Risk-adjustment in hepatobiliary pancreatic surgery

AIM: The present study evaluates the performance of the POSSUM, the American Society of Anesthetists (ASA), APACHE and Childs classification in predicting mortality and morbidity in hepatopancreaticobiliary (HPB) surgery. We describe especially the limitations and advantages of risk in stratifying the patients. METHODS: We investigated 177 randomly chosen patients undergoing elective complex HPB surgery in a single institution with a total of 71 pre-operative and intra-operative risk factors. Primary endpoint was in-hospital mortality and morbidity. Ordered logistic regression analysis was used to identify individual predictors of operative morbidity and mortality. RESULTS: The operative mortality in the series was 3.95%. This compared well with the p-POSSUM and APACHE predicted mortality of 4.31% and 4.29% respectively. Postoperative complications amounted to 45% with 24 (13.6%) patients having a major adverse event. On multrvariate analysis the pre-operative POSSUM physiological score (OR = 1.18, P = 0.009) was superior in predicting complications compared to the ASA (P= 0.108), APACHE (P= 0.117) or Childs classification (P= 0.136). In addition, serum sodium, creatinine, international normalized ratio (INR), pulse rate, and intra-operative blood loss were independent risk factors. A combination of the POSSUM variables and INR offered the optimal combination of risk factors for risk prognostication in HPB surgery. CONCLUSION: Morbidity for elective HPB surgery can be accurately predicted and applied in everyday surgical practice as an adjunct in the process of informed consent and for effective allocation of resources for intensive and high-dependency care facilities.     

IL-10 Restrains IL-17 to Limit Lung Pathology Characteristics following Pulmonary Infection with Francisella tularensis Live Vaccine Strain

IL-10 production during intracellular bacterial infections is generally thought to be detrimental because of its role in suppressing protective T-helper cell 1 (Th1) responses. Francisella tularensis is a facultative intracellular bacterium that activates both Th1 and Th17 protective immune responses. Herein, we report that IL-10–deficient mice (Il10^−/−), despite having increased Th1 and Th17 responses, exhibit increased mortality after pulmonary infection with F. tularensis live vaccine strain. We demonstrate that the increased mortality observed in Il10^−/−-infected mice is due to exacerbated IL-17 production that causes increased neutrophil recruitment and associated lung pathology. Thus, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis live vaccine strain, its production is tightly regulated by IL-10 to generate efficient induction of protective immunity without mediating pathology. These data suggest a critical role for IL-10 in maintaining the delicate balance between host immunity and pathology during pulmonary infection with F. tularensis live vaccine strain.Francisella tularensis, a facultative intracellular bacterium, because of its infectious nature and the severe disease caused by low doses of airborne bacteria, has been classified as a category A select bioterrorism agent.¹ Infection in humans is caused by two main subspecies, F. tularensis (type A) and Francisella holarctica (type B).² An F. tularensis live vaccine strain (LVS) has been developed from the F. tularensis B strain as an experimental vaccine, but is not licensed for use in humans.¹ F. tularensis LVS has been used as a representative attenuated model to address the immune requirements for protection against Francisella. By using this model, the importance of IL-12 in driving interferon γ (IFN-γ) and T-helper cell 1 (Th1) responses in immunity to F. tularensis LVS infection is well described.^3–5 In contrast, IL-17 is generally thought to play a role in protection against extracellular, but not intracellular, pathogens.⁶ However, we and others recently identified a protective role for IL-17 in the induction of cellular immunity to F. tularensis LVS pulmonary infection,^7–9 by driving the production of IFN-γ through IL-12 induction.⁷ IL-17 is a proinflammatory cytokine also known to induce chemokines, such as keratinocyte chemoattractant, macrophage inflammatory protein 2 (MIP-2), and granulocyte colony-stimulating factor (G-CSF), to mediate granulopoiesis, neutrophil recruitment, and inflammation.⁶ Accordingly, the absence of IL-17 during F. tularensis LVS pulmonary infection also results in decreased induction of G-CSF and MIP-2, as well as decreased accumulation of neutrophils and lung inflammation.⁷ Neutrophil depletion alone does not affect bacterial control after pulmonary infection with F. tularensis LVS,¹⁰ suggesting that the role for IL-17 in driving Th1 responses, and not neutrophil recruitment, was the primary immune mechanism mediating protection in this model.⁷ These data together suggest that both IL-17 and IFN-γ are required for generating protective immunity to pulmonary F. tularensis LVS infection.IL-10 is an anti-inflammatory cytokine best studied for its inhibitory effects on IL-12 production and down-regulation of Th1 responses.¹¹ Accordingly, IL-10–deficient mice show enhanced protection in models of intracellular bacterial infections, such as Mycobacterium tuberculosis¹² and Listeria monocytogenes.¹³ In addition, in a cutaneous model of F. tularensis LVS infection, IL-10–deficient mice exhibit increased protection, and this was reversed when IL-17 was depleted.¹⁴ In contrast to these published studies, in the current study, we report that after pulmonary infection with F. tularensis LVS, mice deficient in IL-10 (Il10^−/−) exhibit increased mortality. We clearly demonstrate that the increased mortality in the Il10^−/−-infected mice is not associated with loss of protective immunity, because bacterial burden between wild-type and Il10^−/− mice is similar, but is caused by exacerbated inflammation and increased lung pathology. We demonstrate that the exacerbated inflammation observed in Il10^−/−-infected mice is the result of unrestrained IL-17 production and IL-17–dependent recruitment of neutrophils and resulting lung pathology. These data together suggest that, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis LVS,^7,9 IL-17 production is tightly regulated by anti-inflammatory cytokines, such as IL-10. Our studies highlight how inflammatory cytokines, such as IL-17, can be beneficial for host protection, but when produced unrestrained, can mediate host pathology.     

The Citrus yellow mosaic badnavirus ORFI functions as a RNA-silencing suppressor

Virus Genes - Citrus yellow mosaic badnavirus (CMBV) causes mosaic disease in all economically important citrus cultivars of India, with losses reaching up to 70%. CMBV belongs to the genus...     

Multicomponent synthesis of dispiroheterocycles using a magnetically separable and reusable heterogeneous catalyst

Dispiroheterocycles have been synthesized by pseudo-four component reaction of 6-aminouracil/6-amino-2-thiouracil/2-amino-1,3,4-thiadiazole, p-toluidine and isatins in an ethanol–water mixture as solvent using β-cyclodextrin functionalized Fe₃O₄ nanoparticles as a magnetically separable and reusable heterogeneous catalyst. The nanocatalyst was synthesized and characterized by physicochemical characterization including Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD).

An efficient and sustainable synthetic protocol has been presented for the synthesis of dispiroheterocycles using a magnetically separable and reusable nanostructured heterogeneous catalyst.     

Detecting accidental punctures and lacerations during cholecystectomy in large datasets: Two methods of analysis

Background: After the Institute of Medicine(IOM) report To Err Is Human highlighted the impact of medical errors, the Agency for Healthcare Research and Quality(AHRQ) developed Patient-Safety Indicators(PSI) to improve quality by identifying potential inpatient safety problems. PSI-15 was created to study accidental punctures and lacerations(APL), but PSI-15 may underestimate APLs in populations of patients. This study compares PSI-15 with a more inclusive approach using a novel composite of secondary diagnostic and procedural codes. Methods: We used Nationwide Inpatient Sample(NIS) data(20 0 0–2012) from AHRQ's Healthcare Cost and Utilization Project(H-CUP). We analyzed PSI-15-positive and-negative cholecystectomies. Cross tabulations identified codes that were significantly more frequent among PSI-15-positive cases; these secondary diagnostic and procedural codes were selected as candidate members of a composite marker(CM) of APL. We chose cholecystectomy patients for study because this is one of the most common general operations, and the large size of NIS allows for meaningful analysis of infrequent occurrences such as APL rates. Results: CM identified 1.13 times more APLs than did PSI-15. Patients with CM-detected APLs were significantly older and had worse mortality, comorbidities, lengths of stay, and charges than those detected with PSI-15. Further comparison of these two approaches revealed that time-series analysis for both APL markers revealed parallel trends, with inflections in 2007, and lowest APL rates in July. Conclusions: Although CM may yield more false positives, it appears more inclusive, identifying more clinically significant APLs, than PSI-15. Both measures presented similar trends over time, arguing against inflation in PSI-15 reporting. While arguably less specific, CM may increase sensitivity for detecting APL events during cholecystectomies. These results may inform the interpretation of other large population studies of APLs following abdominal operations.     

Characteristics and survival for HIV-associated multicentric Castleman disease in Malawi

Introduction

Clinical reports of multicentric Castleman disease (MCD) from sub-Saharan Africa (SSA) are scarce despite high prevalence of HIV and Kaposi sarcoma-associated herpesvirus (KSHV). Our objective is to describe characteristics and survival for HIV-associated MCD patients in Malawi. To our knowledge, this is the first HIV-associated MCD case series from the region.

Methods

We describe HIV-positive patients with MCD in Lilongwe, and compare them to HIV-associated lymph node Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) patients treated at our centre. All patients were enrolled into a prospective longitudinal cohort study at a national teaching hospital and cancer referral centre serving half of Malawi''s 16 million people. We included adult patients≥18 years of age with HIV-associated MCD (n=6), lymph node KS (n=5) or NHL (n=31) enrolled between 1 June 2013 and 31 January 2015.

Results and discussion

MCD patients had a median age of 42.4 years (range 37.2–51.8). All had diffuse lymphadenopathy and five had hepatosplenomegaly. Concurrent KS was present for one MCD patient, and four had performance status ≥3. MCD patients had lower median haemoglobin (6.4 g/dL, range 3.6–9.3) than KS (11.0 g/dL, range 9.1–12.0, p=0.011) or NHL (11.2 g/dL, range 4.5–15.1, p=0.0007). Median serum albumin was also lower for MCD (2.1 g/dL, range 1.7–3.2) than KS (3.7 g/dL, range 3.2–3.9, p=0.013) or NHL (3.4 g/dL, range 1.8–4.8, p=0.003). All six MCD patients were on antiretroviral therapy (ART) with median CD4 count 208 cells/µL (range 108–1146), and all with HIV RNA <400 copies/mL. Most KS and NHL patients were also on ART, although ART duration was longer for MCD (56.4 months, range 18.2–105.3) than KS (14.2 months, range 6.8–21.9, p=0.039) or NHL (13.8 months, range 0.2–98.8, p=0.017). Survival was poorer for MCD patients than lymph node KS or NHL.

Conclusions

HIV-associated MCD occurs in Malawi, is diagnosed late and is associated with high mortality. Improvements in awareness, diagnostic facilities, treatment and supportive care are needed to address this likely under-recognized public health problem in SSA.     

Carpometacarpal Joint Fracture Dislocation of Second to Fifth Finger

Background

Carpometacarpal joint fracture dislocation of the second to fifth finger is a rare hand injury associated with high energy trauma. Due to severe swelling and overlapping of bones on the radiograph of wrist-hand, dislocations are missed. We reported a series of six patients with rare carpometacarpal joint fracture dislocation treated with open reduction.

Methods

We retrospectively studied six cases of carpometacarpal joint fracture dislocation. All patients were treated with open reduction and internal fixation with Kirschner wire. Functional assessment was done with Quick Disabilities of the Arm, Shoulder and Hand score (Quick DASH score) at regular intervals.

Results

Average Quick DASH score was improved from 75.76 to 1.9 from 6 weeks to 18 months of duration. Of the six patients, three patients had a Quick DASH score of 0 at the end of 18 months.

Conclusions

Careful hand examination and radiographic assessment is necessary to avoid missed diagnosis of carpometacarpal joint fracture dislocation. Early open reduction and internal fixation lead to excellent recovery of hand function.     

Development and validation of algorithms for heart failure patient care: a Delphi study

INTRODUCTION

Although heart failure (HF) management is available at primary and secondary care facilities in Malaysia, the optimisation of drug therapy is still suboptimal. Although pharmacists can help bridge the gap in optimising HF therapy, pharmacists in Malaysia currently do not manage and titrate HF pharmacotherapy. The aim of this study was to develop treatment algorithms and monitoring protocols for angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers and spironolactone based on extensive literature review for validation and utilisation by pharmacists involved in HF management.

METHODS

A Delphi survey involving 32 panellists from private and government hospitals that provide cardiac services in Malaysia was conducted to obtain a consensus of opinion on the treatment protocols. The panellists completed two rounds of self-administered questionnaires to determine their level of agreement with all the components in the protocols.

RESULTS

Consensus was achieved for most of the sections of the protocols for the four classes of drugs. The panellists’ opinions were taken into consideration when amending the components of the protocols that did not achieve consensus of opinion. Full consensus was achieved with the second survey conducted, enabling the finalisation of the drug titration protocols.

CONCLUSION

The resulting validated HF titration protocols can be used as a guide for pharmacists when recommending the initiation and titration of HF drug therapy in daily clinical practice. Recommendations should be made in collaboration with the patient’s treating physician, with concomitant monitoring of the patient’s response to the drugs.     

Novel therapy for insulin-dependent diabetes mellitus: infusion of in vitro-generated insulin-secreting cells

Insulin-dependent diabetes mellitus (IDDM) is a metabolic disease usually resulting from autoimmune-mediated β-cell destruction requiring lifetime exogenous insulin replacement. Mesenchymal stem cells (MSC) hold promising therapy. We present our experience of treating IDDM with co-infusion of in vitro autologous adipose tissue-derived MSC-differentiated insulin-secreting cells (ISC) with hematopoietic stem cells (HSC). This was an Institutional Review Board approved prospective non-randomized open-labeled clinical trial after informed consent from ten patients. ISC were differentiated from autologous adipose tissue-derived MSC and were infused with bone marrow-derived HSC in portal, thymic circulation by mini-laparotomy and in subcutaneous circulation. Patients were monitored for blood sugar levels, serum C-peptide levels, glycosylated hemoglobin (Hb1Ac) and glutamic acid decarboxylase (GAD) antibodies. Insulin administration was made on sliding scale with an objective of maintaining FBS < 150 mg/dL and PPBS around 200 mg/dL. Mean 3.34 mL cell inoculums with 5.25 × 10⁴ cells/μL were infused. No untoward effects were observed. Over a mean follow-up of 31.71 months, mean serum C-peptide of 0.22 ng/mL before infusion had sustained rise of 0.92 ng/mL with decreased exogenous insulin requirement from 63.9 international units (IU)/day to 38.6 IU/day. Improvement in mean Hb1Ac was observed from 10.99 to 6.72 %. Mean GAD antibodies were positive in all patients with mean of 331.10 IU/mL, which decreased to mean of 123 IU/mL. Co-infusion of autologous ISC with HSC represents a viable novel therapeutic option for IDDM.