝功能均正常.采取腹部器官联合快速切取技术整块切取双肾、全胰及十二指肠节段,先行肾移植,再行胰腺移植,供肾移植于左侧髂窝,供胰移植于右侧髂窝,供者的十二指肠与受者的空肠侧侧吻合,供者的十二指肠内置管,通过受者的空肠引流出体外.例1采用抗白细胞介素受体单克隆抗体诱导的四联免疫抑制方案预防排斥反应;例2术中给予抗胸腺细胞球蛋白和甲泼尼龙,术后继续使用2d,采用他克莫司+吗替麦考酚酯+皮质激素预防排斥反应.结果 2例手术过程顺利,术后移植胰腺功能正常,血糖均于术后10d左右恢复正常,无需胰岛素治疗,移植肾功能1周时恢复正常,第2例1周后血清肌酐渐进性升高,经验性抗排斥反应治疗效果不明显,移植肾活组织检查未见明显排斥反应征象,遂将他克莫司替换为西罗莫司,之后受者的肾功能逐渐恢复正常.目前2例受者已分别随访36个月及9个月,移植肝、肾及胰腺功能均正常.结论 肝移植后合并糖尿病、肾功能衰竭时可考虑行胰肾联合移植,但术后免疫反应复杂,需严密监测移植物功能.     

胰肾联合移植术后并发症的防治(附四例报告)

目的探讨肠腔引流式胰肾联合移植术后并发症的防治。方法对4例胰肾联合移植的患者,通过完善术前准备,术后加强抗感染、抗凝,抑制胰液分泌,合理使用免疫抑制剂,密切观察病情变化等措施来防止并发症的发生、发展;对出现的并发症及时地采用相应的治疗措施。结果4例患者中并发巨细胞病毒性肺炎1例、急性排斥反应3例、慢性排斥反应1例,血栓形成1例,1例因肺部感染、呼吸功能衰竭于术后23d死亡,1例移植肾因慢性排斥失功能,其余并发症均治愈。结论术后并发症严重影响着胰肾联合移植的效果,胰肾联合移植术后各种并发症的防治关键在于早期预防、早期诊断、合理治疗。     

猪胰肾联合移植门静脉回流和体静脉回流术式对急性排斥反应的影响

目的 比较胰肾联合移植门静脉回流（PE）和体静脉回流（SE）两种术式对移植物急性排斥反应的影响.方法 48例无亲缘当地杂交第1代长白猪,随机分成PE组（24只）和SE组（24只）,每组内行交叉配血,相合者组成供受猪.切除受猪胰腺制成1型糖尿病模型,同时切除右肾.PE组门静脉与受猪肠系膜上静脉或门静脉行端侧吻合,SE组门静脉与受猪肝下下腔静脉吻合,外分泌均采用肠道引流.术后1、3、5、7 d监测血糖和移植肾尿液肌酐水平;术后3、7 d开腹取移植胰和肾组织行病理学检查,参照Nakhleh和Banff标准对移植胰腺和肾进行排斥反应评分.结果 PE组和SE组各行12例移植手术,两组移植物冷缺血时间差异无统计学意义[PE组为（231.25±19.86）min ;SE组为（234.60±15.80） min,P〉0.05].两组术后1、3、5、7 d血糖和移植肾尿液肌酐水平差异无统计学意义（P〉0.05）.SE组较PE组移植胰腺和肾急性排斥反应发生早且重,两组急性排斥反应病理评分差异有统计学意义（P〈0.05）.结论 猪胰肾联合移植内分泌PE与SE相比,可减轻和延缓急性排斥反应.     

胰肾联合移植的外科技术探讨

目的 探讨胰液空肠引流式胰肾联合移植的外科技巧和临床应用.方法 中山大学附属第一医院2005年1月-2009年6月共施行了10例胰肾同期联合移植术(SPK),供体胰、十二指肠和肾均采用腹部多器官联合切取方式获得,经腹主动脉、肠系膜上静脉对胰腺及十二指肠同时快速灌注降温.移植胰的外分泌采用胰十二指肠一空肠内引流吻合方式.术后早期均以抗CD25单克隆抗体进行免疫诱导治疗,采用他克莫司、霉酚酸酯及皮质激素预防排斥反应.结果 10例移植手术均获得成功.供体胰十二指肠和肾的热缺血时间为(5.9±2.6)min;移植肾平均冷缺血时间为(5.2±2.2)h,移植胰平均冷缺血时间为(9.3±3.6)h.术后3例出现移植胰伤口感染,经治疗后3～12周愈合.2例出现胰十二指肠一空肠吻合口出血,均经保守治疗止血而治愈.未发生与胰液引流相关的外科并发症.1年内3例发生了急性排斥反应,2例经激素冲击和抗淋巴细胞球蛋白治疗而被逆转;1例顽固性急排患者术后39 d在持续肾脏替代治疗过程中并发脑血管意外死亡.其余9例均痊愈,随访6～12个月,完全停用胰岛素.结论 获取质量良好的供体器官及合理血管整形,是保证胰肾联合移植成功的前提;改进的胰液空肠外分泌引流术式的方法是可靠的.     

他克莫司联合霉酚酸酯应用于胰肾联合移植的初步经验

目的 总结他克莫司(FK506)联合霉酚酸酯(MMF)应用于胰液膀胱引流式胰肾联合移植受者的初步经验. 方法 胰肾联合移植患者14例,术后应用FK506 0.07～0.15mg·kg-1·d-1加MMF 1.0～1.5 g/d加泼尼松25 mg/d三联免疫抑制治疗方案.采用微粒子酶免疫分析法每周测定口服FK506后全血峰谷浓度,依此调整剂量维持最初3个月内FK506全血浓度峰值10～20 μg/L,谷值5～15μg/L.并观察排斥反应的发生及药物的肝肾毒性. 结果 9例患者术后胰肾功能恢复良好,早期无排斥反应发生,血糖及肌酐水平恢复正常.随访18～70个月,平均34个月.存活1～3年者3例,3年～者1例,4年～者1例,>5年者4例,胰肾功能良好,血糖正常,均未使用降糖药.1例因超急性排斥反应术后第2天切除移植胰腺,随访2年肾功能良好.4例死亡,死因分别为术后急性右心功能衰竭、呼吸骤停、急性排斥反应及十二指肠瘘.胰肾联合移植术后各时期FK506全血峰、谷浓度差异均有统计学意义(P<0.05).术后共发生肾脏急性排斥反应4例次,肾毒性2例次,肝毒性1例次. 结论 FK506与MMF在药效上有协同作用,联合应用于胰肾联合移植具有良好的免疫抑制效果,能有效降低排斥反应发生率和提高移植物长期存活率.     

Differential effects of preexisting uremia and a synchronous kidney graft on pancreas allograft functional survival in rats.

Pancreas transplant results have been better in uremic recipients of a simultaneous kidney than in nonuremic recipients of a pancreas alone. We studied the relative effect of uremia versus a double transplant on functional survival by performing bladder-drained pancreas transplants alone (PTA), kidney transplants alone (KTA), and simultaneous pancreas/kidney (SPK) transplants from Buffalo donors to diabetic Lewis rat recipients that were or were not made uremic 2-3 weeks before by 1 4/5 native nephrectomy. Pancreas graft exocrine function was monitored by urinary amylase (UA). In the PTA and SPK recipients made diabetic by streptozotocin, endocrine function was monitored by measuring nonfasting plasma glucose (PG) levels. Kidney graft function was monitored by plasma creatinine (Cr). Rejection of the endocrine pancreas was defined as an increase of PG to greater than 200 mg/dl; of the exocrine pancreas, as a decline in UA to less than 6000 U/L or to less than 100 U/24 hr; and of the kidney, as an elevation of Cr to greater than 3 mg/dl. The mean functional survival times (MST) of both the endocrine (12.0 +/- 2.1 versus 10.1 +/- 1.1 days, P = 0.036) and exocrine (8.0 +/- 2.1 versus 6.3 +/- 1.3 days, P = 0.016) components of the pancreas grafts were significantly longer in SPK than in PTA recipients. The MST of kidney allografts, however, was not significantly longer in nonuremic SPK than nonuremic KTA recipients (6.7 +/- 1.4 versus 5.7 +/- 0.7 days, P = 0.13). In parallel experiments in recipients immunosuppressed with cyclosporine, the graft survival times were longer, but the relative differences between the PTA, SPK, and KTA groups persisted. Histologically, lymphocyte infiltration began in the two organs almost simultaneously, but the severity of the rejection was more vigorous in the kidney than in the pancreas in doubly grafted rats, and destruction of pancreas grafts progressed more slowly in SPK than in PTA recipients. Preexisting uremia delayed pancreas rejection in both SPK (exocrine 10.6 +/- 2.3, P = 0.032, and endocrine 14.8 +/- 3.4 days, P = 0.065, versus nonuremics) and PTA (exocrine 8.5 +/- 1.7, P = 0.007, and endocrine 12.6 +/- 2.5, P = 0.026, versus nonuremics) nonimmunosuppressed recipients. The MST of kidney grafts was not significantly longer in uremic (8.9 +/- 2.8 days) than in nonuremic (6.7 +/- 1.4 days) SPK recipients (P = 0.081). A synchronous kidney transplant and uremia independently down-modulate the rejection response to a pancreas graft, and a simultaneous pancreas graft has no detrimental effect on the survival of a kidney graft.(ABSTRACT TRUNCATED AT 400 WORDS)     

Outcomes after simultaneous kidney‐pancreas versus pancreas after kidney transplantation in the current era

Simultaneous pancreas and kidney (SPK) and pancreas after kidney (PAK) transplant are both potential options for diabetic ESRD patients. Historically, PAK pancreas graft outcomes were felt to be inferior to SPK pancreas graft outcomes. Little is known about outcomes in the modern era of transplantation. We analyzed our SPK and PAK recipients transplanted between 01/2000 and 12/2016. There were a total of 635 pancreas and kidney transplant recipients during the study period, 611 SPK and 24 PAK. Twelve of the PAK patients received a living donor kidney. There were no significant differences between the two groups in kidney or pancreas graft rejection at 1 year. Similarly, 1‐year graft survival for both organs was not different. At last follow‐up, uncensored and death‐censored graft survival was not statistically different for kidney or pancreas grafts. In addition, in Cox regression analysis SPK and PAK were associated with similar graft survival. Although the majority of pancreas transplants are in the form of SPK, PAK is an acceptable alternative. Simultaneous pancreas and kidney avoids donor risks associated with live donation, so may be preferable in regions with short wait times, but PAK with a living donor kidney may be the best alternative in regions with long SPK wait times.     

Donors with a maximum body weight of 50 kg for simultaneous pancreas-kidney transplantation

INTRODUCTION: Pediatric donors are rarely used for simultaneous pancreas-kidney transplantation (SPK). But the age of the donors may be less important than the body weight (BW). Therefore we retrospectively analyzed our data on SPK donors with a maximum BW of 50 kg. METHODS: Between June 1994 and December 2003, 22 patients received SPK transplants from cadaveric donors with a maximum BW of 50 kg (range, 25-50 kg; median, 42.4 kg). The median donor-recipient weight ratio was 0.61 (range, 0.47-0.91). RESULTS: Two kidney grafts (9.1%) displayed delayed graft function (2 and 9 dialyses). One patient needed insulin for 2 days (<20 IU/d), and the other patient for 1 month at a maximum of 7 IU/d. Four pancreas grafts (18.2%) were lost owing to graft thrombosis. One-year survival for patients was 95.5%; for kidneys, 86.4%; and for the pancreas, 72.7%. After a median observation period of 78 months, 6 acute rejection episodes were observed in 5 patients (22.7%). Five acute rejections were treated successfully, but 1 patient lost both organs. Two patients died of severe infections, at 3 months and 3 years, respectively, after SPK. Four kidney and 3 pancreas grafts developed chronic allograft dysfunction. CONCLUSIONS: Our results show that 1-year graft function in this series was less than the results reported to the International Pancreas Transplant Registry. The Main reason for early pancreas loss was graft thrombosis (18.2%). After a median observation period of 78 months, pancreas graft survival was 59.1%.     

Organ donation by living donors in isolated pancreas and simultaneous pancreas-kidney transplantation]

We studied retrospectively 106 pancreas transplants from living donors. Of these, 83 were solitary pancreas transplants, done between June 1979 and December 1997 (51 pancreas transplants alone for non-uremic recipients as well as 32 pancreas-after-kidney transplants for previously uremic recipients with a functioning kidney graft), and 23 were simultaneous pancreas-kidney transplants (SPK), done between March 1994 and December 1997. In all, 105 (99%) donors were genetically related to the recipients. Perioperative donor mortality was 0%. Donor complications included 9 splenectomies as well as 4 operatively drained and 7 percutaneously managed peripancreatic fluid collections. We noted hyperglycemia in 3 (3%) donors (all among the initial cases in this series). The 1-year survival rate was 50% for solitary pancreas recipients and 78% (pancreas) and 100% (kidney) for SPK recipients. Of the 5 pancreas graft losses which occurred after SPK, 3 were due to thrombosis, 1 to pancreatitis and infection, and 1 to chronic rejection. Currently, all kidney grafts and 18 pancreas grafts are functioning in these 23 dual organ recipients (with 0% recipient mortality). Living donor pancreas and SPK grafting is associated with low donor morbidity and good graft outcome. With stringent donor criteria and appropriate counseling of the prospective donor/recipient pairs, living donor pancreas transplants may become a more widely applied therapeutic alternative for selected non-uremic and uremic patients with Type I diabetes.     

A three-year experience with serum anodal trypsinogen as a biochemical marker for rejection in pancreatic allografts. False positives, tissue biopsy, comparison with other markers, and diagnostic strategies.

Serum values of immunoreactive anodal trypsinogen (sAT) have been claimed to correlate well with rejection occurring in pancreatic allografts. We have studied the behavior of sAT in serial serum samples obtained from 39 type I diabetics undergoing whole-organ pancreas transplantation during the past 3 years. Patients had either received a pancreatic allograft simultaneously with a transplanted kidney (SPK, n = 33) or after a previous kidney transplant (pancreas after kidney [PAK] n = 6). The behavior of sAT was studied in relation to the clinical diagnosis of rejection. Graft amylase output for all 39 patients and serum creatinine for the 33 SPK recipients were also studied. Tissue biopsies were obtained from 11 patients with elevated sAT values and a presumptive diagnosis of rejection. Nine of these patients had SPK grafts and simultaneously elevated creatinine values. Tissue was obtained from the simultaneously transplanted kidney; all specimens revealed rejection. Two of the 11 patients had PAK allografts. Biopsies performed on the graft duodenum were consistent with acute rejection. Three additional patients with unchanged sAT values had biopsies for other reasons; these biopsies failed to demonstrate signs of acute rejection. Thus graft biopsy correlated exactly with sAT behavior in every case in which rejection was suspected. Five patients had elevations of sAT not associated with rejection: one resulted from direct trauma, two had outlet obstruction, and two had clinical diagnoses of graft pancreatitis. The sAT was more sensitive and specific than GAO and as sensitive as creatinine for SPK recipients. These studies confirm that sAT is a reliable, graft-specific biochemical marker for the early diagnosis of pancreatic rejection. The use of sAT should allow for the proper timing of graft biopsies and the judicious use of immunosuppressive agents, which will result in increased allograft survival for PAK and pancreas-alone allografts.     

Neoquadruple induction with antithymocyte globulin/azathioprine/cyclosporine/prednisolone in simultaneous pancreas and kidney transplant recipients: 8.5-year results

Ten years ago therapy with antithymocyte globulin or OKT3, azathioprine, cyclosporine, and prednisolone was the most common induction treatment for simultaneous pancreas/ kidney (SPK) recipients. Although immunosuppression was started after surgery, there was a high incidence of acute rejection episodes. In 1995, we modified the application of antithymocyte globulin and prednisolone by starting prior to reperfusion. Between 1995 and 1996, 30 patients underwent a first SPK. Prior to reperfusion, antithymocyte globulin (4-6 mg/kg body weight) and 250 mg prednisolone were administered. Intraoperatively, another 250 mg prednisolone were administered as well as intravenous azathroprine 3 mg/kg. After surgery up to 10 doses of antithymocyte globulin were administered and cyclosporine trough levels targeted to 200 to 250 ng/mL. Prednisolone was reduced gradually. After a median period of 8.5 years (range: 7.8-9.5 years) patient, pancreas, and kidney graft survival were 93.3%, 70%, and 76.7%, respectively. Sixteen acute rejection episodes were diagnosed in 11 patients (36.7%), who were treated with prednisolone bolus (n = 4), prednisolone with OKT3 (n = 8), prednisolone with antithymocyte globulin (n = 1), cyclosporine to tacrolimus conversion (n = 2), or plasmapheresis (n = 1). Two recipients died after SPK due to severe infection or carcinoma with functioning grafts. Seven further pancreas grafts were lost. Five kidney losses were observed besides the two recipients who died with functioning grafts. While previous protocols yielded a rejection incidence after SPK between 50% and 80%, we observed 60% of patients with no rejection episode during an 8.5-year median follow-up.     

Impact of de novo donor‐specific anti‐HLA antibodies on grafts outcomes in simultaneous pancreas–kidney transplantation

De novo donor‐specific antibodies (dDSA) relevance in simultaneous pancreas–kidney (SPK) transplantation has been scarcely investigated. We analyzed dDSA relationship with grafts outcomes in a long‐term follow‐up SPK‐transplanted cohort. In 150 patients that received SPK transplant between 2000 and 2013, post‐transplant anti‐human leukocyte antigen (HLA) antibodies were screened and identified using Luminex‐based assays in sera collected at 3, 6, and 12 months, then yearly. dDSA were detected in 22 (14.7%) patients at a median 3.1 years after transplant. Pretransplant anti‐HLA sensitization (OR = 4.64), full HLA‐DR mismatch (OR = 4.38), and previous acute cellular rejection (OR = 9.45) were significant risk factors for dDSA. dDSA were significantly associated with kidney (in association with acute rejection) and pancreas graft failure. In dDSA+ patients, those with at least one graft failure presented more frequently dDSA against class II or I + II (P = 0.011) and locusDQ (P = 0.043) and had a higher median dDSA number (P = 0.014) and strength (P = 0.030). Median time between dDSA emergence and pancreas and kidney graft failure was 5 and 12 months, respectively. Emergence of dDSA increased the risk of grafts failure in SPK‐transplanted patients. Full HLA‐DR mismatch was associated with dDSA emergence. dDSA characteristics might help identify patients at a higher risk of graft failure.     

胰、肾联合移植六例报告

目的 探讨胰、肾联合移植治疗糖病合并糖尿病肾病的疗效。方法 回顾分析近期施行的6例胰、肾联合移植手术的方法、疗效及并发症的防治。结果 6例患者分别于移植胰腺恢复血液循环后23h、第9d、17h、19h、第5d及1．5h停用外源性胰岛素,移植肾功能于术后第2－4d恢复正常;术后并发症有排斥反应和血尿,其中1例术后5d发生加速性排斥反应,抗排斥治疗无效,于术后11d切除移植胰、肾,其余5例均痊愈出院。结论 胰、肾联合移植是治疗胰岛素依赖型糖尿病及达到胰岛素依赖期的非胰岛素依赖型糖尿病合并糖尿病合并糖尿病肾病的有效方法;加强围手术期管理术后减少各种并发症、取得良好疗效的有效措施。     

Pregnancy outcomes in simultaneous pancreas and kidney transplant recipients: a national French survey study

Simultaneous pancreas and kidney transplantation (SPK) is currently the best therapeutic option for patients with type 1 diabetes and terminal renal failure. Renal transplantation restores fertility enabling women to pursue pregnancies. However, scarcity of available data on pregnancy outcomes in SPK impedes fair medical counseling. Medical files of all pregnancies that lasted ≥3 months among recipients of functional SPK performed between 1990 and 2015 in France were retrospectively analyzed. Twenty‐six pregnancies in 22 SPK recipients were identified. Main maternal complications included gestational hypertension (53.8%) and infections (50%). Cesarean section was performed in 73% of cases. Overall fetal survival was 92.6% with a mean gestational age of 34.2 ± 3 weeks. Four children (16.7% of live births) had a birth weight <10th percentile. Endocrine pancreas graft function remained stable during pregnancy. An acute kidney rejection occurred in two patients, one of which resulting in graft loss. Kidney and pancreas graft survival was, respectively, 96% and 100% at 1 year postconception and did not differ from controls. Pregnancy in SPK is feasible, but patients should be informed of the risks for the fetus, the mother, and the grafts. Planning of pregnancy in SPK women is key to allow a personalized multidisciplinary monitoring, which represents the most straightforward approach to optimize outcomes.