Current evidence regarding the role of adjuvant chemotherapy in rectal cancer patients with pathologic complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.

PURPOSE: The aim of this meta-analysis was to investigate the role of adjuvant chemotherapy (AC) in rectal cancer patients with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) and curative resection. METHODS: This study was completed in accordance to the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The electronic scholar databases (Medline, Web of Science, Scopus) were screened for eligible articles. The level of evidence (LoE) was assessed using the GRADE methodology. RESULTS: Overall, 23 non-randomized studies and 17,406 patients were included in the present meta-analysis. Pooled comparisons confirmed that AC improved overall survival (HR: 0.68, p=0.0003), but not disease-free (p=0.22) and recurrence-free survival (p=0.39). However, the LoE for all outcomes was characterized as "very low," due to the absence of RCTs. CONCLUSIONS: Considering the study limitations and the lack of randomized studies, further high-quality RCTs are required to confirm the findings of our study.

The effect of hexanic extract of Serenoa repens on prostatic inflammation: results from a randomized biopsy study.

PURPOSE: To evaluate the effect of hexanic extract of Serenoa repens (HESr) on prostatic inflammation in patients with diagnosed prostatic inflammation. METHODS: Patients with prostatic inflammation histologically confirmed by TRUS prostatic biopsy were randomized either to receive HESr (320 mg/day) or no treatment. A second biopsy was performed 6 months later according to standard clinical practice. Inflammation was assessed by the Irani's score and immunohistochemical staining using the CD3, CD4 and CD8 (for T-leucocytes), CD20 (for B-leucocytes) and CD163 (for macrophages) antibodies. RESULTS: Overall 97 patients were eligible for analysis. In the HESr group the mean inflammation grading and aggressiveness grading score significantly decreased from 1.55 and 1.55 at baseline to 0.79 (p = 0.001) and 0.87 (p = 0.001) at the second biopsy, respectively. In the control group the mean inflammation grading score was 1.44 at first biopsy and 1.23 at the second biopsy. The mean aggressiveness gradings core was 1.09 and 0.89, respectively. No statistical significance was found (p = 0.09 and p = 0.74).The mean decrease in all inflammation scores was statistically higher in the HESr patients compared to controls. The immunohistochemical staining showed a significant change in the expression of the analyzed antibodies for the HESr patients compared to the first biopsy. In the nontreatment group, no significant difference was found at the second biopsy. The change in expression of each antibody in the HESr group was statistical significant compared to control. CONCLUSIONS: HESr seems to reduce prostatic inflammation in terms of histological and immunohistochemical parameters in this specific patients population.

Adhesion Prevention to Polypropylene Meshes Using Combined Icodextrin Four Percent and Dimetindene Maleate.

BACKGROUND: The use of surgical meshes in ventral hernia repair has significantly reduced hernia recurrence rates. However, when placed intraperitoneally prosthetic materials can trigger the development of peritoneal adhesions. The present experimental study evaluated the combined icodextrin 4% and dimetindene maleate treatment in preventing peritoneal adhesion formation to polypropylene and titanium-coated polypropylene meshes. MATERIALS AND METHODS: Sixty female white rabbits were divided into four groups. A 2 × 2 cm piece of mesh was fixed to intact peritoneum in all animals through a midline laparotomy. A lightweight polypropylene mesh was implanted in groups 1 and 2 and a titanium-coated polypropylene mesh in groups 3 and 4. Groups 2 and 4 were treated, intraoperatively, with intravenous dimetindene maleate (0.1 mg/kg) and intraperitoneal solution of icodextrin 4% (20 mL/kg) and for the next 6 d with dimetindene maleate intramuscularly. The observation period lasted 15 d. Adhesion scores, percentage of mesh affected surface, tissue hydroxyproline levels, and tissue histopathology were examined. RESULTS: All animals in group 1 and 57% of animals in group 3 presented postoperative adhesions. The combination of antiadhesives significantly reduced the extent and severity of adhesions as well as the hydroxyproline levels in groups 2 and 4 compared with groups 1 and 3. On microscopic evaluation, animals in group 1 exhibited higher inflammation scores compared with group 2, whereas animals in groups 2 and 4 had better mesotheliazation compared with groups 1 and 3. CONCLUSIONS: The combined administration of icodextrin 4% and dimetindene maleate reduces the extent and severity of adhesions and may be successfully used to prevent adhesion formation after mesh intraperitoneal placement.

Administration of an Oral Hydration Solution Prevents Electrolyte and Fluid Disturbances and Reduces Readmissions in Patients With a Diverting Ileostomy After Colorectal Surgery: A Prospective, Randomized, Controlled Trial.

BACKGROUND: Patients with a newly formed ileostomy often develop electrolyte abnormalities and dehydration. OBJECTIVE: The study assessed the prophylactic effect of an isotonic hydration solution on dehydration and electrolyte abnormalities in patients with a newly formed ileostomy. DESIGN: This was a prospective, randomized, controlled trial (NCT02036346). SETTINGS: The study was conducted at a single surgical unit of a public university hospital. PATIENTS: Patients scheduled for elective rectosigmoid resection were considered for study inclusion. INTERVENTION: Patients in whom a diverting ileostomy was created were randomly assigned to the intervention group (n = 39), which received an oral isotonic glucose-sodium hydration solution for 40 days postdischarge and the control group (n = 41) which did not receive an intervention. The 2 groups were compared with a group of patients who underwent rectosigmoid resection without diverting ileostomy (n = 37). MAIN OUTCOME MEASURES: Serum electrolyte and renal function markers were assessed preoperatively and at 20 and 40 days postdischarge. RESULTS: At 20 days postdischarge, the serum sodium of the control group appeared lower than the serum sodium of the intervention group and the nonileostomy group (p = 0.007). At the same time point, urea and creatinine levels of the control group were higher than the urea and creatinine levels of the other 2 groups (p = 0.01 and p = 0.02). At 40 days postdischarge, mean sodium and renal function markers improved in the control group, but sodium and creatinine continued to differ in comparison with the intervention and nonileostomy groups (p = 0.01 and p = 0.04). The readmission rate for fluid and electrolyte abnormalities was higher in the control group (24%) than in the other 2 groups, where no rehospitalization for such a reason was required (p = 0.001). LIMITATIONS: The study was limited by its single-center design. CONCLUSION: An oral isotonic drink postdischarge can have a prophylactic effect on patients with a newly formed ileostomy, preventing readmission for fluid and electrolyte abnormalities. See Video Abstract at http://links.lww.com/DCR/A603.

Microvessel Density as a Surrogate Prognostic Marker in Patients with Multiple Myeloma: A Meta-Analysis.

BACKGROUND/AIMS: Bone marrow (BM) angiogenesis is considered a hallmark of multiple myeloma (MM) development and progression, and can be quantified with the use of microvessel density (MVD). The purpose of this study is to provide a review and a meta-analysis of the current literature regarding the prognostic value of MVD in the overall survival (OS) of MM patients. METHODS: MEDLINE was screened for studies evaluating the OS of MM patients with regard to their MVD count in BM trephine. The pooled hazard ratio (HR) and its associated 95% confidence interval (CI) among MM patients with a high and low MVD count was the primary end point. Secondary outcomes included odds ratios (OR) for 12-, 36-, and 60-month survival. RESULTS: Ten eligible trials were identified for the analysis of the primary end point and 9 for the secondary end points. Pooled HR for OS was 1.85 (95% CI: 1.25-2.73, p = 0.002). The pooled OR of survival were 1.59 (95% CI: 1.02-2.46, p = 0.04) at 12 months, 2.90 (95% CI: 1.68-5.03, p = 0.0001) at 36 months, and 3.42 (95% CI: 2.41-4.85, p < 0.00001) at 60 months, in favor of the low MVD group. CONCLUSION: This meta-analysis provides persuasive evidence that MVD has significant impact on the clinical outcome of MM patients.

Endothelin-1 overexpression: a potential biomarker of unfavorable prognosis in non-metastatic muscle-invasive bladder cancer.

Endothelin-1 (ET-1) is a multifunctional peptide exerting its effects via receptors A and B. ET-1 and its receptors, endothelin axis (ET axis), play a promoting role in cancer biology. Alterations of proteins of ET axis have been detected in non-metastatic muscle-invasive bladder cancer (NMMIBC). The objective of this study is to investigate the potential role of ET-1 tumor expression as a biomarker of prognosis, compared to other prognostic parameters (epidemiologic and pathologic), in NMMIBC. We prospectively included 40 consecutive, primary, high-grade NMMIBC patients. Tumor specimens after initial transurethral resection were stained immunohistochemically for ET-1. The ET-1 evaluation of expression was based on staining intensity (SI) of ET-1. SI was classified according to an arbitrary four-tiered scale (negative = 0, mild = 1, moderate = 2, strong = 3). Epidemiologic and pathologic parameters were analyzed, using univariate and multivariate statistics, for disease progression, progression-free survival (PFS), and overall survival (OS). ET-1 overexpression (SI = 3) was the unique parameter which associated significantly, both in univariate (log-rank test, p = 0.033) and multivariate (Cox regression analysis, p = 0.045, HR = 4.849, 95 % CI: 1.039-22.624) analysis, with an increased hazard ratio of progression. ET-1 overexpression (SI = 3) was also the unique parameter which associated, marginally significantly in univariate analysis (log-rank test, p = 0.056) and highly significantly in multivariate analysis (Cox regression analysis, p = 0.005, HR = 7.001, 95 % CI: 1.782-27.501), with an increased hazard ratio of death. Overexpression of ET-1 may be a potential biomarker of unfavorable prognosis in NMMIBC patients.

TNFα induces expression of HIF-1α mRNA and protein but inhibits hypoxic stimulation of HIF-1 transcriptional activity in airway smooth muscle cells.

Airway smooth muscle cells (ASMCs) participate in tissue remodeling characteristic of airway inflammatory diseases like asthma. Inflammation and hypoxia pathways are often interconnected and the regulatory subunit of the hypoxia inducible factor, HIF-1α, has been recently shown to be induced by cytokines. Here we investigate the effect of individual or combined treatment of ASMCs with the inflammatory mediator TNFα and/or hypoxia on the expression of HIF-1α, HIF-1 targets and inflammation markers. TNFα enhances HIF-1α protein and mRNA levels, under both normoxia and hypoxia. TNFα-mediated induction of HIF-1α gene transcription is repressed by inhibition of the NF-κB pathway. Despite the up-regulation of HIF-1α protein, the transcription of HIF-1 target genes remains low in the presence of TNFα at normoxia and is even reduced at hypoxia. We show that the reduction in HIF-1 transcriptional activity by TNFα is due to inhibition of the interaction of HIF-1α with ARNT and subsequent blocking of its binding to HREs. Comparison between hypoxia and TNFα for their effects on the expression of inflammatory markers shows significant differences: hypoxia up-regulates the expression of IL-6, but not RANTES or ICAM, and reduces the induction of VCAM by TNFα. Finally, ex vivo treatment of rabbit trachea strips with TNFα increases HIF-1α protein levels, but reduces the expression of HIF-1 targets under hypoxia. Overall, TNFα induces HIF-1α mRNA synthesis via an NF-κB dependent pathway but inhibits binding of HIF-1α to ARNT and DNA, while hypoxia and TNFα have distinct effects on ASMC inflammatory gene expression.

The impact of parental bonding on sexual distress in women with type 1 diabetes mellitus.

INTRODUCTION: Psychosomatic and social issues have been found to be determinants of sexual distress in diabetic and non-diabetic populations. However, the role of parental bonding as a determinant for sexual distress has not been studied in women with type 1 diabetes mellitus (DM-1). AIM: To study the role of parental care and overprotection, in the pathogenesis of sexual distress in women with DM-1. METHODS: Seventy-seven women with uncomplicated DM-1 and 77 healthy controls were enrolled in the study. The Female Sexual Distress Scale (FSDS), the General Health Questionnaire-28, and the Parental Bonding Instrument were used to evaluate sexual distress, general health and bonding with parents, respectively. MAIN OUTCOME MEASURES: To assess the role of parental bonding as risk factor for sexual distress, in women with DM-1. RESULTS: Women with DM-1 had significantly higher FSDS scores compared with controls. Furthermore, women with DM-1 had significantly higher maternal and paternal care, and lower maternal overprotection in comparison with the healthy ones. Paternal overprotection and general health were similar in both groups (P > 0.05). Sexual distress was more frequent in women with DM-1 (31.43% vs. 8.57% of controls, P < 0.05). Diabetic women with sexual distress had lower maternal care, higher maternal overprotection and lower paternal overprotection compared to diabetics without sexual distress (P < 0.05). No difference was found in the paternal care between the two groups (P > 0.05). Moreover, sexually distressed DM-1 women had worse general health parameters in comparison with the non-sexually distressed diabetics (P < 0.05). In the DM-1 group, low maternal care and low paternal overprotection were significant risk factors for sexual distress (P < 0.05). CONCLUSIONS: Parental care and overprotection can lead to sexual distress and, therefore, to Female Sexual Dysfunction in DM-1 women. Evaluation of parental bonding is necessary in DM-1 women with distressing sexual problems.

Upregulation of VEGF expression is associated with accumulation of HIF-1α in the skin of naïve scleroderma patients.

Systemic sclerosis is a disease hallmarked by microangiopathy; the enlargement and leakage of skin capillaries in active stages develops into extensive avascular areas, clinically associated with severe tissue hypoxia and the formation of digital ulcers. Vascular endothelial growth factor (VEGF) is upregulated in all stages of the disease, with little effect on efficient neovascularization. The oxygen-regulated α-subunit of hypoxia-inducible transcription factor-1 (HIF-1α) represents a key mechanism involved in the transcriptional regulation of VEGF. The aim of this study is to investigate expression of the oxygen-regulated α-subunit of HIF-1 and VEGF in naïve scleroderma patients. For this purpose, skin biopsies (dorsal hand surface) from scleroderma patients were analyzed and compared with control skin biopsies. Immunoreactivity for VEGF was enhanced in scleroderma patients, in contrast to restricted positive immunostaining in suprabasal keratinocytes observed in normal skin. In a similar fashion, all skin biopsies from scleroderma patients were strongly HIF-1α reactive, compared with rare immunoreactivity observed in normal skin. The pattern was similar in all stages of scleroderma. These observations for the first time directly connect constitutive hypoxia with VEGF upregulation in scleroderma patients. The sequence of events needs to be precisely mapped, and the pro- and antiangiogenic switches which may interfere with efficient tissue neovascularization identified, in order to provide meaningful therapeutic strategies.

Nutritional Considerations in Colorectal Surgery in Diverting Ileostomy Patients: A Review.

Colorectal surgery often results in a temporary or permanent ileostomy construction. The general nutritional status and intake of patients with an ileostomy have not received much attention and scientific evidence is lacking. Nutritional complications associated with ileostomy formation and colonic exclusion include fluid (dehydration) and electrolyte abnormalities (mainly hyponatremia), impaired renal function occurring from plasma volume depletion, and reduced energy absorption due to the role of the large bowel in energy assimilation. People with ileostomies frequently avoid specific foods, due to concerns of possible malfunction or food blockages of their stoma, which may produce a negative effect on their overall dietary intake and nutritional status. The present article reviews the existing literature on nutritional considerations for those with an ileostomy and discusses measures to optimize overall nutritional status of this category of patients.

Palliative Treatment of Bowel Obstruction With Colostomy Under Local Anesthesia in Frail Patients: A Single-Site Experience.

INTRODUCTION: Attendance of patients to the emergency department due to acute large bowel obstruction is a common phenomenon. Most of these patients are elderly, critically ill, and with high comorbidity. The literature suggests that more than 50% of these cases are due to colon cancer. Since this condition is considered to be an emergency, immediate intervention and response is imperative. PURPOSE: The aim of the present study is to present our surgical technique of colostomy formation under local anesthesia in selected critically ill patients, with increased perioperative risk and acute large bowel obstruction. MATERIALS AND METHODS: This is a retrospective study of 24 patients, with obstipation, who underwent emergency colostomy under local anesthesia, during the period from 2014 to 2021. RESULTS: The mean age of the patients was 77 years. The vast majority of patients had an American Society of Anesthesiologists (ASA) score of ≥3 and a Charlson score of ≥7. The most common colostomy was transverse colostomy (21/24 patients). The patients' hospitalization ranged from four to 42 days. Only one patient died. All colostomies functioned properly in the immediate postoperative period. Only one patient required postoperative admission to the ICU. CONCLUSIONS: Colostomy under local anesthesia in critically ill, elderly patients is an alternative option for the treatment of ileus.

Bone Mineral Density in Adult Patients with Type 1 Diabetes Mellitus Assessed by Both DXA and QCT.

Purpose: Bone mineral density (BMD) was measured in uncomplicated young adult patients with type 1 diabetes mellitus (T1DM) and sex- and age-matched controls, using both dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) to investigate their diagnostic ability in detecting abnormal values in these patients. Methods: 118 patients with T1DM (65 females, mean age 30.12 ± 8.78 years) and 94 sex- and age-matched controls were studied. BMD was assessed in all participants by DXA and QCT at lumbar spine (LS). Biochemical markers of bone metabolism were also measured. Results: T1DM was associated with lower BMD at L1-L3 vertebrae measured by both DXA and QCT and lower bone turnover compared to sex- and age-matched controls. In T1DM subjects, QCT detected more patients with abnormal BMD values compared to DXA. BMI and HbA1c levels were the only determinants of BMD. Bone turnover markers were lower in patients with longer duration of diabetes. Conclusion: QCT provides a higher sensitivity compared to DXA in detecting abnormal BMD values in patients with uncomplicated T1DM. In these patients, the diabetes-related decreased BMD may be present early, before it is detected by DXA, the clinical gold standard for BMD measurements, and before the presence of any other diabetes complications, stressing the importance of an early intervention for fracture prevention.

The Effect of Fat Supplementation on the Appearance of Symptoms Associated With Dumping Syndrome in Patients Having Undergone Gastric Surgery: Preliminary Results.

BACKGROUND/OBJECTIVES: Data on the effect of dietary fat on dumping syndrome (DS) symptoms are limited. The aim of this study was to assess the effect of the addition of fat to a carbohydrate meal on the appearance of DS symptoms and glycemic response, in patients who had undergone gastric surgery. SUBJECTS/METHODS: This was an interventional crossover study. Patients scheduled for gastric surgical procedures related to DS at two surgical units of two public hospitals (General University Hospital of Larissa and General Hospital of Larissa) were considered for study inclusion. Patients presenting symptoms suggestive of diagnosis (n = 12), after the ingestion of a carbohydrate meal, were used as both intervention and control groups. During the intervention process, a fat supplement was added to the carbohydrate meal that was previously used for diagnosis. Glycemic response and the amount and intensity of DS symptoms provoked by the two meals were assessed at both appointments. RESULTS: Blood glucose levels were significantly lower in the group that consumed the added fat meal compared with the group that consumed the carbohydrate meal 60 minutes after ingestion (p = 0.028). Furthermore, a significant reduction was noted in the amount of late dumping symptoms (p = 0.021) and the intensity of both early and late dumping symptoms (p = 0.007 and p = 0.012 respectively), after fat addition.  Conclusions: Incorporating fat into a carbohydrate meal seems to attenuate postprandial blood glucose rises and reduce the amount and intensity of DS symptoms, in patients who had undergone gastric surgery.

The unrestricted global effort to complete the COOL trial.

BACKGROUND: Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. A further therapeutic option may be open abdomen (OA) management with negative peritoneal pressure therapy (NPPT) to remove inflammatory ascites and attenuate the systemic damage from SCIAS, although there are definite risks of leaving the abdomen open whenever it might possibly be closed. This potential therapeutic paradigm is the rationale being assessed in the Closed Or Open after Laparotomy (COOL trial) ( https://clinicaltrials.gov/ct2/show/NCT03163095 ). Initially, the COOL trial received Industry sponsorship; however, this funding mandated the use of a specific trademarked and expensive NPPT device in half of the patients allocated to the intervention (open) arm. In August 2022, the 3 M/Acelity Corporation without consultation but within the terms of the contract canceled the financial support of the trial. Although creating financial difficulty, there is now no restriction on specific NPPT devices and removing a cost-prohibitive intervention creates an opportunity to expand the COOL trial to a truly global basis. This document describes the evolution of the COOL trial, with a focus on future opportunities for global growth of the study. METHODS: The COOL trial is the largest prospective randomized controlled trial examining the random allocation of SCIAS patients intra-operatively to either formal closure of the fascia or the use of the OA with an application of an NPPT dressing. Patients are eligible if they have free uncontained intraperitoneal contamination and physiologic derangements exemplified by septic shock OR severely adverse predicted clinical outcomes. The primary outcome is intended to definitively inform global practice by conclusively evaluating 90-day survival. Initial recruitment has been lower than hoped but satisfactory, and the COOL steering committee and trial investigators intend with increased global support to continue enrollment until recruitment ensures a definitive answer. DISCUSSION: OA is mandated in many cases of SCIAS such as the risk of abdominal compartment syndrome associated with closure, or a planned second look as for example part of "damage control"; however, improved source control (locally and systemically) is the most uncertain indication for an OA. The COOL trial seeks to expand potential sites and proceed with the evaluation of NPPT agnostic to device, to properly examine the hypothesis that this treatment attenuates systemic damage and improves survival. This approach will not affect internal validity and should improve the external validity of any observed results of the intervention. TRIAL REGISTRATION: National Institutes of Health ( https://clinicaltrials.gov/ct2/show/NCT03163095 ).

Sexual functioning and distress among premenopausal women with uncomplicated type 1 diabetes.

INTRODUCTION: Current studies indicate that women with type 1 diabetes (T1DM) have a high prevalence of sexual disorders although data on the prevalence of sexual dysfunction are limited when sexual distress is included. AIM: The frequency and the possible correlates of distressful sexual disorders in a highly selected group of type 1 diabetic women. METHODS: The sexual function, sexual distress, and general health status were assessed in 44 premenopausal women with uncomplicated T1DM and 47 healthy controls, using the Female Sexual Function Index (FSFI), the Female Sexual Distress Scale (FSDS), and the General Health Questionnaire-28 (GHQ-28). MAIN OUTCOME MEASURES: The impact of sexual distress on the frequency of female sexual dysfunction (FSD). RESULTS: The frequency of sexual disorders according to the FSFI was significantly higher in diabetic compared to control women (25% vs. 8.5%, respectively, P < 0.05). Diabetic women had significantly lower median (first to third quartile) total FSFI score compared to control group (30.55 [26.08-33.08] vs. 33.50 [30.70-34.30], P = 0.001). Desire, arousal, and satisfaction were the sexual domains significantly affected in the diabetic group. Diabetic women had significantly higher median (first to third quartile) FSDS score compared to control group (6.5 [2.3-15.8] vs. 4.0 [1.0-10.5] P = 0.043). FSD (combined pathological FSFI and FSDS scores) was present in higher proportion of diabetic women (15.9%) compared to controls (2.1%) (P = 0.020). GHQ-28 score was comparable between the groups. However, in the diabetic group, FSD was related with anxiety, depression, and low educational level. Diabetes-related factors were not associated with FSD. CONCLUSIONS: Pre-menopausal women with uncomplicated T1DM have significantly higher frequency of FSD compared to healthy controls, when the criterion of sexual distress is included. Psychosomatic and contextual factors implicated in sexual distress are correlates of FSD.

The indoleamine 2,3-dioxygenase inhibitor 1-methyl-tryptophan suppresses mitochondrial function, induces aerobic glycolysis and decreases interleukin-10 production in human lymphocytes.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) suppresses adaptive immunity. It is known that IDO induces T-cell differentiation to regulatory T-cells (Treg) through tryptophan depletion and/or kynurenine pathway products. CD4+ effector T-cells require distinct metabolic programs in order to support their function as compared to Treg cells. Furthermore, glucose metabolism is also known to affect B-cell survival and function. The effect of IDO on glucose metabolism of lymphocytes was evaluated by using its inhibitor 1-methyl-DL-tryptophan (1-MT). METHODS: Ten healthy volunteers vaccinated against tetanus. Peripheral blood mononuclear cells (PBMC) were cultured with or without tetanus toxoid and/or 1-MT. Cell proliferation was assessed by optical microscopy, glucose uptake by measuring its concentration in the supernatant, aerobic glycolysis by assessing lactate concentration in the supernatant, mitochondrial function by XTT assay, and finally production of Tregs' signature cytokine IL-10 by means of ELISA. RESULTS: Primarily, IDO decreases glucose uptake by stimulated lymphocytes. Secondly, IDO increases mitochondrial function in stimulated lymphocytes. In addition, IDO decreases aerobic glycolysis in stimulated lymphocytes. Finally, IDO induces the production of the immunosuppressive cytokine IL-10 by stimulated lymphocytes. CONCLUSION: Considering that cell metabolism plays a significant role in lymphocyte differentiation and function, IDO may exert its immunomodulatory effect by interfering with cell metabolism.

An unusual case of Primary Effusion Lymphoma with aberrant T-cell phenotype in a HIV-negative, HBV-positive, cirrhotic patient, and review of the literature.

Primary effusion lymphoma (PEL) is an unusual, human herpes virus-8 (HHV-8)-associated type of lymphoma, presenting as lymphomatous effusion in body cavities, without a detectable tumor mass. It primarily affects human immunodeficiency virus (HIV)-infected patients, but has also been described in other immunocompromised individuals. Although PEL is a B-cell lymphoma, the neoplastic cells are usually of the 'null' phenotype by immunocytochemistry. This report describes a case of PEL with T-cell phenotype in a HIV-negative patient and reviews all the relevant cases published until now. Our patient suffered from cirrhosis associated with Hepatitis B virus (HBV) infection and presented with a large ascitic effusion, in the absence of peripheral lymphadenopathy or solid mass within either the abdomen or the thorax. Paracentesis disclosed large lymphoma cells with anaplastic features consisting of moderate cytoplasm and single or occasionally multiple irregular nuclei with single or multiple prominent nucleoli. Immunocytochemically, these cells were negative for both CD3 and CD20, but showed a positive reaction for T-cell markers CD43 and CD45RO (VCHL-1). Furthermore, the neoplastic cells revealed strong positivity for EMA and CD30, but they lacked expression of ALK-1, TIA-1, and Perforin. The immune status for both HHV-8 and Epstein-Barr virus (EBV) was evaluated and showed positive immunostaining only for the former. The combination of the immunohistochemistry results with the existence of a clonal rearrangement in the immunoglobulin heavy chain gene (identified by PCR), were compatible with the diagnosis of PEL. The presence of T-cell markers was consistent with the diagnosis of PEL with an aberrant T-cell phenotype.

Laparoscopic bilateral inguinal hernia repair: Should it be the preferred technique?

Inguinal hernias are amongst the most common conditions requiring general surgical intervention. For decades, the preferred approach was the open repair. As laparoscopy became more popular and available and more surgeons became familiarized with this modality, laparoscopic inguinal hernia repair became an alternative. The aim of this study is to assess the effectiveness of laparoscopic inguinal repair, with a focus on bilateral inguinal hernias. Initial reports have shown promising clinical outcomes compared to those of conventional repair of bilateral hernias. However, there are only a few studies concerning laparoscopic repair of bilateral hernias. It is yet to be proven that laparoscopy is the "gold standard" in the treatment of bilateral inguinal hernias. So far, the choice of an inguinal hernia repair technique has been up to each surgeon, depending on their expertise and available resources after taking into consideration each patient's needs.

Poorly differentiated muscle-invasive giant cell tumor of the bladder leads to unfavorable clinical outcome.

Urothelial carcinoma of the urinary bladder is a common clinical entity. Recently, researchers focused on the emerging clinical significance of histologic variants, because they may need special therapy and their prognosis differs. Hereby, we describe a case of a giant cell osteoclast-like urothelial carcinoma of the urinary bladder.

Manual Reduction of Incarcerated Abdominal Wall Hernias. A Feasible Option during COVID-19 Pandemic: A Prospective Study.

Background Incarcerated hernia is a common surgical emergency with considerable morbidity or even mortality. Manual reduction (taxis) and elective surgery could be an alternative management approach. This study examines the role of taxis with the adjuvant use of the visual analogue scale (VAS) score in treating incarcerated hernias and thereby decreasing the emergency surgery rate, especially during the novel coronavirus disease 2019 (COVID-19) pandemic. Methods All adult patients admitted to the emergency department of our hospital with incarcerated hernias of anterior abdominal wall were prospectively submitted to hernia manual reduction. The VAS score was used as an adjuvant tool for monitoring the success of this maneuver. Patients with successful taxis and low VAS score were hospitalized for a 24-hour period of observation. On their discharge, they were scheduled for an elective hernia repair. Patients with unsuccessful taxis or with less than a 50% reduction in VAS score after successful taxis were submitted to emergency surgical repair. Age, sex, type of hernias, time until taxis, VAS scores before and after taxis, length of hospital stay, and adverse events for both groups were recorded. Results Between September 2018 and September 2020, 86 patients with incarcerated hernias were included. The types of hernias were incisional in 8 patients, umbilical in 15 patients, inguinal in 56 patients, and femoral in 7 patients. Taxis was successful in 66% of patients with a mean reduction in VAS score from 83 to 17 mm. Following successful taxis, patients were hospitalized for a 24-hour period of observation. No taxis-related complications were observed. Fifty-two patients were safely discharged from hospital and scheduled for an elective repair during the first month. Thirty-four patients were operated emergently. Five patients had successful taxis but with a reduction of posttaxis VAS score less than 50% (a mean reduction from 86 to 62 mm), while taxis failed in twenty-nine patients. Patients with emergency surgery had longer time until reduction and longer stay of hospitalization. In this group, two patients required admission to the intensive care unit while one patient died. Conclusion In this protocolized approach, taxis is a safe and feasible option for most patients with incarcerated hernias. It should be kept in our armament, especially in times when emergency surgery capabilities are under strain like the ongoing COVID-19 pandemic.