A New Protocol for Venous Thromboembolism Prophylaxis in Bariatric Surgery.

BACKGROUND: Morbidly obese patients are at high risk for developing venous thromboembolism (VTE). The aim of this study was to evaluate the effect of a new VTE prophylaxis protocol (low dosage, low-molecular-weight heparin [LMWH]) with a pneumatic compression device (PCD) in patients undergoing bariatric surgery. MATERIALS AND METHODS: Between November 2015 and December 2017, 368 patients underwent surgery due to obesity. The patients received 0.2 ml of nadroparin (Fraxiparine, GlaxoSmithKline) 12 h before the operation. A PCD (Kendall SCD Compression System) was applied to the patient during the operation and left on the patient during the subsequent 24 h. Nadroparin 0.4 ml was started subcutaneously after the PCD was removed from the patient and the same dosage of nadroparin was given daily for 15 days following the bariatric operation. Ambulation within 2 h of surgery was encouraged and was performed frequently. RESULTS: A total of 368 patients underwent laparoscopic bariatric surgery. The median age was 34.1 years (range, 18-61), the median weight was 128 kg (range, 90-182), and the median body mass index (BMI) was 47.2 kg/m2 (range, 36-72). No thrombotic events were observed postoperatively or at the 1-, 3-, and 6-month follow-up visits. Four bleedings occurred requiring transfusions. None of these patients required a re-laparotomy for hemorrhage control. The mortality rate was 0% at 30 and 90 days and during the hospitalization. CONCLUSION: Low dosage LMWH with PCD is very effective for VTE prophylaxis in bariatric surgery.

Ibrutinib modulates the immunosuppressive CLL microenvironment through STAT3-mediated suppression of regulatory B-cell function and inhibition of the PD-1/PD-L1 pathway.

Ibrutinib, a covalent inhibitor of Bruton Tyrosine Kinase (BTK), is approved for treatment of patients with relapsed/refractory or treatment-naïve chronic lymphocytic leukemia (CLL). Besides directly inhibiting BTK, ibrutinib possesses immunomodulatory properties through targeting multiple signaling pathways. Understanding how this ancillary property of ibrutinib modifies the CLL microenvironment is crucial for further exploration of immune responses in this disease and devising future combination therapies. Here, we investigated the mechanisms underlying the immunomodulatory properties of ibrutinib. In peripheral blood samples collected prospectively from CLL patients treated with ibrutinib monotherapy, we observed selective and durable downregulation of PD-L1 on CLL cells by 3 months post-treatment. Further analysis showed that this effect was mediated through inhibition of the constitutively active signal transducer and activator of transcription 3 (STAT3) in CLL cells. Similar downregulation of PD-1 was observed in CD4+ and CD8+ T cells. We also demonstrated reduced interleukin (IL)-10 production by CLL cells in patients receiving ibrutinib, which was also linked to suppression of STAT3 phosphorylation. Taken together, these findings provide a mechanistic basis for immunomodulation by ibrutinib through inhibition of the STAT3 pathway, critical in inducing and sustaining tumor immune tolerance. The data also merit testing of combination treatments combining ibrutinib with agents capable of augmenting its immunomodulatory effects.

Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity.

Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T cells against leukemia and lymphoma with promising clinical results. Extending this approach to allogeneic T cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen-specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy. We transduced CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9), and demonstrated efficient killing of CD19-expressing cell lines and primary leukemia cells in vitro, with marked prolongation of survival in a xenograft Raji lymphoma murine model. Interleukin-15 (IL-15) production by the transduced CB-NK cells critically improved their function. Moreover, iC9/CAR.19/IL-15 CB-NK cells were readily eliminated upon pharmacologic activation of the iC9 suicide gene. In conclusion, we have developed a novel approach to immunotherapy using engineered CB-derived NK cells, which are easy to produce, exhibit striking efficacy and incorporate safety measures to limit toxicity. This approach should greatly improve the logistics of delivering this therapy to large numbers of patients, a major limitation to current CAR-T-cell therapies.

Use of stapling devices for safe cholecystectomy in acute cholecystitis.

Many techniques are described for the ligation of a difficult cystic duct (CD). The aim of this study is to assess the effectiveness and safety of stapling of a difficult CD in acute cholecystitis using Endo-GIA. From January 2008 to June 2012, 1441 patients with cholelithiasis underwent laparoscopic cholecystectomy (LC) at the Department of General Surgery, Haydarpasa Numune Education and Research Hospital. Of these, 19 (0.62%) were identified as having a difficult CD and were ligated using an Endo-GIA stapler. All patients were successfully treated with a laparoscopic approach. The length of hospital stay was 3.4 days. There were umbilical wound infections in 4 patients (21%). The length of follow-up ranged from 1.0 to 50.4 months. In conclusion, Endo-GIA is a safe and easy treatment method for patients with a dilated and difficult CD. The cystic artery should be isolated and ligated if possible before firing the Endo-GIA stapler. If isolation and stapling are not possible, fibrin sealant can be applied to avoid bleeding. The vascular Endo-GIA can be applied in a large CD, but for acute cholecystitis with an edematous CD, the Endo-GIA roticulator 4.8 or 3.5 stapler is preferred.

An unusual presentation of perforated appendicitis in epigastric region.

INTRODUCTION: Atypical presentations of appendix have been reported including backache, left lower quadrant pain and groin pain from a strangulated femoral hernia containing the appendix. We report a case presenting an epigastric pain that was diagnosed after computed tomography as a perforated appendicitis on intestinal malrotation. PRESENTATION OF CASE: A 27-year-old man was admitted with a three-day history of epigastric pain. Physical examination revealed tenderness and defense on palpation of epigastric region. There was a left subcostal incision with the history of diaphragmatic hernia repair when the patient was 3 days old. He had an intestinal malrotation with the cecum fixed at the epigastric region and the inflamed appendix extending beside the left lobe of liver. DISCUSSION: While appendicitis is the most common abdominal disease requiring surgical intervention seen in the emergency room setting, intestinal malrotation is relatively uncommon. When patients with asymptomatic undiagnosed gastrointestinal malrotation clinically present with abdominal pain, accurate diagnosis and definitive therapy may be delayed, possibly increasing the risk of morbidity and mortality. CONCLUSION: Atypical presentations of acute appendicitis should be kept in mind in patients with abdominal pain in emergency room especially in patients with previous childhood operation for diaphragmatic hernia.

Bacillus cereus catheter related bloodstream infection in a patient with acute lymphoblastic leukemia.

Bacillus cereus infection is rarely associated with actual infection and for this reason single positive blood culture is usually regarded as contamination . However it may cause a number of infections, such catheter-related bloodstream infections. Significant catheter-related bloodstream infections (CRBSI) caused by Bacillus spp. are mainly due to B. cereus and have been predominantly reported in immunocompromised hosts. Catheter removal is generally advised for management of infection. In this report, catheter-related bacteremia caused by B. cereus in a patient with acute lymphoblast c leukemia (ALL) in Istanbul Medical Faculty was presented.

Effects of probiotics on experimental short-bowel syndrome.

BACKGROUND: This study was performed to analyze the potential benefits of probiotics on experimental short-bowel syndrome (SBS). METHODS: Forty-eight male Wistar-Albino rats were used in the study. The animals were divided into 6 groups as follows: control, rats that received probiotics, rats that underwent intestinal transection and anastomosis, rats that underwent anastomosis and received probiotics, rats that underwent 75% intestinal resection, and rats that underwent 75% intestinal resection plus received probiotics. Body weight monitoring, intestinal bowel diameter, villus length and crypt depth measurements, goblet cell count, mitosis, and immunohistochemical evaluation were used for the assessment of intestinal proliferation ability. RESULTS: Statistical analysis showed a significant difference in villus length, crypt depth, goblet cell count in villus and crypt, mitosis, and immunohistochemical evaluation in the jejunum when the SBS group was compared with the SBS group that received probiotics. There was no significant difference in these parameters in ileum. CONCLUSIONS: This trial clearly has shown that probiotics had a positive impact on jejunum in the experimental SBS.

The comparison of heavyweight mesh and lightweight mesh in an incisional animal model.

PURPOSE: An incisional hernia may occur through the incision area following a surgical operation, through the trocar opening and even through drainage exit points. Various synthetic surgical meshes have recently been used for the surgical repair of incisional hernias. In this study, we analysed the burst strength forces of heavyweight mesh and lightweight mesh in an incisional animal model. METHODS: Following experimental formation of incisional hernias in 32 Wistar albino rats, they were divided into four groups. Polypropylene suture was used for closure of the abdominal incision in Group 1. In Groups 2, 3 and 4, polyester, polypropylene + polyglactin and polypropylene meshes, respectively, were fixed on the surface of the fascia after closing the defects in the rats. Polypropylene and polyester meshes are classified as heavy mesh. Light mesh is composed of a non-absorbable part (polypropylene) and an absorbable part (polyglactin), which will disappear 80 days after implantation. The rats were sacrificed at the end of the experiment. The pullout force of the fascia and meshes were recorded by use of a digital tension meter. RESULTS: The mean pullout forces for Groups 1, 2, 3 and 4 were found to be 123.4 +/- 13.3, 292.33 +/- 17.4, 281.66 +/- 16.3 and 310.60 +/- 26.1 N, respectively. CONCLUSION: At the end of the experiment, the polypropylene (25 g/cm(2)) present in the lightweight mesh was found to lose only a small percentage of the burst strength compared to the polypropylene (85 g/cm(2)) present in the heavyweight mesh.

Liver injury in sepsis and abdominal compartment syndrome in rats.

PURPOSE: To evaluate the extent of liver injury after the onset of sepsis and abdominal compartment syndrome (ACS) in rats. METHODS: We divided 60 rats into four groups of 15. Group 1 was the sham group. In group 2, sepsis was induced by cecal puncture and ligation; in group 3, ACS was created by placing a catheter in the abdominal cavity; and in group 4, both sepsis and ACS were induced simultaneously. Liver sections stained with hematoxylin-eosin were assessed pathologically, and liver injury was defined by the following five pathological patterns: spotty necrosis, capsular inflammation, portal inflammation, ballooning degeneration, and steatosis of the liver. We revised a new scoring system, called "Hepatic Injury Severity Scoring" (HISS), to evaluate the liver injury in sepsis, ACS, and sepsis plus ACS. Blood was collected for liver function tests. RESULTS: The total scores of groups 1, 2, 3, and 4 were 18, 92, 86, and 123, respectively. There were significant differences in histopathologic grade between group 1 and groups 2, 3, and 4 (P < 0.05). Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin levels were significantly higher in group 4 than in the other three groups. CONCLUSIONS: The findings of this study showed that liver function severely affected the onset of ACS and sepsis. The liver injury resulting from sepsis plus ACS is more severe than that resulting from either one independently.

Effects of probiotics on the severity of experimental acute pancreatitis.

OBJECTIVE: This study was designed to evaluate the effects of probiotics on the severity of experimental acute pancreatitis. DESIGN: Experimental study. SETTING: Experiments were done in a laboratory at Haydarpasa Numune Teaching and Research Hospital. SUBJECTS: A total of 50 Wistar rats were randomly divided into five groups. INTERVENTIONS: Group 1 was control group. Group 2 received an intraperitoneal injection of a 20% solution in 0.15 mol/l NaCL. Group 3 was injected NaCL and fed with probiotics. Acute pancreatitis was induced in rats by intrperitoneal injection of L-Arginine in groups 4 and 5. The rats in group 5 were treated with probiotics. The pancreas was removed for histologic examination. Evaluation of the pathologic changes was done by a new combined histopathologic grading scale. RESULTS: The mean scores of fibrosis, acinar cell loss, oedema, parenchymal necrosis, mononuclear cells infiltration, polymorphonuclear leucocytes infiltration, ductal damage and atypical reactive regeneration in group 5 were significantly lower than group 4. CONCLUSIONS: We demonstrated that enteral feedings with added probiotics can reduce the severity of acute pancreatitis. SPONSORSHIP: None.

Effects of high bilirubin levels on the healing of intestinal anastomosis.

PURPOSE: This article analyzes the relationship between high biluribin levels and anastomotic healing in the long term. METHODS: Ninety rats were randomly divided into six groups. The first three groups were jaundiced while the other three were unjaundiced. In the jaundiced groups, the rats' common bile ducts were ligated for 1, 2, and 3 weeks and ileal anastomosis was performed. In unjaundiced groups, only anastomosis was performed for 1, 2, and 3 weeks. At the end of the study, the values of the bursting pressures and hydroxyproline levels were determined in all groups. The bilirubin levels were also followed in jaundiced groups. RESULTS: In the jaundiced groups, the mean hydroxyproline contents were 7.5 +/- 4.0, 6.3 +/- 2.3, and 5.6 +/- 2.1 (microHP/mg tissue) and the mean bursting pressures were 178 +/- 38, 171 +/- 23, and 164 +/- 26 mmHg at weeks 1, 2, and 3, respectively. In the unjaundiced groups, the mean hydroxyproline contents were 7.6 +/- 3.2, 8.1 +/- 3.0, and 8.6 +/- 2.5 (microHP/mg tissue) and the mean bursting pressures were 181 +/- 28, 183 +/- 21, and 186 +/- 22 mmHg at weeks 1, 2, and 3, respectively. The bilirubin levels were 3.8 +/- 1.5, 6.5 +/- 2.3, and 11.2 +/- 2.9 mg/dl at weeks 1, 2, and 3, respectively, in the jaundiced groups and 0.6 +/- 0.06, 0.6 +/- 0.03, and 0.7 +/- 0.04 mg/dl in the unjaundiced groups. CONCLUSION: This study showed that the bilirubin levels can lead to a deterioration depending on the magnitude of the rise in the bilirubin levels.

The role of omentoplasty in the surgical management of remnant cavity in hepatic hydatid cyst.

BACKGROUND: Cyst hydatid disease of the liver is still endemic in certain regions of the world. Currently, surgical operation remains the treatment of choice in hydatidosis. The cyst cavity can be managed by using capitonnage, external drainage, introflexion or omentoplasty. METHODS: Two hundred and thirty-five patients operated for hydatid cyst between January 1990 and February 2001 were analysed retrospectively. Either omentoplasty, external drainage, capitonnage or introflexion were used to treat residual cyst cavity. RESULTS: Patients were categorised into three groups to evaluate complications: omentoplasty alone (group A), omentoplasty combined with other techniques (group B) and other techniques (group C). The overall mortality rates were <1%. Overall morbidity rates were 8.8% for group A, 19% for group B and 25% for group C, respectively. Mean hospital stay was 7.6 days for group A, 11.9 days for group B and 15.8 days for group C. DISCUSSION: Postoperative surgical site infection, bile fistula, recurrence rate and overall morbidity were seen less frequently in patients who underwent omentoplasty in our series. Mean duration of hospital stay was significantly shorter in patients who underwent omentoplasty operations. Because omentum has a high absorptive capacity and the capability to fill the residual cavity, we recommend omentoplasty to manage patients with hydatid cyst of the liver, whether complicated or uncomplicated.

Effect of human pancreatic juice and bile on the tensile strength of suture materials.

BACKGROUND: Several suture materials are used for pancreatojejunal anastomosis. In this study, we tested the durability of these suture materials in human pancreatic juice and bile. METHODS: Plain and chromic catgut, polyglactin 910, polyglycolic acid, polydioxanone, polypropylene, and silk sutures were incubated in pancreatic juice and bile that was collected from patients. Fifteen samples of each type of suture material were placed in human juices for 1, 3, and 7 days. Tensile strengths were measured with a tensionmeter. RESULTS: Plain and chromic catgut disintegrated in pancreatic juice and pancreatic juice plus bile mixture. Polyglycolic acid and polyglactin 910 suture materials were vulnerable to pancreatic juice within 7 days. Polydioxanone retained most of its initial strength in pancreatic juice and bile. Polypropylene and silk retained 84% and 92% of their initial strength, respectively. CONCLUSIONS: We found that polidioxanone was the strongest suture material in pancreatic juice.

A novel reconstructive procedure after pancreaticoduodenectomy: J-pouch dunking pancreaticojejunostomy.

Leakage of the pancreaticojejunostomy remains a major complication after pancreaticoduodenectomy. Several methods have been advocated in order to reduce anastomotic fistula but none of them reached a significant difference in preventing the leakage. We developed a new technique called "J-pouch dunking pancreaticojejunostomy". A "J" pouch is made from the distal 20 to 30 cm of jejunum by using a GIA linear stapler. A transverse incision is made on the jejunal base. As a result, we have enough jejunal stoma to anastomose the pancreatic remnant. A soft pancreas and small pancreatic size are known to be risk factors in pancreatic anastomosis. This technique is designed to eliminate the several factors related to pancreatic anastomotic leakage.

The Cockayne Syndrome group B gene product is involved in general genome base excision repair of 8-hydroxyguanine in DNA.

Cockayne Syndrome (CS) is a human genetic disorder with two complementation groups, CS-A and CS-B. The CSB gene product is involved in transcription-coupled repair of DNA damage but may participate in other pathways of DNA metabolism. The present study investigated the role of different conserved helicase motifs of CSB in base excision repair. Stably transformed human cell lines with site-directed CSB mutations in different motifs within its putative helicase domain were established. We find that CSB null and helicase motif V and VI mutants had greater sensitivity than wild type cells to gamma-radiation. Whole cell extracts from CSB null and motif V/VI mutants had lower activity of 8-hydroxyguanine incision in DNA than wild type cells. Also, 8-hydroxyguanine accumulated more in CSB null and motif VI mutant cells than in wild type cells after exposure to gamma-radiation. We conclude that a deficiency in general genome base excision repair of selective modified DNA base(s) might contribute to CS pathogenesis. Furthermore, whereas the disruption of helicase motifs V or VI results in a CSB phenotype, mutations in other helicase motifs do not cause this effect. The biological functions of CSB in different DNA repair pathways may be mediated by distinct functional motifs of the protein.

Simple, high-yield purification of xanthine oxidase from bovine milk.

Xanthine oxidase, a commercially important enzyme with a wide area of application, was extracted from fresh milk, without added preservatives, using toluene and heat. The short purification procedure, with high yield, consisted of extraction, ammonium sulfate fractionation, and DEAE-Sepharose (fast flow) column chromatography. Xanthine oxidase was eluted as a single activity peak from the column using a buffer gradient. The purification fold, specific activity and yield for the purified xanthine oxidase were 328, 10.161 U/mg and 69%, respectively. The enzyme was concentrated by ultrafiltration, although 31% of the activity was lost during concentration, no change in specific activity was observed. Activity and protein gave coincident staining bands on native polyacrylamide gels. The intensity and the number of bands were dependent on the oxidative state(s) of the enzyme; reduction by 2-mercaptoethanol decreased the intensity of the slow-moving bands and increased the intensity of the fastest-moving band. Following sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), two major bands (molecular masses of 152 and 131 kDa) were observed, accounting for > or = 95% of xanthine oxidase. Native- and SDS-PAGE showed that the purified xanthine oxidase becomes a heterodimer due to endogenous proteases.

A simple and sensitive method for the activity staining of xanthine oxidase.

Xanthine oxidase is a commercially-important enzyme. Several biochemical compounds have been quantitated by xanthine oxidase. Xanthine oxidase has been used as an auxiliary enzyme in the staining of several enzymes or tissues, however, there is no direct staining method available for it, on polyacrylamide gels. Partially-purified xanthine oxidase from cow milk was used as the enzyme source for the development of an activity-staining method on polyacrylamide gels. Staining was very sensitive. Detection of 0.02 microU of the enzyme on polyacrylamide gels was possible. Staining of 0.05 microU takes about 1 min whereas staining of 0.5 microU will take less than 5 s. Addition of TEMED is not essential for activity staining but it did increase both the rate and the intensity of the staining. The stained gels must be washed with distilled water, extensively, in order to remove excess unoxidized nitroblue tetrazolium, and must be protected from light, for a clear background and sharp activity-band staining. This method might be useful for quality control of xanthine oxidase obtained from different sources.

Sympathetic skin response in patients with chronic renal failure.

Sympathetic skin response (SSR) was measured in 20 normal healthy subjects and in 22 patients with chronic renal failure on regular hemodialysis, and its correlation with abnormalities of sensorimotor nerve conduction study and clinical autonomic symptoms was investigated. Nerve conduction studies (NCS) were abnormal in 17 of 22 patients (77.3%), and SSR was absent in 14 of 22 patients (63.6%). Patients were divided into three groups based on their SSR response: patients with normal SSR (n: 8, 36.4%), patients with absent SSR in the foot only (n: 9, 40.9%), and patients with absent SSR in both hand and foot (n: 5, 22.7%). Good correlation between abnormalities of NCS and absent SSR was observed. No correlation was noted between patient age, sex, duration of hemodialysis, duration of renal failure history, and absent SSR. However, statistically significant correlation was found between mean amplitude of the foot SSRs and sensorimotor nerve conduction velocities, and weekly frequency of hemodialysis.