Alexander T. Hawkins

Low CD4 count plus coma predicts cryptococcal meningitis in Tanzania

BackgroundLargely due to the lack of diagnostic reagents, the prevalence and clinical presentation of cryptococcal meningitis in Tanzania is poorly understood. This in turn is limiting the impact of increased fluconazole availability.MethodsWe evaluated a cohort of 149 consecutive HIV-infected adult inpatients presenting with headache or altered mental status for clinical features, CD4 count, cryptococcal infection, and outcome. Cryptococcal meningitis was diagnosed via India ink and latex agglutination assay of CSF (n = 24 and 40 positive, respectively). Associations between cryptococcal meningitis and clinical features were evaluated by t-test. The sensitivity, specificity, and positive likelihood ratio of such features were determined.ResultsCryptococcal meningitis was associated with confusion, social withdrawal, seizures, fever, tachycardia, meningismus, oral candidiasis, and low Glasgow coma scales and CD4 count. CD4 count < 100/μl provided the highest sensitivity for the diagnosis (93%), coma (Glasgow coma scale ≤ 8) provided the highest specificity (84%), and the combination provided the highest positive likelihood ratio (3.8). All cryptococcal meningitis patients were initiated on 800 milligrams of fluconazole daily and 50% survived to discharge, however no clinical or laboratory findings correlated with prognosis.ConclusionCryptococcal meningitis is common among Tanzanian HIV inpatients presenting with headache or altered mental status. Purely clinical features are insensitive for establishing the diagnosis or prognosis. We advocate expanding laboratory capacity for cryptococcal antigen testing to maximize survival.

Wound dehiscence after abdominoperineal resection for low rectal cancer is associated with decreased survival.

BACKGROUND: Abdominoperineal resection for low rectal adenocarcinoma is a common procedure with high morbidity, including perineal wound complications. OBJECTIVE: The purpose of this study was to determine risk factors for perineal wound dehiscence and to investigate the effect of wound dehiscence on survival. DESIGN: This was a retrospective medical chart review. SETTINGS: The study was conducted in a tertiary care university medical center. PATIENTS: Patients included in the study were those with low rectal adenocarcinoma who underwent abdominoperineal resection between January 2001 and June 2012. MAIN OUTCOMES MEASURES: We assessed the incidence of perineal wound dehiscence, as well as survival, after surgery. RESULTS: A total of 249 patients underwent abdominoperineal resection for rectal carcinoma. The mean age was 62.6 years (range, 23.0–98.0 years), 159 (63.8%) were male, and the mean BMI was 27.9 (range, 16.7–58.5). There were 153 patients (61.1%) who survived for 5 years after surgery. Sixty-nine patients (27.7%) developed wound dehiscence. Multivariable analysis revealed the following associations with dehiscence: BMI (OR, 1.09; 95% CI, 1.03–1.15; p = 0.002), IBD (OR, 6.6; 95% CI, 1.4–32.5; p = 0.02), history of other malignant neoplasm (OR, 3.1; 95% CI, 1.5–6.6), and abdominoperineal resection for cancer recurrence (OR, 2.8; 95% CI, 1.2–6.3; p = 0.01). In the survival analysis, wound dehiscence was associated with decreased survival (mean survival time for dehiscence vs no dehiscence, 66.6 months vs 76.6 months; p = 0.01). This relationship persisted in the multivariable analysis (HR, 1.7; 95% CI, 1.1–2.8; p = 0.02). LIMITATIONS: This was a retrospective, observational study from a single center. CONCLUSIONS: The adjusted risk of death was 1.7 times higher in patients who experienced dehiscence than in those who did not. Attention to perineal wound closure with consideration of flap creation should at least be given to patients with a history of malignant neoplasm, those with IBD, those with rectal cancer recurrence, and women undergoing posterior vaginectomy. Preoperative weight loss should also reduce dehiscence risk.

A systematic review of functional and quality of life assessment after major lower extremity amputation.

BACKGROUND When judging the success or failure of major lower extremity (MLE) amputation, the assessment of appropriate functional and quality of life (QOL) outcomes is paramount. The heterogeneity of the scales and tests in the current literature is confusing and makes it difficult to compare results. We provide a primer for outcome assessment after amputation and assess the need for the additional development of novel instruments. METHODS MEDLINE, EMBASE, and Google Scholar were searched for all studies using functional and QOL instruments after MLE amputation. Assessment instruments were divided into functional and QOL categories. Within each category, they were subdivided into global and amputation-specific instruments. An overall assessment of instrument quality was obtained. RESULTS The initial search revealed 746 potential studies. After a review of abstracts, 102 were selected for full review, and 40 studies were then included in this review. From the studies, 21 different assessment instruments were used 63 times. There were 14 (67%) functional measures and 7 (33%) QOL measures identified. Five (36%) of the functional instruments and 3 (43%) of the QOL measures were specific for MLE amputees. Sixteen instruments were used >1 time, but only 5 instruments were used >3 times. An additional 5 instruments were included that were deemed important by expert opinion. The 26 assessment instruments were rated. Fourteen of the best-rated instruments were then described. CONCLUSIONS The heterogeneity of instruments used to measure both functional and QOL outcomes make it difficult to compare MLE amputation outcome studies. Future researchers should seek to use high-quality instruments. Clinical and research societies should endorse the best validated instruments for future use in order to strengthen overall research in the field.

Factors predicting resource utilization and survival after major amputation

OBJECTIVE Major amputation is associated with increased short-term healthcare resource utilization (RU), early mortality, and socioeconomic status (SES) disparities. Our objective is to study patient-specific and SES-related predictors of long-term RU and survival after amputation. METHODS This retrospective analysis identified 364 adult patients who underwent index major amputation for critical limb ischemia from January 1995 through December 2000 at two tertiary centers with outcomes through December 2010. Age, gender, SES (race, income, insurance, and marital status), comorbidities (congestive heart failure [CHF], diabetes, diabetes with complications, and renal failure [RF]), subsequent procedures, cumulative length of stay (cLOS), and mortality were analyzed. Bivariate and multivariate Poisson regression for subsequent procedures and cLOS and Cox proportional hazard modeling for all-cause mortality were undertaken. RESULTS During a mean follow-up of 3.25 years, amputation patients had mean cLOS of 71.2 days per person-year (median, 17.6), 19.5 readmissions per person-year (median, 2.1), 0.57 amputation-related procedures (median, 0), and 0.31 cardiovascular procedures (median, 0). Below-knee amputation as the index procedure was performed in 70% of patients, and 25% had additional amputation procedures. Of readmissions at ≤ 30 days, 52% were amputation-related. Overall mortality during follow-up was 86.9%; 37 patients (10.2%) died within 30 days. Among patients surviving >30 days, multivariate Poisson regression demonstrated that younger age (incidence rate ratio [IRR], 0.98), public insurance (IRR, 1.63), CHF (IRR, 1.60), and RF (IRR, 2.12) were associated with increased cLOS. Diabetes with complications (IRR, 1.90) and RF (IRR, 2.47) affected subsequent amputation procedures. CHF (IRR, 1.83) and RF (IRR, 3.67) were associated with a greater number of cardiovascular procedures. Cox proportional hazard modeling indicated older age (hazard ratio [HR], 1.04), CHF (HR, 2.26), and RF (HR, 2.60) were risk factors for decreased survival. Factors associated with SES were not significantly related to the outcomes. CONCLUSIONS This study found that RU is high for amputees, and increased RU persists beyond the perioperative period. Results were similar across SES indices, suggesting higher SES may not be protective against poor outcomes when limb salvage is no longer attainable. These findings support the hypothesis that SES disparities may be more modifiable during earlier stages of care for critical limb ischemia.

Retrospective evaluation of elastic stain in the assessment of serosal invasion of pT3N0 colorectal cancers.

Peritoneal involvement is an important adverse prognostic factor in colorectal cancer (CRC) and determines a shift in the pathologic tumor node metastasis stage. Because peritoneal involvement is difficult to identify, use of special stains highlighting the peritoneal elastic lamina and mesothelial surface has been proposed. This study aims to determine whether use of elastic stain or CK7 immunohistochemistry on a single tissue section can refine the level of tumor invasion and determine whether restaging based on this assessment has prognostic significance in pT3N0 CRCs. Elastic stains were applied to 1 block per case from 244 consecutively resected pT3N0M0 CRCs. CK7 was evaluated in a 169-case subset. The elastic lamina was identified in only 101 cases (41%). Of those, 60 cases (24.6%) displayed elastic lamina invasion (ELI). This finding was associated with significantly worse (P<0.001) disease-free survival (DFS) (5-y DFS=60%) and significantly worse (P=0.01) overall survival (OS) (5-y OS=66.7%) compared with patients with no ELI (5-y DFS=87.8%, OS=92.7%) and those for whom no elastic lamina was identified (5-y DFS=82.5%, OS=86.0%). CK7 staining highlighted mesothelial cells in only 27 of 169 cases tested and helped demonstrate serosal invasion in only 5 cases (3%). In summary, the use of a single elastic stain is a useful and inexpensive method to demonstrate peritoneal involvement by tumor and should be considered for routine use in all pT3N0 CRCs. As tumors with ELI have an adverse prognosis, we propose that they should be upstaged compared with pT3N0 tumors without ELI.

Impact of Expanded Insurance Coverage on Racial Disparities in Vascular Disease: Insights From Massachusetts.

Objective:To evaluate the impact of health insurance expansion on racial disparities in severity of peripheral arterial disease. Background:Lack of insurance and non-white race are associated with increased severity, increased amputation rates, and decreased revascularization rates in patients with peripheral artery disease (PAD). Little is known about how expanded insurance coverage affects disparities in presentation with and management of PAD. The 2006 Massachusetts health reform expanded coverage to 98% of residents and provided the framework for the Affordable Care Act. Methods:We conducted a retrospective cohort study of nonelderly, white and non-white patients admitted with PAD in Massachusetts (MA) and 4 control states. Risk-adjusted difference-in-differences models were used to evaluate changes in probability of presenting with severe disease. Multivariable linear regression models were used to evaluate disparities in disease severity before and after the 2006 health insurance expansion. Results:Before the 2006 MA insurance expansion, non-white patients in both MA and control states had a 12 to 13 percentage-point higher probability of presenting with severe disease (P < 0.001) than white patients. After the expansion, measured disparities in disease severity by patient race were no longer statistically significant in Massachusetts (+3.0 percentage-point difference, P = 0.385) whereas disparities persisted in control states (+10.0 percentage-point difference, P < 0.001). Overall, non-white patients in MA had an 11.2 percentage-point decreased probability of severe PAD (P = 0.042) relative to concurrent trends in control states. Conclusions:The 2006 Massachusetts insurance expansion was associated with a decreased probability of patients presenting with severe PAD and resolution of measured racial disparities in severe PAD in MA.

National variation in the utilization of alternative imaging in peripheral arterial disease

OBJECTIVE The value and cost-effectiveness of less invasive alternative imaging (AI) modalities (duplex ultrasound scanning, computed tomography angiography, and magnetic resonance angiography) in the care of peripheral arterial disease (PAD) has been reported; however, there is no consensus on their role. We hypothesized that AI utilization is low compared with angiography in the United States and that patient and hospital characteristics are both associated with AI utilization. METHODS The Nationwide Inpatient Sample (2007-2010) was used to identify patients with an International Classification of Diseases-Ninth Edition diagnosis of claudication or critical limb ischemia (CLI) as well as PAD treatment (surgical, endovascular, or amputation). Patients with AI and those with angiography or expected angiography (endovascular procedures without imaging codes) were selected and compared. Multivariable logistic regression was performed for receiving AI stratified by claudication and CLI and adjusting for patient and hospital factors. RESULTS We identified 290,184 PAD patients, of whom 5702 (2.0%) received AI. Patients with AI were more likely to have diagnosis of CLI (78.8% vs 48.6%; P < .0001) and receive open revascularizations (30.4% vs 18.8%; P < .0001). Van Walraven comorbidity scores (mean [standard error] 5.85 ± 0.22 vs 4.10 ± 0.05; P < .0001) reflected a higher comorbidity burden in AI patients. In multivariable analysis for claudicant patients, AI was associated with large bed size (odds ratio [OR], 3.26, 95% confidence interval [CI], 1.16-9.18; P = .025), teaching hospitals (OR, 1.97; 95% CI, 1.10-3.52; P = .023), and renal failure (OR, 1.52; 95% CI, 1.13-2.05; P = .006). For CLI patients, AI was associated with black race (OR, 1.53; 95% CI, 1.13-2.08; P = .006) and chronic heart failure (OR, 1.29; 95% CI, 1.04-1.60; P = .021) and was negatively associated with renal failure (OR, 0.80; 95% CI, 0.67-0.95; P = .012). The Northeast and West regions were associated with higher odds of AI in claudicant patients (OR, 2.41; 95% CI, 1.23-4.75; P = .011; and OR, 2.59; 95% CI, 1.34-5.02; P = .005, respectively) and CLI patients (OR, 4.31; 95% CI, 2.20-8.36; P < .0001; and OR, 2.18; 95% CI, 1.12-4.22; P = .021, respectively). Rates of AI utilization across states were not evenly distributed but showed great variability, with ranges from 0.31% to 9.81%. CONCLUSIONS National utilization of AI for PAD is low and shows great variation among institutions in the United States. Patient and hospital factors are both associated with receiving AI in PAD care, and AI utilization is subject to significant regional variation. These findings suggest differences in systems of care or practice patterns and call for a clearer understanding and a more unified approach to imaging strategies in PAD care.

Impact of Rising Grades of Internal Rectal Intussusception on Fecal Continence and Symptoms of Constipation.

BACKGROUND: A theory of rectal intussusception has been advanced that intrarectal intussusception, intra-anal intussusception, and external rectal prolapse are points on a continuum and are a cause of fecal incontinence and constipation. OBJECTIVE: This study evaluates the association among rectal intussusception, constipation, fecal incontinence, and anorectal manometry. DESIGN: Patients undergoing defecography were studied from a prospectively maintained database and classified according to the Oxford Rectal Prolapse Grade as normal or having intra-rectal, intra-anal, or external intussusception. Patient symptoms were assessed using the Constipation Severity Index and the Fecal Incontinence Severity Index. Quality-of-life surveys were also used. Patients also underwent anorectal manometry. SETTINGS: The study was conducted at a tertiary care university medical center (Massachusetts General Hospital). PATIENTS: The study included 147 consecutive patients undergoing evaluation for evacuatory dysfunction and involved defecography, symptoms questionnaires, and anorectal physiology testing from January 2011 to December 2013. MAIN OUTCOME MEASURES: Symptom severity and quality-of-life scores were measured, as well as anal manometry results. RESULTS: Increasing Oxford grade was associated with an increase in severity of fecal incontinence (median score: normal = 23.9, intrarectal = 21.0, intra-anal = 30.0, external prolapse = 35.3; &bgr; = 4.71; p = 0.009), which persisted in a multivariable model including age (&bgr; = 2.13; p = 0.03), and decreased sphincter pressures (median mean resting pressure: normal = 75.4, intra-rectal = 69.7, intra-anal = 64.3, external prolapse = 48.3; &bgr; = –8.57; p = 0.003), which did not persist in a multivariable model. Constipation severity did not increase with rising intussusception (mean score: normal = 37.4, intrarectal = 35.0, intra-anal = 41.4, external prolapse = 32.9; p = 0.79), and balloon expulsion improved rather than worsened (normal = 47.1%, intrarectal = 60.5%, intra-anal = 82.9%, external prolapse = 93.1%; p < 0.001). LIMITATIONS: The study was limited because it was an observational study from a single center. CONCLUSIONS: Increasing grades of rectal intussusception are associated with increasing fecal incontinence but not constipation.

Watch and Wait: Is Surgery Always Necessary for Rectal Cancer?

Opinion statementDespite decades of high-quality research, the treatment of rectal cancer remains a work in progress. The interplay between chemotherapy, radiotherapy, and surgery is under constant rearrangement and refinement. Through this all, the desire to preserve the anal sphincters and quality of life remains at the forefront. In the past decade, standard of care for stage II or III rectal cancers in the USA has been neoadjuvant chemoradiation therapy (CRT) followed by radical surgical resection of the rectum. While timing and sequence of the CRT continues to evolve, surgical resection has remained essential in treatment. This stands in contrast to anal cancer, where surgery is reserved purely for salvage. This article describes a treatment strategy that attempts to treat rectal adenocarcinoma with CRT alone, reserving surgery for failure or salvage. Of the studies performed to date, a number are methodologically sound and show promise. However, the body of evidence has yet to reach a size to sway practitioners from the established trinity of chemotherapy, radiotherapy, and surgery. Interestingly, few trials administer post treatment full-dose systemic chemotherapy, which is the standard of care in patients undergoing surgical resection. Better identification of patients that will have complete cure from this approach, combined with long-term outcome data on salvage patients, is necessary for this therapy to be universally embraced.

The effect of surgeon specialization on outcomes after ruptured abdominal aortic aneurysm repair

OBJECTIVE Although mortality after elective abdominal aortic aneurysm (AAA) repair has steadily declined, operative mortality for a ruptured AAA (rAAA) remains high. Repair of rAAA at hospitals with a higher elective aneurysm workload has been associated with lower mortality rates irrespective of the mode of treatment. This study sought to determine the association between surgeon specialization and outcomes after rAAA repair. METHODS The American College of Surgeons National Surgical Quality Improvement Project database from 2005 to 2010 was used to examine the 30-day mortality and morbidity outcomes of patients undergoing rAAA repair by vascular and general surgeons. Multivariable logistic regression analysis was performed for each death and morbidity, adjusting for all independently predictive preoperative risk factors. Survival curves were compared using the log-rank test. RESULTS We identified 1893 repairs of rAAAs, of which 1767 (96.1%) were performed by vascular surgeons and 72 (3.9%) were performed by general surgeons. There were no significant differences between patients operated on by general vs vascular surgeons in preoperative risk factors or method of repair. Overall 30-day mortality was 34.3% (649 of 1893). After risk adjustment, mortality was significantly lower in the vascular surgery group compared with the general surgery group (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.30-0.86; P = .011). The risk of returning to the operating room (OR, 0.58; 95% CI, 0.35-0.97; P = .038), renal failure (OR, 0.54; 95% CI, 0.31-0.95; P = .034), and a cardiac complication (OR, 0.53; 95% CI, 0.28-0.99; P = .047) were all significantly less in the vascular surgery group. CONCLUSIONS Despite similar preoperative risk factors profiles, patients who were operated on by vascular surgeons had lower mortality, less frequent returns to the operating room, and decreased incidences of postoperative renal failure and cardiac events. These data add weight to the case for further centralization of vascular services.