May a comprehensive mineralogical study of a jackstone calculus and some other human bladder stones unveil health and environmental implications?

This paper represents the first result of an active collaboration between the University of Sannio and the San Pio Hospital (Benevento, Italy), started in the 2018, that aims to a detailed mineralogical investigation of urinary stones of patients from Campania region. Herein, selected human bladder stones have been deeply characterized for clinical purposes and environmental biomonitoring, focusing on the importance to evaluate the concentration and distribution of undesired trace elements by means of microscopic techniques in the place of conventional wet chemical analyses. A rare bladder stone with a sea-urchin appearance, known as jackstone calculus, were also investigated (along with bladder stones made of uric acid and brushite) by means a comprehensive analytical approach, including Synchrotron X-ray Diffraction and Simultaneous Thermal Analyses. Main clinical assumptions were inferred according to the morpho-constitutional classification of bladder stones and information about patient's medical history and lifestyle. In most of the analyzed uroliths, undesired trace elements such as copper, cadmium, lead, chromium, mercury and arsenic have been detected and generally attributable to environmental pollution or contaminated food. Simultaneous occurrence of selenium and mercury should denote a methylmercury detoxification process, probably leading to the formation of a very rare HgSe compound known as tiemannite.

Late-onset presentation and phenotypic heterogeneity of the rare R377W PSEN1 mutation.

BACKGROUND AND PURPOSE: Mutations in the PSEN1 gene are the most common cause of autosomal-dominant Alzheimer's disease and have been associated with the earliest disease onset. We describe an unusual presentation of the rare R377W PSEN1 mutation with a late age of onset, and we provide for the first time in vivo pathological evidence for this mutation. METHODS: A 71-year-old female patient with progressive cognitive decline in the past 3 years and positive family history for dementia underwent neurological evaluation, neuropsychological testing, lumbar puncture, conventional brain imaging, amyloid-positron emission tomography (PET) and extensive genetic screening with a next-generation sequencing technique. RESULTS: The diagnostic workup revealed mixed behavioural and amnestic disease features on neuropsychological tests, magnetic resonance imaging, and 18-fluorodeoxyglucose (FDG)-PET. Amyloid-PET detected amyloid deposition in the frontal areas, in the parietal lobes and the precunei. The genetic screening revealed the presence of the rare R377W mutation in the PSEN1 gene. CONCLUSIONS: Extensive genetic screening is also advisable for late-onset presentations of Alzheimer's disease, especially in the presence of a positive family history or atypical clinical features.

Reinfusion-drains reduce blood transfusions in total joint arthroplasty.

This study aims to evaluate the effect of postoperative blood recovery with reinfusion drains on hematologic parameters and blood transfusion rate in patients undergoing total joint arthroplasty. Three-hundred-and-forty-four patient records were reviewed and 271 patients were included in the study; 56.8% of patients were treated with postoperative cell salvage procedure using reinfusion drains (PCS) and 43.2% had closed-suction drain (CSD) postoperatively. In comparison to the CSD group, the PCS group showed higher hemoglobin (Hb) levels on the first and second days postoperatively but no statistical differences were noted at the day of discharge. 75.2% and 37.7% of patients required blood transfusions in the CSD and PCS groups, respectively. The PCS group had a lower number of blood transfusions than the CSD group. At multivariate analysis, Hb loss rate was related to preoperative Hb values, total amount of drained blood and chronic antiplatelet therapy. The number of blood transfusions was related to preoperative Hb values, closed-suction drains, preoperative platelet count, TKA surgery and BMI. This study supports the use of PCS with reinfusion drains after THA and TKA at least for the short-term.

Inequalities in access to biological treatments for psoriasis: results from the Italian Psocare registry.

BACKGROUND: Limited evidence is available on the impact of socioeconomic factors on drug prescriptions for psoriasis. OBJECTIVES: To investigate factors influencing prescription of conventional vs. biological treatment for patients with psoriasis, based on the Italian Psocare registry, with a special focus on socioeconomic factors. METHODS: This was a cross-sectional study evaluating the baseline data of patients included in the Psocare registry. All of the consecutive adult patients with a diagnosis of chronic plaque psoriasis or psoriatic arthritis who were prescribed a systemic treatment for psoriasis at participating centres were included in this study. Univariate and multivariate analyses of the baseline factors associated with a biologics prescription were performed. RESULTS: From September 2005 to September 2009, 12 838 patients were identified. A multivariate analysis revealed that, among other factors, completing a level of education higher than lower secondary school and being employed as a manager or a professional were independent factors associated with a biologics prescription at entry in the registry. Additional analyses on the association between these two variables and a severe psoriasis condition [Psoriasis Area Severity Index (PASI) score > 20] revealed a significantly increasing trend of severe disease towards lower educational attainment, while unemployed patients were more likely to have a more severe condition compared with the other categories of workers. CONCLUSIONS: We documented inequalities of drug prescriptions for psoriasis in Italy, with a trend towards a higher frequency of prescription for more expensive biologics in higher socioeconomic sectors of the population.

Dose adjustment of biologic therapies for psoriasis in dermatological practice: a retrospective study.

INTRODUCTION: Despite the large routine use of biologic drugs in psoriasis treatment, the majority of studies do not take into consideration dose-adjustment practice in 'real-life' dermatological setting. In routine clinical practice, the disease management may include a large number of conditions requiring non-standard dosage regimens, including dose escalation, dose reduction and/or off-label treatment interruption. OBJECTIVE: The ONDA (Outcome of non-standard dosing regimen in Psoriasis and Psoriatic Arthritis) study aim was to retrospectively analyse dose-adjustment strategies among biologic therapies for psoriasis in dermatological practice during a 3-year period. RESULTS: This retrospective, observational, multicentre study was carried out in 350 patients (68% male, 32% female) affected by plaque-type psoriasis (Pso) with a coexistence of psoriatic arthritis in 164 patients (46.9%). At baseline mean PASI score was 14.9 (SD 7.2). Dose adjustment was demonstrated to be a common practice with 70/350 patients (20%) who needed a dose variation during the treatment time, in particular a dose increase in 20/70 patients (28.6%) and a dose reduction in 50/70 patients (71.4%). Dose increase was due to inefficacy on Pso parameters in 60% of cases and to inefficacy of PsA parameters in 40% of cases, while dose reduction (or temporary off-label treatment interruption) was due to prolonged remission in 54% of cases, other reason in 18% of cases, patient choice or request in 14% of cases, occurrence of concomitant event in 12% of cases. CONCLUSION: Dose adjustment is a common clinical practice, consisting of frequent dose reduction when a disease prolonged remission is obtained or dose increase to improve efficacy on Pso and PsA disease parameters.

Inflammatory molecules in Frontotemporal Dementia: cerebrospinal fluid signature of progranulin mutation carriers.

Mutations in progranulin gene (GRN) are one of the major causes of autosomal dominant Frontotemporal Lobar Degeneration (FTLD). Progranulin displays anti-inflammatory properties and is likely a ligand of Tumor Necrosis Factor (TNF) receptor 2, expressed on microglia. A few cytokines and chemokines are altered in cerebrospinal fluid (CSF) from patients with sporadic FTLD, whereas no information is available in familial cases. We evaluated, through BioPlex, levels of 27 inflammatory molecules, including cytokines, chemokines, and related receptors, in CSF and matched serum, from FTLD patients carrying GRN mutations as compared with sporadic FTLD with no GRN mutations and controls. Mean±SD Monocyte Chemoattractant Protein-1 (MCP-1) levels were significantly increased in CSF from sporadic FTLD patients as compared with controls (334.27±151.5 versus 159.7±49pg/ml; P⩽0.05). In GRN mutation carriers versus controls, CSF levels of MCP-1 were unchanged, whereas Interferon-γ-inducible protein-10 (IP-10) levels were increased (809.17±240.0 versus 436.61±202.5pg/ml; P=0.012). In the same group, TNFα and Interleukin (IL)-15 levels were decreased (3.18±1.41 versus 35.68±30.5pg/ml; P=0.013 and 9.34±5.54 versus 19.15±10.03pg/ml; P=0.023, respectively). Conversely, Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES) levels were decreased in patients, with or without mutations, as compared with controls (4.63±3.30 and 2.58±20 versus 87.57±70pg/ml, respectively; P<0.05). Moreover, IP-10, IL-15 and RANTES CSF levels were not influenced by age, whereas MCP-1 levels increased with age (ρ=0.48; P=0.007). In conclusion, inflammatory de-regulation was observed in both sporadic FTLD and GRN carriers compared to controls, with a specific inflammatory profile for the latter group.

Investigating strontium isotope linkage between biominerals (uroliths), drinking water and environmental matrices.

This study presents the mineralogy and strontium isotope ratio (87Sr/86Sr) of 21 pathological biominerals (bladder and kidney stones) collected from patients admitted between 2018 and 2020 at the Department of Urology of the San Pio Hospital (Benevento, southern Italy). Urinary stones belong to the calcium oxalate, purine or calcium phosphate mineralogy types. Their corresponding 87Sr/86Sr range from 0.707607 for an uricite sample to 0.709970 for a weddellite one, and seem to be partly discriminated based on the mineralogy. The comparison with the isotope characteristics of 38 representative Italian bottled and tap drinking waters show a general overlap in 87Sr/86Sr with the biominerals. However, on a smaller geographic area (Campania Region), we observe small 87Sr/86Sr differences between the biominerals and local waters. This may be explained by external Sr inputs for example from agriculture practices, inhaled aerosols (i.e., particulate matter), animal manure and sewage, non-regional foods. Nevertheless, biominerals of patients that stated to drink and eat local water/wines and foods every day exhibited a narrower 87Sr/86Sr range roughly matching the typical isotope ratios of local geological materials and waters, as well as those of archaeological biominerals from the same area. Finally, we conclude that the strontium isotope signature of urinary stones may reflect that of the environmental matrices surrounding patients, but future investigations are recommended to ultimately establish the potential for pathological biominerals as reliable biomonitoring proxies, taking into the account the contribution of the external sources of Sr.

Improvement in health status and quality of life in patients with osteoporosis treated with denosumab: results at a mean follow-up of six years.

OBJECTIVE: The clinical efficacy and tolerability of denosumab in severe osteoporosis are well-known. However, the evaluation on general health and quality of life over time and compared to population norms is still lacking. We aimed at evaluating denosumab effectiveness in a real-world clinical sample with a 6-years average follow-up. PATIENTS AND METHODS: In this retrospective-matched study with prospective data collection, a total of 101 patients affected by severe osteoporosis and treated with denosumab between 2014 and 2020 were evaluated. All patients completed the self-perceived quality of life (36-Item Short Form - SF-36) survey and visual analogue scale (VAS) before and after treatment. RESULTS: Overall, 13 patients died of causes unrelated to the procedure, 12 stopped therapy with denosumab, and 30 did not participate in the follow-up; thus, 46 patients completed the study. There were 44 (95.7%) women and 93.4% of patients reported history of osteoporotic fractures. The mean follow-up was 59±17.8 months and the mean age at follow-up was 73.9±10.6 years. We found a significant improvement in bodily pain (baseline 53.8±33.4, follow-up 62.7±26.6; p=0.002) and in general health (baseline 35±25.4, follow-up 41.7±24.2; p=0.002) over time. The bodily pain score at follow-up was similar to the mean of the age-matched healthy population (62.7±26.6 vs. 67.6±26, p=0.374). The MCS-36 scores were higher than the normative values before treatment and at follow-up (51.6±9.8 vs. 45.8±9, p=0.004 and 50.6±11.7 vs. 45.8±9, p=0.030, respectively). The PCS-36 score at follow-up was comparable to the normative values (39.4±10.4 vs. 42.7±9, p=0.107). CONCLUSIONS: Denosumab is effective to improve bone health and global mental and physical wellbeing, and quality of life over time.

Cervical spondylodiscitis mimicking Pott's disease: a case report.

INTRODUCTION: The leading cause of pyogenic vertebral osteomyelitis is Staphylococcus aureus, and its incidence is rising, particularly in the elderly. We report an unusual case of cervical spondylodiscitis and epidural abscess mimicking Pott's disease. CASE REPORT: A 67-year-old man was admitted to our institution with a 15-day history of neck pain radiating to the head, shoulders and left arm that was associated with weakness and paresthesia. Laboratory tests showed a mild leucocytosis and high levels of inflammatory markers. The MRI showed contrast enhancement of C6-C7 with an abscess infiltration extending to the intervertebral disc, the anterior epidural space, and the medullary cord. The patient had a medical history of a positive Mantoux tuberculin skin test 25 years prior, and the interferon-gamma release assay (IGRA) was positive for the identification of latent tuberculosis infection. All other examinations for diagnosis of spinal tuberculosis were inconclusive. Intravenous antibiotic therapy was initiated with teicoplanin 800 mg and levofloxacin 750 mg daily with a fast recovery of symptoms. CONCLUSIONS: Cervical spondylodiscitis can be an unusual cause of severe neck pain with a challenging differential diagnosis. Conservative treatment should always be considered for patients without neurological symptoms as long as close follow-up evaluations are performed.

Parental authority, patient's best interest and refusal of resuscitation at borderline gestational age.

Potential conflict exists when parents refuse a medical intervention for their child that the physician feels obligated to provide. For the anticipated delivery of a preterm newborn, this conflict might exist if the parents refuse resuscitation. At borderline viability, most neonatologists are likely to respect the parents' wishes. However, there will be some gestational age threshold above which the physician will feel compelled to resuscitate despite parental refusal, and will be ethically justified in doing so. The location of that threshold should be determined by the application of sound ethical reasoning, rather than relying on habit or arbitrary standards. That reasoning should include an honest assessment of the benefits and burdens to the child, short-term and long-term, of attempted resuscitation, made in light of relevant mortality and morbidity data. However, a rational analysis will also require consideration of whether the patient's best interest standard should be strictly applied, or whether the interests of others, such as family members, should also be taken into account.

Reutilization of surfactant phosphatidylglycerol and lysophosphatidylcholine by adult rabbits.

Adult rabbits reutilize the phosphatidylcholine (PC) of surfactant much less efficiently than developing rabbits (22% vs. 95%). Comparisons of reutilization efficiency of other components of surfactant in adult rabbits have not been determined. We injected adult rabbits intratracheally with [3H]dipalmitoylphosphatidylcholine (DPPG) mixed with [14C]lysophosphatidylcholine (lysoPC) and natural surfactant or [14C]DPPC mixed with [3H]dipalmitoylphosphatidylglycerol (DPPG) and natural surfactant. Recovery in the alveolar wash and lamellar bodies of labelled DPPC, lysoPC and DPPG was determined at different times after injection. By plotting the ratio of [3H]DPPG to [14C]DPPC in the alveolar wash versus time after injection we found that phosphatidylglycerol was reutilized with an efficiency of only 0-7% which was much less than the reutilization of PC in these animals. At early times after injection, adult rabbits injected with [14C]lysoPC had a ratio of [14C]PC in their alveolar wash to lamellar bodies that was larger than 1.0. By comparison, 3-day old rabbits injected intratracheally with [14C]lysoPC had a ratio of [14C]PC in alveolar wash to lamellar bodies less than 1.0 at the earliest times measurable. Thus adult rabbits demonstrate a pathway for accumulation of PC in their alveolar space prior to its appearance in lamellar bodies. This was not detected in developing rabbits. As in developing rabbits, adult rabbits reutilize the phosphatidylglycerol of surfactant less efficiently than the PC of surfactant.

Surface tension and pulmonary compliance in premature rabbits.

In vitro surface properties of pulmonary surfactant thought to be essential to its ability to increase pulmonary compliance include minimum surface tension less than 10 dyn/cm and large surface tension variability and hysteresis. We tested four surface-active agents (Tween 20, a detergent; and FC-100, FC-430, and FC-431, industrial fluorocarbons), all lacking these properties, for their ability to increase pulmonary compliance in surfactant-deficient premature rabbits. Fetal rabbits were delivered by cesarean section at 27 days (full term = 31 days) and injected via tracheostomy with 50% lactated Ringer solution, adult rabbit surfactant, or one of the four experimental agents. Dynamic compliance was measured using 1 h of mechanical ventilation followed by alveolar lavage. Each experimental agent produced a dynamic compliance significantly higher than 50% lactated Ringer solution and statistically equal to or greater than natural surfactant. Equilibrium surface tension of the agents and minimum and equilibrium surface tension of the alveolar washes each correlated with compliance (P less than 0.05). This suggests that some surface properties of pulmonary surfactant believed to be essential are not, although surface tension does seem to play a role in pulmonary compliance.

Antenatal steroids, postnatal surfactant, and pulmonary function in premature rabbits.

Antenatal corticosteroids reduce the incidence of the respiratory distress syndrome and improve pulmonary mechanics at least in part by mechanisms other than surfactant stimulation. We measured several aspects of pulmonary function in rabbits to better understand the mechanisms involved. Seven does were given intramuscular betamethasone and six were given vehicle on days 25 and 26 of gestation. Delivery was on day 27 (term = 31). Half of the fetuses from each litter were given rabbit surfactant before the first breath. All fetuses were then ventilated at a consistent tidal volume for 1 h. Pulmonary function tests included static and dynamic compliance, expiratory time constant, stress relaxation, total lung resistance, and total lung conductance. Steroid or surfactant treatment increased dynamic compliance, and the effects of both together were greater than either alone. Static compliance was affected more by surfactant than steroids, whereas lung resistance and conductance were affected more by steroids. The differences in action of the two therapies help account for the increased dynamic compliance seen with combination therapy.

Effect of artificial surfactant on pulmonary function in preterm and full-term lambs.

We hypothesized that agents very different from surfactant may still support lung function. To test this hypothesis, we instilled FC-100, a fluorocarbon, and Tween 20, a detergent, which have higher minimum surface tensions and less hysteresis than surfactant, into 15 full-term and 14 preterm lambs. FC-100 and Tween 20 were as efficient as natural surfactant in improving gas exchange and compliance in preterm lambs with respiratory failure. Dynamic compliance correlated with the equilibrium surface tension of the alveolar wash in both full-term (P less than 0.02) and preterm (P less than 0.008) lambs. Functional residual capacity in full-term and preterm lambs was lower after treatment with the two test agents than with surfactant, findings consistent with qualitative histology. Oxygenation in full-term lambs correlated with mean lung volumes (P less than 0.003), suggesting that the hysteresis and/or low minimum surface tension of surfactant may improve mean lung volume, and hence oxygenation, by maintaining functional residual capacity. The effects of the test agents suggest that agents with biophysical properties different from surfactant may still aid lung expansion.

Hypertension in a group of centenarians.

The aim of the present study was to evaluate the frequency of hypertension in a group of extremely old persons: 73 centenarians resident in Calabria were studied, aged 100-110 years, (mean age 102.95 +/- 2.0), 54 women (73.9%) and 19 men (26.1%), in the period January 1st and April 30th, 1994. All the centenarians were visited at their homes. Hypertensive centenarians were 14 (19.1%), women 12 (85.7%) and men 2 (14.3%). Even if blood pressure progressively increases with age, we have not found it in centenarians. The lesser frequency of hypertension in centenarians certainly depends on genetic and constitutional factors, but also their way of life and alimentary habits (decreased sodium intake, increase of calcium and potassium intake), as we have proven in a recent work, could be determinant. Moreover, the presence of hypertensive centenarians might mean that hypertension does not prevent to reach an age by far above the average, if it is the only risk factor.

Multidimensional evaluation in a group of centenarians.

A group of 40 Calabrian centenarians (12 males, 28 females) was studied from June 1 to December 31, 1993. Their age was ranging from 100 to 107 years (mean age: 102.3 +/- 1.8 years). Clinical evaluation was performed by recording anamnestic data, an objective examination, and by assessing cognitive performance, emotional and nutritional status, as well as functional activity. The following tests were applied: mini mental state examination (MMSE), geriatric depression scale (CDS), activity of daily living (ADL), and instrumental activity of daily living (IADL). The nutritional status was estimated by collecting answers to a questionnaire regarding nutritional habits and by measuring body weight, height and calculating body mass index (BMI). In assessment of the socio-economic conditions, the following parameters were considered: years of education, type of job, type of residence ownership, heating system used, toilet set available and the regular income. Our multidimensional evaluation has revealed, in agreement with other findings, that the Calabrian centenarians seem to be a selected population with an amazingly high activity, who overcame severe age-dependent diseases, probably because of their genetic pattern and of the environmental factors which may favor longevity.

Aspects of sleep in centenarians.

Sleeping habits of 48 Calabrian centenarians (12 males, 36 females) were evaluated. Their average age was 102 +/- 1.87 years (range 100-107 years). Quantitative and qualitative aspects of sleep were recorded, such as the length of sleeping (hrs), the time of falling asleep (regular or variable) and the time of awakening (regular or variable). Moreover, we recorded and included in the global hours an eventual afternoon sleeping, during a 24-hour-period. The quality of sleeping was classified as: night sleeping, and morning sleeping; and for the subjects were grouped as short sleepers (subjects that fall asleep easily), and long sleepers (subjects with problems to fall asleep). We also considered if sleeping was uninterrupted or interrupted during the night and if the subjects followed particular habits to facilitate the sleeping (sleeping pills, alcohol, etc.). This study demonstrated that all the examined centenarians go to sleep early in the evening, have no problems in falling asleep, wake up early in the morning, take a nap in the afternoon and do not take pills before going to bed. Among the environmental factors, the quality, the quantity and the habits of sleeping might have great influence for longevity.

Cutaneous blastomycosis.

We report on a patient with cutaneous blastomycosis and no evidence of systemic involvement. This diagnosis was made on the basis of clinical findings and confirmed by histologic examination and results of culture. The primary lesion in blastomycosis is almost always pulmonary. However, occasionally, as in our patient, the pulmonic focus resolves spontaneously before the patient presents. Disseminated lesions occur most often in the skin, followed by bone, genitourinary tract, and central nervous system. Our patient had an excellent response to ketoconazole without adverse effects.