National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma.

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

Reconnoitering the capabilities of nodule endophytic Pantoea dispersa for improved nodulation and grain yield of chickpea (Cicer arietinum L.).

Microorganisms belonging to root and soil provide a wide range of services and benefits to the plant by promoting plant growth and controlling phytopathogens. This study aimed to isolate endophytic bacteria from the root nodules of chickpea (Cicer arietinum L.) and determine their potential in improving plant growth. A total of nineteen different bacterial morphotypes were isolated from root nodules of chickpea and characterized in vitro for plant growth promotion abilities. All bacterial isolates were able to produce indole acetic acid at varying levels, out of which MCA19 was screened as the most efficient indole acetic acid producer (10.25 µg mL-1). MCA8, MCA9, MCA10, MCA11, MCA16, MCA17 and MCA19 were positive for phosphate solubilization, out of which MCA9 was best phosphate solubilizer (18.8 µg mL-1). All bacterial strains showed varying ability to grow on nitrogen-free media. Hydrogen cyanide, pectinase, and cellulase production ability were also observed in isolates, in which MCA9, MCA12, MCA17 and MCA19 were found best. Based on in vitro testing, five isolates MCA2, MCA9, MCA11, MCA17 and MCA19 were selected for further studies. Bacterial isolates MCA9, MCA11, MCA17 and MCA19 were identified by 16S rRNA gene sequence analysis as Pantoea dispersa while MCA2 as Rhizobium pusense. This is the first report on the existence of Pantoea dispersa in the root nodules of chickpea. In pot experiment, a maximum increase of 30% was recorded in plant dry weight upon the application of MCA19. Under field conditions, bacterial isolates, MCA2, MCA11 and MCA19 significantly enhanced nodulation and yield parameters of chickpea, compared to control. Pantoea dispersa MCA19 displayed the highest plant growth-promoting potential by increasing 38% grain yield. Our results indicate that Pantoea dispersa MCA19 is a promising biofertilizer for future applications.

Biofertilizer microorganisms accompanying pathogenic attributes: a potential threat.

Application of biofertilizers containing living or dormant plant growth promoting bacterial cells is considered to be an ecofriendly alternative of chemical fertilizers for improved crop production. Biofertilizers opened myriad doors towards sustainable agriculture as they effectively reduce heavy use of chemical fertilizers and pesticides by keeping soils profuse in micro and macronutrients, regulating plant hormones and restraining infections caused by the pests present in soil without inflicting environmental damage. Generally, pathogenicity and biosafety testing of potential plant growth promoting bacteria (PGPB) are not performed, and the bacteria are reported to be beneficial solely on testing plant growth promoting characteristics. Unfortunately, some rhizosphere and endophytic PGPB are reported to be involved in various diseases. Such PGPB can also spread virulence and multidrug resistance genes carried by them through horizontal gene transfer to other bacteria in the environment. Therefore, deployment of such microbial populations in open fields could lead to disastrous side effects on human health and environment. Careless declaration of bacteria as PGPB is more pronounced in research publications. Here, we present a comprehensive report of declared PGPB which are reported to be pathogenic in other studies. This review also suggests the employment of some additional safety assessment protocols before reporting a bacteria as beneficial and product development.

Diagnosis and Management of Diffuse Large B-Cell Lymphoma: Society of Medical Oncology, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology Joint Clinical Practice Guideline.

Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma encountered by hematopathologists and oncologists. Management guidelines for DLBCL are developed and published by countries with high income and do not cater for practical challenges faced in resource-constrained settings. This report by a multidisciplinary panel of experts from Pakistan is on behalf of three major national cancer societies: Society of Medical Oncology Pakistan, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology. The aim is to develop a practical and standardized guideline for managing DLBCL in Pakistan, keeping in view local challenges, which are similar across most of the low- and middle-income countries across the globe. Modified Delphi methodology was used to develop consensus guidelines. Guidelines questions were drafted, and meetings were convened by a steering committee to develop initial recommendations on the basis of local challenges and review of the literature. A consensus panel reviewed the initial draft recommendations and rated the guidelines on a five-point Likert scale; recommendations achieving more than 75% consensus were accepted. Resource grouping initially suggested by Breast Health Global Initiative was applied for resource stratification into basic, limited, and enhanced resource settings. The panel generated consensus ratings for 35 questions of interest and concluded that diagnosis and treatment recommendations in resource-constrained settings need to be based on available resources and management expertise.

Molecular characterization of Chickpea chlorotic dwarf virus strain D in Chickpea (Cicer arietinum) from District Dera Ismail Khan Khyber Pakhtunkhwa, Pakistan.

Chickpea chlorotic dwarf virus (CpCDV), a member of genus Mastrevirus (family Geminiviridae) is an important viral pathogen of chickpea and other legume crops in Middle East, North Africa, India and Pakistan. Among sixteen known strains of CpCDV three are known to infect legume crops in Punjab province of Pakistan. In this study diversity of CpCDV was explored in Khyber Pakhtunkhwa (KP) province of Pakistan. In year 2016, during a survey in the chickpea growing areas of district Dera Ismail Khan, CpCDV infected plants were identified. Leaf samples were collected, and a diagnostic PCR confirmed mastreivrus infection in 4 out of 100 samples. From these samples full-length genome of CpCDV was amplified using specific back-to-back primers. Virus molecules were sequenced to their entirety and sequence analysis of a molecule KRF4 (GenBank accession # KY952837) showed the highest pair wise sequence identity of 97% with a CpCDV molecule (KM229787) isolated from chickpea plant. An SDT analysis revealed it to be the D strain of CpCDV and a recombination detection program (RDP) showed it to be a recombinant between C (KM229780) and L (KT634301) strains of CpCDV. Thus, further supporting the intra-species recombination for CpCDV and presence of the same strain in chickpea growing areas of Pakistan other than Punjab province. This is the first identification of CpCDV (genus Mastrevirus family Geminiviridae) from chickpea (Cicer arietinum) plants in District Dera Ismail Khan, KP province, Pakistan.

Accelerated growth of skin carcinoma following fludarabine therapy for chronic lymphocytic leukemia.

We present four patients with chronic lymphocytic leukemia treated with fludarabine, who developed aggressive skin cancer after years of quiescence, a short time after institution of treatment. Their leukemias responded well to therapy with fludarabine with initial treatment as well as relapse. Three patients had recurrence with basal cell carcinomas with multiple, rapidly growing tumors and one had recurrence of both basal and squamous cancers and eventually died of metastatic squamous cell carcinoma. Fludarabine induces prolonged period of lymphopenia, affecting especially the T cell population, which is crucial in the defense against skin cancers. There appears to be a direct association between fludarabine and the flare up of skin cancers in these patients, possibly analogous to the increased incidence of these malignancies in patients on chronic cyclosporine immunosuppression.