Anti-interleukin-23 for psoriasis in elderly patients: guselkumab, risankizumab and tildrakizumab in real-world practice.

BACKGROUND: Elderly patients (aged ≥ 65 years) represent an increasing proportion of patients with psoriasis and 15% of these have moderate to severe disease. Biologics are being used frequently in this group of patients even though safety and efficacy data are limited. In addition, owing to anti-interleukin (IL)-23 therapies being a relatively recent option, no data have been reported about their use in elderly patients with psoriasis. AIM: To evaluate and compare the safety and efficacy of guselkumab, risankizumab and tildrakizumab in real-world practice in elderly patients. METHODS: This was a single-centre retrospective study that enrolled patients aged ≥ 65 years with moderate to severe plaque psoriasis, treated with guselkumab, risankizumab or tildrakizumab. The length of the study for each group depended on the drug (44 weeks for risankisumab, 40 weeks for guselkumab and 28 weeks for tildrakizumab, owing to its more recent availability in Italy). RESULTS: In total, 34 patients were enrolled (n = 20 on guselkumab; n = 8 on risankizumab; n = 6 on tildrakizumab). At Week 4, 29.4% reached 90% improvement in Psoriasis Area and Severity Index (PASI90) and 8.8% reached 100% improvement in PASI (PASI100); at Week 28, PASI90 and PASI100 was reached by 58.8% and 29.4%, respectively. At the final follow-up (Week 40 or 44, depending on drug), data were available only for the risankizumab (Week 40) and guselkumab (Week 44) and groups, and showed that 71.4% of patients had reached PASI90 and 53.5% had reached PASI100. Four patients (11.7%) discontinued treatment. No significant differences were found between the three groups. The limitations of the study included its retrospective nature of the study, small sample size, and different numbers of patients and follow-up duration for the different groups (highest for guselkumab, lowest for tildrakizumab). CONCLUSION: The three anti-IL-23 therapies assessed are promising, safe and effective options in elderly patients, and there was no significant difference between them. However, more data are needed to confirm our results and to understand their role in the management of this group of patients.

Review of oral minoxidil as treatment of hair disorders: in search of the perfect dose.

Topical minoxidil has been used for many years as treatment for different hair disorders. Even though it is an effective therapy, many patients show poor compliance due to the cosmesis, cost and side-effects. During the last few years, low-dose oral minoxidil has proven to be an alternative for patients with alopecia. We performed a literature search including all the articles that used oral minoxidil as a primary treatment in various hair diseases in order to evaluate the efficacy and safety of low-dose oral minoxidil as an alternative to topical minoxidil. Androgenetic alopecia was the most common studied condition, but others included telogen effluvium, tractional alopecia, postchemotherapy-induced alopecia, monilethrix, loose anagen hair syndrome, alopecia areata and scarring alopecias (frontal fibrosing alopecia and lichen planopilaris). Larger randomized comparative studies including standardized objective measurements should be done in order to clarify the best treatment protocol, including dosage and treatment duration. Oral minoxidil has proven to be a successful and well-tolerated alternative for patients with hair loss, including those with poor adherence to other therapies. Different dosing regimens have been utilized in scarring and non-scarring alopecia, varying from 0.25 to 5 mg daily. Higher doses have not been studied in men or women. Available literature suggests women require lower doses, from 0.25 to 2.5 mg daily, while men require higher doses for maximal efficacy, from 1.25 to 5 mg a day.

Capillaroscopy: A Valuable Diagnostic Tool. / Capilaroscopia: una herramienta diagnóstica valiosa.

Capillaroscopy produces in vivo images of skin microcirculation. It is a simple, noninvasive tool for analyzing microvascular abnormalities and, as such, can be used in both adults and children. Capillaroscopy has proven useful in many diseases, but it is of particular value in Raynaud phenomenon and other autoimmune diseases. The test is used to analyze capillaroscopic patterns in the nailfold bed of the second to fifth fingers of each hand. A normal capillaroscopic pattern is characterized by the presence of 7 to 11 capillaries in a hairpin shape. Pathologic patterns are characterized by morphologic and structural alterations, such as ectasias, giant capillaries, pathologic hemorrhages, avascular areas, and neoangiogenesis. In this article, we review the fundamentals of capillaroscopy, with an emphasis on the technique and its indications, diagnostic value, and use as a prognostic tool for rheumatologic disorders.

Risk factors associated with prolonged postoperative ileus after elective colon resection.

BACKGROUND: There is a coordinated inhibition of motility of the colon after its surgical manipulation that contributes to the accumulation of fluids and gas, in turn characterized by nausea,vomiting, pain, abdominal distension, and constipation. Motility is recovered in the majority of patients within the first 72 hours. A delay in its resolution is known as prolonged postoperative ileus. AIMS: To study the preoperative, intraoperative, and postoperative risk factors for developing prolonged ileus in patients that underwent elective colon resection.Materials and methods: The association between 25 perioperative variables and the presentation of prolonged ileus was analyzed in 85 patients that underwent colon resection at Hospital Christus Muguerza Alta Especialidad within the time frame of 2011 and 2014. RESULTS: Postoperative ileus occurred in 22.3% of the patients. The statistically significant predictors of ileus were obesity (OR 1.119, P=.048) and admission to the intensive care unit (OR3.571, P=.050). The use of peridural anesthesia during the surgical act was found to be a protective factor (OR 0.363, P=.050). CONCLUSIONS: The presence of these risk factors can alert the physician to the need for a closer follow-up in patients at high risk for postoperative ileus, and the use of peridural anesthesiacan possibly lower the incidence of ileus.

Reproductive outcomes in patients with male infertility because of Klinefelter's syndrome, Kartagener's syndrome, round-head sperm, dysplasia fibrous sheath, and 'stump' tail sperm: an updated literature review.

PURPOSE OF REVIEW: To describe the reproductive outcomes of a heterogeneous group of male infertility conditions causing severe alterations in the sperm parameters (counts, motility, and morphology) because of chromosomal, genetic, or still unknown causes. Source of sperm, fertilization, pregnancy, live birth, and miscarriage rates of patients with Klinefelter's syndrome, Kartagener's syndrome, round-head sperm, dysplasia of the fibrous sheath (DFS), and stump-tail sperm were reviewed. RECENT FINDINGS: There are differences in the outcome according to the conditions and the source of sperm (ejaculated versus testicular). Klinefelter's syndrome patients have better reproductive outcomes when sperm is present in the ejaculate. Kartagener's syndrome shows better fertilization when testicular sperm is used; however, pregnancy rates and live births did not differ between ejaculated and testicular sperm. Samples with round-head sperm have a lower fertilization potential, pregnancy and live birth compared with Klinefelter's and Kartagener's syndromes. In men with DFS and stump-tail sperm, the reproductive outcome is poor, with low fertilization and very few babies born. SUMMARY: In Klinefelter's and Kartagener's syndrome, the fertilization potential and the live-birth rate are close to that obtained from nonspecific causes of sperm defects. Round-head sperm shows a lower fertility potential, but the addition of assisted oocyte activation and the use of intracytoplasmic morphologically selected sperm injection increased the rates of live birth. Conditions such as DFS and stump tail have a poor prognosis, but the number of cases described in the literature is too limited for drawing final conclusions.

[677T mutation of the MTHFR gene in adenomas and colorectal cancer in a population sample from the Northeastern Mexico. Preliminary results]. / Mutación 677T del gen MTHFR en adenomas y cáncer colorrectal en una muestra de la población del noreste de México. Resultados preliminares.

INTRODUCTION: Adequate intake of folates has been associated to low prevalence of colon cancer. Methylenetetrahydrofolate reductase enzyme (MTHFR) plays an important role in folate metabolism. The role of the 677 mutation at the MTHFR gene in the risk for colorectal cancer remains controversial. A recent report established that this mutation has a high prevalence in the healthy Mexican population. AIMS: To analyze the prevalence of 677T MTHFR mutation in patients with colorectal cancer and controls without chronic gastrointestinal disorders. METHODS: Seventy-four colorectal cancer, 32 adenomas and 110 normal samples were analyzed. Patients and controls were matched for sex and age. For each sample, DNA isolation, PCR, and mutation detection by restriction enzyme digestion were performed to determine the allele at the 677 position in the MTHFR gene. RESULTS: Genotype 677C/677C was found in 18.7, 20.3, and 30.9% in adenomas, cancer lesions and controls, respectively. Frequencies of the 677C/677T genotype were 59.4, 56.7, and 47.3%, in adenomas, cancer lesions, and controls, respectively. Genotype 677T/677T was found in 21.9, 23.0, and 21.8% in adenomas, cancer lesions, and controls, respectively. The odds ratio between genotypes carrying the mutation (T/T and C/T) and normal genotype (CC) was 1.81 (IC 95% 0.97-3.3), chi 2 = 3.5, p = 0.06. CONCLUSION: Our results showed that persons who carry the 677T mutation at MTHFR locus have a tendency for an increased risk for colorectal cancer. This study supports the basic concept that low levels of folic acid contribute with the colorectal cancer pathogenesis. Our lack of statistic significance may be due to reduced sample size.

Absence seizures effects on reading revealed by video-electroencephalography.

OBJECTIVE: The effects of absence seizures on reading have not been studied. The purpose of this paper is to show some alterations in reading during absence seizures in patients with video-electroencephalographic recordings. METHODS: Patients were selected if absences seizures were the only type of seizures. They were studied at rest with eyes closed and while reading aloud a text by simultaneous bipolar electroencephalographic and video recordings. RESULTS: Eight patients were studied with 34 events. Absences ranged from 1-12 events in twenty-five minutes recording, seizures duration ranged from 1.5-16 seconds. Brief seizures results on non-stop reading, but reading arrest with latency of 1-3 seconds after seizure onset were present in the longer events. Post-absence amnesia ranged from 1-4.5 seconds. Re-start reading occurs mainly in other reading place in the text, but two patients in one event re-started reading in the right place. Classic symptoms during absence were present and reading alterations found were: reading arrest, lost of reading point, bradylexia, dysprosodic reading, grapheme substitution, reading loudness reduction, repeating of phrases. Events occurred without patient seizure awareness, except in one patient by means of the time lost between onset to the end of the event. CONCLUSIONS: This study showed that acute reading alterations during absence seizures are frequent in longer seizures, producing many neuropsychological symptoms that alter reading without seizure awareness.

Antibody detection against Borrelia burgdorferi in horses located in the suburban areas of Monterrey, Nuevo León.

The aim of the present study was to determine the presence of Borrelia burgdorferi antibodies in horses from the metropolitan area of Monterrey, Nuevo León, México. Blood serum was obtained from a total of 100 horses residing at different counties in the area. From each animal data was obtained on age, sex, county of residence, presence of ectoparasites and clinical signs. All sera samples were analyzed by indirect immunofluoresence and the sera that resulted positive to this test was analyzed by Western blot. The serological test yielded 34 positive sera at 1:64 dilution, and from them 6 were positive at 1:128 dilution, 3 at 1:256, and only one at 1:512. Confirmation of the infection by Western blot was obtained only in the sample positive at the 1:512 dilution. These results shown a low frequency of seropositivity to B. burgdorferi of the horses in the area, confirming previous studies indicating that in northeast Mexico Lyme disease is present in different animal species.

Combining suramin and a chimeric toxin directed to basic fibroblast growth factor receptors increases therapeutic efficacy against human melanoma in an animal model.

BACKGROUND: Suramin, which binds to and blocks autocrine and paracrine growth factors required for the proliferation of neoplastic cells, is a clinically effective antitumor agent against some human tumors; however, efficacy often is limited by toxicity. In this study, suramin treatment was combined with a fibroblast growth factor (FGF) receptor-directed toxin chimera, basic FGF-saporin (bFGF-SAP), based on the authors' previous observations that autocrine-mediated resistance to bFGF-SAP in melanoma in vitro is abrogated by suramin treatment. METHODS: Severe-combined immunodeficient-Beige mice bearing SK-Mel-5 human melanoma xenografts received weekly treatments of suramin (200 or 75 mg/kg intraperitoneally) beginning on Day 5 after tumor implantation followed 18 hours later by a treatment with bFGF-SAP (0.5-5 microg/kg intravenously) for 4 weeks. The optimal interlude between the administration of suramin and bFGF-SAP was determined by tumor excision assays. The efficacy of combination therapy as a function of alternative dosing regimens was determined by tumor growth inhibition (TGI) studies. RESULTS: Fifty days after implantation, a 79-82% TGI was observed in animals receiving the suramin (200 mg/kg) plus bFGF-SAP combination regimens compared with median tumor volumes from vehicle-treated controls (3070+/-440 mm(3)). TGI observed for combination therapies varied significantly (P<0.05-0.001) from TGI observed in treatment groups receiving suramin alone (57%) or bFGF-SAP alone (34-38%). Combining bFGF-SAP (5 microg/kg) with a low, therapeutically ineffective dose of suramin (75 mg/kg) produced a 68% rate of TGI compared with controls, thus lowering the therapeutic effective dose of suramin and eliminating the suramin-related lethal toxicity (12% mortality rate) observed in animals treated with high dose suramin. CONCLUSIONS: The results of the current study suggest that combining suramin with receptor-directed therapies offers a more effective regimen for the treatment of malignant melanoma.

Frequency and clinicopathology associations of K-ras mutations in colorectal cancer in a northeast Mexican population.

Activation of the ras family gene has been implicated in colorectal tumorigenesis, K-ras being the most frequently altered gene. The frequency of K-ras codon 12, 13 and 61 point mutations in patients with colorectal neoplasias was examined. We employed a polymerase chain reaction-restriction fragment length polymorphism assay and single-strand conformational polymorphism to detect mutations. We found that point mutations at codons 12 and 13 were present in 53% and 39% of the tumors, respectively, but none at codon 61. These results agree with previous reports. Point mutations were more frequent in adenomas than in carcinomas, with villous adenomas presenting a higher incidence of mutations than other adenomas. The association between clinical and histopathological parameters was investigated. Our study is the beginning of a new research line in molecular epidemiology of colorectal cancer and is the first to be carried out in one part of the Mexican population.

Characterization of epiphycan, a small proteoglycan with a leucine-rich repeat core protein.

The epiphysis of developing bones is a cartilaginous structure that is eventually replaced by bone during skeletal maturation. We have separated a dermatan sulfate proteoglycan, epiphycan, from decorin and biglycan by using dissociative extraction of bovine fetal epiphyseal cartilage, followed by sequential ion-exchange, gel permeation, hydrophobic, and Zn2+ chelate chromatographic steps. Epiphycan is a member of the small leucine-rich proteoglycan family, contains seven leucine-rich repeats (LRRs), is related to osteoglycin (osteoinductive factor) (Bentz, H., Nathan, R. M., Rosen, D. M., Armstrong, R. M., Thompson, A. Y., Segarini, P. R., Mathews, M. C., Dasch, J., Piez, K. A., and Seyedin, S. M. (1989) J. Biol. Chem. 264, 20805-20810), and appears to be the bovine equivalent of the chick proteoglycan PG-Lb (Shinomura, T., and Kimata, K. (1992) J. Biol. Chem. 267, 1265-1270). The intact proteoglycan had a median size of approximately 133 kDa. The core protein was 46 kDa by electrophoretic analysis, had a calculated size of 34,271 Da, and had two approximately equimolar N termini (APTLES ... and ETYDAT ... ) separated by 11 amino acids. There were at least three O-linked oligosaccharides in the N-terminal region of the protein, based on blank cycles in Edman degradation and corresponding serine or threonine residues in the translated cDNA sequence. The glycosaminoglycans ranged in size from 23 to 34 kDa were more heterogeneous than those in other dermatan sulfate small leucine-rich proteoglycans and were found in the acidic N-terminal region of the protein core, N-terminal to the LRRs. A four-cysteine cluster was present at the N terminus of the LRRs, and a disulfide-bonded cysteine pair was present at the C terminus of the protein core. The seventh LRR and an N-linked oligosaccharide were between the two C-terminal cysteines. An additional potential N-glycosylation site near the C terminus did not appear to be substituted at a significant level.

Dietary fiber, Hispanics, and breast cancer risk?

The cancer rates of immigrant populations in the United States must be taken into account when looking at the importance of diet and culture as it relates to cancer prevention. Unfortunately, some nutrition studies targeted toward nontraditional white populations have not adequately confronted the issue of cultural meaning in efforts to gather dietary data accurate enough to support nutritional analyses, identify marginal diets, or relate risk to dietary patterns. The study presented here resolves many of the culturally specific issues utilizing awareness, attention, and judicious combination of culturally sensitive qualitative and quantitative research techniques. The importance of such a study in an Hispanic population is based on the fact that the age-adjusted rate of breast cancer in countries such as Mexico is among the lowest in the world. In addition, although one of the fastest-growing minority groups in the United States, Hispanic women living in this country have been shown to have the lowest incidence of the mortality rates from this disease across most geographic regions of the United States. Therefore, one might speculate that dietary factors, which have been shown to play a role in breast cancer prevention, may account for this difference. It is well recognized that the traditional Hispanic diet is rich in protective nutrients such as dietary fiber. It is known that through complex mechanisms, dietary fiber works to reduce the amount of estrogens in the body. Research also indicates that it is the level of endogenous estrogen in the body that may influence the onset of breast cancer. In order to better understand how dietary factors may be associated with breast cancer in Hispanic women, it is important that one develop the proper tools to discern any potential differences. Therefore, we developed an approach to obtaining dietary fiber information from a small cohort of 22 Houston-area Hispanic women as a vanguard study for a larger breast cancer prevention trial. Two separate dietary assessment instruments were utilized, a three-day food record and the Southwest Food Frequency Questionnaire. The mean intake of dietary fiber was 16 g/day according to the food record and 21 g/day according to the SWFFQ. Fruits, vegetables, breads, cereals, and beans provided for most of the participants' dietary fiber intake. These results support evidence that the Hispanic population's dietary fiber intake is higher than that for other groups, and this may help explain the lower incidence of breast cancer among some Hispanic populations.

Characterization of human DSPG3, a small dermatan sulfate proteoglycan.

PG-Lb is a small dermatan sulfate proteoglycan that has been previously characterized in chicken. In the developing limb, chick PG-Lb appears to be exclusively expressed in the zone of flattened chondrocytes. We have cloned and sequenced the human homolog to chick PG-Lb from two human chondrocyte cDNA libraries and a human chondrocyte RNA sample. The human homolog has been named DSPG3, as it is the third member of the small dermatan sulfate proteoglycan family to be identified and characterized along with biglycan (PG-I) and decorin (PG-II). DSPG3 maps to chromosome 12q21 and is composed of 1515 nucleotides of cDNA that code for a 322-amino-acid protein. The protein contains three potential glycosaminoglycan attachment sites, two N-glycosylation sites, a poly- glutamic acid stretch, and six cysteines. By Northern analysis, we have demonstrated that DSPG3 is expressed in cartilage, as well as ligament and placental tissues.

Mixed iota-kappa carrageenan gels.

Studies have been made of the gelation of mixtures of iota and kappa carrageenan. Differential scanning calorimetry (DSC) studies suggest that the iota and kappa components gel independently of each other. The DSC data conflict with evidence presented for the currently accepted Domain model for carrageenan gelation (Morris, E.R., Rees, D.A. and Robinson, G.J. J. Mol. Biol. 1980; 138:349). In particular, the present data suggest that iota carrageenan gels show thermoreversible setting and melting behaviour associated with the coil-helix transition. Analysis of rheological data favours an interpenetrating network (IPN) model for gelation of the mixtures.