Trends over Time of Lung Function and Radiological Abnormalities in COVID-19 Pneumonia: A Prospective, Observational, Cohort Study.

Radiological and functional sequelae of Coronavirus Disease 2019 (COVID-19) pneumonia are still poorly understood. This was a prospective, observational, physiological, cohort study on consecutive adult patients with COVID-19 pneumonia admitted in April-May 2020 in the high dependency respiratory unit of L. Sacco University Hospital in Milan (Italy). During hospitalization, patients underwent chest computed tomography (CT), blood gas analysis, spirometry, and lung diffusion capacity for carbon monoxide (DLco), which were repeated 6 weeks post-discharge. Chest CTs were individually read by two expert radiologists, that calculated the total severity score (TSS). Twenty patients completed the study (mean age 58.2 years, 70% males). During the acute phase, mean DLco, alveolar volume (VA), and vital capacity (VC) were 56.0 (16.3), 64.8 (14.0), and 71.7 (16.9) % predicted, respectively, and were inversely associated with PaO2/FiO2 ratio. Fifty percent of patients had a restrictive ventilatory pattern; mean TSS was 7.9 (4.0). At follow up, gas exchange parameters were normalized; consolidations persisted in 10% of cases, while DLco was <80% predicted in 65% of patients and was independently predicted by Log10D-dimer at admission (ß -18.675; 95%CI, -28.373--9.076; p = 0.001). In conclusion, functional abnormalities in COVID-19 pneumonia survivors can persist during follow up and are associated with the severity of the disease.

Characteristics and outcomes in hospitalized COVID-19 patients during the first 28 days of the spring and autumn pandemic waves in Milan: An observational prospective study.

BACKGROUND: The therapeutic approach to COVID-19 and healthcare system preparedness improved during 2020. We compared characteristics and outcomes of hospitalized COVID-19 patients during the first 28 days of the March and October pandemic waves in Milan, Italy. MATERIAL AND METHODS: A prospective, observational study enrolling adult patients hospitalized with COVID-19 pneumonia during March 7-April 4 (1st period) and October 15-November 12 (2nd period). During the 1st period hydroxychloroquine, lopinavir/ritonavir and therapeutic enoxaparin when thrombosis was confirmed were administered; systemic corticosteroids were given in case of severe pneumonia. During the 2nd period dexamethasone, methylprednisolone, remdesivir, thromboprophylaxis or anticoagulation were administered according to international recommendations. Patients with respiratory distress on oxygen masks initiated CPAP. Outcomes were: length of hospital stay, all-cause in-hospital mortality and need for intubation. RESULTS: We included 70 patients (75% males) during the 1st and 76 patients (51% males, p = 0.522) during the 2nd period. Prevalence of severe respiratory failure (30% vs. 12%, p = 0.006), and D-dimer >3000 FEU (34% vs. 15%, P = 0.012) were reduced during the 2nd period, while anticoagulation and corticosteroids were more frequently administered (both p < 0.01). Mortality and time to referral were also reduced (39.4% vs. 22.4%, p = 0.019 and 6 vs. 5 days, p = 0.014), while need for intubation didn't change. Hospitalization length was comparable, but the proportion of patients discharged home was higher during the 2nd period (28.2% vs. 55.4%, p = 0.001). CONCLUSIONS: Changing treatment paradigms and early referral might have reduced mortality in COVID-19 patients. The effects of specific therapeutic regimens needs further confirmation in future clinical studies.

Changes in quality of life and dyspnoea after hospitalization in COVID-19 patients discharged at home.

BACKGROUND: To date, the effects of COVID-19 pneumonia on health-related quality of life (HRQoL) and dyspnoea are unknown. METHODS: In a real-life observational study, 20 patients with COVID-19-related pneumonia received usual care plus erdosteine (300 mg twice daily) for 15 days after hospital discharge following local standard operating procedures. At discharge (T0) and on Day 15 (T1), participants completed the St George's Respiratory Questionnaire (SGRQ), the modified Medical Research Council (mMRC) scale of dyspnoea during daily activity, the BORG scale for dyspnoea during exertion, and Visual Analogue Scale (VAS) for dyspnoea at rest. Paired t-tests compared scores at T0 and T1. RESULTS: The mean (SD) SGRQ total score decreased from 25.5 (15.5) at T0 to 16.9 (13.2) at T1 (p<0.01); 65% of patients achieved a clinically important change of ≥4 points. SGRQ domain scores (symptoms, activity, and impact) were also significantly reduced (all p<0.01). The mean (SD) VAS score decreased from 1.6 (1.7) to 1.4 (2.5); p<0.01. The mean mMRC score decreased significantly (p=0.031) and 30% of patients achieved a clinically important change of ≥1 point. The mean (SD) Borg score increased from 12.8 (4.2) to 14.3 (2.4); p<0.01. CONCLUSION: The present proof of concept study is the first to report HRQoL in patients with COVID-19. During 15 days after hospital discharge, patients reported significant improvements in HRQoL and dyspnoea at rest and during daily activities.

Effect of continuous positive airway pressure on respiratory drive in patients with obstructive sleep apnea.

OBJECTIVE: Patients with obstructive sleep apnea (OSA) have an altered control of breathing during wakefulness. Thus far, whether and how treatment with continuous positive airway pressure (CPAP) may restore these abnormalities has been poorly understood. The aim of this study was to investigate the long-term effects of CPAP on the breathing pattern, ventilatory drive (VDr), and chemoreceptor sensitivity in OSA patients. PATIENTS AND METHODS: This was a prospective, observational study, carried out in an academic sleep outpatient clinic. A total of 62 patients with OSA (mean age [SD], 51 [11] years) underwent polysomnography (PSG), breathing pattern assessment, mouth occlusion pressure, ventilatory response to hypoxemia (Ve/SaO2), and hypercapnia (Ve/PETCO2) before and after CPAP titration and during 12-month follow-up. A total of 48 age-matched healthy subjects served as controls. Patients with good (≥6 h/night) and poor (<6 h/night) compliance with CPAP were also compared. RESULTS: At baseline, VDr as well as thoracic and inspiratory impedances were greater in patients with OSA compared with controls and were reduced by CPAP treatment, starting from the night of titration (P < 0.01), especially in patients with good compliance with CPAP. Baseline Ve/SaO2 was higher in OSA patients (P < 0.05) and was progressively normalized during CPAP treatment (P < 0.001). The pathophysiological changes were mainly due to a reduction in tidal volume. The remaining breathing pattern parameters were unaltered by CPAP treatment and were similar between groups. CONCLUSION: In OSA patients, the mechanics of breathing are inefficient because of an imbalance of the VDr. Regular CPAP treatment improves the efficiency of the respiratory system and normalizes the hypoxemic stimulus.

Rationale underlying the measurement of fractional exhaled nitric oxide in systemic sclerosis patients.

Systemic sclerosis (SSc) is an autoimmune disease characterised by tissue fibrosis leading to vascular injury. Nitric oxide (NO) has been implicated in the pathogenesis of autoimmune diseases. A deficiency in basal NO production by the constitutive endothelial isoform of nitric oxide synthase may promote vasoconstriction and vascular wall thickening. In January 2017, we searched the PubMed/Medline, Cochrane Library and Enbase/Medline databases for studies analysing physio-pathological correlations with lung fractional exhaled NO (FeNO) production. This review describes the rationale underlying possible applications of FeNO measurements in the management of SSc. Measuring NO levels at multiple expiratory flow rates makes it possible to distinguish airway NO production and distal airway/alveolar NO concentration (ANOC), and there is increasing evidence indicating that it may be useful in many non-respiratory conditions. FeNO levels are increased in SSc patients with fibrosing lung disease, whereas those with pulmonary hypertension have relatively low FeNO levels, thus suggesting that NO plays an important role in regulating pulmonary vascular resistance in SSc. However, a number of studies have shown increased ANOC in SSc patients without increased FeNO levels. The relationship between lung diffusing capacity for carbon monoxide and ANOC may be related to increased alveolar membrane thickness impeding NO diffusion or alveolar inflammation in SSc lung disease. The findings concerning the usefulness of FeNO measurements in SSc patients are discordant, but the available papers suggest that ANOC is a more accurate indicator of progressive lung dysfunction and an increase in ANOC could assess the extent of interstitial lung disease non-invasively.

Usefulness of six-minute walk test in systemic sclerosis.

The 6-minute walk test (6MWT) is a standardised, feasible and reliable measure of sub-maximal exercise capacity that has never been fully validated in systemic sclerosis (SSc). A variety of data suggest that many non-pulmonary aspects of SSc contribute to the test results, thus blunting the ability of the 6MWT to measure changes in lung function. Sources of variability are a training effect, technician experience, subject encouragement, medication, other activities on day of testing, deconditioning and the effects of musculoskeletal conditions and pain. Another cause of variability is the anatomical site the probe is attached to: a forehead probe is preferable to a finger or earlobe sensor. The indiscriminate use of the 6MWT for all SSc patients is not useful. It should be used in patients with pulmonary involvement, combined with diffusion capacity of the lung for carbon monoxide (DLCO) and its components (membrane diffusion and capillary volume) or the Sclerodermia Health Assessment Questionnaire Disability Index. The use of these combined parameters may indicate the onset of pulmonary hypertension. Recent studies suggest two alternatives to the 6MWT: maximal cardiopulmonary exercise testing and DLCO testing during effort. However, their use must still be validated.

Psoriasis and Respiratory Comorbidities: The Added Value of Fraction of Exhaled Nitric Oxide as a New Method to Detect, Evaluate, and Monitor Psoriatic Systemic Involvement and Therapeutic Efficacy.

Psoriasis is a chronic inflammatory systemic disease characterized by a wide range of comorbidities. Respiratory comorbidities are currently poorly characterized and with discordant results. The systemic state of inflammation caused by psoriasis acts de novo on respiratory tissues and amplifies preexisting inflammation from asthma or chronic obstructive pulmonary disease. Because the lungs act as a gas exchanger between the internal and external environment, the impact of chronic psoriasis inflammation may be easily assessed through the analysis of exhaled breath. The fraction of exhaled nitric oxide test (FeNO) is a potential noninvasive solution that can provide quantitative and qualitative indices of respiratory airway inflammation. FeNO is routinely used to screen and manage asthmatic patients. Recent pilot studies contain encouraging data that underscore its possible use with systemic inflammatory nonpulmonary diseases, such as psoriasis. FeNO may therefore be a useful tool to evaluate underestimated airway inflammation and at the same time globally evaluate the impact of systemically antipsoriatic therapies.

[Renal Infarction: multicentric cases in Piedmont].

We describe factors associated to renal infarction, clinical, instrumental and laboratoristic features, and therapeutic strategies too. This is an observational, review and polycentric study of cases in Nephrologic Units in Piedmont during 2013-2015, with diagnosis of renal infarction by Computed Tomography Angiography (CTA). We collected 48 cases (25 M, age 57±16i; 23 F age 70±18, p = 0.007), subdivided in 3 groups based on etiology: group 1: cardio-embolic (n=19) ; group 2: coagulation abnormalities (n= 9); group 3: other causes or idiopathic (n=20). Median time from symptoms to diagnosis, known only in 38 cases, was 2 days (range 2 hours- 8 days). Symptoms of clinical presentation were: fever (67%), arterial hypertension (58%), abdominal o lumbar pain (54%), nausea/vomiting (58%), neurological symptoms (12%), gross hematuria (10%). LDH were increased (>530 UI/ml) in 96% of cases (45 cases out of 47), PCR (>0.5 mg/dl) in 94% of cases (45 out of 48), and eGFR <60 ml/min in 56% of cases (27 out of 48). Comparison of the various characteristics of the three groups shows: significantly older age (p=0.0001) in group 1 (76±12 years) vs group 2 (54±17 years) and group 3 (56±17 years); significantly more frequent cigarette smoking (p = 0.01) in group 2 (67%; 5 cases out of 9) and group 3 (60%; 12 cases out of 20) than group 1 (17%). No case has been subjected to endovascular thrombolysis. In 40 out of 48 cases, anticoagulant therapy was performed after diagnosis: in 12 (32%) cases no treatment, in 12 cases (30%) heparin, in 8 cases (20%) low molecular weight heparin, in 4 cases (10%) oral anticoagulants, in 3 cases fondaparinux (7%), in 1 case (2%) dermatan sulfate. CONCLUSIONS: Although some characteristics may guide the diagnosis, latency between onset and diagnosis is still moderately high and is likely to affect timely therapy.

Are there any relations among transplant centre volume, surgical technique and anatomy for donor graft selection? Ten-year multicentric Italian experience on mini-invasive living donor nephrectomy.

BACKGROUND: Selection of the right or left living donor kidney for transplantation is influenced by many variables. In the present multi centric study including 21 Italian transplant centres, we evaluated whether centre volume or surgical technique may influence the selection process. METHODS: Intra- and perioperative donor data, donor kidney function, and recipient and graft survival were collected among 693 mini-invasive living donor nephrectomies performed from 2002 to 2014. Centre volume (LOW, 1-50 cases; HIGH, >50 cases) and surgical technique (FULL-LAP, full laparoscopic and robotic; HA-LAP, hand-assisted laparoscopy; MINI-OPEN, mini-lumbotomy) were correlated with selection of right or left donor kidney and with donor and recipient outcome. RESULTS: HIGH-volume centres retrieved a higher rate of donor right kidneys (29.3% versus 17.6%, P < 0.01) with single artery (83.1% versus 76.4%, P < 0.05) compared with LOW-volume centres. Surgical technique correlated significantly with rate of donor right kidney and presence of multiple arteries: MINI-OPEN (53% and 13%) versus HA-LAP (29% and 22%) versus FULL-LAP (11% and 23%), P < 0.001 and P < 0.05, respectively. All donors had an uneventful outcome; donor bleeding was more frequent in LOW-volume centres (4% versus 0.9%, P < 0.05). CONCLUSIONS: Centre volume and surgical technique influenced donor kidney side selection. Donor nephrectomy in LOW-volume centres was associated with higher risk of donor bleeding.

Influence of autonomic nervous system dysfunction in the genesis of sleep disorders in fibromyalgia patients.

OBJECTIVES: Fibromyalgia (FM) is characterised by chronic musculoskeletal pain, autonomic nervous system (ANS) dysfunction, and disturbed sleep. The aim of this study was to evaluate the influence of ANS dysfunction on the genesis of sleep disorders. METHODS: Fifty female FM patients and 45 healthy subjects matched for age, gender and body mass index underwent a clinical, polysomnographic and autonomic profile evaluation at rest and during a tilt test in order to determine muscle sympathetic nerve activity (MSNA), plasma catecholamine levels, and the spectral indices of cardiac sympathetic (LFRR) and vagal (HFRR) modulation computed by means of the spectrum analysis of RR during sleep. RESULTS: The FM patients had a higher heart rate (HR), more MSNA and a higher LF/HF ratio, and lower HFRR values at rest (p<0.05), and showed no increase in MSNA, a smaller decrease in HFRR, and an excessive rate of syncope (46%) during the tilt test. Their sleep was less efficient (p<0.01), and they had a higher proportion of stage 1 non-REM sleep (p<0.001), experienced many arousals and periodic limb movements (PLMs) per hour of sleep (p<0.001) and a high proportion of periodic breathing (PB%) (p<0.0001). Their cyclic alternating pattern (CAP) rate was significantly increased (p<0.001). During sleep, they had a higher HR and LF/HF ratio, and a lower HFRR (p<0.001). The number of tender points, CAP rate, PB% and PLMI correlated positively with HR and the LF/HF ratio, and negatively with HFRR during sleep. CONCLUSIONS: Our findings seem to show that sleep causes the same effects as a stressful test in FM patients. A vicious circle is created during sleep: pain increases sympathetic cardiovascular activation and reduces sleep efficiency, thus causing lighter sleep, a higher CAP rate, more arousals, a higher PLMI, and increasing the occurrence of PB, which gives rise to abnormal cardiovascular neural control and exaggerated pain sensitivity.

Oxygen therapy in COPD patients with isolated nocturnal hypoxemia; comparison of quality of life and sleep between bronchitis and emphysema phenotype: A prospective observational study.

BACKGROUND: COPD is a heterogeneous disease composed by two main phenotypes: bronchitis (COPDb) and emphysema (COPDe) with different clinical presentation, physiology, imaging, response to therapy and decline in lung function. The aim of this study is to evaluate whether nocturnal hypoxemic COPDb and COPDe have a different behaviour during sleep and the effect of nocturnal oxygen supplementation (nO2LT). MATERIALS AND METHODS: 75 COPDb and 120 COPDe were enrolled. All patients performed polysomnography, Pittsburgh and Maugeri Foundation Respiratory Failure questionnaire, and pulmonary function before and after six months of nO2LT. RESULTS: At baseline, compared to COPDb, COPDe have decreased sleep efficiency (SE) (67.5±6% vs. 76.9±3% p<0.05) and higher arousals (A/I) (18.1±3 event/h vs. 8.7±1 event/h p<0.05). Oxygen desaturation index (ODI) was increased during REM (7.1±1 event/h vs. 2.3±0.5 event/h p<0.05). nO2LT in COPDe improves SE (77±4% vs. 67.5±6% p<0.05) and decreases A/I (9±5 event/h vs. 18.1±3 event/h p<0.05). ODI during REM (3.5±2 event/h vs. 7.1±1 p<0.05) decreases and quality of life (QoL) improves (MFR-28 total 56±22 vs 45±20 p<0.05), due to an improvement in cognitive abilities (45±30 vs 33±31 p<0.05) and daily activities (61±29 vs 53±21 p>0.05). In COPDb nO2LT reduces ST90 (15±6% vs. 43±8% p<0.05) less than in COPDe (15±6% vs. 8±4% p<0.05); improves A/I (10±2 event/h vs. 8.7±1 p<0.05) and there is no evidence of an improvement in QoL. CONCLUSIONS: Six months of nO2LT improve quality of life in COPDe, not in COPDb. We found a difference in sleep quality between COPDe and COPDb.

Impaired lung transfer factor in fibromyalgia syndrome.

OBJECTIVES: The aim of this study was to evaluate whether pulmonary diffusing capacity is impaired in patients with fibromyalgia (FM) as it is in those with other diseases characterised by autonomic nerve system (ANS) dysfunction such as type 1 diabetes. METHODS: Forty-five consecutive anti-nuclear antibody (ANA)-negative female Caucasian patients aged 50.1± 5.6 years with FM and compared with 45 healthy female control volunteers matched in terms of age and body mass index (BMI). The autonomic function has been evaluated by means of standard electrocardiography (ECG), finger blood pressure respiration, and muscle sympathetic nerve activity (MSNA) at rest and during a stepwise tilt test up to 75°. Their autonomic profiles were drawn up on the basis of MSNA, plasma catecholamine levels, and spectral indices of cardiac sympathetic and vagal modulation, and sympathetic vasomotor control computed by means of the spectrum analysis of RR and systolic arterial pressure (SAP) variability. Lung volumes and dynamic spirometry parameters were assessed by means of plethysmography. All of the patients were clinically evaluated and completed the FQI and COMPASS questionnaire. RESULTS: There was no difference in lung volumes between the FM patients and healthy controls, but DLCO (83±4 vs. 96±5; p<0.001), Kco (84±5 vs 98±5; p<0.001), DM (12.7±2.4 vs 13.6±1.8; p<0.05) and Vc (48±3.9 vs 65±7; p<0.001) were significantly reduced in the patients. The COMPASS-31, RCS and pain VAS scores significantly correlated with DLCO, Kco and Vc with the correlation being particularly close in the case of Vc. Furthermore, univariate Cox proportional hazard analysis showed that the three scores were all significantly associated with an increased risk of impaired DLCO (respectively, χ(2) 16.21, p<0.0005; χ(2) 7.09, p<0.005; χ(2) 6.37, p<0.01). CONCLUSIONS: FM impairs DLCO mainly as a result of a reduction in Vc, and that this defect is inversely proportional to the severity of the dysfunction suggesting a relationship between impaired DLCO and autonomic nerve dysfunction.

A new approach to detect early lung functional impairment in very light smokers.

PURPOSE: The aim of our study is to investigate if lung carbon monoxide diffusing capacity (DLCO) measured during effort is able to detect early respiratory functional impairment. METHODS: We enrolled 25 very light smokers and 20 healthy non smokers. Subjects underwent plethysmography, DLCO (single breath technique) and calculated effective pulmonary blood flow (Qc) by rebreathing method. During exercise by cycle ergometer (duration 10±2min; recovery 11±3min) DLCO and Qc were calculated at 25% and 50% of theoretical maximum workload. RESULTS: At baseline lung function and Qc did not differ between groups. DLCO and DLCO/Qc measured during exercise were significantly greater in non smokers (p<0.001); Qc was not statistically different. In very light smokers, DLCO, DLCO/Qc measured during exercise significantly correlated with the number of pack years (r=-0.60 p<0.001; r=-0.58 p<0.05; r=-0.55 p<0.05, respectively). CONCLUSIONS: In very light smokers there is lung function impairment and our data show that DLCO during exercise may reveal this underlying early damage.

Performance capacity evaluated using the 6-minute walk test: 5-year results in patients with diffuse systemic sclerosis and initial interstitial lung disease.

OBJECTIVES: To identify factors indicating exercise-induced oxygen desaturation during the 6-minute walk test (6MWT) in patients with diffuse systemic sclerosis (SSc) and initial interstitial lung disease (ILD). METHODS: The study involved 121 consecutive adult anti-Scl 70 autoantibody-positive SSc patients with initial ILD, 93 of whom were followed up for five years. Before enrolment and then annually, the patients underwent high-resolution computed tomography (HRCT), functional lung tests, with carbon monoxide diffusion capacity of the lung (DLCO) and its components (alveolar-capillary membrane [Dm] and pulmonary blood volume [Vc]), the evaluation of dyspnea before and after the 6MWT using the Borg scale, and transthoracic echocardiography. A decrease in peripheral capillary oxygen saturation (SpO2) of ≥4% during the 6MWT was used to define desaturation, the appearance of which led to the patient being withdrawn from follow-up. RESULTS: There were no significant differences in HRCT score during the follow-up, but 32 patients (35%) desaturated during the 6MWT, including 12 (37%) who experienced a severe decrease SpO2 to ≤88%, indicating a high risk of mortality. At baseline, there was no statistically significant difference in any considered clinical characteristics between the desaturating and non-desaturating patients but, at the time of desaturation, the desaturators had lower minimum SpO2% levels during the 6MWT (p<0.0001), and lower DLCO (p<0.0001) and Dm (p<0.0001). Comparison of the desaturators defined on the basis of a reduction in SpO2 to ≤88% and those defined on the basis of a decrease in SpO2 of ≥4% showed that, at baseline, the former had lower minimum SpO2% levels during 6MWT (p<0.001), lower DLCO (p=0.01), a lower DLCO/VA ratio (p=0.05), lower Dm (p<0.005) and Vc values (p<0.5), and higher RVsystP (p=0.01). At the time of desaturation, the desaturators' minimum SpO2 levels during the 6MWT correlated with their DLCO (r=0.78; p<0.001), Dm (r=0.65; p<0.01), Vc (r=0.52;p<0.05) and RV-systP values (r = -0.53; p<0.05). CONCLUSIONS: Our data seem to confirm the close interdependence between pulmonary diffusion and oxygen desaturation during exercise. In SSc combined 6MWT, DLCO and its components may indicate patients at increased risk of developing pulmonary hypertension.

Diffusing Pulmonary Capacity Measured During Effort: A Possible Early Marker of Pulmonary Involvement In Systemic Sclerosis.

BACKGROUND: Interstitial lung involvement is common and potentially limits the quality of life in patients with systemic limited sclerosis (SScl). OBJECTIVES: To study the lung carbon monoxide diffusion (DLCO) measured during effort in order to identify a possible subclinical impairment. METHODS: We enrolled 20 SScl patients without interstitial lung involement and 20 healthy controls. At enrolment all subjetcs underwent plethysmography, DLCO by single-breath technique, and evaluation of pulmonary blood flow (Qc) with the rebreathing CO2 method. Skin involvement in the SScl patients was rated using the modified Rodman skin score (mRSS). During exercise on a cycle ergometer, DLCO, DLCO/ alveolar volume (Kco) and Qc were calculated at 25% and 50% of predicted maximum workload (25% pmw and 50% pmw). RESULTS: At baseline two groups did not differ in age, body mass index, lung function or Qc. In the controls, DLCO, Kco and DLCO/Qc measured at 25% pmw and 50% pmw were significantly higher than in SScl patients, while Qc was not different. Based on response to effort, SScl patients were divided into two groups: responders, with an increase of DLCO(25%pmw) and DLCO(50%pmw) at least 5% and 10% respectively, and non-responders. The non-responders showed greater skin involvement and significantly reduced DLCO, Kco and DLCO/Qc values at rest than responders. CONCLUSIONS: Moderate effort in SScl patients may reveal a latent impairment in gas diffusion through the alveolar/capillary membrane, thus confirmig that exertional DLCO can identify lung damage at an earlier stage than DLCO at rest.

Calcium-sensing-related gene mutations in hypercalcaemic hypocalciuric patients as differential diagnosis from primary hyperparathyroidism: detection of two novel inactivating mutations in an Italian population.

BACKGROUND: Inactivating mutations of the calcium-sensing receptor (CaSR), of the G-protein subunit α11 (GNA11) and of the adaptor-related protein complex 2, sigma 1 subunit (AP2S1) genes are responsible for familial hypocalciuric hypercalcaemia (FHH). The aim of this study was to analyse prevalence and pathogenicity of CaSR, GNA11 and AP2S1 mutations in patients with an FHH phenotype and to compare them with a sample of patients with primary hyperparathyroidism (PHPT) in order to identify the most useful laboratory parameter for a differential diagnosis. METHODS: Patients with an FHH phenotype were studied with polymerase chain reaction amplification and direct sequencing of the entire CaSR, GNA11 and AP2S1 coding sequences. Novel mutations were introduced in a Myc-tagged human wild-type (WT) CaSR cDNA-expressing vector, and functional assay was performed on human embryonic kidney cells evaluating expression and function of mutated proteins. RESULTS: Among 16 FHH patients, none had an inactivating GNA11 or AP2S1 mutation while 3 (18.8%) carried a CaSR mutation and 10 (62.5%) at least one CaSR polymorphism. Within the latter group, 7 of 10 patients had more than one polymorphism (4.1 ± 2.1 per patient). Two novel CaSR mutations [c.2120A>T (E707V) and c.2320G>A (G774S)] were identified: the E707V mutation prevented CaSR expression (western blot), whereas the G774S mutation determined a reduced receptor sensitivity to calcium (IP3 assay). PHPT patients showed significantly (P < 0.001) higher serum calcium, parathyroid hormone, urinary calcium and calcium-creatinine clearance ratio (CCCR) and significantly lower serum phosphate than FHH ones. CONCLUSIONS: FHH should be clearly differentiated by PHPT to avoid unnecessary surgery: CCCR could be a useful screening tool while genetic analysis should include the two novel CaSR mutations herein described. The role of multiple polymorphisms deserves further investigation in patients with an FHH phenotype.

Unexpectedly high prevalence of rare genetic disorders in kidney transplant recipients with an unknown causal nephropathy.

BACKGROUND: Patients with a rare genetic disease may receive renal transplantation (KTx) without a correct diagnosis of causal nephropathy and therefore develop unexpected and even severe complications. The aim of the study was to describe the cases of rare genetic disorders diagnosed after KTx, in order to draw clinical lessons for the transplant physician. METHODS: We retrospectively assessed all patients who had received a diagnosis of a rare genetic disorder after KTx. RESULTS: In our center, more than 30% (278/911) of kidney transplant (KTx) recipients were diagnosed with a causal nephropathy: Prevalence of rare genetic disorders in this group was 4.32% (12/278), including 2,8-dihydroxyadeninuria (2,8-DHA) disease (n = 2), HNF-1B-associated nephropathy (n = 2), UMOD-related nephropathy (n = 5), Fabry disease (n = 1), INF2 focal segmental glomerulosclerosis (n = 1), and Senior-Løken syndrome (n = 1). 2,8-DHA nephropathy relapsed in both patients causing an acute renal failure and jeopardizing the graft. CONCLUSIONS: Kidney transplant recipients without a diagnosis of causal nephropathy appear to be a selected population in which rare genetic diseases might be more common than expected. As even a belated diagnosis after KTx can have a significant impact on graft and patient survival and on other family members, this possibility should be evaluated in KTx recipients without a known causal nephropathy.

Transurethral resection of the prostate in kidney transplant recipients: urological and renal functional outcomes at long-term follow-up.

OBJECTIVES: To assess prospectively the safety and efficacy of transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms attributable to benign prostatic hyperplasia (BPH) in patients who have undergone renal transplantation (RT). To assess the impact of TURP on renal graft function. PATIENTS AND METHODS: Urological and renal functional outcomes of TURP performed in RT recipients for treatment of lower urinary tract obstruction attributable to BPH were prospectively assessed in a series of 32 consecutive patients with follow-up of ≥48 months. Maximum urinary flow rate (Qmax ) at uroflowmetry, International Prostate Symptom Score (IPSS), post-void residual urine volume (PVR), haemoglobin and serum creatinine (sCr) levels were recorded before TURP and 1, 6, 24 and 48 months after the procedure. The trends in these variables after TURP were evaluated. Early and delayed complications were assessed and graded according to the Clavien classification system. RESULTS: TURP was performed at a mean of 6 months after RT. No intraoperative complications occurred. Seven postoperative complications were observed (21.9%): two Clavien grade II and five Clavien grade IIIa. Qmax , IPSS and PVR improved significantly after surgery and the improvement was maintained until 48 months. No patient required a repeat TURP during follow-up. SCr levels significantly decreased 1 and 6 months after TURP and did not significantly increase at long-term follow-up. CONCLUSIONS: TURP for lower urinary tract obstruction attributable to BPH in RT recipients is safe and effective since it improves urinary flow, bladder emptying and related urinary symptoms. TURP allows an early significant improvement of graft function that is maintained at a follow-up of 48 months.