Ultrasound-guided kidney biopsy: a ten-year retrospective single-center experience and the promising role of clinical hypnosis.

This retrospective analysis investigates the outcomes and complications of 682 kidney biopsies performed at ARNAS G. Brotzu from 2010 to 2021. Our findings indicate a minor complication rate of 9.1%, with severe complications being exceedingly rare at 0.3%. Age did not contribute to an increased risk, underscoring the procedure's safety across age groups. Clinical hypnosis was incorporated into the biopsy protocol in a subset of patients (n = 45) from April 2019 to December 2023. Over 90% of these patients reported no perception of the procedure, and 60% experienced no pain. According to STAY-Y test scores, this approach significantly reduced anxiety post-procedure (p = 0.001); no major or minor complications were observed in this group. While our study reaffirms the very low risk of severe complications in kidney biopsies, it also highlights the potential benefits of adjunct clinical hypnosis in enhancing patient comfort and cooperation during the procedure. This exploration opens a promising avenue for further investigation to improve patient experiences and procedural outcomes in kidney biopsies.

Acute Kidney Disease in Oncology: A New Concept to Enhance the Understanding of the Impact of Kidney Injury in Patients with Cancer.

Background Cancer patients are prone to developing acute kidney disease (AKD), yet this phenomenon remains understudied compared to acute kidney injury [AKI). Acute kidney disease, which often develops insidiously, can cause treatment interruptions, extended hospital stays, and increased mortality. Summary This perspective article explores the intricate relationship between AKD and cancer, focusing on prevalence, risk factors, implications for anticancer therapy, and long-term outcomes, including chronic kidney disease progression. Key Messages To emphasize the importance of early detection and intervention, this work advocates for increased research and awareness among clinicians to improve patient outcomes and manage healthcare burdens associated with AKD in cancer patients.

[An Integrated Multidisciplinary Approach to the Care of Renal Cancer Patients Undergoing Nephrectomy].

Kidney cancer is one of the most common cancers globally, ranking 9th and 14th among men and women, respectively. Advances in diagnostic techniques have enabled earlier and potentially less invasive interventions, however, this progress poses a challenge in managing low-malignancy tumors that were previously undiagnosed. To navigate treatment pathways, a deep understanding of the bidirectional relationship between Chronic Kidney Disease (CKD) and Renal Cell Carcinoma (RCC) is essential, influenced by risk factors such as hypertension and obesity. The debate between partial (PN) and radical nephrectomy (RN) continues to be fueled by a rich body of studies in the last two decades, aiming to determine the precise benefits of renal function preservation and overall survival. However, long-term monitoring remains inadequate. There is an urgent need for heightened clinical vigilance, urging meticulous periodic evaluations that include both eGFR and the urinary albumin-creatinine ratio, to identify potential deteriorations early. Furthermore, non-neoplastic renal parenchyma requires equal attention, often overshadowed by the assessment of tumor mass. A nuanced analysis is necessary to identify a range of nephropathies that guide more effective therapeutic strategies. A collaborative strategy that brings nephrologists, urologists, nuclear radiologists, oncologists, and pathologists together on a unified platform, focusing on a personalized medicine approach grounded on a profound analysis of individual risk factors, is pivotal in shaping the future of management and prevention strategies. This approach ensures a detailed therapeutic outlook and facilitates early interventions, marrying vigilance with interdisciplinary cooperation, thereby guarding against late diagnoses and offering patients a robust shield in their battle against kidney afflictions.

[Transplant Candidate with Cancer: Should We Proceed?]

Individuals who suffer from end-stage renal disease are at a higher risk of developing certain types of tumors. This risk increases as kidney function deteriorates further. Dialysis patients often witness a surge in the incidence of such malignancies. Interestingly, after the initial period following a kidney transplant, there is a dip in the number of deaths related to neoplasms. However, a long-term view reveals a progressive increase in the risk of developing tumors. The evaluation process for transplant candidacy is thorough, taking into account several factors, including the individual's history of neoplasms and the implications of immunosuppressive therapy. Immunosuppressive therapy is a double-edged tool in managing post-transplant complications, as it can foster environments conducive to neoplasm growth. It is essential to reevaluate, with the aid of an oncological opinion, the waiting time between cancer recovery and the listing for kidney transplantation, based on clinical data and follow-up. Independent of the type of tumor, the requirement to treat and achieve remission delays the listing process, consequently extending the time spent with end-stage renal disease and undergoing dialysis. These factors correlate with increased mortality, heightened risk of cardiovascular disease, and graft loss.

[Classification and Management of MGRS Related Diseases].

Monoclonal Gammopathies of Renal Significance (MGRS) are a complex group of disorders characterized by the production of aberrant monoclonal proteins that interact with kidney structures, causing tissue damage. Unlike neoplastic forms, kidney damage in MGRS does not correlate with clone mass or circulating monoclonal protein levels, conferring unique pre-neoplastic or non-neoplastic properties to the responsible clones. This manuscript explores the heterogeneity of monoclonal proteins involved, varying from full immunoglobulins to free light chains (FLC), and how they result in a spectrum of kidney lesions with differing prognoses. We also elaborate on diagnostic challenges, emphasizing the indispensable role of kidney biopsy, including advanced techniques like laser microdissection and mass spectrometry (LMD/MS) for deposit characterization, particularly in ambiguous or complex cases. Clinical management and treatment considerations, including the necessity for clone identification, are also discussed.

Glomerular diseases in pregnancy: pragmatic recommendations for clinical management.

Our understanding of the various aspects of pregnancy in women with kidney diseases has significantly improved in the last decades. Nevertheless, little is known about specific kidney diseases. Glomerular diseases are not only a frequent cause of chronic kidney disease in young women, but combine many challenges in pregnancy: immunologic diseases, hypertension, proteinuria, and kidney tissue damage. An international working group undertook the review of available current literature and elicited expert opinions on glomerular diseases in pregnancy with the aim to provide pragmatic information for nephrologists according to the present state-of-the-art knowledge. This work also highlights areas of clinical uncertainty and emphasizes the need for further collaborative studies to improve maternal and fetal health.

History of Preeclampsia in Patients Undergoing a Kidney Biopsy: A Biphasic, Multiple-Hit Pathogenic Hypothesis.

Introduction: It is not fully elucidated whether preeclampsia (PE) is a marker or a cause of chronic kidney disease (CKD). To test the hypothesis of a biphasic relationship between PE and CKD, we assessed PE prevalence in women who underwent a kidney biopsy. Methods: This retrospective, observational study recruited patients who underwent a kidney biopsy after delivery in 2014 to 2019 in 3 Italian Centers (Cagliari, Bari, Messina); low-risk pregnancies observed in Cagliari served as controls. A history of PE was assessed on the clinical charts and by phone interview. Results: In the biopsy cohort (379 pregnancies, 205 patients; 38 PE in 32 patients), kidney biopsy shows clustering in the first 5 years after PE (11 of 32). Pre-existing CKD was detected in 8 of 11 of these cases. Focal-segmental glomerulosclerosis (FSGS) and complex lesions were found in 12 of 32 biopsies. The odds ratio (OR) of having had a PE episode, compared with 561 low-risk pregnancies, was 10.071 (95% CI: 4.859-20.875; P < 0.001); multiparity maintained a protective effect (OR: 0.208). The delivery-to-biopsy time was significantly shorter in women with PE, both considering the first or the last PE versus the first or last delivery in patients with or without PE episodes. The characteristics of PE did not differ as compared with low-risk controls. Conclusion: Within the limitation of the retrospective design, our study, quantifying the association between needing a kidney biopsy and history of PE, suggests a biphasic pattern, with a peak in the first 5 years after delivery (probably due to pre-existing diseases) and a later increase, suggesting that PE may have later played as one hit in a multiple-hit pathogenesis.

Contraception in chronic kidney disease: a best practice position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology.

Even though fertility is reduced, conception and delivery are possible in all stages of CKD. While successful planned pregnancies are increasing, an unwanted pregnancy may have long-lasting deleterious effects, hence the importance of birth control, an issue often disregarded in clinical practice. The evidence summarized in this position statement is mainly derived from the overall population, or other patient categories, in the lack of guidelines specifically addressed to CKD. Oestroprogestagents can be used in early, non-proteinuric CKD, excluding SLE and immunologic disorders, at high risk of thromboembolism and hypertension. Conversely, progestin only is generally safe and its main side effect is intramestrual spotting. Non-medicated intrauterine devices are a good alternative; their use needs to be carefully evaluated in patients at a high risk of pelvic infection, even though the degree of risk remains controversial. Barrier methods, relatively efficacious when correctly used, have few risks, and condoms are the only contraceptives that protect against sexually transmitted diseases. Surgical sterilization is rarely used also because of the risks surgery involves; it is not definitely contraindicated, and may be considered in selected cases. Emergency contraception with high-dose progestins or intrauterine devices is not contraindicated but should be avoided whenever possible, even if far preferable to abortion. Surgical abortion is invasive, but experience with medical abortion in CKD is still limited, especially in the late stages of the disease. In summary, personalized contraception is feasible, safe and should be offered to all CKD women of childbearing age who do not want to get pregnant.

Risk of Preeclampsia and Adverse Pregnancy Outcomes after Heterologous Egg Donation: Hypothesizing a Role for Kidney Function and Comorbidity.

BACKGROUND AND OBJECTIVES: Preeclampsia (PE) is a risk factor for kidney diseases; egg-donation (ED) increasingly used for overcoming fertility reduction, is a risk factor for PE. CKD is also a risk factor for PE. However, kidney function is not routinely assessed in ED pregnancies. Objective of the study is seeking to assess the importance of kidney function and maternal comorbidity in ED pregnancies. DESIGN: retrospective observational study from clinical charts. SETTING: Sant'Anna Hospital, Turin, Italy (over 7000 deliveries per year). SELECTION: cases: 296 singleton pregnancies from ED (gestation > 24 weeks), who delivered January 2008-February 2019. Controls were selected from the TOrino Cagliari Observational Study (1407 low-risk singleton pregnancies 2009-2016). MEASUREMENTS: Standard descriptive analysis. Logistic multiple regression analysis tested: PE; pregnancy-induced hypertension; preterm delivery; small for gestational age; explicatory variables: age; BMI; parity; comorbidity (kidney diseases; immunologic diseases; thyroid diseases; other). Delivery over time was analyzed according to Kaplan Meier; ROC (Relative Operating Characteristic) curves were tested for PE and pre-term delivery, employing serum creatinine and e-GFR as continuous variables. The analysis was performed with SPSS v.14.0 and MedCalc v.18. RESULTS: In keeping with ED indications, maternal age was high (44 years). Comorbidity was common: at least one potential comorbid factor was found in about 40% of the cases (kidney disease: 3.7%, immunologic 6.4%, thyroid disease 18.9%, other-including hypertension, previous neoplasia and all other relevant diseases-10.8%). No difference in age, parity and BMI is observed in ED women with and without comorbidity. Patients with baseline renal disease or "other" comorbidity had a higher risk of developing PE or preterm delivery after ED. PE was recorded in 23% vs. 9%, OR: 2.513 (CI 1.066-5.923; p = 0.039); preterm delivery: 30.2% vs. 14%, OR 2.565 (CI: 1.198-5.488; p = 0.044). Limiting the analysis to 124 cases (41.9%) with available serum creatinine measurement, higher serum creatinine (dichotomised at the median: 0.67 mg/dL) was correlated with risk of PE (multivariate OR 17.277 (CI: 5.125-58.238)) and preterm delivery (multivariate OR 2.545 (CI: 1.100-5.892). CONCLUSIONS: Within the limits of a retrospective analysis, this study suggests that the risk of PE after ED is modulated by comorbidity. While the cause effect relationship is difficult to ascertain, the relationship between serum creatinine and outcomes suggests that more attention is needed to baseline kidney function and comorbidity.

Incremental dialysis in ESRD: systematic review and meta-analysis.

BACKGROUND: Incremental dialysis may preserve residual renal function and improve survival in comparison with full-dose dialysis; however, available evidence is limited. We therefore compared all-cause mortality and residual kidney function (RKF) loss in incremental and full-dose dialysis and time to full-dose dialysis in incremental hemodialysis (IHD) and incremental peritoneal dialysis (IPD). METHODS: We performed a systematic review and meta-analysis of cohort studies of adults with ESRD starting IHD and IPD. We identified in PubMed and Web of Science database all cohort studies evaluating incremental dialysis evaluating three outcomes: all-cause mortality, RKF loss, time to full dialysis. IPD was defined as < 3 daily dwells in Continuous Ambulatory Peritoneal Dialysis and < 5 sessions per week in Automated Peritoneal Dialysis, while IHD was defined as < 3 HD sessions per week. RESULTS: 22 studies (75,292 participants), 15 in HD and 7 in PD, were analyzed. Mean age at dialysis start was 62 and 57 years in IHD and IPD subjects, respectively. When compared to full dose, incremental dialysis (IHD or IPD) had an overall mortality risk of 1.14 [95% CI 0.85-1.52] with high heterogeneity among studies (I2 86%, P < 0.001), and lower mean RKF loss (- 0.58 ml/min/months, 95% CI 0.16-1.01, P = 0.007). Overall, time to full-dose dialysis was 12.1 months (95% CI 9.8-14.3) with no difference between IHD and IPD (P = 0.217). CONCLUSIONS: Incremental dialysis allows longer preservation of RKF thus deferring full-dose dialysis, by about 1 year in HD and PD, with no increase in mortality risk. Large and adequate studies are needed to confirm these findings.

Where Are You Going, Nephrology? Considerations on Models of Care in an Evolving Discipline.

Nephrology is a complex discipline, including care of kidney disease, dialysis, and transplantation. While in Europe, about 1:10 individuals is affected by chronic kidney disease (CKD), 1:1000 lives thanks to dialysis or transplantation, whose costs are as high as 2% of all the health care budget. Nephrology has important links with surgery, bioethics, cardiovascular and internal medicine, and is, not surprisingly, in a delicate balance between specialization and comprehensiveness, development and consolidation, cost constraints, and competition with internal medicine and other specialties. This paper proposes an interpretation of the different systems of nephrology care summarising the present choices into three not mutually exclusive main models ("scientific", "pragmatic", "holistic", or "comprehensive"), and hypothesizing an "ideal-utopic" prevention-based fourth one. The so-called scientific model is built around kidney transplantation and care of glomerulonephritis and immunologic diseases, which probably pose the most important challenges in our discipline, but do not mirror the most common clinical problems. Conversely, the pragmatic one is built around dialysis (the most expensive and frequent mode of renal replacement therapy) and pre-dialysis treatment, focusing attention on the most common diseases, the holistic, or comprehensive, model comprehends both, and is integrated by several subspecialties, such as interventional nephrology, obstetric nephrology, and the ideal-utopic one is based upon prevention, and early care of common diseases. Each model has strength and weakness, which are commented to enhance discussion on the crucial issue of the philosophy of care behind its practical organization. Increased reflection and research on models of nephrology care is urgently needed if we wish to rise to the challenge of providing earlier and better care for older and more complex kidney patients with acute and chronic kidney diseases, with reduced budgets.

A best-practice position statement on pregnancy after kidney transplantation: focusing on the unsolved questions. The Kidney and Pregnancy Study Group of the Italian Society of Nephrology.

Kidney transplantation (KT) is often considered to be the method best able to restore fertility in a woman with chronic kidney disease (CKD). However, pregnancies in KT are not devoid of risks (in particular prematurity, small for gestational age babies, and the hypertensive disorders of pregnancy). An ideal profile of the potential KT mother includes "normal" or "good" kidney function (usually defined as glomerular filtration rate, GFR ≥ 60 ml/min), scant or no proteinuria (usually defined as below 500 mg/dl), normal or well controlled blood pressure (one drug only and no sign of end-organ damage), no recent acute rejection, good compliance and low-dose immunosuppression, without the use of potentially teratogen drugs (mycophenolic acid and m-Tor inhibitors) and an interval of at least 1-2 years after transplantation. In this setting, there is little if any risk of worsening of the kidney function. Less is known about how to manage "non-ideal" situations, such as a pregnancy a short time after KT, or one in the context of hypertension or a failing kidney. The aim of this position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology is to review the literature and discuss what is known about the clinical management of CKD after KT, with particular attention to women who start a pregnancy in non-ideal conditions. While the experience in such cases is limited, the risks of worsening the renal function are probably higher in cases with markedly reduced kidney function, and in the presence of proteinuria. Well-controlled hypertension alone seems less relevant for outcomes, even if its effect is probably multiplicative if combined with low GFR and proteinuria. As in other settings of kidney disease, superimposed preeclampsia (PE) is differently defined and this impairs calculating its real incidence. No specific difference between non-teratogen immunosuppressive drugs has been shown, but calcineurin inhibitors have been associated with foetal growth restriction and low birth weight. The clinical choices in cases at high risk for malformations or kidney function impairment (pregnancies under mycophenolic acid or with severe kidney-function impairment) require merging clinical and ethical approaches in which, beside the mother and child dyad, the grafted kidney is a crucial "third element".

Controversial issues in CKD clinical practice: position statement of the CKD-treatment working group of the Italian Society of Nephrology.

This position paper of the study group "Conservative treatment of Chronic Kidney Disease-CKD" of the Italian Society of Nephrology addresses major practical, unresolved, issues related to the conservative treatment of chronic renal disease. Specifically, controversial topics from everyday clinical nephrology practice which cannot find a clear, definitive answer in the current literature or in nephrology guidelines are discussed. The paper reports the point of view of the study group. Concise and practical advice is given on several common issues: renal biopsy in diabetes; dual blockade of the renin-angiotensin-aldosterone system (RAAS); management of iron deficiency; low protein diet; dietary salt intake; bicarbonate supplementation; treatment of obesity; the choice of conservative therapy vs. dialysis. For each topic synthetic statements, guideline-style, are reported.

Pregnancy in Chronic Kidney Disease: questions and answers in a changing panorama.

Chronic kidney disease (CKD) is increasingly encountered in pregnancy because of greater diagnostic awareness, which is a reflection of the newer, broader definitions (i.e., any changes in blood or urine composition or at imaging, or a glomerular filtration rate (GFR) of <60 mL/min lasting at least 3 months) and of increased incidence (higher maternal age and better outcomes of several kidney diseases). CKD is extremely heterogeneous and may be described by the degree of GFR reduction (CKD stages), the presence of proteinuria and hypertension and the type of kidney disease; the risk of adverse pregnancy-related events increases as GFR decreases and it is affected by proteinuria and hypertension. Specific risks are reported in various diseases such as lupus nephropathy or diabetic nephropathy. While transplantation at least partially restores fertility in end-stage kidney disease, pregnancy on dialysis is increasingly reported. This chapter deals with the available evidence on the management of CKD patients in pregnancy.

Pregnancy in women with pre-existing lupus nephritis: predictors of fetal and maternal outcome.

BACKGROUND: Only few data are available on pregnancy in patients with lupus nephritis (LN) diagnosed before conception. The aim of this study was to identify the risk factors for complicated pregnancy in women with pre-existing LN. METHODS: In a multicentre study, we collected data on 113 pregnancies occurring in 81 women with pre-existing biopsy-proven LN. Primary outcomes were fetal loss including perinatal death and renal flares during and 12 months after pregnancy. Univariate and logistic regression analyses were used to identify predictors of outcomes. RESULTS: Renal biopsy performed 7.2 +/- 4.9 years before pregnancy showed the following WHO classes: 6 patients in II, 8 in III, 48 in IV and 19 in V. At conception, most patients were in complete (49%) or partial (27%) remission. There were nine spontaneous abortions, one stillbirth and five neonatal deaths. Thirty-one deliveries were preterm. Birth weight was <2500 g in 34 newborns. During pregnancy or after delivery, there were 34 renal flares, most of which (20) were reversible. Three patients had a progressive decline of glomerular filtration rate (one on dialysis). At logistic regression analysis, the pregnancy outcome was predicted by hypocomplementaemia at conception (RR 19.02; 90% CI 4.58-78.96) and aspirin during pregnancy (RR 0.11; 90% CI 0.03-0.38). Renal flare was predicted by renal status (partial remission RR 3.0; 90% CI 1.23-7.34, nonremission RR 9.0; 90% CI 3.59-22.57). CONCLUSIONS: Pregnancy can be successful in most women with pre-existing LN, even for those with a severe renal involvement at onset. Renal flares during and after pregnancy are not uncommon and can be predicted by renal status assessed before pregnancy. Normocomplementaemia and low-dose aspirin therapy during pregnancy are independent predictors of a favourable fetal outcome.

Analysis of the factors conditioning the diffusion of peritoneal dialysis in Italy.

BACKGROUND: The diffusion of peritoneal dialysis (PD) in Italy is lower than expected on the basis of indications and contraindications reported in literature. METHODS: To analyse the factors influencing the use of PD in Italy, we used data from the first National Census of the Italian Society of Nephrology relating to 9773 incident patients (Incid(HD + PD)) in 2004 and 43 293 prevalent patients dialysed in 658 centres at 31/12/2004 (337 public centres, 286 private centres, 12 paediatric centres, 15 research or religious institutions and 8 unspecified). RESULTS: The percentages on PD of total incident (Inc(PD)%) and prevalent dialysis patients (Prev(PD)%) were 15.9% and 10.3%, respectively with considerable variations from region to region and from centre to centre. The Inc(PD)% was higher in regions with fewer patients on dialysis in private centres. In the private centres, the Inc(PD)% was 0.4%. Of the 325 non-paediatric public centres, 116 (35.7%) do not use PD: compared with the 209 centres which do, these centres have a lower mean Inc(HD + PD) and Prev(HD + PD) per centre (13.0 +/- 12.3 vs 28.6 +/- 18.0 - 51.8 +/- 35.7 vs 117.3 +/- 66.4 patients, P < 0.0001), and more haemodialysis (HD) stations available (3.0 vs 3.5 patients per HD station, P < 0.0001). However, the significant influence of cultural and motivational factors on the use of this method is demonstrated by the fact that it is used by 34% of the smaller non-paediatric public centres, and is not used by 19% of the larger non-pediatric public centres.

Immunosuppressive treatment in dialysis patients.

Immunosuppressive treatment is a critical procedure in dialysis patients, in whom an increased risk of infection is already present. Haemodialytic treatment increases the patient's susceptibility to bacterial infection, mainly by impairing polymorphonuclear leukocyte phagocytosis, but it can also restore the patient's immunological defences by improving the T-cell function, which is reduced by pre-dialysis uraemia. Patients on dialysis usually continue the immunosuppressive treatment that had been established for the illness that caused their renal failure [e.g. systemic lupus erythematosus (SLE) or renal vasculitis]. Less frequently, patients on dialysis need immunosuppression for immunological or inflammatory diseases that appear 'de novo' after initiation of dialysis. SLE and antineutrophil cytoplasmic antibody (ANCA)-related vasculitides are immunological illnesses that frequently cause end-stage renal failure (ESRF). A reduction in serological and/or clinical activity is usually observed in SLE patients after they reach ESRF, but a similar or increased frequency of extrarenal relapse episodes in lupus patients after the beginning of the dialysis, compared with the pre-dialysis period, has also been described. Frequency of relapse episodes in patients on dialysis treatment for ANCA-related vasculitides varies from 10 to 30% per patient/year in different reports, and it is higher than the frequency of relapses after renal transplantation; anti-rejection therapy seems to be the most likely protective factor in these conditions. The treatment of relapse episodes in SLE or ANCA vasculitis in dialysis-dependent patients is usually not different from treatment of relapses in patients with dialysis-independent renal function. However, the risk of severe infection caused by immunosuppressive treatment is relevantly higher in dialysis patients. Furthermore, there is a lack of prospective controlled studies indicating the optimal management of immunosuppressive protocols in dialysis patients. A particularly careful assessment of the patient's risks and benefits is necessary in deciding how long immunosuppressive treatment should last after acute or rapidly progressive renal damage, that should require dialysis treatment, in patients with SLE or ANCA vasculitis. In the above conditions, the risks of prolonging immunosuppressive treatment must be balanced against the relatively good prognosis offered to these patients by dialysis and renal transplantation. In a retrospective review of 24 patients receiving long-term steroid therapy (>3 months) in our dialysis unit in the past 5 years, we found relevant clinical differences in the patients receiving steroid treatment compared with 24 controls. Steroid-treated patients showed less favourable nutritional conditions, with lower serum albumin and body mass index vs non-steroid-treated patients; moreover, C-reactive protein values were persistently higher in the steroid-treated group. Steroid treatment in these patients was usually performed at the beginning of regular dialysis, as a continuation of the treatment that started before the initiation of dialysis. Only two patients, who needed a prolonged low-dose steroidal treatment to control a malnutrition-inflammation-atherosclerosis (MIA) syndrome, started steroids many years after beginning dialysis. Steroid treatment was effective in improving the nutritional condition and inflammatory symptoms in these two patients after all conventional measures had failed.