Thoracoscopic approach as surgical management of esophageal epiphrenic diverticulum.

BACKGROUND: Management of diverticulum of the lower esophagus or epiphrenic diverticulum can be performed using the abdominal or thoracic approach. In some cases, the thoracic approach is preferred, but few studies have described thoracoscopic resection. The objective of the present study was to investigate the thoracoscopic approach for management of epiphrenic esophageal diverticulum. MATERIAL AND METHODS: From 2008 to 2018, all patients undergoing surgery for epiphrenic esophageal diverticulum by the thoracoscopic approach were included in this single-center, retrospective, observational study. Data on diverticulum, surgery and follow-up were assessed. RESULTS: During the study period, 14 patients underwent surgery. Two patients had two diverticula. The mean location of the superior edge of the diverticulum was 7cm (2-14cm) above the gastro-esophageal junction. The mean size of the diverticulum was 39 millimeters (20-60). Thoracoscopic approach was used in all patients. No conversion to thoracotomy was required. Mean operative time was 168min (120-240). No postoperative mortality occurred. The overall complication rate was 40% (6 complications out of 15 resections), with three major complications including leaks (n=2) and a case of bronchoesophageal fistula (n=1). Median length of hospital stay was 12 days (8-40). At a mean postoperative follow-up of 20.7 months (5-71), 85% of patients had complete disappearance of preoperative symptoms without recurrence of the diverticulum on the barium swallow study test. CONCLUSION: Thoracoscopic approach as management of epiphrenic diverticulum is feasible, with acceptable short-term morbidity. The thoracoscopic approach is also effective in resolving preoperative symptoms.

In vivo analysis at the cellular level reveals similar steatosis induction in both hepatitis C virus genotype 1 and 3 infections.

Steatosis is a frequent histological feature of hepatitis C virus (HCV) infection. Cohort studies of patients with chronic hepatitis C identified HCV genotype 3 (HCV GT3) as the prevalent steatotic genotype. Moreover, Huh-7 cells over-expressing HCV GT3 core protein accumulate more triglyceride in larger lipid droplets than cells expressing core proteins of other HCV genotypes. However, little is known about the relationship of steatosis and HCV infection at the cellular level in vivo. In this study, we used highly sensitive multiplex in situ hybridization methodology together with lipid staining to investigate HCV-induced lipid droplet accumulation at the cellular level in liver biopsies. Consistent with previous reports, histological steatosis grades were significantly higher in GT3 compared to GT1 infected livers, but independent of viral load. Using nile red lipid stainings, we observed that the frequency of lipid droplet containing cells was similar in HCV GT1- and HCV GT3-infected livers. Lipid droplet formation preferentially occurred in HCV-infected cells irrespective of the genotype, but was also observed in noninfected cells. These findings demonstrate that the main difference between GT1- and GT3-induced steatosis is the size of lipid droplets, but not the number or relative distribution of lipid droplets in infected vs uninfected hepatocytes.

Laparoscopy in the second and third trimesters of pregnancy for abdominal surgical emergencies.

OBJECTIVE: To assess complications and outcomes of pregnancies following laparoscopic abdominal surgery during the second and third trimesters of pregnancy. MATERIAL AND METHODS: Retrospective single-center study of 23 cases of laparoscopic surgery in the second or third trimesters of pregnancy between January 2005 and May 2016. RESULTS: The laparoscopies were performed between 15 and 33 weeks of gestation, a mean of 23 weeks+2 days, with 6 cases in the 3rd trimester. The operations were: 11 cholecystectomies, 6 appendectomies, 1 intestinal occlusion (volvulus on a gastric band), 3 adnexal torsions, 1 ovarian cyst and 1 paratubal cyst with torsion. No secondary laparotomy was required. The postoperative courses were favorable in most cases. However, 3 appendectomies were complicated, one by chorioamnionitis and miscarriage at 20½ weeks of gestation and 2 by right iliac fossa abscesses requiring percutaneous radiological drainage, one of these women delivered a healthy term baby and the other had chorioamnionitis and preterm delivery at 34 weeks, followed by neonatal death. CONCLUSION: Laparoscopy can be safely performed for surgical indications in the second and third trimesters of pregnancy. In case of abdominal symptoms, a timely diagnosis is required to decide whether or not to operate and imaging should not be withheld particularly in case of suspected appendicitis which has a high risk of complications.

Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area.

Tafamidis is a transthyretin (TTR) stabilizer able to prevent TTR tetramer dissociation. There have been a few encouraging studies on Tafamidis efficacy in early-onset inherited transthyretin amyloidosis (ATTR) due to Val30Met mutation. However, less is known about its efficacy in later disease stages and in non-Val30Met mutations. We performed a multi-center observational study on symptomatic ATTR patients prescribed to receive Tafamidis. We followed up patients according to a standardized protocol including general medical, cardiological and neurological assessments at baseline and every 6 months up to 3 years. Sixty-one (42 males) patients were recruited. Only 28 % of enrolled subjects had the common Val30Met mutation, mean age of onset was remarkably late (59 years) and 18 % was in advanced disease stage at study entry. Tafamidis proved safe and well-tolerated. One-third of patients did not show significant progression along 36 months, independently from mutation type and disease stage. Neurological function worsened particularly in the first 6 months but progression slowed significantly thereafter. Autonomic function remained stable in 33 %, worsened in 56 % and improved in 10 %. Fifteen percent of patients showed cardiac disease progression and 30 % new onset of cardiomyopathy. Overall, Tafamidis was not able to prevent functional progression of the disease in 23 (43 %) subjects, including 16 patients who worsened in their walking ability and 12 patients who reached a higher NYHA score during the follow-up period. A higher mBMI at baseline was associated with better preservation of neurological function. In conclusion, neuropathy and cardiomyopathy progressed in a significant proportion of patients despite treatment. However, worsening of neurological function slowed after the first 6 months and also subjects with more advanced neuropathy, as well as patients with non-Val30Met mutation, benefited from treatment. Body weight preservation is an important favorable prognostic factor.

Hyperthermic intraperitoneal chemotherapy with cisplatin: Amifostine prevents acute severe renal impairment.

UNLABELLED: Surgical cytoreduction combined with intraperitoneal chemo-hyperthermia (HIPEC) has shown to provide survival benefits in the management of some peritoneal carcinomatosis. The cisplatin (CP) used in HIPEC carries a risk of renal impairment (RI). This risk could be reduced by administration of amifostine (A). The aim of our study was to assess the utility of A in preventing RI during IPCH with CP. PATIENTS AND METHODS: Retrospective study including patients who underwent HIPEC between January 2007 and June 2013. The HIPEC involved administration of CP and mitomycin C, between 41 and 43 °C. The peri-anaesthetic management was consistent to use A after 2010. Renal function was assessed from the measured creatinine clearance (CreatCl) and the change between D0 and D4 was compared between patients who received A (group A+) and those who did not (group A-). Severe RI was defined as the development of a CreatCl of <30 ml/min. The statistical analysis used a Student t-test and Fischer's exact test. A p-value of <0.05 was deemed to be statistically significant. RESULTS: Over the studied period, seventy five patients underwent HIPEC and the findings from fifty two patients were analysed: thirty one in group A+ and twenty one in group A-. The change in mean CreatCl from D0 to D4 did not differ between the two groups although between D1 and D4 a significantly higher percentage of severe RI was seen in group A-. CONCLUSIONS: This study has shown A to offer benefit in terms of reducing severe RI when CP is used in HIPEC. These results, however, will need to be confirmed in prospective series on larger numbers of patients.

Hepatitis C virus dysregulates glucose homeostasis by a dual mechanism involving induction of PGC1α and dephosphorylation of FoxO1.

The maintenance of glucose homeostasis is a complex process in which the insulin signalling pathway plays a major role. Disruption of insulin-regulated glucose homeostasis is frequently observed in chronic hepatitis C (CHC) infection and might potentially contribute to type 2 diabetes mellitus (T2DM) development. Presently, the mechanism that links HCV infection to insulin resistance remains unclear. Previously, we have reported that HCV protein expression in HCV transgenic mice (B6HCV) leads to an overexpression of protein phosphatase 2A (PP2A) through an ER stress response. In the present work, we describe an association of FoxO1 hypophosphorylation and upregulation of both PGC-1α and G6Pase to phenotypic hyperglycaemia and insulin resistance in B6HCV mice. In vitro, we observed that PGC1α is concomitantly induced with PP2A. Moreover, we show that the enhanced PP2A expression is sufficient to inhibit insulin-induced FoxO1 phosphorylation via blockade of insulin-mediated Akt activation or/and through direct association and dephosphorylation of pS-FoxO1. Consequently, we found that the gluconeogenic gene glucose-6-phosphatase is upregulated. These observations were confirmed in liver biopsies obtained from CHC patients. In summary, our results show that HCV-mediated upregulation of PP2A catalytic subunit alters signalling pathways that control hepatic glucose homeostasis by inhibiting Akt and dephosphorylation of FoxO1.

Neuroprotective effects of progesterone in chronic experimental autoimmune encephalomyelitis.

Observations so far obtained in experimental autoimmune encephalomyelitis (EAE) have revealed the promising neuroprotective effects exerted by progesterone (PROG). The findings suggest that this neuroactive steroid may potentially represent a therapeutic tool for multiple sclerosis (MS). However, up to now, the efficacy of PROG has been only tested in the acute phase of the disease, whereas it is well known that MS expresses different features depending on the phase of the disease. Accordingly, we have evaluated the effect of PROG treatment in EAE induced in Dark Agouti rats (i.e. an experimental model showing a protracted relapsing EAE). Data obtained 45 days after EAE induction show that PROG treatment exerts a beneficial effect on clinical score, confirming surrogate parameters of spinal cord damage in chronic EAE (i.e. reactive microglia, cytokine levels, activity of the Na(+) ,K(+) -ATPase pump and myelin basic protein expression). An increase of the levels of dihydroprogesterone and isopregnanolone (i.e. two PROG metabolites) was also observed in the spinal cord after PROG treatment. Taken together, these results indicate that PROG is effective in reducing the severity of chronic EAE and, consequently, may have potential with respect to MS treatment.

Importancia de la terapia básica pre-tratamiento ortodóncico / The importance of pre-orthodontic treatment basic therapy

Introducción: la capacidad de los microorganismos para formar y mantenerse en el biofilm tiene un alto impacto en las infecciones crónicas, pues el mismo protege y nutre a comunidades de microorganismos que pueden influir en el tratamiento ortodóncico, aumentando la incidencia de caries y enfermedad periodontal. Objetivo: comparar la condición periodontal inicial y la alcanzada luego de la terapia básica periodontal de los pacientes que concurren a la consulta para iniciar un tratamiento ortodóncico. Materiales y métodos: se evaluaron 10 pacientes entre 14 y 30 años que concurrieron al servicio de la Cátedra de Ortodoncia de la Facultad de Odontología de la UBA. Se tomaron el índice de placa de Silness y Loe y gingival de Loe y Silness, la profundidad de sondaje y hemorragia gingival al sondaje en todas las piezas dentarias presentes en la boca del paciente. De la zona de los primeros premolares superiores se eliminó la placa supragingival y se tomaron muestras subgingivales, las cuales fueron colocadas en solución fisiológica y medio de transporte VMGAIII. Simultáneamente se realizaron extendidos del materiales y se coloreó con la técnica de Gram y de Giemsa. Luego de que los pacientes recibieran enseñanza de técnicas de higiene bucal y/o terapia básica periodontal, se volvieron a registrar dichos índices. Resultados: el índice de placa inicial presentó una mediana de 2.5 y post terapia básica, una mediana de 1.0 con una diferencia estadísticamente significativa (p=0.005) según Wilcoxon Signed Rank Test. El indice gingival inicial presentó una mediana de 2.0 y post terapia básica fue de 1.0 con una diferencia estadísticamente significativa (p<0.005 Wilcoxon Signed Test). La profundidad de sondaje pretratamiento presentó una mediana de 3.0mm con sangrado al sondaje positivo y microbiota compatible con gingivitis y periodontitis leve. Luego de enseñanza de técnicas de higiene bucal la misma fue de 1 mm con sangrado al sondaje negativo.

Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients.

Molecular mechanisms of azole resistance in Candida albicans, including alterations in the target enzyme and increased efflux of drug, have been described, but the epidemiology of the resistance mechanisms has not been established. We have investigated the molecular mechanisms of resistance to azoles in C. albicans strains displaying high-level fluconazole resistance (MICs, > or =64 microg/ml) isolated from human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis. The levels of expression of genes encoding lanosterol 14alpha-demethylase (ERG11) and efflux transporters (MDR1 and CDR) implicated in azole resistance were monitored in matched sets of susceptible and resistant isolates. In addition, ERG11 genes were amplified by PCR, and their nucleotide sequences were determined in order to detect point mutations with a possible effect in the affinity for azoles. The analysis confirmed the multifactorial nature of azole resistance and the prevalence of these mechanisms of resistance in C. albicans clinical isolates exhibiting frank fluconazole resistance, with a predominance of overexpression of genes encoding efflux pumps, detected in 85% of all resistant isolates, being found. Alterations in the target enzyme, including functional amino acid substitutions and overexpression of the gene that encodes the enzyme, were detected in 65 and 35% of the isolates, respectively. Overall, multiple mechanisms of resistance were combined in 75% of the isolates displaying high-level fluconazole resistance. These results may help in the development of new strategies to overcome the problem of resistance as well as new treatments for this condition.

Multiple resistance mechanisms to azole antifungals in yeast clinical isolates.

The use of antifungal agents, especially the azole class, has increased in parallel with a higher incidence of fungal infections, particularly in immunocompromised patients. This situation has favored the appearance of Candida species, prominent among them C. albicans and C. globrata, with acquired resistance to these agents. This review focuses on the latest developments in investigations of molecular mechanisms contributing to azole resistance. Multiple resistance mechanisms have been described that can coexist in resistant clinical isolates. Understanding resistance mechanisms is of value not only for the design of new antifungal agents but also the development of strategies of overcome or delay the emergence of resistance.

Nursing issues in the management of urinary diversions in women.

Cancer and urinary diversion via orthotopic or cutaneous stomas in women result in significant physiological and psychosocial issues. Patient counseling, education, and follow-up care are best achieved by the intervention of a multidisciplinary health care team. Urologic and enterostomal therapy nursing support in these endeavors can contribute to facilitating a positive outcome.

Maintaining quality of care and patient satisfaction with radical prostatectomy in the era of cost containment.

OBJECTIVES: To determine the effect of shortened hospital stay after radical retropubic prostatectomy on costs, adverse surgical outcomes, and patient satisfaction. METHODS: The effect of changes in preoperative counseling, perioperative care, and analgesic management on hospital length of stay; mean cost per case and cost per hospital day; and 30-day complication, hospital readmission, and mortality rates were analyzed for a consecutive sample of 374 patients undergoing radical prostatectomy between July 1989 and November 1995. Satisfaction with length of stay, analgesic regimen, and surgical outcome was assessed in a random subset of 150 patients by anonymous questionnaire. RESULTS: Length of stay (LOS) was shortened from a median 7 to 2 nights after surgery during the study (P < 0.0001), whereas the acute complication, 30-day readmission, and 30-day mortality rates remained constant. Reducing LOS resulted in a 43% decrease in mean cost per case while mean cost per day increased by 22% to 35%. Overall patient satisfaction was high, with 83.5% of patients rating LOS as "just right" and 89.2% reporting they were "satisfied" or "very satisfied" with their pain control after surgery. CONCLUSIONS: Shortened LOS after radical retropubic prostatectomy can be accomplished safely and can meet with high levels of patient satisfaction while significantly reducing hospital-related costs. The potential for further incremental reductions in cost with reductions in LOS to less than 2 nights appears to be small, and future efforts at cost reduction for this procedure should center on decreasing the intensity of care during hospitalization.

Characterization of bone cells isolated on discontinuous Percoll gradients: distribution in sequentially derived populations.

Bone cell populations obtained by sequential digestion of newborn mouse calvariae remain morphologically heterogeneous despite well-documented biochemical differences. Fractionation of these populations on Percoll gradient reveal three major cell groups of low, intermediate, and high buoyant density (1.056, 1.070, and 1.095 g/ml) that are present in different ratios in early and late released populations. Cells of low and intermediate density dominate in early released populations. In contrast, late released populations contain mostly high-density cells. Basal levels of alkaline phosphatase are highest in cells of intermediate buoyant density. All cells respond to PTH with cAMP production and morphologic transformation, but biochemical responses to PTH, such as secretion of insulin-like growth factor I (IGF-I) and stimulation of alkaline phosphatase activity, occur mostly in cells of intermediate density. These data suggest that (1) subclasses of osteoblasts can be further separated by density and (2) PTH effects on alkaline phosphatase activity and IGF-I secretion are probably expressed by osteoblasts of a certain subclass and/or stage of development.

Clinical evaluation of physical therapy in the management of internal derangement of the temporomandibular joint.

This clinical cross-sectional study examines the favorable functional improvement in patients undergoing physical therapy for mild to moderate internal disc derangements of the temporomandibular joint. Sixty-eight patients with internal derangements were treated with physical therapeutic modalities as described by Rocabado. A success rate of 86% was achieved in patients with early- to mid-opening and late- to mid-closing clicks of the temporomandibular joint. Approximately one third of these patients required short-term occlusal bite appliances to assist in their management. A success rate of 7% was achieved in patients with late-opening and late-closing clicks. No patient with clicking on mediolateral movement was successfully managed with physical therapy. Likewise, patients with nonreducing anteriorly displaced discs of the temporomandibular joint did not respond well to physical therapy. Pain management was evaluated separately and showed subjective improvement in 82% of patients with mild to moderate disc dysfunction and pain. Only 29% of patients with late-opening clicking or locked joints experienced pain relief. When patients were classified according to occurrence of the clicking phenomenon, interesting trends relating to duration of symptoms were found. Twenty-two patients who did not respond favorably to physical therapy underwent surgical procedures. Findings in these patients offer suggestions about why nonsurgical therapy is not successful in certain cases.