Risk Factors for Persistent Anosmia and Dysgeusia in Children with SARS-CoV-2 Infection: A Retrospective Study.

BACKGROUND: Olfactory and gustative dysfunctions are two of the most common post-acute sequelae of SARS-CoV-2 infection in children, which can have a negative impact on the routines of children and families. As several children have had COVID-19 since the Omicron variant, it is important to investigate if this increase in infections is reflected in higher olfactory/taste disfunctions. The primary aim of this study was to characterize the presence of olfactory/gustative problems in a cohort of children, its evolution, and its association with risk factors such as COVID-19 variant, hospitalization, presence of olfactory/gustative dysfunction during the acute phase, and vaccination. METHODS: This was a retrospective analysis of children with microbiologically confirmed SARS-CoV-2 infection evaluated in person at a referral pediatric post-COVID-19 clinic in Rome, Italy. We included children younger than 19 years old, evaluated from the beginning of the pandemic up to October 2022. At specific timepoints, we investigated the presence of olfactory/taste disfunctions and evaluated them according to the SARS-CoV-2 variants circulating at the time of infection. RESULTS: A total of 1250 children (650 females; 52.0%) with a mean age of 6.77 (±4.12) years were included in the study. At 3, 6, 12, and 18 months, 12 (9.6%), 7 (5.6%), 2 (1.6%), and 1 (0.8%) of the children reported anosmia and dysgeusia post-COVID-19 infection, respectively. The presence of anosmia and dysgeusia during the acute phase of infection and being infected with a pre-Omicron variant were found to be significant risk factors for persistent olfactory and gustatory dysfunction during all follow-up periods. CONCLUSIONS: anosmia and dysgeusia symptoms tended to decrease gradually over time, but not all children recovered quickly.

A Simplified Low-Dose 10-Day Quadruple Therapy with a Galenic Formulation of Bismuth Salicylate Is Highly Effective for Helicobacter pylori Eradication.

BACKGROUND: Earlier studies have shown that a modified low-dose bismuth quadruple therapy given for 10 to 14 days is highly effective for the treatment of Helicobacter pylori infection in Sardinia. However, bismuth is not universally available. AIM: We aimed to investigate the efficacy of a simplified low-dose 10-day quadruple therapy containing a galenic formulation of bismuth salicylate for H. pylori infection. PATIENTS AND METHODS: Adult patients positive for H. pylori infection were assigned to a quadruple therapy containing a galenic formulation of bismuth salicylate (200 mg) plus tetracycline 500 mg, metronidazole 500 mg and rabeprazole 20 mg, given twice a day with the midday and evening meals for 10 days. A negative stool antigen test or 13C-Urea Breath Test defined successful eradication. Compliance and adverse events were recorded 30-40 days after the end of treatment. RESULTS: In this open-label pilot study, 42 patients were enrolled (mean age 54.1 ± 12.0 years; 64% female). Among the study participants, 35 were naïve to H. pylori treatment. The treatment regimen was completed by 41 patients, with an overall success rate of 95.1%. More specifically, the eradication rate was 95.1% PP; 95% confidence interval (CI) = 86.6-100 and 92.9% by ITT; 95%CI = 85.1-100%, respectively. For naïve patients, the cure rate was 97.1%. Compliance was excellent. Side effects were absent or mild overall. CONCLUSIONS: The modified low-dose 10-day quadruple therapy provided high eradication rates of H. pylori infection, despite the replacement of colloidal bismuth subcitrate with bismuth salicylate. In regions where bismuth is unavailable in the market, the galenic formulation should be a valid option.

Congenital Adrenal Hyperplasia (CAH) and Gitelman Syndrome (GS): Overlapping Symptoms in an Uncommon Association.

BACKGROUND: Classical salt-wasting (SW) congenital adrenal hyperplasia (CAH) and Gitelman syndrome (GS) are two genetic conditions in which dyselectrolytemia may occur. No association between the two conditions has been previously described. Case Presentation. We present the case of a boy with a neonatal diagnosis of SW-CAH who showed low potassium blood levels from the age of 15 years. This electrolytic alteration was, at first, attributed to an excessive action of mineralocorticoid drugs. Due to persistence of hypokalemia, SLC12A3 whole genome sequencing was performed, showing a heterozygous C to T base pair substitution at position 965 in gene SLC12A3. This mutation is related to Gitelman syndrome with autosomal recessive transmission. CONCLUSIONS: SW-CAH and GS determine opposite values of potassium in the absence of specific therapy, with a natural tendency to compensate each other. The symptom overlap makes diagnosis difficult. Organic causes of hypokalemia in patients undergoing life-saving therapy should not be excluded.

Rapalog-Mediated Repression of Tribbles Pseudokinase 3 Regulates Pre-mRNA Splicing.

Rapalogs have become standard-of-care in patients with metastatic breast, kidney, and neuroendocrine cancers. Nevertheless, tumor escape occurs after several months in most patients, highlighting the need to understand mechanisms of resistance. Using a panel of cancer cell lines, we show that rapalogs downregulate the putative protein kinase TRIB3 (tribbles pseudokinase 3). Blood samples of a small cohort of patients with cancer treated with rapalogs confirmed downregulation of TRIB3. Downregulation of TRIB3 was mediated by LRRFIP1 independently of mTOR and disrupted its interaction with the spliceosome, where it participated in rapalog-induced deregulation of RNA splicing. Conversely, overexpression of TRIB3 in a panel of cancer cell lines abolished the cytotoxic effects of rapalogs. These findings identify TRIB3 as a key component of the spliceosome, whose repression contributes significantly to the mechanism of resistance to rapalog therapy. SIGNIFICANCE: Independent of mTOR signaling, rapalogs induce cytoxicity by dysregulating spliceosome function via repression of TRIB3, the loss of which may, in the long term, contribute to therapeutic resistance.

Dynamic Membrane Localization of RNase Y in Bacillus subtilis.

Metabolic turnover of mRNA is fundamental to the control of gene expression in all organisms, notably in fast-adapting prokaryotes. In many bacteria, RNase Y initiates global mRNA decay via an endonucleolytic cleavage, as shown in the Gram-positive model organism Bacillus subtilis This enzyme is tethered to the inner cell membrane, a pseudocompartmentalization coherent with its task of initiating mRNA cleavage/maturation of mRNAs that are translated at the cell periphery. Here, we used total internal reflection fluorescence microscopy (TIRFm) and single-particle tracking (SPT) to visualize RNase Y and analyze its distribution and dynamics in living cells. We find that RNase Y diffuses rapidly at the membrane in the form of dynamic short-lived foci. Unlike RNase E, the major decay-initiating RNase in Escherichia coli, the formation of foci is not dependent on the presence of RNA substrates. On the contrary, RNase Y foci become more abundant and increase in size following transcription arrest, suggesting that they do not constitute the most active form of the nuclease. The Y-complex of three proteins (YaaT, YlbF, and YmcA) has previously been shown to play an important role for RNase Y activity in vivo We demonstrate that Y-complex mutations have an effect similar to but much stronger than that of depletion of RNA in increasing the number and size of RNase Y foci at the membrane. Our data suggest that the Y-complex shifts the assembly status of RNase Y toward fewer and smaller complexes, thereby increasing cleavage efficiency of complex substrates like polycistronic mRNAs.IMPORTANCE All living organisms must degrade mRNA to adapt gene expression to changing environments. In bacteria, initiation of mRNA decay generally occurs through an endonucleolytic cleavage. In the Gram-positive model organism Bacillus subtilis and probably many other bacteria, the key enzyme for this task is RNase Y, which is anchored at the inner cell membrane. While this pseudocompartmentalization appears coherent with translation occurring primarily at the cell periphery, our knowledge on the distribution and dynamics of RNase Y in living cells is very scarce. Here, we show that RNase Y moves rapidly along the membrane in the form of dynamic short-lived foci. These foci become more abundant and increase in size following transcription arrest, suggesting that they do not constitute the most active form of the nuclease. This contrasts with RNase E, the major decay-initiating RNase in E. coli, where it was shown that formation of foci is dependent on the presence of RNA substrates. We also show that a protein complex (Y-complex) known to influence the specificity of RNase Y activity in vivo is capable of shifting the assembly status of RNase Y toward fewer and smaller complexes. This highlights fundamental differences between RNase E- and RNase Y-based degradation machineries.

[Peritoneal dialysis in the Lazio region: results from 2017 regional audit].

In 2011, a first peritoneal dialysis audit was held in the Lazio region to analyze the problems hindering the spread of this method and to improve the quality of care through the sharing of best practices across Centers. A scientific board was therefore set up, representing all the Centers offering PD, in order to assess clinical effectiveness using KPIs (Key Performance Indicators) and to quantify the objectives to be achieved. The analysis made it possible to identify the main problems and take action, all the while monitoring progress through KPIs. A second audit was carried out in 2017 and the collected data was analyzed and compared with the findings of the previous study. Overall, data showed an increase in prevalence, although the incidence showed a slight decrease. Indicators on the change of dialysis treatment, the dropout from domiciliary treatment and the incidence of late referral appeared stable over time. A slight improvement was observed in clinical data on peritonitis and on the length of hospitalization. All participants in the audit declared that sharing and discussing clinical practices had been really useful. In addition, through the drafting of practical documents (guides for patients, guidance on informed consent, protocols of clinical follow-up), a number of tools have been provided to ensure a uniformly high level of care across the different regional Centers.

[PD in Italy: the 5th GSDP-SIN Census 2014].

OBJECTIVES: To know PD modalities and results in Italy. METHODS: The Census was carried out by means of an on-line questionnaire in ALL the 225 non-pediatric public centers which PERFORMED PD in 2014. The results were compared with those of previous Censuses (2005:Cs-05; 2008:Cs-08; 2010:Cs-10; 2012:Cs-12). RESULTS: Incidence. In 2014 PD was begun (first treatment for ESRD) by 1,652 pts (CAPD: 57.2%) and HD by 4,442 pts (%PD-incidence= Cs-14: 27,1%; Cs-12: 23.4%; Cs-10: 23.3%; Cs-08: 22.8%; Cs-05: 24.2%). For the first time Incremental PD does not increase (Cs-14: 27,5%; Cs-12: 28,8%; Cs-10: 22,8%; Cs-08: 18,3%; Cs-05: 11,9%). Prevalence. At 31/12/2014 there were 4,480 patients on PD (CAPD: 46.9%) (%PD-prevalence= Cs-14: Cs-12: 17.1%; Cs-10: 16.6%; Cs-08: 16.7%; Cs-05:16.8%; p=NS), 24.3% of whom were on assisted PD (family members: 83.6%; paid caregivers: 11.5%; nurses: 1.1%; NH: 2.8%). Out. In 2014 there was no change in the PD drop-out rate (32.0 ep/100yrs-pt) (death: 502; transplant: 329; switch to HD: 528 pts). The main reason for transferring to HD remained peritonitis (24.8%). Choice (9.3%) and impossibility to continue PD (15.2%) are increasing. Peritonitis. The peritonitis rate (953 episodes) was 0.224 ep/yrs-pt. The incidence of new cases of EPS in 2013-14 (39 cases=0.444 ep/100yrs-pt) is decreasing (2011-12= 0.505; 2009-10= 0.529; 2004-08= 0.701 ep/100-yrs-pt). Other results. Compared to 2012, in 2014 the number of Centers using 3.86% for PET increased (41.3%) (Cs-12: 30.8%; Cs-10: 15.6%; p <0.001), while the number carrying out home visits (59.6%) remained unchanged (56.3% in 2012, 59.4% in 2010). CONCLUSION: Cs-14 confirms the extensive use, stability and good results of PD in Italy. Incremental PD and assisted PD are unchanged, peritonitis are decreased and EPS remains a rare event. PET-3.86% is increasingly used.

Dermoscopy for the Diagnosis of Conjunctival Lesions.

This article describes the present literature on dermoscopy of conjunctiva and shows the results of a dermoscopy study of 147 conjunctival tumors. Melanomas were characterized by a heavy pigmentation, irregular dots, and a higher prevalence of gray color compared with nevi. Squamous cell carcinomas had peculiar hairpin and glomerular vessels. Primary acquired melanoses were characterized by regularly distributed light brown dots. A large part of nevi had small cysts.

[CKD-MBD in Peritoneal Dialysis].

CKD-MBD is a systemic disorder of the mineral and bone metabolism as a result of CKD. The clinical relevance of this syndrome has led to the identification of the biochemical targets to be achieved in order to improve the outcome of the patient. However, in hemodialysis (HD) and peritoneal dialysis (DP) patients, these targets are not reached. Hyperphosphatemia is a predictor of cardiovascular and all-cause mortality. In DP the removal of phosphorus (P) occurs by diffusion and convection, with a contribution of ultrafiltration of about 11%. P clearance is time dependent, with differences between CAPD and APD and depending on membrane transport characteristics. Residual renal function plays a key role in the P balance. Calcium (Ca) clearance in PD depends on the calcium levels, calcium concentration in dialysate and ultrafiltration. Positive Ca balance brings to Adynamic Bone Disease. Several bone-derived substances, some of them with hormonal action, have shed new light on the bone- cardiac axis. The hormonal functions of bone are likely to be related to histological lesions that develop during chronic renal failure. Compared to the past, recent data show less obvious differences in bone histomorphometry parameters between HD patients and PD patients. However, in PD patients fewer fractures are reported, probably due to different bone quality.

BMI, nephroangiosclerosis and glomerulonephritis: Is there any meeting point?

AIM: Overweight has been related to renal arteriolosclerosis and is able to modify intrarenal haemodynamics. Increasing evidence suggests an association between weight in excess and primary glomerulonephritis (GN). The aim of this study was to evaluate the relationship between nutritional status and intrarenal arterial stiffness in primary GN associated to arteriolosclerosis. We have considered the glomerular diameter (GD) as morphological parameter in overweight and obese patients. METHODS: Clinical, laboratory, anthropometric data and renal Doppler ultrasound were performed immediately before kidney biopsy. RESULTS: Primary GN was diagnosed in 92 patients. Mild arteriolosclerosis was found in 19.6% of patients, moderate in the 20.6%, severe in the 10.9% while nephroangiosclerosis was diagnosed in 8.7% of patients. A positive correlation was found between body mass index (BMI) and renal resistive index (RRI) (P < 0.01, r = 0.34). RRI were significantly higher in patients with severe arteriolosclerosis at kidney biopsy (P < 0.05). Furthermore, higher BMI (P < 0.01) was found in patients with renal arteriolosclerosis than patients without renal arteriolosclerosis (26.1 ± 4.4 kg/m2 vs. 24.4 ± 4.5 kg/m2 ). Finally, in overweight and obesity patients we found a positive correlation between maximal GD and BMI (P < 0.01) and maximal GD and RRI (P < 0.01). CONCLUSION: In overweight and obese patients affected by primary GN, it might be found not only glomerular but also renal vascular lesions. Finally, we believe that nephroangiosclerosis, in combination with weight in excess, is able to modify intrarenal haemodynamic parameters. Moreover, in response to these changes, the renal tissue morphologically promotes a GD increase regardless of the underlying GN.

[Peritoneal Dialysis in Italy: the fourth GSDP-SIN census 2012].

OBJECTIVE: To know PD modalities and results in Italy. METHODS: The Census was carried out by means of an on-line questionnaire in all the 224 non-pediatric public centers which performed PD in 2012. The results were compared with those of previous Censuses. RESULTS: Incidence. In 2012 PD was begun (first treatment for ESRD) by 1,433 pts (CAPD: 54.3%) and HD by 4,700 pts (%PD-incidence= Cs-12: 23.4%; Cs-10: 23.3%; Cs-08: 22.8%; Cs-05: 24.2%; p=NS), with a further increase in incremental PD (Cs-12: 28.8%; Cs-10: 22.8%; Cs-08: 18.3%; Cs-05: 11.9%; p-0.001). Prevalence. At 31/12/12 there were 4,299 patients on PD (CAPD: 46.1%) (%PD-prevalence= Cs-12: 17.1%; Cs-10: 16.6%; Cs-08: 16.7%; Cs-05:16.8%; p=NS), 24.5% of whom were on assisted PD (family members: 82.3%; paid caregivers: 12.4%; nurses: 0.7%; NH: 3.0%). Out. In 2012 there was no change in the PD drop-out rate (30.9 ep/100yrs-pt) (death: 481; transplant: 290; switch to HD: 511 pts). The main reason for transferring to HD remained peritonitis (28.2%). Peritonitis. The peritonitis rate (1,179 episodes) was 0.284 ep/yrs-pt. EPS. The incidence of new cases of EPS in 2011-12 (43 cases=0.505 ep/100yrs-pt) remained unchanged (2009-10= 0.529; 2004-08= 0.701 ep/100-yrs-pt). Other results. Compared to 2010, in 2012 the number of Centers using 3.86% for PET increased (30.8% vs 15.6%-p-0.001), while the number carrying out home visits remained unchanged (56.3 vs 59.4%). CONCLUSIONS: Cs-12 confirms the extensive use, stability and good results of PD in Italy. Incremental PD is on the increase. EPS remains a rare event.

Incremental start to PD as experienced in Italy: results of censuses carried out from 2005 to 2014.

BACKGROUND: It is not known how widely used in Italy an incremental start to in peritoneal dialysis (Incr-PD) is. METHODS: By analyzing the peritoneal dialysis (PD) censuses conducted by the PD Study Group (GSDP-SIN) for the years 2005, 2008, 2010, 2012 and 2014 in all the Centers performing PD in Italy, the use of Incr-PD, i.e. continuous ambulatory peritoneal dialysis (CAPD) with 1 or 2 exchanges/day or automated peritoneal dialysis (APD) with 3-4 sessions/week, was examined among incident PD patients. RESULTS: In 2014 PD was started in Italy by 1,652 patients, 455 (27.5%) of whom incrementally (Incr-CAPD 82.2% vs. Incr-APD 17.8%). Incr-PD was used in 53.5% of the 225 Centers. The number of patients and of Centers using Incr-DP increased constantly over the years up to 2012 (in 2005 Incr-PD was used in 33.4% of Centers, and in 11.9% of patients). The use of Incr-PD was greater in Centers with a more extensive PD program and greater use of PD in general. The most widely-used modality in Incr-PD was CAPD. CONCLUSIONS: Incr-PD is used in Italy in a large number of incident PD patients. The reasons for this increase need to be clarified, as current adequacy targets are based on full-dose studies with a very low glomerular filtration rate (GFR).

[Best practices on peritoneal dialysis: the audit of Lazio Region]. / Best practices in dialisi peritoneale: l'audit della regione Lazio.

The diffusion of peritoneal methodology can not be something out of the real organizational context and the regional directive can not be the only means to encourage the diffusion. There is the need to provide effective and sustainable levels of assistance through a clinical scientific support and sharing of best-practises. On one side, the aim is to provide an aid by the centers with great expertise in the methodology, recognized as reference points; on the other side, to establish the shared K.P.I.s (Key Performance Index), to asses the clinical effectiveness and measure the objectives to be achieved, through a modality of valuation to establish the real applicability. For this purpose, a scientific board was founded, composed by the heads of UU.OO, that provide the peritoneal dialysis, to determine which aspects to investigate and identify factors of supply improvement. The selected method was the clinical audit. The analysis of the 2011 data has allowed us to capture the situation of the peritoneal dialysis in the Lazio Region. The formative procedure has enabled the centers to share and standardize protocols and therapeutic procedures, identify the strengths of peritoneal dialysis in the Lazio Region and define the KPIs through whose compare and monitor the centers over time. The conclusive analysis of the audit has enabled to identify a series of activities to be undertaken together in order to improve the situation of the peritoneal dialysis in the Lazio Region. In the following years, surveys will be carried out to verify the KPIs trend.

Renal parenchymal resistance in patients with biopsy proven glomerulonephritis: Correlation with histological findings.

Renal Doppler ultrasound is increasingly used in nephrology for the evaluation of renovascular disease, allograft dysfunction, and chronic nephropathies. We compared intrarenal hemodynamic parameters to biopsy findings of glomerular sclerosis, tubular atrophy, interstitial fibrosis, crescents, arteriolosclerosis, and clinical variables in 100 patients. A positive correlation exists between renal function and percentage of glomerular sclerosis (P <0.01, r = 0.26), conversely a negative correlation exists between glomerular filtrate rate and percentage of glomerular sclerosis(P <0.0001, r = -0.35). The percentage of glomerular sclerosis correlate positively with pulsatile index (PI) (P <0.05, r = 0.21) and renal resistive index (RI) (P <0.05, r = 0.20). The percentage of crescents correlates positively with PI(P <0.05, r = 0.21) and RI (P <0.05, r = 0.20). Classifying arteriolosclerosis in four groups according to a severity scale, from absence to severe, PI (P <0.05) and RI (P <0.01) were significantly different. In the post hoc analysis, the median values of PI and RI are significantly different in patients with severe arteriolosclerosis than others. Ultrasound examination is a non-invasive diagnostic technique used on patients with suspected or established renal disease. Our study shows a close correlation between kidney function, ultrasound parameters, and histological findings. Measurement of renal parenchymal resistance by ultrasound could be used in association with biopsy and glomerular function for the evaluation of renal damage in patients with glomerulonephritis.

Ribosomal RNA depletion or exclusion has negligible effect on the detection of viruses in a pan viral microarray.

Pan viral DNA microarrays, which can detect known, novel and multiple viral infections, are major laboratory assets contributing to the control of infectious diseases. The large quantity of ribosomal RNA (rRNA) found in tissue samples is thought to be a major factor contributing to the comparatively lower sensitivity of detecting RNA viruses, as a sequence-independent PCR is used to amplify unknown samples for microarray analysis. This study aimed to determine whether depletion or exclusion of rRNA can improve microarray detection and simplify its analysis. Therefore, two different rRNA depletion and exclusion protocols, RiboMinus™ technology and non-rRNA binding hexanucleotides, were applied to the microarray sample processing and the outcome was compared with those of the sequence-independent amplification protocol. This study concludes that the two procedures, described to deplete or exclude rRNA, have negligible effect on the microarrays detection and analysis and might only in combination with further techniques result in a significant enhancement of sensitivity. Currently, existing protocols of random amplification and background adjustment are pertinent for the purpose of sample processing for microarray analysis.

Renal involvement in Waldenström's macroglobulinemia: case report and review of literature.

Waldenström's macroglobulinemia (WM) is a rare lymphoid neoplasia, accounting for 2% of all hematological malignancies. Renal complications occur rather rarely compared to multiple myeloma. The most common renal manifestations are mild proteinuria and microhematuria. We describe a case of MW presenting with acute renal failure and NS. A 67-year-old man was referred to our hospital for sudden onset nephrotic syndrome. Electrophoresis revealed a monoclonal component in the gamma region, which was classified as an IgM k. During hospitalization, acute kidney injury developed, with creatinine up to 5 mg/dL, despite adequate hydration and alkalinization. A kidney biopsy was performed, showing minimal change disease (MCD) with interstitial and capsular lymphoid infiltrates of B-Lymphocytes CD20+. B-lymphocytes infiltration suggested the possibility of renal localization of lymphoproliferative disorder. So, bone marrow histology was performed, revealing lymphoplasmacytic lymphoma (WM). The patient was treated with bortezomib, desamethasone, and rituximab, with partial recovery of renal function (creatinine 1.5 mg/dL) and complete remission of proteinuria after 8-month follow-up. The remission of NS in our patient with rituximab seems to emphasize the pathogenetic role of B cells in MCD, although a coincident effect of immunosuppression on both the underlying renal disease and the hematologic disease cannot be excluded.

Bacillus subtilis RNase Y activity in vivo analysed by tiling microarrays.

RNase Y is a key endoribonuclease affecting global mRNA stability in Bacillus subtilis. Its characterization provided the first evidence that endonucleolytic cleavage plays a major role in the mRNA metabolism of this organism. RNase Y shares important functional features with the RNA decay initiating RNase E from Escherichia coli, notably a similar cleavage specificity and a preference for 5' monophosphorylated substrates. We used high-resolution tiling arrays to analyze the effect of RNase Y depletion on RNA abundance covering the entire genome. The data confirm that this endoribonuclease plays a key role in initiating the decay of a large number of mRNAs as well as non coding RNAs. The downstream cleavage products are likely to be degraded by the 5' exonucleolytic activity of RNases J1/J2 as we show for a specific case. Comparison of the data with that of two other recent studies revealed very significant differences. About two thirds of the mRNAs upregulated following RNase Y depletion were different when compared to either one of these studies and only about 10% were in common in all three studies. This highlights that experimental conditions and data analysis play an important role in identifying RNase Y substrates by global transcriptional profiling. Our data confirmed already known RNase Y substrates and due to the precision and reproducibility of the profiles allow an exceptionally detailed view of the turnover of hundreds of new RNA substrates.

Fludarabine in chronic lymphocytic leukemia with membranous nephropathy.

Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in Western countries. Despite its relative frequency, the association of glomerular disease is extremely rare. We present a case of membranous nephropathy (MN) during CLL treated with fludarabine. A 74-year-old man was admitted to our hospital because of the onset of nephrotic syndrome (proteinuria was 7 g/24 h). Six years before, he had been diagnosed with CLL. Biochemical analysis showed the following results: creatinine was 1.7 mg/dL (creatinine clearance was 39 mL/min), urea was 64 mg/dL, hemoglobin was 8.6 g/dL, and white blood cells was 16,580/mm(3) (60% lymphocytes). The urine sediment revealed 7-8 red blood cells and many hyaline and granular casts. No monoclonal peak was demonstrated in either serum or urine electrophoresis. Bence-Jones proteinuria was negative. The patient underwent renal biopsy that showed MN with an extensive lymphocyte perivascular infiltration; immunohistochemistry on renal biopsy specimen showed that infiltrating lymphocytes were CD20+. Moreover, DNA from tissue fractions was analyzed by qualitative polymerase chain reaction-based detection of clonal gene rearrangements of the immunoglobulin heavy chain gene, confirming the monoclonality of the infiltrating lymphocytes. The patient was started on fludarabine as monotherapy, with complete remission of proteinuria and recovery of renal function (creatinine clearance was 75 mL/min) after 1 year of follow-up.

Analysis of past and present methods of measuring and estimating body surface area and the resulting evaluation of its doubtful suitability to universal application.

Body surface area (BSA) is probably the most used tool for indexing physiological functions. The most relevant past and present measuring methods have been examined, and an analysis of selected methods used to measure and to estimate was performed. The evaluation of methods demonstrates a relationship between past and present measuring methods, but also highlights the doubtfulness of their suitability due to the criteria used to select the population for measurements and to estimate BSA by formulae, due to the weight variance according to the same height and the lack of a numeric estimate of the body shape. The use of BSA formulae generated from a population with anthropometric measures different from those of a population where the formulae are applied, and the change in today's BSA towards 1.73 m(2) can induce risks by incorrectly estimating GFR and in planning dialysis prescriptions.