Recovery from acute haemorrhagic leucoencephalitis secondary to COVID-19.

A man in his 50s presented with sudden onset expressive aphasia and right-sided facial droop after experiencing coryzal symptoms and malaise for 7 days prior to admission. A brain MRI showed a rapidly progressive mass effect across both hemispheres and cerebrospinal fluid analysis revealed neutrophil predominance with raised protein levels. Acute disseminated encephalomyelitis was provisionally diagnosed, and high-dose methylprednisone was initiated.On admission to the high dependency unit, the patient tested positive for COVID-19 and was treated with appropriate therapeutic agents for severe COVID-19. A subsequent brain biopsy confirmed a demyelinating process, strongly indicating a diagnosis of acute haemorrhagic leucoencephalitis when correlated with the presence of severe oedema on imaging. Nine sessions of plasma exchange were provided over 18 days.At the time of writing, the patient has made an excellent recovery. We urge clinicians to consider this diagnosis and these treatment options for an otherwise devastating condition.

The significance of BAP1 and MTAP/CDKN2A expression in well-differentiated papillary mesothelial tumour: a series of 21 cases and a review of the literature.

The nomenclature and diagnostic criteria of well-differentiated papillary mesothelial tumour (WDPMT) have been changed in the 2021 World Health Organization (WHO) classification of thoracic tumours, and a new entity, mesothelioma in situ (MIS), introduced. Histologically these two entities may be similar. However, MIS is regarded as a precursor to invasive mesothelioma and requires demonstration of loss of BAP1 and/or MTAP/CDKN2A for diagnosis, whereas performance of these ancillary tests is desirable but not essential for a diagnosis of WDPMT, in which the significance of BAP1 and/or MTAP/CDKN2A loss is not well understood or well defined. Against this backdrop, we undertook an investigation of 21 cases of WDPMT, identified from our case files and diagnosed according to 2021 WHO criteria, to explore the relationship between histology and BAP1 and MTAP/CDKN2A expression with clinical features including asbestos exposure, focality of tumours and clinical outcome. There were 18 women and three men, with ages ranging from 23-77 years (median 62 years), in which six had a history of asbestos exposure, two had no exposure, and in 13 exposure history was unavailable. Of 20 peritoneal tumours and one pleural tumour, 13 were detected incidentally at the time of surgery for unrelated conditions and eight peritoneal tumours were multifocal at the time of diagnosis. BAP1 immunohistochemistry (IHC) was performed in all 21 tumours, with nine tumours showing BAP1 expression loss. MTAP/CDKN2A testing was performed in 14 tumours, comprising MTAP IHC in 12 and CDKN2A fluorescence in situ hybridisation (FISH) in two, with three tumours showing MTAP/CDKN2A expression loss. Two tumours with MTAP/CDKN2A loss also showed BAP1 expression loss. Four patients progressed to invasive mesothelioma, including one male with a pleural tumour and asbestos exposure, and three females with multifocal peritoneal tumours, two with asbestos exposure and one without exposure. BAP1 expression loss was seen in all tumours from the four patients who progressed to invasive mesothelioma, whilst two of these tumours showed retained MTAP IHC and two were not tested. There was one patient with a tumour with MTAP loss and retained BAP1 who died from unrelated causes 5 months after diagnosis. Eight patients received WDPMT-specific treatment in addition to the initial excision. Survival for all patients ranged from 4-218 months, with one patient dying of mesothelioma at 49 months. Based on our results in this series of 21 patients with WDPMT diagnosed according to 2021 WHO criteria, we propose that WDPMT with BAP1 expression loss may best be regarded as papillary MIS and that a history of asbestos exposure and the presence of multifocal tumours in patients diagnosed with WDPMT should prompt ancillary testing with BAP1 IHC. Further we propose that BAP1 IHC should be essential in the diagnosis of WDPMT, with the diagnosis restricted to those tumours which show retained BAP1 expression. However more studies in larger cohorts of patients are needed to explore the relationship between BAP1 expression and MTAP loss in WDPMT, which will help to define this entity and separate it more clearly from MIS and invasive mesothelioma.

Acute abdomen with a parasitic smooth muscle tumor of uncertain malignant potential (STUMP) in pregnancy; a unique case report.

INTRODUCTION AND IMPORTANCE: Diagnosis of a smooth muscle tumor of uncertain malignant potential (STUMP) during pregnancy is rare. Furthermore; the investigation of an intra-abdominal mass during pregnancy is clinically challenging due to anatomical changes and additional considerations of the developing fetus and radiation exposure. The unusual nature and diagnostic dilemma of such a case warrants a case report to serve as an educational prompt to clinicians who may encounter pregnant patients with undifferentiated intra-abdominal masses and/or suspecting of STUMP. CASE PRESENTATION: We report a rare case of a parasitic STUMP diagnosed during pregnancy. The patient presented with a new umbilical hernia and deranged liver function tests (LFT's) during her third trimester. MRI reported a large mass in the left mid flank with intra-abdominal varices extending into the umbilical hernia. She went on to develop an acute abdomen requiring laparotomy where a parasitic fibroid adherent to the omentum was excised and a preterm infant was delivered via caesarean section. Histology was difficult due to pregnancy related changes but ultimately confirmed a diagnosis of STUMP. CLINICAL DISCUSSION: STUMP in pregnancy is rare and diagnosis is further complicated by histological challenges due to pregnancy related changes. Postoperative diagnosis is challenging due to lack of universally accepted diagnostic criteria and Uncertainty regarding prognostic factors makes management and follow-up of patients with STUMP challenging. Studies have shown that younger patients are more likely to demonstrate recurrence. CONCLUSION: Investigation and management of intra-abdominal masses in pregnancy is challenging. It requires timely multi-disciplinary team (MDT) input. Additional complications and considerations relate to the preterm fetus. Knowledge and understanding of these difficulties will better equip clinicians working with such patients to formulate a structured and well informed approach to the pregnant patient with a new intra-abdominal mass. Diagnosis of STUMP during pregnancy may be challenging for the pathologist and require further exert opinion.

Beware the pancreatic incidentaloma in colorectal tumours: pancreatic adenocarcinoma with metastases to the colon and rectum.

Colorectal cancer (CRC) is the third most diagnosed malignancy in the Western world. Routine staging of CRC often identifies incidental lesions on cross-sectional imaging. Appropriate treatment is dependent on a correct histological diagnosis. Pancreatic Ductal Adenocarcinoma (PDAC) is a rarer and often devastating diagnosis for which the treatment pathway differs significantly to CRC. We report two rare cases: the first recorded case of PDAC with synchronous rectal metastasis and a case of an acute presentation with large bowel obstruction from synchronous colonic metastasis. Both cases presented a significant diagnostic challenge. The management of both cases would have been altered had the histological diagnosis been known prior to surgery. Clinicians treating CRC should be wary of incidental lesions on staging investigations as they rarely represent an occult extra-intestinal primary malignancy. Immunohistochemistry plays an important role in ascertaining the origin of gastrointestinal malignancy.

BCG Vaccination Program Mitigates COVID19 Related Mortality: A Reality Check.

Since its origin in the Wuhan province of China in December 2019, Coronavirus Disease 19 (COVID-19) has spread to most parts of the world and has infected millions of people. However, the significant variability in the mortality rate across the world indicates some underlying factors, especially the immunity factors that may have a potential role in this variability. One such factor that is being discussed and tested is the Bacillus Calmette-Guerin (BCG) vaccine. The available evidence suggests that BCG vaccination provides broad protection against respiratory infections as well as other infections. Therefore, BCG may prove to be a barrier for COVID-19 infection and may offer a ray of hope. In this review, we contrasted BCG vaccination program with COVID-19 mortality and analyzed trained immunity and cross protection against unrelated pathogens due to BCG vaccination. On analyzing the available data, we observed that countries without universal BCG vaccination policy are severely affected, while countries having universal BCG policies are less affected. Based on these data, we propose that the SARS-CoV-2 related qualified immunity, cross protection against unrelated pathogens and COVID-19 impact variations could be partly explained by the different national policies regarding BCG childhood vaccination. The combination of reduced morbidity and mortality may make BCG vaccination a potential new tool in the fight against COVID-19.

Medicinal Plant Compounds for Combating the Multi-drug Resistant Pathogenic Bacteria: A Review.

BACKGROUND: Globally, people utilize plants as the main source of remedy to heal various ailments. Medicinal plants have been utilized to treat ailments since the invention of modern scientific systems of medicine. The common remedy of infectious diseases mainly depends on the inhibition capacity of compounds or killing potential. The issue may give a clue for the development of a novel antimicrobial agent. METHODS: Currently, microorganisms which are resistant towards antibiotics are probably a matter of serious concern for the overall well-being of health. At the moment, new therapeutic targets aside from the microorganism wall-based activities are in progress. For instance, the autoinducer molecules produced by the quorum sensing system are used to control antibiotic resistance and biofilm formation. RESULTS: This therapeutic target is well-studied worldwide, however, the scientific data are not updated and only current studies started to gain insight into its perspective as a target to struggle against infectious diseases. Microbial resistance against antimicrobial compounds is a topic of serious concern in recent time. CONCLUSION: Hence, this paper aims to confer a current overview of the novel compounds, quorum sensing, quorum quenching, biofilm formation in the development of antibiotic resistance and an update on their importance as a potential target for natural substances.

Combined effect of microRNA, nutraceuticals and drug on pancreatic cancer cell lines.

AIM: We proposed to investigate the combination effect of microRNA, nutraceuticals and drug (MND), in two pancreatic cancer cell lines to assess the therapeutic potential. MATERIALS AND METHODS: MIA PaCa-2 and PANC-1 cells transfected with miR-101 or miR-24-2 were treated with Betulinic acid or Thymoquinone and gemcitabine independently and in combination and assessed for the extent of synergism in both experimental and control conditions, considering significance at the p value of <0.05. RESULTS: miR-101 or miR-24-2 over-expressing cells when treated with lower than IC50 doses of the dietary compounds and drug showed a reduced (37-50%) viability in two cell lines with differential synergistic effect and the outcome for Pro-caspase3, Poly (ADP-ribose) polymerase (PARP) cleavage and PKM2 expression. CONCLUSION: Two independent microRNA backgrounds showed promise in therapeutic intervention of gemcitabine sensitive, MIA PaCa-2 and resistant, PANC-1 pancreatic cancer cells, in combination with dietary agents and drug.

Synergistic combination of gemcitabine and dietary molecule induces apoptosis in pancreatic cancer cells and down regulates PKM2 expression.

Gemcitabine, an effective agent in treatment of cancer of pancreas, has undergone failures in many instances after multiple cycles of therapy due to emergence of drug resistance. Combination of dietary compounds with clinically validated drugs has emerged as an effective therapeutic approach to treat pancreatic tumors, refractory to gemcitabine therapy. In order to optimize a possible synergistic combination of Gemcitabine (GCB) with dietary molecules, Betuilnic acid (BA) and Thymoquinone (TQ), stand-alone IC50 dose of GCB, BA and TQ was calculated for pancreatic cancer cell lines. Fixed IC50 dose ratio of the dietary molecules in combination with reduced IC50 dose of GCB was tested on GCB resistant PANC-1 and sensitive MIA PaCa-2 cells for synergism, additive response and antagonism, using calcusyn. Combination index (CI) revealed that pre-treatment of BA and TQ along with GCB synergistically inhibited the cancer cell proliferation in in-vitro experiments. Pyruvate kinase (PK) M2 isoform, a promising target involved in cancer cell metabolism, showed down-regulation in presence of TQ or BA in combination with GCB. GCB with BA acted preferentially on tumor mitochondria and triggered mitochondrial permeability transition. Pre-exposure of the cell lines, MIA PaCa-2 and PANC-1, to TQ in combination with GCB induced apoptosis. Thus, the effectiveness of BA or TQ in combination with GCB to inhibit cell proliferation, induce apoptosis and down-regulate the expression of PKM2, reflects promise in pancreatic cancer treatment.

Concepts and Strategies for the Site Specific Delivery of Nanocarrier Based Delivery Systems for Treating Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is most common lethal malignancy worldwide. About 80% of liver cancer cases are attributed to the combined effects of Hepatitis B and C virus infections. The factors affecting development of HCC include cirrhosis and histological markers of increased liver cell proliferation, environmental, dietary and lifestyle of the person. Treatment options depend on the presence or absence of cirrhosis, number and size of tumors, and degree of hepatic deterioration. The primary option for some of the patients include hepatic resectioning, locoregional ablation, liver transplantation, ultrasound-guided tumor injection with absolute ethanol or tumor thermoablation with radiofrequency. Most common drugs like sorafenib, doxorubicin and daunorubicin have been used widely for treatment of HCC. A number of novel formulations like polymeric nanoparticles, nanocapsules, liposomes, nanoemulsions, microsphere, hydrogels, dendrimers, polymeric micelles has been reported for the treatment of HCC. The advantages of novel drug delivery systems (NDDS) is based on the ability to modify the bio-distribution, pharmacokinetics and pharmacological activity, prolonged efficacy and duration of drug activity, improved patient compliance, drug targeting to the site of action, enhancement of solubility, bioavailability, protection from toxicity, enhancement of stability. The carriers for liver specific drug delivery include liver-specific asialoglycoprotein receptor on mammalian hepatocytes. The natural ligand i.e. asialofeutin, or synthetic ligands with galactosylated or lactosylated polymers have been developed for significant targeting to the liver.

Pharmacosomes: an emerging novel vesicular drug delivery system for poorly soluble synthetic and herbal drugs.

In the arena of solubility enhancement, several problems are encountered. A novel approach based on lipid drug delivery system has evolved, pharmacosomes. Pharmacosomes are colloidal, nanometric size micelles, vesicles or may be in the form of hexagonal assembly of colloidal drug dispersions attached covalently to the phospholipid. They act as befitting carrier for delivery of drugs quite precisely owing to their unique properties like small size, amphiphilicity, active drug loading, high entrapment efficiency, and stability. They help in controlled release of drug at the site of action as well as in reduction in cost of therapy, drug leakage and toxicity, increased bioavailability of poorly soluble drugs, and restorative effects. There has been advancement in the scope of this delivery system for a number of drugs used for inflammation, heart diseases, cancer, and protein delivery along with a large number of herbal drugs. Hence, pharmacosomes open new challenges and opportunities for improved novel vesicular drug delivery system.

Ocular trauma epidemiology: 10-year retrospective study.

AIMS: This study is performed to determine the epidemiology and incidence of ocular trauma in Waikato, New Zealand. METHODS: The data was analysed on age, sex, ethnicity and type of trauma. Visual acuity (VA) at presentation and discharge was recorded. Details of slit lamp examination were noted. RESULTS: There were a total of 821 injuries. Men had higher rate of ocular trauma than women (74% vs 26%, p<0.001). Mean age was 31 years for males and 37 years for females respectively. Highest number of ocular trauma was seen in age group 15-20 (11.5%). There were 253 open globe injuries (OGI) and 568 closed globe injuries (CGI) (p<0.001). The most frequent causes of eye injuries in men were related to outdoor activities (25.9%) and work (20.7%). In women, outdoor activity was also the highest cause (10%). The annual rate of ocular trauma was 20.5 per 100,000 populations. Final VA of greater than and equal to 6/12 was found in 590 eyes, 6/12-6/60 in 143 eyes and greater than and equal to 6/60 in 88 eyes. Primary or secondary vitreoretinal procedures were performed in 54 eyes. There were three cases (0.3%) of endophthalmitis (inflammation of the internal coats of the eye). CONCLUSION: This study provides insight into epidemiology of ocular trauma in Waikato, New Zealand.

Microbial keratitis in Waikato, New Zealand.

BACKGROUND: Bacterial keratitis is a potentially sight-threatening condition. This study is performed to identify the common causative organisms for bacterial keratitis in Waikato region and the antibiotic sensitivities to these organisms. DESIGN: Retrospective, observational, case series. PARTICIPANTS: The microbiology records of all patients with bacterial keratitis who presented to the Ophthalmology department, Waikato Hospital, New Zealand between January 2003 and December 2007. METHODS: The corneal scrape results were reviewed. Antibiotic sensitivity for the organism was tested following National Committee for Clinical Laboratory Standards (NCCLS) method. MAIN OUTCOME MEASURES: In vitro laboratory susceptibility testing of ocular isolates to various antibiotics. RESULTS: A total of 265 scrapes were performed. Gram stain was positive in 35 (13.2%) eyes. Positive culture was seen in 174 (65.6%) scrapes; 78.2% were Gram-positive and 20.2% were Gram-negative organisms. Most common Gram-positive organisms were coagulase-negative Staphylococci (40.8%) and Staphylococcus aureus (11.5%). Most common Gram-negative organisms were Moraxalla species (8.0%) and Pseudomonas aeroginosa (3.4%). Of the bacterial organisms 99% were sensitive to ciprofloxacin. All Gram-negative organisms and 95.5% Gram-positive organisms were sensitive to tobramycin; 96.6% Gram-positive organisms and 98.3% Gram-negative organisms were sensitive to cefuroxime. CONCLUSIONS: Our results are comparable to other regions in New Zealand but the incidence of coagulase-negative Staphylococcus is much higher in this region compared with other New Zealand studies. It seems appropriate to start patients with corneal ulcers initially on fluoroquinolone monotherapy while awaiting culture results.

Pregnancy following gastric bypass surgery: what is the expected course and outcome?

AIM: To examine the course of pregnancy, labour, and the neonatal period in a group of women who have become pregnant following gastric bypass surgery for severe obesity. METHODS: Women who had experienced pregnancy following gastric bypass surgery were identified by an initial questionnaire. A second questionnaire was sent to those identified by the first questionnaire, who were willing to provide details concerning such pregnancies. RESULTS: Seventeen women experienced a total of 24 pregnancies and 25 live births. Five had experienced difficulties with conception or pregnancy prior to surgery. The average maternal weight gain was 6.13 kg. No major problems with fetal growth were observed. Babies were delivered at a mean gestational age of 37.5 weeks and with a mean birth weight of 3038 g. Six women reported a complication during pregnancy (25%) and five a complication in labour (20%). Two babies born to the same mother had congenital abnormalities attributable to a rare genetic disorder. CONCLUSION: The course of pregnancy and labour appears normalised for severely obese women following gastric bypass surgery. The weight loss and marked reduction in food intake following gastric bypass surgery does not lead to growth or development problems for offspring. Careful monitoring of expectant mothers who have undergone gastric bypass surgery is nevertheless to be recommended.