Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

Fistula Following Laparoscopic Sleeve Gastrectomy: a Proposed Classification and Algorithm for Optimal Management.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an accepted restrictive procedure with a hormonal component. There is no definitive course of treatment for post-LSG fistula; it remains a feared complication. We aimed to classify post-LSG fistulas and propose an algorithm to optimize their treatment. METHODS: Following primary and revisional LSG in obese patients, a retrospective observational study of fistulas was undertaken. Radiological studies were performed to identify anatomically distinct types of fistulas. An algorithm was elaborated for the classification and evolving treatment of each type of fistula. RESULTS: Twenty post-LSG fistulas were studied (13 [2.5%] from our center, 7 referred) with a mean body mass index of 43.1 ± 10.2 kg/m2 (32.0-76.0) and mean age of 33.1 ± 11.4 years (20.0-56.0). In all cases, the clinically suspected diagnosis was radiologically confirmed by water-soluble upper gastrointestinal series and double-contrast abdomino-pelvic CT scan. Three anatomical fistula types were characterized: type I, a small leak with no collection; type II, a leak with associated intra-abdominal abscess; and type III, a leak with multiple internal or external abscesses, a complex fistula. In accord with our algorithm, patients without sepsis received conservative treatment initially; this was sufficient for type I leaks. Type II abscesses received internal or external percutaneous drainage, and in some cases, stenting or endoprosthesis. Surgery was reserved for failure of conservative options and type III fistula. In cases of sepsis, surgery was mandatory. CONCLUSION: A radiologically defined, anatomically based classification system and treatment algorithm proved effective in clinical management of post-LSG fistula.

Aerosolized ribavirin: the most expensive drug for pneumonia.

Dramatic, overnight cost increases of important orphan and generic medications have recently come under public and government scrutiny. We highlight the case of aerosolized ribavirin, an important antiviral agent in hematopoietic stem cell transplantation which, because of substantial price increases, may now cost more than the transplant procedure itself.

Symptomatic BK Virus Infection Is Associated With Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients.

Nephropathy due to BK virus (BKV) infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation (HSCT). We hypothesized that BKV infection was a marker of kidney function decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic HSCT at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the Chronic Kidney Disease Epidemiology equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline, and the Fine-Gray method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic HSCT, BK viruria was detected in 25% (n = 629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease (GVHD), chronic GVHD, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (p < 0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. After allogeneic HSCT, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT.

Ertapenem usage in cancer patients with and without neutropenia: a report on 97 cases from a comprehensive cancer center.

PURPOSE: Ertapenem is being increasingly utilized in cancer patients, but published data regarding its usage are limited. Our objective was to describe the various indications for ertapenem therapy and its safety and efficacy in cancer patients. METHODS: We conducted a retrospective cohort study of cancer patients who received monotherapy with ertapenem for at least 72 h, between January 2007 and February 2013. RESULTS: Among 97 unique patients who received ertapenem monotherapy, the most common indications were: (1) To facilitate discharge from the hospital of stable patients still requiring antimicrobial therapy (46 %). (2) Primary therapy of various documented infections (bacteremia, pneumonia, urinary tract infection, skin and skin structure infection) with ertapenem (28 %). (3) De-escalation from a different broad-spectrum agent or regimen to ertapenem within the hospital setting in patients not ready for discharge (25 %). The median age of the 97 patients studied was 59 years (range 9-87 years) with 52 % being men. Most patients had underlying hematologic malignancies (54 %), and 7 % were recipients of hematopoietic stem cell transplantation. Twenty-nine patients (30 %) were neutropenic, 26 % were diabetic, and 6 % had chronic lung disease. Primary ertapenem monotherapy was successful in all patients, de-escalation in 95.8 % of patients, and the strategy of discharge on outpatient therapy with ertapenem in 95.6 % of patients. Patients failing de-escalation or early discharge responded to alternative regimens. We documented no significant ertapenem associated toxicity or adverse events. CONCLUSIONS: Ertapenem appears to be safe and effective for several indications in cancer patients.

Fecal colonization and infection with Pseudomonas aeruginosa in recipients of allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Pseudomonas aeruginosa, especially multidrug-resistant (MDR) isolates, is an important pathogen in allogeneic hematopoietic stem cell transplant (HCT) recipients. The ability to identify patients at risk for these infections and administer appropriate empiric therapy, particularly during episodes of neutropenia, may improve outcomes and also direct infection control and antimicrobial stewardship efforts. Many transplant centers obtain routine surveillance stool cultures (SSCs) from HCT recipients to test for colonization with vancomycin-resistant enterococci, and extended-spectrum beta lactamase-producing Enterobacteriaceae. Our center initiated the performance of SSCs for P. aeruginosa, because of a perceived increase in the frequency of infection with MDR strains. The aim of this study was to determine the utility of this practice. METHODS: We conducted a 2-year (2010-2011) retrospective review of the medical records of all patients who underwent allogeneic HCT at our cancer center to (a) determine the frequency of fecal colonization with P. aeruginosa, including MDR strains; (b) to determine the overall frequency of subsequent P. aeruginosa infection, as well as the frequency of infection with MDR strains; (c) to ascertain the proportion of subsequent infections likely arising from the intestinal tract; and (d) to determine risk factors for progression from colonization to infection. RESULTS: Of 794 study patients, 58 (7.3%) had at least 1 positive SSC for P. aeruginosa; 19/58 (32.8%) developed a subsequent pseudomonal infection (11 with matching antimicrobial resistance patterns). On the other hand, 37/736 (5%) of the patients who were not colonized, developed a pseudomonal infection. The type of infection observed was pneumonia in 26 (46%) patients, bloodstream infection in 20 (36%), urinary tract infection in 8 (14%), and infections at other sites in 2 (4%). The incidence of MDR P. aeruginosa in the entire cohort was 2.2% (18 of 794): 12 had positive SSCs and 7 of these patients later developed MDR P. aeruginosa infections. Patients with acute myelogenous leukemia were more likely to be colonized and to develop subsequent infection. No infection-related deaths were observed during the first 30 days after infection. CONCLUSIONS: The incidence of P. aeruginosa colonization and subsequent infection was low. Patients who were not colonized had a low chance of developing P. aeruginosa infection. Most patients who developed infection did not have fecal colonization, suggesting a different source of infection. SSCs for P. aeruginosa provide incomplete information regarding the source of infection.

Vaccination guidelines after hematopoietic stem cell transplantation: practitioners' knowledge, attitudes, and gap between guidelines and clinical practice.

BACKGROUND: Hematopoietic stem cell transplant (HCT) recipients are more susceptible to infections from vaccine-preventable diseases than the general population. Despite the development of international consensus guidelines addressing immunization after HCT, studies have shown that deviations from recommended immunization practices commonly occur. METHODS: An anonymous survey aimed at determining awareness of the guidelines and attitudes toward vaccination was distributed to our HCT clinicians. In parallel, we retrospectively evaluated patients' characteristics and post-HCT vaccine administration practices from 2010 to 2013. RESULTS: The majority of survey respondents (96%) were familiar with post-HCT vaccination protocols. Seventy-four percent of respondents reported that influenza vaccines were given to >70% of their patients, and 41% stated that they prescribed live vaccines to eligible patients. However, our pharmacy database review revealed that 38% of patients received the first series of vaccinations by the recommended 6 months post HCT, and 60% received them by 1 year after HCT. Most patients who had their vaccines withheld had relapsed disease or were undergoing treatment for graft-versus-host disease. Furthermore, we identified lower immunization rates in non-English speaking individuals, African-Americans, and Hispanic patients. CONCLUSIONS: Survey respondents reported being aware of current guidelines; however, adherence to the recommendations varied, likely connected to conflicting data on vaccine effectiveness and a lack of clear recommendations in complex clinical scenarios. Similar to the general population, patient barriers also could have contributed to lower vaccination rates in some cases. To decrease the large gap between the post-HCT vaccination guidelines and clinical practice, further studies on vaccine effectiveness and specific populations are warranted.

Efficacy and safety of antiretrovirals in HIV-infected patients with cancer.

At 30 years into the HIV infection epidemic, the optimal antiretroviral (ARV) regimen for infected patients with cancer remains unknown. We therefore sought to retrospectively study different ARV regimens used in this population. Data from HIV-infected patients seen at The University of Texas MD Anderson Cancer Center in Houston, Texas, USA, from 2001 to 2012 were reviewed. Patients received nucleoside reverse transcriptase inhibitors (NRTIs) plus protease inhibitors (PIs), non-NRTIs (NNRTIs), integrase strand-transfer inhibitors (INSTIs), or combinations of these. A total of 154 patients were studied. Most patients were male (80%), white (51%) and had haematological malignancies (HMs) (58%). NRTIs were combined with PIs (37%), NNRTIs (32%), INSTIs (19%) or combinations of these (11%). INSTIs were the most commonly used in patients with HM and in those receiving high-dose steroids or topoisomerase inhibitors (p <0.05). Side-effects occurred in 35%, 14%, 3% and 6% of patients receiving PIs, NNRTIs, INSTIs and combinations, respectively (p 0.001). Grade 3-4 adverse events were uncommon. Multivariate logistic regression analysis demonstrated that INSTIs and NNRTIs were nine times (95% confidence interval (CI), 1.4-50.8) and 11 times (95% CI, 1.9-64.7) more likely to be effective at 6 months, respectively, than PIs. This is the largest reported analysis studying different ARV regimens in HIV-infected cancer patients. Combinations that included PIs were the least favourable. NNRTIs and INSTIs had comparable efficacy, but INSTIs appeared to be the better tolerated ARVs in patients with HM or those receiving various chemotherapeutic agents.

Adenoviral infections in adult allogeneic hematopoietic SCT recipients: a single center experience.

Disseminated adenoviral infection (AI) is associated with profound immunosuppression and poor outcome after allogeneic hematopoietic SCT (allo-HSCT). A better understanding of AI in allo-HSCT recipients can serve as a basis to develop more effective management strategies. We evaluated all adult patients who received allo-HSCT at MD Anderson Cancer Center between 1999 and 2008. Among the 2879 allo-HSCT patients, 73 (2.5%) were diagnosed with AI. Enteritis (26%) and pneumonia (24%) were the most common clinical manifestations; pneumonia was the most common cause of adenovirus-associated death. A multivariable Bayesian logistic regression showed that when the joint effects of all covariates were accounted for, cord blood transplant, absolute lymphocyte count (ALC) ≤ 200/mm(3) and male gender were associated with a higher probability of disseminated AI. The OS was significantly worse for patients with AI that was disseminated rather than localized (median of 5 months vs median of 28 months, P<0.001) and for patients with ALC ≤ 200/mm(3) (P<0.001). Disseminated AI, in patients who received allo-HSCT, is a significant cause of morbidity and mortality. Strategies for early diagnosis and intervention are essential, especially for high-risk patients.

Value of a preoperative checklist for laparoscopic appendectomy and cholecystectomy.

UNLABELLED: Laparoscopy is a complex technique where incidents related to equipment failure/malfunction commonly occur. The purpose of the WHO preoperative safety checklist is to significantly reduce surgically associated complications and mortality. GOAL: The goal of this study was to show that a preoperative checklist for laparoscopy could improve procedure efficiency by reducing lost time due to these incidents. MATERIAL AND METHODS: This prospective study compared the occurrence of incidents related to equipment, patient installation and the time loss attributed to these incidents, before and after the initiation of a preoperative checklist. Two hundred consecutive laparoscopic procedures (appendectomies and cholecystectomies) were studied; the first hundred without the preoperative checklist and the second hundred after the initiation of this laparoscopic checklist. RESULTS: The risk of at least one incident to occur during the procedure was increased 3-fold ([1.36 vs. 6.64], P=0.007) when the checklist was not used compared to when the preoperative checklist was used. Likewise, the number of incidents increased 2.4-fold ([1.15; 5.01], P=0.02), compared to when the preoperative checklist was used. The checklist significantly reduced the proportion of incidences during which time was lost from 22% to 10% (P=0.03). CONCLUSION: A preoperative checklist for laparoscopic procedures is feasible and seems useful to prevent adverse events in the operating room.

Prognostic factors of postoperative morbidity and mortality in strangulated groin hernia.

OBJECTIVE: Strangulated groin hernia is a serious surgical emergency, as it is associated with high morbidity and mortality (2.6-9 %). This retrospective study aimed to find significant prognostic factors of postoperative morbidity and mortality. METHODS: From January 2000 to August 2011, we analyzed all patients who had undergone surgery in emergency for strangulated groin hernia. Forty-nine patients out of 2,917 were operated on strangulated groin hernia in an emergency. RESULTS: The occurrence of strangulated hernia during this period was 1.7 %. Thirty patients out of 49 had inguinal (61.2 %) and 19 femoral (38.8 %) strangulated hernias. The median age was 68.9 years ± 15.3. Patients with strangulated femoral hernia were significantly older than those with inguinal hernia (P = 0.03). There was a significant predominance of men in the inguinal hernia group and a female predominance in the femoral hernia group (P = 0.001). An additional exploration was performed on 12 patients (24.5 %). This exploration was done through a midline laparotomy in 8 patients, a laparoscopy in a single patient and the hernioscopy technique was beneficial in exploring the peritoneal cavity in 3 patients. Intestinal resection was necessary in 10.2 %. In our experience, 50 % of midline laparotomies were performed without any intestinal resection. Fisher's test identified midline laparotomy as the only prognostic factor of postoperative morbidity. CONCLUSION: First intention exploratory laparotomy in strangulated hernia surgery was, in our study, a major cause of postoperative complication.

Infections in non-myeloablative hematopoietic stem cell transplantation patients with lymphoid malignancies: spectrum of infections, predictors of outcome and proposed guidelines for fungal infection prevention.

The overall risk of infections is lower in patients undergoing non-myeloablative allogeneic stem cell transplantation (NST) than in conventional stem cell transplant recipients. We sought to evaluate conditions associated with increased risk of infections after NST. In 81 patients, 187 infection episodes were noted; chronic lymphocytic leukemia (138 episodes/100 person-years) and recipients of matched unrelated donor graft (128 episodes/100 person-years) had higher risk of infection. Only half of the cytomegalovirus (CMV) infections occurred 31-100 days after transplantation. Most patients with CMV infection were non-neutropenic (100%), had lymphoma (76%), were younger (<55 years; 72%) and had received matched related donor (MRD) graft (72%). However, graft-versus-host disease (GVHD) was present in only 15% of these patients. Seven (78%) of nine invasive fungal infections (IFI) were diagnosed >100 days after NST and were associated with high mortality (78%). Most patients with IFI were also not neutropenic (100%), had received MRD graft (100%), had lymphoma (78%) and were given systemic steroids (78%); unlike CMV infection, 67% of these patients also had GVHD. On the basis of our results, we propose that NST recipients with lymphoma treated with high-dose corticosteroids for GVHD be considered for antifungal prophylaxis or pre-emptive antifungal therapy.

The efficacy of catheters coated with minocycline and rifampin in the prevention of catheter-related bacteremia in cancer patients receiving high-dose interleukin-2.

High-dose interleukin-2 (HDIL-2) has proven to be an effective treatment for metastatic renal cell carcinoma and melanoma. Previous studies have shown an increase in catheter-related bacteremia (CRB) in patients on HDIL-2. The primary objective of this study was to evaluate the effectiveness of minocycline and rifampin-coated catheters (M/R-C) in reducing CRB in cancer patients on HDIL-2. This was a retrospective study where non-coated catheters (NC-C) and M/R-C were used for the administration of HDIL-2 before and after December 2004, respectively. Data collected included demographics, cancer type, catheter type, antibiotic prophylaxis, and infection rates. A total of 107 episodes of catheter use for HDIL-2 were evaluated in 78 patients (30 episodes in patients with M/R-C vs. 77 with NC-C). A total of nine episodes of CRB were identified, all in patients with NC-C (M/R-C 0% vs. NC-C 12%; p=0.06). The median time to bacteremia was 11 days (range 1-315 days). A log-rank test showed a trend that the M/R-C group had lower probability of getting CRB than the NC-C group (p=0.06). The use of M/R-C in patients on HDIL-2 therapy for advanced melanoma and renal cell carcinoma may have reduced the risk of CRB to nil. CRB still occurred despite antibiotic prophylaxis in patients with NC-C.

Utility of galactomannan enzyme immunoassay and (1,3) beta-D-glucan in diagnosis of invasive fungal infections: low sensitivity for Aspergillus fumigatus infection in hematologic malignancy patients.

Previous studies have reported that galactomannan (GM) enzyme immunoassay and 1,3 beta-glucan (BG) assay may be useful diagnostic tools, but their sensitivities are variable. We compared the performances of both tests. Between October 2002 and May 2005, 82 patients were prospectively monitored for 12 weeks. A total of 414 samples were tested by GM assay and 409 samples were tested by BG assay for the following four groups of patients: those with invasive aspergillosis (IA), those with other mold infections (Fusarium, scedosporium, zygomycosis, etc.), those with candidemia, and control patients. Blood samples were obtained twice on week 1 and once every other week for a total of 12 weeks. Patients in the invasive fungal infection groups had comparable risk factors. The sensitivity of the GM test was significantly higher for patients with IA due to non-fumigatus Aspergillus species than for patients with IA due to Aspergillus fumigatus (49% versus 13%; P < 0.0001) or with other mold infections (49% versus 6%; P < 0.0001). However, the sensitivity range (47% to 64%) and specificity (88%) of the BG assay were comparable among all patients tested, regardless of the infecting pathogen. The performance of GM-based diagnosis appears to be better for detecting non-fumigatus Aspergillus species. The diagnostic marker BG was shown to have a higher sensitivity than that of GM in detecting IA and other mold infections in hematologic malignancy patients.

Severe parainfluenza virus type 2 supraglottitis in an immunocompetent adult host: an unusual cause of a paramyxoviridae viral infection.

Parainfluenza virus is a major cause of respiratory illness in humans, manifesting from mild upper respiratory tract infection to bronchiolitis and pneumonia, especially in children. We report - to our knowledge - the first case of a nonimmunocompromised adult patient with human parainfluenza type 2 supraglottitis immediately after returning from China.

Fatal cytomegalovirus pneumonia in patients with haematological malignancies: an autopsy-based case-control study.

Cytomegalovirus (CMV) pneumonia is a life-threatening infection in patients with haematological malignancies (HMs) or in haematopoietic stem cell transplant (HSCT) recipients. To assess the incidence and risk factors for developing fatal CMV pneumonia in these patients, a case-control study based on 999 autopsies was performed at The University of Texas M. D. Anderson Cancer Center, Houston, Texas (January 1990 to December 2004). Twenty-five cases (patients who died with CMV pneumonia) were matched with 34 controls (patients who died without CMV pneumonia) by type of HM or HSCT, year of autopsy, age and gender. The incidence of CMV pneumonia declined between January 1990 to June /1997 and July 1997 to December 2004 (CMV pneumonia rates were 22/620 and 3/379 autopsies, respectively; p 0.006). Logistic regression analysis identified complete remission and sustained lymphopenia as independent predictors of CMV pneumonia (all p <0.05). The incidence of fatal CMV pneumonia has decreased over the last 15 years, which might reflect earlier diagnosis or the use of pre-emptive therapy or more effective preventive strategies. Complete remission of an HM does not preclude the development of CMV pneumonia among patients with prolonged lymphopenia.

Anti-adherence activity and antimicrobial durability of anti-infective-coated catheters against multidrug-resistant bacteria.

OBJECTIVES: To investigate the anti-adherence and antimicrobial durability of anti-infective catheters against multidrug-resistant (MDR) Staphylococcus aureus (resistant to vancomycin, rifampicin and methicillin) and MDR Gram-negative bacteria (Stenotrophomonas maltophilia, Acinetobacter baumannii/calcoaceticus and Enterobacter agglomerans) that are often associated with catheter-related bloodstream infections (CRBSIs). METHODS: Catheters impregnated with minocycline and rifampicin (M/R) or with silver-platinum and carbon (SPC) or with chlorhexidine and silver sulfadiazine (CHX/SS) were compared with non-coated catheters. Adherence of organisms was tested by using an established biofilm colonization model. All isolates were rifampicin-resistant. Antimicrobial durability was tested by soaking 1 cm segments of the catheter in serum and determining zones of inhibition against the tested organisms at weekly intervals. RESULTS: The M/R catheters showed significantly superior anti-adherence activity and more prolonged antimicrobial durability when compared with CHX/SS-central venous catheter (CVC), SPC-CVC and uncoated control catheters against MDR and vancomycin-resistant S. aureus (MDR VRSA) (all P values < or = 0.02), MDR S. maltophilia (all P values < 0.005) and MDR A. baumannii/calcoaceticus (all P values < 0.002), respectively. M/R-CVC and CHX/SS-CVC had comparable anti-adherence and antimicrobial durability against MDR E. agglomerans, and these two were superior to SPC-CVC and the uncoated control catheters (all P values < 0.001). CONCLUSIONS: M/R-CVC demonstrated superior anti-adherence activity and more prolonged antimicrobial durability when compared with other approved anti-infective catheters against MDR VRSA and/or MDR Gram-negative bacteria that are often associated with CRBSIs. This finding could explain their efficacy and better performance in clinical studies.

The role of vitamin B6 in the prevention of haematological toxic effects of linezolid in patients with cancer.

BACKGROUND: Linezolid is the first approved synthetic oxazolidinone with activity against multidrug-resistant gram-positive pathogens. However, haematological toxic effects of linezolid frequently limit its prolonged use, especially in patients with poor marrow reserves such as those with cancer receiving chemotherapy. Previous authors have reported that administration of vitamin B6 with linezolid reversed pancytopenia in two patients. METHODS: This is an open-label study of 31 patients with cancer who received linezolid at 600 mg twice daily and vitamin B6 at 50 mg/day for at least 2 weeks mean therapy duration and they were matched to 62 control patients who received linezolid without vitamin B6 to determine whether the concomitant use of vitamin B6 attenuates the haematological toxicity of linezolid in patients with cancer. RESULTS: Patients were matched according to age, underlying disease, duration of therapy, creatinine level and use of chemotherapy. We found no significant differences in the rate of haematological toxic effects between the two patient groups. The rate of thrombocytopenia was 13% in the vitamin B6 group and 15% in the control group (P = 0.82). Also, the rate of leucopenia was 7% versus 5%, respectively (P = 0.75). None of the patients in the vitamin B6 group had anaemia compared with 5% in the control group. CONCLUSIONS: Vitamin B6 given at 50 mg/day may have an impact on anaemia but did not prevent linezolid-induced thrombocytopenia or leucopenia in cancer patients.