Spectrum and management of rare Candida/yeast infections in Kuwait in the Middle East.

Invasive fungal infections (IFIs) are associated with high mortality rates and mostly affect patients with compromised immunity. The incidence of IFIs is increasing worldwide with the expanding population of susceptible patients. Candida and other yeast infections represent a major component of IFIs. Rare Candida/yeast infections have also increased in recent years and pose considerable diagnostic and management challenges as they are not easily recognized by routine phenotypic characteristic-based diagnostic methods and/or by the automated yeast identification systems. Rare Candida/yeasts also exhibit reduced susceptibility to antifungal drugs making proper management of invasive infections challenging. Here, we review the diagnosis and management of 60 cases of rare Candida/yeast IFIs described so far in Kuwait, an Arabian Gulf country in the Middle East. Interestingly, majority (34 of 60, 56.7%) of these rare Candida/yeast invasive infections occurred among neonates or premature, very-low-birth-weight neonates, usually following prior bacteremia episodes. The clinical details, treatment given, and outcome were available for 28 of 34 neonates. The crude mortality rate among these neonates was 32.2% as 19 of 28 (67.8%) survived the infection and were discharged in healthy condition, likely due to accurate diagnosis and frequent use of combination therapy. Physicians treating patients with extended stay under intensive care, on mechanical ventilation, receiving broad spectrum antibiotics and with gastrointestinal surgery/complications should proactively investigate IFIs. Timely diagnosis and early antifungal treatment are essential to decrease mortality. Understanding the epidemiology and spectrum of rare Candida/yeast invasive infections in different geographical regions, their susceptibility profiles and management will help to devise novel diagnostic and treatment approaches and formulate guidelines for improved patient outcome.

Singleton mutations in large-scale cancer genome studies: uncovering the tail of cancer genome.

Singleton or low-frequency driver mutations are challenging to identify. We present a domain driver mutation estimator (DOME) to identify rare candidate driver mutations. DOME analyzes positions analogous to known statistical hotspots and resistant mutations in combination with their functional and biochemical residue context as determined by protein structures and somatic mutation propensity within conserved PFAM domains, integrating the CADD scoring scheme. Benchmarked against seven other tools, DOME exhibited superior or comparable accuracy compared to all evaluated tools in the prediction of functional cancer drivers, with the exception of one tool. DOME identified a unique set of 32 917 high-confidence predicted driver mutations from the analysis of whole proteome missense variants within domain boundaries across 1331 genes, including 1192 noncancer gene census genes, emphasizing its unique place in cancer genome analysis. Additionally, analysis of 8799 TCGA (The Cancer Genome Atlas) and in-house tumor samples revealed 847 potential driver mutations, with mutations in tyrosine kinase members forming the dominant burden, underscoring its higher significance in cancer. Overall, DOME complements current approaches for identifying novel, low-frequency drivers and resistant mutations in personalized therapy.

Role of Algal-derived Bioactive Compounds in Human Health.

Algae is emerging as a bioresource with high biological potential. Various algal strains have been used in traditional medicines and human diets worldwide. They are a rich source of bioactive compounds like ascorbic acid, riboflavin, pantothenate, biotin, folic acid, nicotinic acid, phycocyanins, gamma-linolenic acid (GLA), adrenic acid (ARA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), etc. Beta-carotene, astaxanthin, and phycobiliproteins are different classes of pigments that are found in algae. They possess antioxidant, anti-inflammatory and anticancer properties. The sulfur-coated polysaccharides in algae have been used as an anticancer, antibacterial, and antiviral agent. Scientists have exploited algal-derived bioactive compounds for developing lead molecules against several diseases. Due to the surge in research on bioactive molecules from algae, industries have started showing interest in patenting for the large-scale production of bioactive compounds having applications in sectors like pharmaceuticals, food, and beverage. In the food industry, algae are used as a thickening, gelling, and stabilizing agent. Due to their gelling and thickening characteristics, the most valuable algae products are macroalgal polysaccharides such as agar, alginates, and carrageenan. The high protein, lipid, and nutrient content in microalgae makes it a superfood for aquaculture. The present review aims at describing various non-energy-based applications of algae in pharmaceuticals, food and beverage, cosmetics, and nutraceuticals. This review attempts to analyze information on algal-derived drugs that have shown better potential and reached clinical trials.

Isolation, preparation and investigation of leaf extracts of Aloe barbadensis for its remedial effects on tumor necrosis factor alpha (TNF-α) and interleukin (IL-6) by in vivo and in silico approaches in experimental rats.

Aloe barbadensis is a stemless plant with a length of 60-100 cm with juicy leaves which is used for its remedial and healing properties in different suburbs of various countries. The present study was conducted to investigate the effect of A. barbadensis leaf extract (aqueous and ethanolic) in yeast induced pyrexia and acetic acid induced writhing in rat model to evaluate the antipyretic biomarkers and its phytochemical screening with computational analysis. For analgesic activity model 60 Albino rats (160-200 kg) were divided into four groups. Of the 4 groups, control consisted of 6 rats (Group I) treated with normal saline, standard comprised of 6 rats treated with drug diclofenac (Group I). Experimental groups consisted of 48 rats, treated with A. barbadensis ethanolic and aqueous leaf extracts at doses of 50 mg/kg, 100 mg/kg, 200 mg/kg, and 400 mg/kg (Group III. IV). For antipyretic activity group division was same as in analgesic activity. All groups were treated the same as in the analgesic activity except for the second group which was treated with paracetamol. In both antipyretic and analgesic activity at the dose of 400 mg/kg, group III showed significant inhibition. TNF-α and IL-6 showed significant antipyretic activity at a dose of 400 mg/kg. For molecular docking aloe emodin and cholestanol were used as ligand molecules to target proteins Tnf-α and IL-6. Acute oral toxicity study was performed. There was no mortality even at the dose of 2000 mg/kg. Quantitative and qualitative phytochemical screening was performed for the detection of various phytochemicals. Hence, A. barbadensis leaf extracts can be used in the form of medicine for the treatment of pain and fever.

Deciphering the mechanisms of action of progesterone in breast cancer.

A practice-changing, randomized, controlled clinical study established that preoperative hydroxyprogesterone administration improves disease-free and overall survival in patients with node-positive breast cancer. This research perspective summarizes evidences from our studies that preoperative hydroxyprogesterone administration may improve disease-free and overall survival in patients with node-positive breast cancer by modulating cellular stress response and negative regulation of inflammation. Non-coding RNAs, particularly DSCAM-AS1, play a regulatory role in this process, along with the upregulation of the kinase gene SGK1 and activation of the SGK1/AP-1/NDRG1 axis. Progesterone-induced modification of the progesterone receptor and estrogen receptor genomic binding pattern is also involved in orchestrating estrogen signaling in breast cancer, preventing cell migration and invasion, and improving patient outcomes. We also highlight the role of progesterone in endocrine therapy resistance, which could lead to novel treatment options for patients with hormone receptor-positive breast cancer and for those who develop resistance to traditional endocrine therapies.

Development and characterization of a patient­derived orthotopic xenograft of therapy­resistant breast cancer.

Numerous years of cell line­based studies have enhanced the current understanding of cancer and its treatment. However, limited success has been achieved in treating hormone receptor­positive, HER2­negative metastatic breast cancers that are refractory to treatment. The majority of cancer cell lines are unsuitable for use as pre­clinical models that mimic this critical and often fatal clinical type, since they are derived from treatment­naive or non­metastatic breast cancer cases. The aim of the present study was to develop and characterize patient­derived orthotopic xenografts (PDOXs) from patients with endocrine hormone receptor­positive, HER2­negative metastatic breast cancer who had relapsed on therapy. A patient who progressed on endocrine hormone therapy provided her tumor via a biobank. This tumor was implanted in mice. It was then serially passaged by implanting PDOX tumor fragments into another set of mice to develop further generations of PDOXs. These tissues were characterized using various histological and biochemical techniques. Histological, immunofluorescence and western blot analyses indicated that the PDOX tumors retained a similar morphology, histology and subtype­specific molecular features to that of the patient's tumor. The present study successfully established PDOXs of hormone­resistant breast cancer and characterized them in comparison with those derived from the original breast cancer tissue of the patient. The data highlight the reliability and usefulness of PDOX models for studies of biomarker discovery and preclinical drug screening. The present study was registered with the clinical trial registry of India (CTRI; registration no. CTRI/2017/11/010553; registered on 17/11/2017).

TMC-SNPdb 2.0: an ethnic-specific database of Indian germline variants.

Cancer is a somatic disease. The lack of Indian-specific reference germline variation resources limits the ability to identify true cancer-associated somatic variants among Indian cancer patients. We integrate two recent studies, the GenomeAsia 100K and the Genomics for Public Health in India (IndiGen) program, describing genome sequence variations across 598 and 1029 healthy individuals of Indian origin, respectively, along with the unique variants generated from our in-house 173 normal germline samples derived from cancer patients to generate the Tata Memorial Centre-SNP database (TMC-SNPdb) 2.0. To show its utility, GATK/Mutect2-based somatic variant calling was performed on 224 in-house tumor samples to demonstrate a reduction in false-positive somatic variants. In addition to the ethnic-specific variants from GenomeAsia 100K and IndiGenomes databases, 305 132 unique variants generated from 173 in-house normal germline samples derived from cancer patients of Indian origin constitute the Indian specific, TMC-SNPdb 2.0. Of 305 132 unique variants, 11.13% were found in the coding region with missense variants (31.3%) as the most predominant category. Among the non-coding variations, intronic variants (49%) were the highest contributors. The non-synonymous to synonymous SNP ratio was observed to be 1.9, consistent with the previous version of TMC-SNPdb and literature. Using TMC SNPdb 2.0, we analyzed a whole-exome sequence from 224 in-house tumor samples (180 paired and 44 orphans). We show an average depletion of 3.44% variants per paired tumor and significantly higher depletion (P-value < 0.001) for orphan tumors (4.21%), demonstrating the utility of the rare, unique variants found in the ethnic-specific variant datasets in reducing the false-positive somatic mutations. TMC-SNPdb 2.0 is the most exhaustive open-source reference database of germline variants occurring across 1800 Indian individuals to analyze cancer genomes and other genetic disorders. The database and toolkit package is available for download at the following: Database URL  http://www.actrec.gov.in/pi-webpages/AmitDutt/TMCSNPdb2/TMCSNPdb2.html.

Computational-aided design: minimal peptide sequence to block dengue virus transmission into cells.

Dengue virus (DV) infection is one of the main public health concerns, affecting approximately 390 million people worldwide, as reported by the World Health Organization. Yet, there is no antiviral treatment for DV infection. Therefore, the development of potent and nontoxic anti-DV, as a complement for the existing treatment strategies, is urgently needed. Herein, we investigate a series of small peptides inhibitors of DV antiviral activity targeting the entry process as the promising strategy to block DV infection. The peptides were designed based on our previously reported peptide sequence, DN58opt (TWWCFYFCRRHHPFWFFYRHN), to identify minimal effective inhibitory sequence through molecular docking and dynamics studies. The in silico designed peptides were synthesized using conventional Fmoc solid-phase peptide synthesis chemistry, purified by RP-HPLC and characterized using LCMS. Later, they were screened for their antiviral activity. One of the peptides, AC 001, was able to reduce about 40% of DV plaque formation. This observation correlates well with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) analysis - AC 001 showed the most favorable binding affinity through 60 ns simulations. Pairwise residue decomposition analysis has revealed four key residues that contributed to the binding of these peptides into the DV2 E protein pocket. This work identifies the minimal peptide sequence required to inhibit DV replication and explains the behavior observed on an atomic level using computational study.Communicated by Ramaswamy H. Sarma.

Molecular characterisation of Candida auris isolates from immunocompromised patients in a tertiary-care hospital in Kuwait reveals a novel mutation in FKS1 conferring reduced susceptibility to echinocandins.

BACKGROUND: Candida auris is an emerging, potentially multidrug-resistant pathogen that exhibits clade-specific resistance to fluconazole and also develops resistance to echinocandins and amphotericin B easily. This study analysed 49 C auris isolates for alterations in hotspot-1 and hotspot-2 of FKS1 for the detection of mutations conferring reduced susceptibility to echinocandins. METHODS: C auris isolates (n = 49) obtained from 18 immunocompromised patients during June 2016-December 2018 were analysed. Antifungal susceptibility testing was performed by Etest and broth microdilution-based MICRONAUT-AM assay. Mutations in hotspot-1 and hotspot-2 regions of FKS1 were detected by PCR sequencing and fingerprinting of the isolates was done by short tandem repeat typing. RESULTS: The patients had multiple comorbidities/risk factors for Candida spp. infection including cancer/leukaemia/lymphoma/myeloma (n = 16), arterial/central line (n = 17), urinary catheter (n = 17), mechanical ventilation (n = 14) and major surgery (n = 9) and received antifungal drugs as prophylaxis and/or empiric treatment. Seven patients developed C auris candidemia/breakthrough candidemia, nine patients had candiduria with/without candidemia and four patients developed surgical site/respiratory infection. Resistance to fluconazole and amphotericin B was detected in 44 and four isolates, respectively. Twelve C auris isolates from eight patients showed reduced susceptibility to echinocandins. Seven isolates contained hostspot-1 mutations and three isolates from a candidemia patient contained R1354H mutation in hotspot-2 of FKS1. Ten patients died, five were cured, two were lost to follow-up and treatment details for one patient were not available. CONCLUSIONS: Our findings describe development of a novel mutation in FKS1 conferring reduced susceptibility to echinocandins in one patient during treatment and unfavourable clinical outcome for many C auris-infected patients.

A Large Case Series of Neurocysticercosis in Kuwait, a Nonendemic Arabian Gulf Country in the Middle East Region.

Neurocysticercosis (NCC), a leading global cause of severe progressive headache and epilepsy, in developed or affluent countries is mostly diagnosed among immigrants from poor or developing Taenia solium taeniasis-endemic countries. Taeniasis carriers in Kuwait are routinely screened by insensitive stool microscopy. In this study, enzyme-linked immunoelectrotransfer blot (EITB) was used as a confirmatory test for NCC. Screening was performed on 970 patients referred for suspected NCC on the basis of relevant history and/or ring-enhancing lesions on computed tomography and/or magnetic resonance imaging during a 14-year period in Kuwait. Demographic data and clinical details were retrieved from laboratory or hospital records. EITB was positive in 150 subjects (15.5%), including 98 expatriates mostly originating from taeniasis-endemic countries and, surprisingly, 52 Kuwaiti nationals. The clinical details of 48 of 50 NCC cases diagnosed during 2014-2019 were available. Most common symptoms included seizures, persistent headache with/without fever, and fits or loss of consciousness. Cysticercal lesions were located at various brain regions in 39 of 48 patients. Multiple members of 3 families with NCC were identified; infection was linked to domestic workers from taeniasis-endemic countries and confirmed in at least 1 family. Our data show that NCC is predominantly imported in Kuwait by expatriates originating from taeniasis-endemic countries who transmit the infection to Kuwaiti citizens.

An Update on the Epidemiological Features of Imported Schistosomiasis and Cystic Echinococcosis in Kuwait, 2010-2018.

OBJECTIVE: Kuwait is considered a non-endemic country for most parasitic infections. However, ∼70% of 4.7 million residents in Kuwait are expatriates from Asian and African countries, which are endemic for parasitic infections. Results of microbiological investigations for schistosomiasis and cystic echinococcosis (CE) performed in a reference national laboratory were retrospectively collected and analyzed to provide an insight on the epidemiology of these 2 neglected tropical diseases in Kuwait. SUBJECTS AND METHODS: Schistosoma infection in fecal and urine specimens from suspected patients was detected by microscopy. Schistosoma and CE infections were also detected by indirect hemagglutination assays (IHAs) using blood specimens. Patients' epidemiological data were extracted from the laboratory records. RESULTS: The overall prevalence rates of schistosomiasis and CE were 19.0 and 5.8%, respectively. Almost all schistosomiasis cases were seen among Egyptians, especially among males, and a significantly higher prevalence (p < 0.05) was seen for CE cases among the Syrian residents. A decreasing annual trend was observed for both the parasitic infections over time in Kuwait. CONCLUSIONS: This study confirmed that schistosomiasis is not autochthonous in Kuwait, as all cases were detected among expatriates from Schistosoma-endemic countries. Our data also showed that CE remains endemic among humans and livestock in Kuwait as is also seen in other Middle Eastern countries.

Performance Comparison of GeneXpert MTB/RIF and ProbeTec ET Tests for Rapid Molecular Diagnosis of Extrapulmonary Tuberculosis in a Low TB/MDR-TB Incidence Country.

OBJECTIVE: This study evaluated the performance of GeneXpert MTB/RIF (Xpert) and ProbeTec ET (PTec-ET) assays in diagnosing extrapulmonary tuberculosis (EPTB) in Kuwait. MATERIALS AND METHODS: We tested nonrespiratory clinical specimens (n = 3,995) collected from 3,995 patients suspected to have EPTB. These included cavitary fluids (n = 2,054), fine-needle aspirate (FNA)/pus/tissue biopsy (n = 1,461), urine (n = 302), cerebrospinal fluid (CSF, n = 118), and others (n = 60). All specimens were processed for acid-fast bacilli (AFB), culture in mycobacteria growth indicator tube 960 system, and nucleic acid detection by Xpert and PTec-ET according to manufacturer's instructions. RESULTS: Of 3,995 specimens, 95 were AFB-positive, 403 were culture-positive, and an additional 86 samples had histopathology suggestive of TB. Using culture as reference, the sensitivity and specificity values were 88.33 and 97.3% for Xpert and 72.95 and 97.80% for PTec-ET, respectively. Although performance of both tests was comparable in AFB-positive samples, Xpert detected significantly more cases in culture-positive samples. Among culture-negative samples, Xpert detected 18 more cases including 16 with histopathological evidence of TB. Lowest positivity was detected for both tests in cavitary fluids. Xpert performed better than PTec-ET in culture-positive FNA/pus/tissue biopsy and CSF samples. CONCLUSIONS: Although performance of both tests was suboptimal for AFB-negative/culture-positive samples, Xpert performed better than PTec-ET and also detected more cases of AFB-negative/culture-negative/histopathology-positive samples. PTec-ET was positive in 3, while Xpert was positive in all 6 culture-positive CSF specimens for rapid diagnosis of TB meningitis. Xpert was thus superior to PTec-ET or smear microscopy in rapid diagnosis of EPTB.

Cysticercosis, a Potential Public Health Concern in Kuwait: A New Diagnostic Method to Screen Taenia solium Taeniasis Carriers in the Expatriate Population.

OBJECTIVE: Taenia solium infection is not endemic to Kuwait, butseveral casesof cysticercosis have been detected in Kuwaiti nationals with no history of travelling to endemic countries. Infected domestic helpers/food handlers from endemic countries who may have escaped detection of infection by microscopy at the time of their arrival in Kuwait have been suspected as the possible source of infection. This study determined the seroprevalence of T. solium among domestic helpers/food handlers by screening their blood using a sensitive taeniasis-specific anti-rES33 antibody assay. SUBJECTS AND METHODS: Newly arrived domestic helpers (n = 500) and food handlers (n = 500) from endemic countries were enrolled in the period 2015-2017. T. solium-specific rES33 antigen was expressed and purified from human embryonic kidney (HEK)293-6E cells using the pTT5 mammalian expression vector. Stool samples were processed for microscopy, and blood samples were screened to detect anti-T. soliumtaeniasis-specific IgG antibodies by ELISA. RESULTS: All stool samples were negative for T. soliumparasiteeggs by microscopy. However, 42 individuals (4.2%) tested positive for T. soliumtaeniasis-specific IgG antibodies. Though statistically not significant, the IgG seropositivity was higher in individuals with a lower education level, a low-income background, and a lower frequency of hand-washing. CONCLUSIONS: This is the first report from Kuwait and the Middle East on the detection of anti-T. soliumtaeniasis-specific serum IgG antibodies among the high-risk expatriate population. The results emphasize the importance of efficient and sensitive screening of T. solium carriers and thus the prevention of infection transmission and development of cysticercosis in the local population.

Allergic Fungal Sinusitis Caused by Exserohilum rostratum and Literature Review.

A case of allergic fungal sinusitis (AFS) caused by Exserohilum rostratum, proven by culture and histopathology of the biopsy material, is described. The identity of the isolate was confirmed by sequencing of ITS region of rDNA. To the best of our knowledge, this is the first report of allergic E. rostratum sinusitis from Kuwait and Arabian Peninsula. Ten previously described cases of AFS have been reviewed. The report highlights the emerging importance of E. rostratum as a human pathogen in this region and role of molecular methods in its accurate identification.

Invasive Candida auris infections in Kuwait hospitals: epidemiology, antifungal treatment and outcome.

PURPOSE: Candida auris is a recently recognized yeast pathogen, which has attracted worldwide attention due to its multidrug-resistant nature and associated high mortality rates. Its persistence in hospital environment and propensity of nosocomial transmission underscores the need of continuous monitoring to prevent outbreaks. Since the first case of C. auris candidemia in May, 2014, we have identified 17 additional invasive cases, which are described here. METHODS: Identity of 17 isolates originating from proven or possible cases of invasive C. auris infection and identified as Candida haemulonii by Vitek 2 yeast identification system was confirmed by PCR-sequencing of rDNA. Information about risk factors, treatment and outcomes were retrospectively retrieved from case files. Antifungal susceptibility testing was performed by Etest. RESULTS: Thirteen cases of candidemia and 4 cases of other invasive infections were detected in 6 hospitals across Kuwait. Major risk factors included adult patients with cancer, diabetes, gastrointestinal/liver diseases and extended (> 25 days) hospital stay. All isolates were resistant to fluconazole. Additionally, 5 and 4 isolates were also resistant to voriconazole and amphotericin B, respectively. Despite antifungal treatment, 9 of 15 patients died. Most patients (n = 12) were hospitalized in 2 hospitals that are in close proximity, whereas 5 other patients were from 3 hospitals that are situated > 10 km apart. CONCLUSIONS: Occurrence of successive cases of invasive C. auris infections with resulting mortality in nine patients suggests persistence of this multidrug-resistant yeast in major hospitals in Kuwait. Early detection by continuous surveillance and enforcement of infection control measures are recommended.

Myocardial protection with Glucose-Insulin-Potassium infusion during adult cardiac surgery.

BACKGROUND & OBJECTIVE: Recent meta-analysis reports have called for more randomized trials to evaluate the effectiveness of GIK solution in patients of cardiac surgery. So this study was conducted to evaluate the effectiveness of Glucose-insulin-potassium (GIK) solutions in non-diabetic patients undergoing coronary artery bypass grafting. METHODS: A total number of one hundred and sixty (160) patients were randomized into two equal groups; GIK Group and non-GIK group. In GIK group, 5% dextrose containing 70 IU/L regular insulin and 70 meq/L of potassium was administered. The infusion was started at a rate of 30 ml/hour after induction of anesthesia and before the start of cardiopulmonary bypass. The infusion was started again after removal of aortic cross clamp and was continued for six hours after the operation. RESULTS: In early post-operative period, peak CKMB levels were high in non-GIK group 48.50±19.79 IU/L versus 33.40±14.69 IU/L in GIK group (p-value <0.001). There was no statistically significant difference in requirements of inotropic support between the groups. The mean duration of inotropic support in GIK group was only 5.50±6.88 hours in GIK group and 8.64±7.74 hours in non-GIK group (p-value 0.008). Mean ventilation time in GIK group was 5.06±2.39 hours versus 6.55±3.58 hours in non-GIK group (p-value 0.002). Similarly, ICU stay period was also shorter in GIK group (p-value 0.01). We did not found any detrimental effect of GIK infusion on non-cardiac complications e.g. renal, pulmonary and neurologic complications. CONCLUSION: Glucose-insulin-potassium (GIK) infusion has a beneficial role in myocardial protection and is associated with better post-operative outcomes without increasing the risk of non-cardiac complications.

Locked compression plating for peri- and intra-articular fractures around the knee.

OBJECTIVE: To evaluate the role of locked compression plates (LCPs) in management of peri- and intra-articular fractures around the knee. METHODS: Twenty distal femoral and 20 proximal tibial fractures were fixed with LCPs. The types of femoral fractures were A1 (four), A2 (three), A3 (two), C1 (one), C2 (seven) and C3 (three). The types of tibial fractures were A2 (one), A3 (two), B2 (two), C1 (four), C2 (five) and C3 (six). All patients were followed up for up to 18 months (mean, 12 months). Fourteen patients with distal femoral fractures and 19 with proximal tibial fractures underwent surgery using a minimally invasive percutaneous plate osteosynthesis (MIPPO) technique. The others were treated by open reduction. The average time of fixation was 8 days after injury (0-31 days). Knee Society scores were used for clinical and functional assessment. RESULTS: All fractures, except one of the distal femur and one of the proximal tibia, united. The mean union times for distal femoral and proximal tibial fractures were 15.2 and 14.9 weeks, respectively. One patient with a distal femoral fracture had implant failure. One patient was quadriplegic and did not recover the ability to walk. The average Knee Society scores of the remaining 18 patients were 82.66 (excellent) and 77.77 (functional score, good). There was one case of implant failure and one of screw breakage in distal femoral fractures. One case of nonunion occurred in a proximal tibial fracture. CONCLUSION: Provided it is applied with proper understanding of biomechanics, LCP is one of the best available options for management of challenging peri- and intra-articular fractures.

Extracorporeal delivery of rAAV with metabolic exchange and oxygenation.

Over the past decade much progress has been made towards the treatment of disease with recombinant adeno-associated viral vectors, ranging from cancer to muscular dystrophies, and autoimmune diseases to cystic fibrosis. Given inherent challenges of vector delivery we developed a system incorporating commercially available dialysis equipment. This concept was evaluated in vitro utilizing rAAV expressing the reporter gene human placental alkaline phosphatase. A number of pre-circulating conditions were assessed. Vector recovery was evaluated by quantitative vector genome analysis and cellular transduction assays. A dialysis circulation time course was established, and results were recorded across varied conditions ranging from approximately 2 to 90% retention of viable vector. This approach is unique in that it focuses on efficient localized, isolated and continual delivery of vector to target tissues, provides for the preservation of tissue integrity with dialysis for metabolic exchange and allows for the transfer of oxygen through a secondary membrane post-dialysis.

Pyrenochaeta romeroi: a causative agent of phaeohyphomycotic cyst.

A subcutaneous phaeohyphomycotic cyst caused by Pyrenochaeta romeroi in a 47-year-old Indian female is described. The organism was isolated repeatedly from the aspirated material from the cyst. It was identified by colony and microscopic characteristics, and sequencing of internal transcribed spacer regions of the rDNA. Although the patient recovered without antifungal therapy, the isolate appeared resistant to commonly used antifungal agents. To the best of our knowledge, this is only the second report of subcutaneous phaeohyphomycotic cyst caused by Pyrenochaeta romeroi.