Quality of Pulmonary Function Tests in Participants with Down Syndrome

IntroductionPeople with Down syndrome (DS) have high respiratory morbidity, evaluating their respiratory health with standardized, objective tests is desirable. Thus, the objective of this study was to evaluate the technical quality of Pulmonary Function Tests (PFTs) to determine which ones are most suitable for this population.MethodsParticipants included children, teenagers and adults with DS, 5 years of age or older (n = 302). The technical quality of the impulse oscillometry system (IOS), forced spirometry, lung-diffusing capacity for carbon monoxide (DL_CO), and 6-min walk test (6MWT) were analyzed by age group. Capnography and pulse oximetry were included in the study. Technical quality was determined on the basis of current international PFTs standards.ResultsFifty-one percent of participants were males. A total of 184 participants (71%) who completed the IOS fulfilled the quality criteria, while 210 (70%) completed the 6MWT. Performance on forced spirometry and DL_CO was poor. All pulse oximetries and 96% percent heart rates obtained had good quality, but exhaled carbon dioxide (PetCO₂) and respiratory rate (RR) showed deficient repeatability.ConclusionsIOS appears to be the most reliable instrument for evaluating lung mechanics in individuals with DS.     

Syringocystadenocarcinoma papilliferum associated with atypical stroma: A hitherto undocumented variant of sarcomatoid carcinoma

Carcinosarcomas are biphasic tumors composed of admixed malignant epithelial and mesenchymal components. Numerous terms have been used to name such neoplasms; therefore, terminological confusion is frequent. Most examples of carcinosarcomas are encountered in non‐cutaneous sites, with approximately 100 cases of cutaneous carcinosarcomas reported so far in the English literature. Although different theories have been suggested to explain the occurrence of these peculiar neoplasms, histogenetic mechanisms should be better hypothesized depending on each individual case. Even though prognosis tends to be related to the specific components of the lesion, especially the epithelial one, it seems that cases of cutaneous localization usually have a better outcome. We report an exceedingly rare case of syringocystadenocarcinoma papilliferum which showed an atypical stroma with sarcomatoid appearance, and highlight that the terminology used for this spectrum of lesions is disorganized and confusing.     

Response to chemoradiotherapy and lymph node involvement in locally advanced rectal cancer

AIM: To establish the association between lymph node involvement and the response to neoadjuvant therapy in locally advanced rectal cancer.METHODS: Data of 130 patients with mid and low locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation followed by radical surgery over a 5-year period were reviewed. Tumor staging was done by endorectal ultrasound and/or magnetic resonance imaging. Tumor response to neoadjuvant therapy was determined by T-downstaging and tumor regression grading (TRG). Pathologic complete response (pCR) is defined as the absence of tumor cells in the surgical specimen (ypT0N0). The varying degrees TRG were classified according to Mandard’s scoring system. The evaluation of the response is based on the comparison between previous clinico-radiological staging and the results of pathological evaluation. χ² and Spearman’s correlation tests were used for the comparison of variables.RESULTS: Pathologic complete response (pCR, ypT0N0, TRG1) was observed in 19 cases (14.6%), and other 18 (13.8%) had only very few residual malignant cells in the rectal wall (TRG2). T-downstaging was found in 63 (48.5%). Mean lymph node retrieval was 9.4 (range 0-38). In 37 cases (28.5%) more than 12 nodes were identified in the surgical specimen. Preoperative lymph node involvement was seen in 77 patients (59.2%), 71 N1 and 6 N2. Postoperative lymph node involvement was observed in 41 patients (31.5%), 29 N1 and 12 N2, while the remaining 89 were N0 (68.5%). In relation to ypT stage, we found nodal involvement of 9.4% in ypT0-1, 22.2% in ypT2 and 43.7% in ypT3-4. Of the 37 patients considered “responders” to neoadjuvant therapy (TRG1 and 2), there were only 4 N+ (10.8%) and the remainder N0 (89.2%). In the “non responders” group (TRG 3, 4 and 5), 37 cases were N+ (39.8%) and 56 (60.2%) were N0 (P < 0.001).CONCLUSION: Response to neoadjuvant chemoradiation in rectal cancer is associated with lymph node involvement.     

Endoscopy mitigation strategy with telemedicine and low-cost device use for COVID-19 prevention: A fourth-level Colombian center experience

Background and study aimsThe COVID-19 outbreak has reorganized surgical team conditions regarding endoscopy. The number of interventions has been reduced, the number of healthcare professionals must be limited, and both the patients and physicians are more protected than ever.Patients and MethodsIn the highest peak of contagion in Colombia, endoscopy, colonoscopy, and esophagogastroduodenoscopy were performed using a low-cost disposable device. A total of 1388 procedures were performed. Every patient was assessed for symptoms via a telephone call, at the health center, and after the procedure, following specific attention routes.ResultsAfter procedure follow-up, no positive cases of COVID-19 were noted.ConclusionThe methodology reduced the risk of infection during the COVID-19 pandemic.     

Osteogenic alveolar distraction: a review of the literature.

OBJECTIVE: Alveolar distraction is a relatively novel procedure by which alveolar bone and underlying mucosa are regenerated. The low predictability of other vertical or horizontal bone regeneration methods has increased interest in this promising technique. This article was designed to review published clinical and experimental results on alveolar distraction, including basic research in other disciplines (maxillofacial and orthopedic distraction) related to or with influence on alveolar distraction. STUDY DESIGN: A review of the international literature was performed to summarize results of clinical and experimental studies on alveolar distraction and on distraction at other anatomical sites that contribute important findings on tissue biology, molecular mechanisms, and other factors that influence and participate in the alveolar distraction process. RESULTS: Research into alveolar distraction has addressed the latency phase, distraction phase, and consolidation phase, yielding highly variable results. Little experimental research has been carried out on this procedure, and most publications are clinical studies with a short follow-up period. Published studies have reported a high rate of complications, attributable to our current lack of understanding of the process. CONCLUSIONS: Definitive conclusions on alveolar distraction are hampered by the lack of clinical and experimental studies to date. Greater knowledge of the factors that influence the distraction process will lead to a more predictable and efficacious distraction technique and a better distractor design.     

Meta-analysis of drop-out rates in randomised clinical trials, comparing typical and atypical antipsychotics in the treatment of schizophrenia.

OBJECTIVE: To assess antipsychotic medication in the treatment of schizophrenia, based on trial drop-out rates. METHOD: The studies included were randomised controlled trials that compared any of the four clinically best-established atypical antipsychotics (quetiapine, olanzapine, risperidone or clozapine) against either of two typical antipsychotics regarded as the gold standard (haloperidol or chlorpromazine). RESULTS: Meta-analysis indicated less risk of all-cause patient withdrawal from atypical medication trials where dosage was flexible, in both the short, relative risk (RR) 0.70 (95% CI 0.64-0.76), P<0.00001, and long term, RR 0.72 (0.65-0.80), P<0.00001. Similar results were observed for withdrawal due to adverse events, RR: 0.54 (0.41-0.72), P<0.0001. Nevertheless, the favourable effects of atypical medication disappeared in trials relying on fixed dosage. CONCLUSIONS: We detected a significant positive effect in terms of the outcome of treatment discontinuation for atypical versus typical medication, though only where the use of flexible rather than fixed doses (closer to an experimental control situation) was possible.     

HLA markers in familial Lichen Sclerosus

Background: Lichen sclerosus (LS) has been identified with increased frequency in families,often associated with HLA markers, mainly DQ7. A genetic co‐etiology seems likely in this setting. Moreover, there is an association of LS with autoimmune disorders, such as the presence of anti‐thyroid peroxidase autoantibodies (anti‐TPO), a hallmark of autoimmune thyroid diseases. Patients and Methods: In 3 families affected by LS, we verified their HLA markers, and identified previously undiagnosed cases of LS and autoimmune disorders. 30 individuals were examined with history, skin biopsy, HLA class I and II typing by PCR‐SSP, and measurement of anti‐TPO, free thyroxine and thyroidstimulating hormones (TSH) levels. Results: There were 8 cases of LS, 50 % of them anti‐TPO+. Autoimmune disorders were found in 40 % (total) and in 87.5 % of those affected. Most common HLA markers were B*15, B*57, CW*03, CW*07, CW*18, DRB1*04, DRB1*07, DRB4*. The three latter have been previously associated with LS. Conclusion: New cases of LS and autoimmune disorders can be detected in first degree relatives of patients with LS. The presence of anti‐TPO antibodies strongly suggests autoimmune thyroiditis. There is intra‐familial association between the haplotype HLA‐B*15 ‐DRB1*04 ‐DRB4* and anti‐TPO,emphasizing their link with thyroiditis. New familial approaches might help to make clear the pathogenesis of LS and its association with autoimmune diseases.     

Strategies to enhance transductional efficiency of adenoviral-based gene transfer to primary human fibroblasts and keratinocytes as a platform in dermal wounds

Genetically modified keratinocytes and fibroblasts are suitable for delivery of therapeutic genes capable of modifying the wound healing process. However, efficient gene delivery is a prerequisite for successful gene therapy of wounds. Whereas adenoviral vectors (Ads) exhibit superior levels of in vivo gene transfer, their transductional efficiency to cells resident within wounds may nonetheless be suboptimal, due to deficiency of the primary adenovirus receptor, coxsackie-adenovirus receptor (CAR). We explored CAR-independent transduction to fibroblasts and keratinocytes using a panel of CAR-independent fiber-modified Ads to determine enhancement of infectivity. These fiber-modified adenoviral vectors included Ad 3 knob (Ad5/3), canine Ad serotype 2 knob (Ad5CAV-2), RGD (Ad5.RGD), polylysine (Ad5.pK7), or both RGD and polylysine (Ad5.RGD.pK7). To evaluate whether transduction efficiencies of the fiber-modified adenoviral vectors correlated with the expression of their putative receptors on keratinocytes and fibroblasts, we analyzed the mRNA levels of CAR, alpha upsilon integrin, syndecan-1, and glypican-1 using quantitative polymerase chain reaction. Analysis of luciferase and green fluorescent protein transgene expression showed superior transduction efficiency of Ad5.pK7 in keratinocytes and Ad5.RGD.pK7 in fibroblasts. mRNA expression of alpha upsilon integrin, syndecan-1 and glypican-1 was significantly higher in primary fibroblasts than CAR. In keratinocytes, syndecan-1 expression was significantly higher than all the other receptors tested. Significant infectivity enhancement was achieved in keratinocytes and fibroblasts using fiber-modified adenoviral vectors. These strategies to enhance infectivity may help to achieve higher clinical efficacy of wound gene therapy.