In Vivo Emergence of Pandrug-Resistant Acinetobacter baumannii Strain: Comprehensive Resistance Characterization and Compassionate Use of Sulbactam-Durlobactam.

The treatment of patients with infection secondary to carbapenem-resistant Acinetobacter baumannii with emerging cefiderocol resistance remains challenging and unclear. We present a case of in vivo emergence of pandrug-resistant A baumannii that was successfully treated with the compassionate use of investigational sulbactam-durlobactam-based antibiotic regimen. We also performed a longitudinal genomic analysis of the bacterial isolates and showed the development of resistance and genetic mutations over time.

Extracorporeal life support in pregnant and postpartum women with COVID-19-related acute respiratory distress syndrome.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is an intervention used for patients with acute respiratory distress syndrome (ARDS) from COVID-19 who have failed conventional ventilatory strategies. Very few studies have given insight into the outcomes of pregnant and postpartum patients requiring ECMO support. METHODS: Single center, retrospective, observational study of female pregnant and postpartum patients suffering COVID-19 ARDS and requiring ECMO. RESULTS: Eight SARS-CoV-2 positive patients were identified. The average age was 31 ± 4 years, with Body Mass Indices (BMI) and SOFA scores ranging between 32-49 and 8-11, respectively. Two patients were pregnant at the time of ECMO initiation, two were peripartum, and four were postpartum. Five patients (63%) had bleeding, and one patient had a hysterectomy. Seven patients (88%) were supported by V-V ECMO and one with V-A ECMO. Patients had between one and three circuit exchanges due to oxygenator failure or clots in the circuit. All patients were in ICU between 7 and 74 days, with hospital length of stay between 8 and 81 days. All patients were weaned off ECMO and were successfully discharged from the hospital. All newborns were born via cesarean section, and all survived to discharge. CONCLUSION: Our study shows a 100% neonatal and maternal survival rate demonstrating that ECMO in this patient population is safe. These patients should be transferred to experienced high-volume ECMO centers with the ability to perform emergent cesarean sections. ECMO should be considered a life-saving therapy for pregnant women with severe COVID-19 with an overall excellent maternal and neonatal survival rate.

Pretreatment risk stratification of feeding tube use in patients treated with intensity-modulated radiotherapy for head and neck cancer.

BACKGROUND: The purpose of this study was to establish a risk stratification model for feeding tube use in patients who undergo intensity-modulated radiotherapy (IMRT) for head and neck cancers. METHODS: One hundred thirty-nine patients treated with definitive IMRT (+/- concurrent chemotherapy) for head and neck mucosal cancers were included in this study. Patients were recommended a prophylactic feeding tube and followed up by a dietician for at least 8 weeks postradiotherapy (post-RT). Potential prognostic factors were analyzed for risk and duration of feeding tube use for at least 25% of dietary requirements. RESULTS: Many variables had significant effects on risk and/or duration of feeding tube use in univariate analyses. Subsequent multivariable analysis showed that T classification ≥3 and level 2 lymphadenopathy were the best independent significant predictors of higher risk and duration of feeding tube use, respectively, in oral cavity, pharyngeal, and supraglottic primaries. CONCLUSION: In patients treated with definitive IMRT, T classification ≥3 and level 2 lymphadenopathy can potentially stratify patients into 4 risk groups for developing severe dysphagia requiring feeding tube use.

Palliative chemoradiotherapy versus radiotherapy alone for dysphagia in advanced oesophageal cancer: a multicentre randomised controlled trial (TROG 03.01).

BACKGROUND: A short course of radiotherapy is commonly prescribed for palliative relief of malignant dysphagia in patients with incurable oesophageal cancer. We compared chemoradiotherapy with radiotherapy alone for dysphagia relief in the palliative setting. METHODS: This multicentre randomised controlled trial included patients with advanced or metastatic oesophageal cancer who were randomly assigned (1:1) through a computer-generated adaptive biased coin design to either palliative chemoradiotherapy or radiotherapy alone for treatment of malignant dysphagia at 22 hospitals in Australia, Canada, New Zealand, and the UK. Eligible patients had biopsy-proven oesophageal cancer that was unsuitable for curative treatment, symptomatic dysphagia, Eastern Cooperative Oncology Group performance status 0-2, and adequate haematological and renal function. Patients were stratified by hospital, dysphagia score (Mellow scale 1-4), and presence of metastases. The radiotherapy dose was 35 Gy in 15 fractions over 3 weeks for patients in Australia and New Zealand and 30 Gy in ten fractions over 2 weeks for patients in Canada and the UK. Chemotherapy consisted of one cycle of intravenous cisplatin (either 80 mg/m2 on day 1 or 20 mg/m2 per day on days 1-4 of radiotherapy at clinician's discretion) and intravenous fluorouracil 800 mg/m2 per day on days 1-4 of radiotherapy in week 1. Patients were assessed weekly during treatment. The primary endpoint was dysphagia relief (defined as ≥1 point reduction on the Mellow scale at 9 weeks and maintained 4 weeks later), and key secondary endpoints were dysphagia progression-free survival (defined as a worsening of at least 1 point on the Mellow scale from baseline or best response) and overall survival. These endpoints were analysed in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00193882. This trial is closed. FINDINGS: Between July 7, 2003, and March 21, 2012, 111 patients were randomly assigned to chemoradiotherapy and 109 patients to radiotherapy. One patient in the chemoradiotherapy group was omitted from analysis because of ineligibility. 50 (45%, 95% CI 36-55) patients in the chemoradiotherapy group and 38 (35%, 26-44) in the radiotherapy group obtained dysphagia relief (difference 10·6%, 95% CI -2 to 23; p=0·13). Median dysphagia progression-free survival was 4·1 months (95% CI 3·5-4·8) versus 3·4 months (3·1-4·3) in the chemoradiotherapy and radiotherapy groups, respectively (p=0·58), and median overall survival was 6·9 months (95% CI 5·1-8·3) versus 6·7 months (4·9-8·0), respectively (p=0·88). Of the 211 patients who commenced radiotherapy, grade 3-4 acute toxicity occurred in 38 (36%) patients in the chemoradiotherapy group and in 17 (16%) patients in the radiotherapy group (p=0·0017). Anaemia, thrombocytopenia, neutropenia, oesophagitis, diarrhoea, nausea and vomiting, and mucositis were significantly worse in patients who had chemoradiotherapy than in patients who had radiotherapy. INTERPRETATION: Palliative chemoradiotherapy showed a modest, but not statistically significant, increase in dysphagia relief compared with radiotherapy alone, with minimal improvement in dysphagia progression-free survival and overall survival with chemoradiotherapy but at a cost of increased toxicity. A short course of radiotherapy alone should be considered a safe and well tolerated treatment for malignant dysphagia in the palliative setting. FUNDING: National Health and Medical Research Council, Canadian Cancer Society Research Institute, Canadian Cancer Trials Group, Trans Tasman Radiation Oncology Group, and Cancer Australia.

High-dose palliative radiotherapy for malignant pleural mesothelioma.

INTRODUCTION: High-dose radiotherapy to the hemithorax for patients with malignant pleural mesothelioma is a controversial treatment. Between 2003 and 2013 our institution had a policy of giving hemithoracic radiotherapy to at least 45 Gy. This retrospective study reports survival, progression and toxicity associated with this policy. METHODS: Seventy-one patients with pleural mesothelioma were irradiated with doses of 45-60 Gy. Conformal radiotherapy (3D-CRT) to the lower hemithorax was used for 17 and intensity-modulated radiotherapy (IMRT) to the whole hemithorax for 54 patients. All patients have been followed up for at least 2 years from commencement of radiotherapy. RESULTS: Sixty-four patients (90%) completed planned radiotherapy and seven stopped early, usually due to progressive disease. Median overall survival was 9.5 months (95% CI: 7.7-12.4) and median progression-free survival was 4.9 months (95% CI: 4.4-5.8). Eighty-seven per cent of patients progressed or died within 2 years: 25% in-field, 49% outside the RT field and 13% died without progression. Severe toxicity (grade 3-5) was observed in 53% of 3D-CRT and 78% of IMRT patients, most commonly pulmonary fibrosis 27%, radiation dermatitis 18%, dyspnoea 11%, GGT increased 11%, pneumonitis 10%, pleuritic pain 8% and fatigue 8%. There were two, possibly three, treatment-related deaths. CONCLUSION: High-dose radiotherapy to the hemithorax caused significant toxicity to most patients with no improvement in survival. Lower doses of radiotherapy to limited volumes may be useful for palliative purposes.

Risk Factors for Glaucoma in a Cohort of Patients with Fuchs Heterochromic Iridocyclitis.

PURPOSE: To describe the incidence and risk factors for ocular hypertension and/or glaucoma in patients with Fuchs heterochromic iridocyclitis (FHC). METHODS: Retrospective analysis of 88 patients with FHC. Kaplan-Meier curves estimated the time to develop cataract and ocular hypertension/glaucoma. Possible prognostic factors were investigated in univariate Kaplan-Meier analyses using the Mantel-Cox logrank test. RESULTS: At presentation with FHC, 52% of patients had a cataract and 26% of patients had ocular hypertension/glaucoma. The estimated percentage of patients with a cataract or ocular hypertension/glaucoma by 4 years after presentation was 71% (CI: 58-81%) and 39% (CI: 28-51%), respectively. Patients aged ≥50 years had significantly greater risk of developing glaucoma (p = 0.0065). After adjusting for age-group, having a cataract at presentation was associated with increased risk of glaucoma (p = 0.032). CONCLUSIONS: Risk factors for development of ocular hypertension/glaucoma were increasing patient age and having a cataract at presentation with FHC.

Evaluation of pneumococcal vaccination rates after vaccine protocol changes and nurse education in a tertiary care teaching hospital.

BACKGROUND: Pneumococcal vaccination in eligible patients is recommended by the Infectious Disease Society of America and the Centers for Disease Control (CDC) Advisory Committee on Immunization Practices. Because hospitalization provides an opportunity to vaccinate patients at high risk for developing serious pneumonia complications, eligibility screening and administration of the pneumococcal vaccine prior to discharge in qualified patients are evaluated by the Joint Commission and the Centers for Medicare Medicaid Services (CMS) as part of pneumococcal vaccination core quality measures. Among patients with an inpatient diagnosis of pneumonia in 2008, 56% in our 580-bed tertiary care teaching hospital, compared with 84% nationwide, received pneumococcal vaccination. To improve pneumococcal vaccination rates for all patients in the study facility and not just those with pneumonia, a multifaceted intervention including a revised nurse screening tool, rescheduling of the vaccine order, storage of the vaccine in automated dispensing cabinets on the nursing unit, and creation of a vaccine tracking system was developed and implemented between August 2009 and October 2009. OBJECTIVE: To determine the impact of a multifaceted intervention on pneumococcal vaccine screening and administration rates in eligible patients according to the CDC recommendations who were admitted to an internal medicine unit of a tertiary care teaching hospital. METHODS: All patients aged 18 years or older from 2 internal medicine units were identified during 4-month time intervals before (pre-intervention, April through July 2009) and after (post-intervention, November 2009 through February 2010) implementation of the multifaceted pneumococcal vaccine protocol. Of these, 150 patients from each 4-month period were randomly selected for electronic medical record review. Eligibility for pneumococcal vaccination was derived from the CDC recommendations and consensus of the vaccine steering committee at the study institution; the criteria included aged 65 years or older, admitting diagnosis of pneumonia, at least 1 of several chronic diseases, immunocompromising condition, cochlear implant, cerebrospinal fluid leak, current tobacco smoking, pregnancy or having a child in the home less than aged 6 months, or awaiting solid organ transplantation. Patients who had vaccine contraindications/precautions or had been vaccinated in the previous 5 years were ineligible. Data on demographics, presence of vaccine screening, indication, administration, rescheduling, and refusal were collected. The primary endpoint was the rate of pneumococcal vaccine administration in eligible medicine patients. Secondary endpoints included changes in screening rates, vaccine refusal, and order rescheduling. Descriptive statistics and Student's t-test were used to evaluate patient demographic data. Pearson chi-square was used to compare the pre- and post-implementation periods. RESULTS: The rate of pneumococcal vaccine administration in eligible patients significantly improved post-implementation compared with pre-implementation (74.2% vs. 19.1%, respectively, P < 0.001). Rates of vaccine screening were similar pre-implementation (96.0%) and post-implementation (99.3%, P = 0.056). The rates of vaccine refusal in the pre- and post-implementation periods did not significantly differ (10.6% vs. 22.6%, respectively, P = 0.203). CONCLUSIONS: Implementation of vaccine protocol changes was associated with improved pneumococcal vaccination rates in eligible medicine patients. Protocol changes were relatively easy to implement in a large institution, and a similar approach may be implemented at other institutions as an effective way to improve pneumococcal vaccination rates.

Insulin glargine versus neutral protamine Hagedorn insulin for treatment of diabetes in pregnancy.

We compared maternal and neonatal outcomes in diabetic pregnancies treated with either insulin glargine or neutral protamine Hagedorn (NPH) insulin. We performed a retrospective chart review of diabetic pregnant patients using the Diabetes Care Center of Wake Forest University during the years 2000 to 2005. Outcomes of interest included maternal hemoglobin A1C, average fasting and 2-hour postprandial blood sugars, mode of delivery, birth weight, 5-minute Apgar score < 7, umbilical artery pH < 7.20, incidence of neonatal hypoglycemia, and pregnancy complications. A total of 52 diabetic pregnant patients were included in this study. Twenty-seven women used insulin glargine. A total of 13 women used insulin glargine during the first trimester. Glycemic control was similar in women who used NPH insulin and insulin glargine, as determined by hemoglobin A1C levels and mean blood sugar values. There were no differences in mode of delivery, average birth weight, or neonatal outcomes. Maternal and fetal/neonatal outcomes appear similar in pregnant diabetic women who use either NPH insulin or insulin glargine in combination with a short-acting insulin analogue to achieve adequate glycemic control during pregnancy. Insulin glargine appears to be an effective insulin analogue for use in women whose pregnancies are complicated by diabetes.

Identifying risk factors for uterine rupture.

Uterine rupture, whether in the setting of a prior uterine incision or in an unscarred uterus, is an obstetric emergency with potentially catastrophic consequences for both mother and child. Numerous studies have been published regarding various risk factors associated with uterine rupture. Despite the mounting data regarding both antepartum and intrapartum factors, it currently is impossible to predict in whom a uterine rupture will occur. This article reviews the data regarding these antepartum and intrapartum predictors for uterine rupture. The author hopes that the information presented in this article will help clinicians assess an individual's risk for uterine rupture.

Intrapartum predictors of uterine rupture.

This case-controlled study reviewed 26 cases of uterine rupture at an academic medical center. Controls were selected in a 2:1 design by reviewing the immediate successful vaginal birth after cesarean delivery (VBAC) before and after each case of uterine rupture. At less than 2 hours before delivery or acute uterine rupture, mild and severe variable decelerations, persistent abdominal pain, and hyperstimulation were more common in cases of uterine rupture as compared to controls and had statistically significant positive likelihood ratios (LR). Mild and severe variable fetal heart rate decelerations, especially in the presence of persistent abdominal pain, may predict uterine rupture in patients attempting VBAC.

Oxytocin for induction of labor.

Oxytocin is the most common pharmacologic agent used for the induction and augmentation of labor. Oxytocin protocols can be divided into high-dose and low-dose protocols depending on the initial dose and the amount and rate of sequential increase in dose. Despite the frequency with which oxytocin in used in clinical practice, there is little consensus regarding which protocol is most appropriate. The purpose of this chapter is to review the most current data concerning recommendations for the use of oxytocin in the induction of labor, including cases of intrauterine fetal demise and vaginal birth after cesarean.

Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05).

BACKGROUND AND PURPOSE: Despite numerous randomized trials investigating radiotherapy (RT) fractionation schedules for painful bone metastases, there are very few data on RT for bone metastases causing pain with a neuropathic component. The Trans-Tasman Radiation Oncology Group undertook a randomized trial comparing the efficacy of a single 8 Gy (8/1) with 20 Gy in 5 fractions (20/5) for this type of pain. MATERIALS AND METHODS: Eligible patients had radiological evidence of bone metastases from a known malignancy with no change in systemic therapy within 6 weeks before or anticipated within 4 weeks after RT, no other metastases along the distribution of the neuropathic pain and no clinical or radiological evidence of cord/cauda equina compression. All patients gave written informed consent. Primary endpoints were pain response within 2 months of commencement of RT and time to treatment failure (TTF). The hypothesis was that 8/1 is at least as effective as 20/5 and the planned sample size was 270 patients. RESULTS: Between February 1996 and December 2002, 272 patients were randomized (8/1:20/5=137:135) from 15 centres (Australia 11, New Zealand 3, UK 1). The commonest primary cancers were lung (31%), prostate (29%) and breast (8%); index sites were spine (89%), rib (9%), other (2%); 72% of patients were males and the median age was 67 (range 29-89). The median overall survival (95% CI) for all randomized patients was 4.8 mo (4.2-5.7 mo). The intention-to-treat overall response rates (95% CI) for 8/1 vs 20/5 were 53% (45-62%) vs 61% (53-70%), P=0.18. Corresponding figures for complete response were 26% (18-34%) vs 27% (19-35%), P=0.89. The estimated median TTFs (95% CI) were 2.4 mo (2.0-3.3 mo) vs 3.7 mo (3.1-5.9 mo) respectively. The hazard ratio (95% CI) for the comparison of TTF curves was 1.35 (0.99-1.85), log-rank P=0.056. There were no statistically significant differences in the rates of re-treatment, cord compression or pathological fracture by arm. CONCLUSIONS: 8/1 was not shown to be as effective as 20/5, nor was it statistically significantly worse. Outcomes were generally poorer for 8/1, although the quantitative differences were relatively small.

Optimism and survival in lung carcinoma patients.

BACKGROUND: It is popular belief that the psychologic response to a diagnosis of cancer influences survival in patients with cancer; however, research has produced contradictory results. In this prospective study, the authors investigated the relation between pretreatment levels of optimism and survival in patients with nonsmall cell lung carcinoma (NSCLC). METHODS: Two hundred four patients who were participating in a randomized trial that compared accelerated and conventional radiotherapy with and without carboplatin chemotherapy were asked to complete two questionnaires assessing optimism. The first assessment was just prior to commencing treatment and the second assessment took place after completing treatment. Survival was measured from the date of randomization to the date of death. Surviving patients were followed until February 8, 2001. RESULTS: The pretreatment questionnaire was completed by 179 patients, and 148 of those patients completed the posttreatment questionnaire. There was a small but significant reduction in optimism scores after treatment (P = 0.005). There was no association noted between pretreatment optimism and progression-free survival (P = 0.52, unadjusted; P = 0.22, adjusted for Eastern Cooperative Oncology Group performance status and patient age), nor was there an association noted between pretreatment optimism and overall survival (P = 0.36, unadjusted; P = 0.19, adjusted for disease stage). CONCLUSIONS: There was no evidence that a high level of optimism prior to treatment enhanced survival in patients with NSCLC. Encouraging patients to "be positive" only may add to the burden of having cancer while providing little benefit, at least in patients with NSCLC.

Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age.

Relapsed or refractory multiple myeloma has a poor outlook. Some patients respond to thalidomide; however, criteria for predicting response have not been conclusively identified. We initiated a prospective multicenter phase 2 trial in patients with relapsed/refractory myeloma using thalidomide up to the maximum dose, 800 mg/d. Interferon-alpha-2B (1.5-3.0 x 10(6) U, subcutaneously, 3 times per week) was added at week 12 if disease was responsive or stable. Patients intolerant of interferon continued thalidomide alone. Thalidomide with or without interferon was continued until disease progression. Objectives were to determine toxicity, response rate (RR), progression-free survival (PFS), and overall survival (OS) and to elucidate relevant prognostic factors. We enrolled 75 patients, with median age 64 years (range, 36-83 years). Median individual maximum-tolerated dose of thalidomide was 600 mg/d; 41% reached 800 mg/d. Overall RR was 28%, and 55% stable disease (SD). The only predictor for response was age 65 years or younger (38% versus 17%; P =.043). At 18 months median follow-up, the actuarial median PFS and OS were 5.5 and 14.6 months, respectively. Multivariate analysis for OS demonstrated age exceeding 65 years (median, 9.2 months versus longer than 26 months; P =.011), raised serum lactate dehydrogenase (P =.002), and raised serum creatinine (P =.007) predicted inferior outcomes. Nineteen patients received interferon. Ten discontinued owing to toxicity. Four of 12 patients who received interferon for longer than 4 weeks were converted from SD to partial response. Our findings confirm substantial activity of thalidomide in relapsed/refractory myeloma. Interferon may improve response in selected patients, but is often not tolerated. The inferior outcome demonstrated in those with the identified prognostic factors is important in planning management for such patients.