Expert commentary on the challenges and opportunities for surgical site infection prevention through implementation of evidence-based guidelines in the Asia-Pacific Region.

INTRODUCTION: Surgical site infections (SSIs) are a significant source of morbidity and mortality in the Asia-Pacific region (APAC), adversely impacting patient quality of life, fiscal productivity and placing a major economic burden on the country's healthcare system. This commentary reports the findings of a two-day meeting that was held in Singapore on July 30-31, 2019, where a series of consensus recommendations were developed by an expert panel composed of infection control, surgical and quality experts from APAC nations in an effort to develop an evidence-based pathway to improving surgical patient outcomes in APAC. METHODS: The expert panel conducted a literature review targeting four sentinel areas within the APAC region: national and societal guidelines, implementation strategies, postoperative surveillance and clinical outcomes. The panel formulated a series of key questions regarding APAC-specific challenges and opportunities for SSI prevention. RESULTS: The expert panel identified several challenges for mitigating SSIs in APAC; (a) constraints on human resources, (b) lack of adequate policies and procedures, (c) lack of a strong safety culture, (d) limitation in funding resources, (e) environmental and geographic challenges, (f) cultural diversity, (g) poor patient awareness and (h) limitation in self-responsibility. Corrective strategies for guideline implementation in APAC were proposed that included: (a) institutional ownership of infection prevention strategies, (b) perform baseline assessments, (c) review evidence-based practices within the local context, (d) develop a plan for guideline implementation, (e) assess outcome and stakeholder feedback, and (f) ensure long-term sustainability. CONCLUSIONS: Reducing the risk of SSIs in APAC region will require: (a) ongoing consultation and collaboration among stakeholders with a high level of clinical staff engagement and (b) a strong institutional and national commitment to alleviate the burden of SSIs by embracing a safety culture and accountability.

Analysis of MPO-ANCA subtypes in a patient with propylthiouracil-induced vasculitis with multiple complications.

BACKGROUND: We report a 16 year-old girl with propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-positive glomerulonephritis combined with Henoch-Schönlein purpura nephritis (HSPN) and antiphospholipid syndrome (APS). CASE AND METHODS: The patient had Graves' disease and had been treated with PTU for about 6 years. She complained of arthralgia, epigastralgia, purpura of the lower extremities, anemia, and abnormal urinalysis. Lupus anticoagulant was positive. Additionally, a high level of anti-myeloperoxidase (MPO) antibodies (IgG) and a low level of coagulation factor XIII were recognized. She had several complications including lung bleeding, lacuna infarctions of the right frontal and parietal brain lobes, and deep vein thrombosis of the left lower extremity. We studied tissue histology and carried out MPO-ANCA subtype analysis by immunofluorescence and flow cytometry and MPO-ANCA epitope analysis. RESULTS: Histologically, purpura showed leukocytoclastic vasculitis with perivascular depositions of IgA and complement C3. Renal biopsy showed necrotizing glomerulonephritis with crescents and mesangial IgA deposits. Notably, IgG, IgM, and IgA ANCA were detected in the patient's serum by flow cytometry and immunofluorescence. We diagnosed an overlap syndrome of ANCA-positive vasculitis, HSPN, and APS. A change in the reactivity of MPO-ANCA from recognition of only the Hg epitope in the C-terminal region to recognition of multiple MPO epitopes was accompanied by a remission of symptoms. CONCLUSIONS: This report may provide a very rare description of an overlap syndrome of PTU-induced ANCA vasculitis, HSPN, and APS in which not only IgG ANCA but also IgA and IgM ANCA were found. Epitope analysis may be a useful marker for disease-monitoring of PTU-induced ANCA-positive vasculitis. This case may provide insight into the pathological mechanism underlying each of these diseases.

The impact of ultrasound scanning in the staging and follow-up of patients with clinical stage I cutaneous melanoma.

In 85 patients with intermediate to high risk cutaneous melanoma, concomitant palpation and ultrasound scanning (US) of the axillary and inguinal sites were performed in order to detect any locoregional lymph node metastases at pre-operative staging and postoperative monitoring. At 12 months follow-up, US identified 12 out of 13 (92%) histologically proven metastases, while palpation indicated metastatic disease in only 3 (23%) patients. Metastases were intranodal in 6 out of 12 cases detected with US, and extranodal in all the 3 cases identified by palpation, thus confirming that US is more effective than palpation in the early detection of lymph node metastases from melanoma. US was also more effective in discriminating all non-neoplastic lymph nodes: its overall specificity was 100% versus 85% for palpation. Thus, when carried out by well-trained radiologists, US is a very useful diagnostic tool for the surgical oncologist dealing with melanoma patients.

Tubular injury as a cardinal pathologic feature in human heme oxygenase-1 deficiency.

Heme oxygenase (HO) catalyzes degradation of heme to biliverdin, iron, and carbon monoxide. It consists of three isoforms: an inducible form (HO-1), a constitutive form (HO-2), and the third isoform (HO-3), with properties similar to HO-2. There is limited evidence to suggest that the induction of HO-1 may have anti-inflammatory effects in an in vivo model of oxidative stress-mediated renal injury. We experienced the first human case of HO-1 deficiency. The patient had persistent proteinuria and hematuria, with biochemical evidence of renal tubular injury. We obtained three consecutive renal specimens: two from renal biopsies at 2 and 5 years of age and the third from autopsy at 6 years of age. The patient had systemic vascular endothelial-cell injury with massive intravascular hemolysis. The serum was loaded with heme and a large amount of heme-conjugated haptoglobin. A high concentration of haptoglobin was also detectable in urine. Mesangial proliferation or change in glomerular capillary-wall thickness was relatively mild to moderate in all specimens. Electron microscopic examination showed widespread endothelial detachment and subendothelial deposits of an unidentifiable material. It was striking that tubulointerstitial injury, with tubular dilatation and/or atrophy, interstitial fibrosis, and inflammatory cell infiltration, advanced progressively. Tubular epithelial cells were injured, and massive deposition of iron and haptoglobin was detectable. Bowman's capsules were dilated significantly, probably secondary to the collapse of atrophic tubuli. This is the first report to show that HO-1 has critical roles in vivo in protecting renal tubuli, in addition to vascular endothelium, from oxidative injury.

Management of primary sarcomas of the retroperitoneum.

We here report on our 10-year experience of surgery in 25 patients with primary retroperitoneal sarcoma and make an appraisal of the more effective available clinical approach. Ten patients had leiomyosarcoma, eight liposarcoma, and seven had other tumor types. Histological grading was G1 in seven patients, G2 in six patients and G3 in 12. Ten patients (40%) underwent wide tumor excision, five (20%) marginal excision, four (16%) partial excision and six (24%) wedge biopsy at laparotomy. Adjacent organ resection was required in 10 of the 15 patients who underwent wide or marginal resection, seven of whom had adjuvant chemoradiotherapy. After wide resection, local recurrences were observed in 2/10 patients; the 10-year survival rate was 33%. Three out of five patients who underwent marginal resection had local recurrences; one is alive 10 years after surgery and chemo-radiotherapy. Histological grading was the most important prognostic factor. Radical resection is the only effective available treatment for retroperitoneal sarcomas, and patients with low-grade tumors benefit most from it with respect to survival and local recurrence rate. The efficacy of adjuvant treatment has yet to be clarified.

Proliferating cell nuclear antigen (PCNA) and recurrence in patients with cutaneous melanoma.

A positive correlation between PCNA and the most important histoprognostic factors of cutaneous melanoma has been demonstrated. The aim of our work was to evaluate the efficacy of PCNA in predicting melanoma recurrence and to compare it with that of Breslow thickness. One-hundred and fifteen patients (75 women, 40 men; mean age 50 years) with primary cutaneous melanoma were retrieved. pTNM stages were as follows: stage I, 54 patients; stage II, 31 patients; stage III, 26 patients; and stage IV, four patients. The mean follow-up period was 55 months (range 2-260). Six patients developed lymph node metastases and 28 developed distant metastases; 27 patients died within 2-202 months from diagnosis. Tumour thickness was re-evaluated for each case. PCNA immunostaining was performed using the avidin-biotin complex method and the percentage of PCNA-positive tumour cells was indicated as the PCNA index. In order to evaluate and compare the PCNA index and Breslow thickness as predictors of recurrence, the receiver-operating characteristic (ROC) curve method, based on true-positive and false-positive rates was used. The PCNA index showed the highest true-positive rates and the lowest false-positive rates in the 5-30 interval. The PCNA index optimal cut-off is 20, characterized by 70% sensitivity and 80% specificity; Breslow thickness optimal cut-off is 3.5 mm, with 40% sensitivity and 90% specificity. Our results indicate that the PCNA index has a higher efficacy in predicting locoregional and distant recurrences in patients presenting primary cutaneous melanoma.

Detection and clinical usefulness of urinary interleukin-6 in the diseases of the kidney and the urinary tract.

Interleukin-6 (IL-6) plays a key role in inflammatory and immune responses in the host. In the present study, the IL-6 activity in urine from patients with various renal diseases was examined to elucidate the pathological and clinical significance of urinary IL-6. In patients with mesangial proliferative glomerulonephritis (mes-PGN) including, IgA nephropathy, the urinary IL-6 activity tended to increase with the progression of mesangial hypercellularity. In four patients with IgA nephropathy, urinary IL-6 activity increased markedly but transiently during episodes of acute exacerbation associated with upper respiratory tract infection. In addition, it was demonstrated that urine from patients with other types of PGN such as poststreptococcal acute glomerulonephritis and membrano-proliferative glomerulonephritis contained large quantities of IL-6. However, the levels of urinary IL-6 activity were almost within the normal range in non-proliferative glomerular diseases such as membranous nephropathy, minimal change nephrotic syndrome and lupus nephritis (WHO class I and V), non-glomerular bleeding and orthostatic proteinuria. It should be noted that a marked increase in urinary IL-6 was often observed in the patients with urinary tract infection. These results indicated that IL-6 in urine might be derived from various types of cells participating in inflammatory reactions not only in the renal parenchyma but also in the urinary tract.

Palmoplantar pustulosis with pustulotic arthroosteitis involving temporal osteomyelitis and meningitis.

A 46-year-old man who had been suffering from palmoplantar pustulosis (PPP) for 3 years had anterior chest pain and left temporal pain from six months after the onset of his disease. A bone scan revealed abnormal uptake at the sternoclavicular joint and left temporal region. The head CT and MRI gave the diagnosis of temporal osteomyelitis with meningitis and myositis. His headache continued even after tonsillectomy and was effectively treated with cyclosporine A (3 mg/kg/day). Oral cyclosporine A was beneficial for the osteomyelitis and skin lesions. Sterile lytic bone lesions occurring most often at the sternocostoclavicular joint have been associated with PPP. However, there have been no reports of a PPP patient with temporal osteomyelytic involvement.

Association of generalized granuloma annulare with autoantibodies.

Granuloma annulare is a degenerative disease of the skin histopathologically characterized by focal degeneration of collagen with a surrounding infiltrate of lymphoid cells, histiocytic cells, and multinucleated giant cells. Immunological abnormalities such as delayed-type hypersensitivity and vasculitic origin are suspected in the pathogenesis. We describe three patients with generalized granuloma annulare, in whom autoantibodies, including antinuclear antibody, antithyroid stimulating hormone receptor antibody, and immune complex, were detected.

Congenital rubella syndrome with rubella virus-associated generalized brownish macules, indurated erythemas, papules, and pigmentation.

BACKGROUND: We examined an infant with congenital rubella syndrome (CRS). The purpose of this report is to describe the skin manifestations in this patient and to prove that they were associated with rubella virus. OBSERVATIONS: A 7-month-old boy presented with generalized brownish macules, indurated erythemas, papules, and pigmentation. They first appeared at around 3 months of age. His mother had contracted rubella during the 14th gestational week. At the time of examination, rubella-specific IgM antibody was positive in both serum and cerebrospinal fluid of the baby. A physical exam had revealed deafness, mental and physical retardation, interstitial pneumonitis, and hepatosplenomegaly. A skin biopsy specimen showed a dense infiltration mainly of lymphocytes, with B cells predominant in the deep dermis. Electron microscopically abundant tubuloreticular structures were observed in capillary endothelial cells, lymphocytes, and dermal fibroblasts. Polymerase chain reaction (PCR) analysis suggested that rubella virus RNA was present in the patient's skin specimen, cerebrospinal fluid, and total blood. CONCLUSIONS: The cutaneous manifestations of our patient were extraordinary and informative. These prominent skin lesions should be recognized as cutaneous markers of CRS.

[Clinical study of fluconazole-injectable and -granules in pediatric patients].

In this study, we have investigated the clinical effectiveness of fluconazole (FLCZ) given intravenously or orally to pediatric patients with systemic fungal infections. FLCZ was administered intravenously to two patients with acute leukemia (multiple hepatosplenic candidiasis and aspergillosis) and orally to two mycosis complicated with neuroblastoma and aplastic anemia, respectively. Clinical efficacies were excellent and no side effects were observed in any patients. Pharmacokinetic analysis in 6 neonates revealed that the plasma half-life is 37-41 hours after administration of single dose of intravenous infusion of 3 mg/kg of FLCZ.

Molecular and immunohistochemical detection of rotavirus in urinary sediment cells of children with rotavirus gastroenteritis.

This is the first report showing that rotavirus infects the urinary sediment cells in immunocompetent children with rotavirus gastroenteritis. We found that inclusion-bearing cells were frequently detected in the urine samples of patients with rotavirus gastroenteritis. These cells were positive for cytokeratin, which was sometimes coexpressed with rotavirus antigen, in our immunohistochemical analysis. Moreover, in nested RT-PCR experiments, we detected rotavirus double-stranded RNA in some urine samples of patients with rotavirus gastroenteritis. We concluded that rotavirus could lead to infection of the urinary sediment cells concomitantly with rotavirus gastroenteritis.

[A case of amyopathic dermatomyositis presenting blister and oral ulcer].

An 84-year old man was admitted to Mitoyo General Hospital because of progressive malaise and edematous erythema on both eyelids (Heliotrope erythema). He also noted blister on his neck as well as erythema on the extensor surface of finger joints (Gottron's sign), elbows and knees. Neither weakness nor pain of his proximal muscle was elicited on physical examination on admission. His blood test disclosed positive inflammatory signs (i.e., mild elevation of ESR and positive CRP) without elevated value of muscle enzymes. Electromyogram showed normal pattern. Infiltration of inflammatory cells was not revealed by histological examination of biopsied muscle. A diagnosis of 'amyopathic dermatomyositis' was made based on these observations. Computed tomography of his chest disclosed interstitial pneumonia spreading over both lower lung fields. Colon fiberscopy revealed a polyp in his descending colon, which was classified into group I on cytological examination. He was treated with two sets of methylprednisolone (mPSL) pulse therapy (500 mg/day, 3 consecutive days, intravenously) followed by 30 mg/day of oral prednisolone (PSL). His skin lesions responded well to the above treatment and the dose of oral PSL was tapered. One month after the initiation of treatment, severe stomatitis as well as a large ulcer beneath his tongue developed accompanying an intractable pain. Mucosal biopsy revealed necrotizing vasculitis in medium-sizedartery at the bottom of ulcer. Another set of mPSL pulse therapy brought a prompt relief of his symptom and prohibited the recurrence of oral lesion. It should be noted that our patient did not fulfill the diagnostic criteria for DM because of the lack of muscular symptoms whereas he had characteristic skin lesions. Regarding the frustration possibly encountered at the time of diagnosing amyopathic DM, both sensitivity and specificity of the skin lesion for the diagnosis of DM were investigated. Moreover, the rarity of blister as a skin manifestation of DM was discussed as well.

Peculiar facial erythematosquamous lesions in two siblings with cyclical summer improvement and winter relapse: a variant of keratosis lichenoides chronica?

A 7-year-old girl had erythematous hyperkeratotic papules and plaques that improved in summer and recurred in winter since the age of 4 months. She had had irregular, ridge-like erythematosquamous lesions on the arms with the same seasonal variation. The lesions on the arms improved with age. Light and electron microscopic examination showed marked degeneration of keratinocytes and prominent apoptosis. Her older brother had a similar but milder dermatosis. We believe these cases may represent a variant of keratosis lichenoides chronica.

Increased levels of urinary interleukin-6 in Kawasaki disease.

Kawasaki disease (KD) often presents with abnormal urinary findings, such as aseptic pyuria, mild proteinuria and microscopic haematuria. In this study, we measured urinary interleukin-6 (IL-6) by a sensitive sandwich ELISA assay using mouse monoclonal antibodies against recombinant IL-6 to elucidate the role of IL-6 in the pathogenesis of renal lesions in KD. Serum IL-6 levels were increased in acute KD as well as in febrile controls. Importantly, urinary IL-6 levels were consistently elevated in patients with acute KD, but much lower in febrile controls. Urinary IL-6 levels returned steadily to normal during the convalescent phase. In addition to IL-6, urinary levels of N-acetyl-beta-D-glucosaminidase (NAG) and beta 2-microglobulin (beta 2-mg) were also elevated during the acute phase of this disease. Eosinophils and macrophages were identifiable in urinary sediments from these patients. The increased levels of urinary IL-6 in combination with increased NAG and beta 2-mg seemed to suggest the presence of certain renal parenchymal lesions with cellular infiltration during the acute phase of the disease. IL-6 may serve as clinically useful parameter for the detection and monitoring of the renal involvement in KD.

Cutaneous T-cell lymphoma associated with granular lymphocytic leukemia in its terminal stage.

A 79-year-old woman had cutaneous T cell lymphoma. After a long clinical course, numerous tumors and an enormous increase in peripheral granular lymphocytes without lymphadenopathy developed suddenly. Surface markers and DNA analysis of the tumor cells from her skin and peripheral blood and electron microscopic examination suggested that granular lymphocytic leukemia had developed in the terminal stage of cutaneous T cell lymphoma. To our knowledge this association has not been reported previously.