Efficacy and Safety of Infliximab Versus Adalimumab in Adult Subjects With Moderate to Severe Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Ulcerative colitis (UC) is an inflammatory disorder affecting the colon, and typically, during the disease course, the condition may exacerbate, relapse, and remit. One of the most successful lines for inducing and maintaining clinical remission in subjects with UC is biological therapy with anti-tumor necrosis factor α (anti-TNF) agents, including adalimumab (ADA) and infliximab (IFX). This meta-analysis is an attempt to obtain complementary information driven by real-world experience (RWE) concerning the efficacy and safety of two of the most popular anti-TNFs in treating UC. This is a systematic review and meta-analysis of RWE studies comparing ADA and IFX as naïve anti-TNF agents for the treatment of subjects with UC. Studies were obtained by searching Scopus, Google Scholar, the Cochrane Central Register of Controlled Trials, Embase, and the PubMed Central databases. Patients treated with IFX showed significantly higher induction responses. No statistically significant difference was found in the comparison of response in the maintenance treatment period. Higher overall adverse events were related to IFX treatment, with serious adverse events that were nonsignificantly higher in the ADA-treated group. In conclusion, IFX demonstrated significantly higher induction responses compared to ADA in patients with moderate-to-severe UC. IFX was associated with higher overall adverse events, whereas serious adverse events were non-significantly higher in the ADA-treated group. IFX may be favored as a first-line agent for its induction efficacy, and the choice between IFX and ADA should be individualized based on comprehensive clinical evaluation.

Fluvoxamine Ameliorates the Damage to the Neuro-Behavioral Status of Rats Caused by the Administration of Valproic Acid by Preventing Cognitive Memory Deficits and Decreased Hippocampal Cellular Proliferation.

Fluvoxamine is a major antidepressant of the selective serotonin-reuptake inhibitor class, previously studied as a drug that improves cognitive memory by enhancing hippocampal cell division and proliferation. Valproic acid (VPA) is a commonly used antiepileptic drug and mood stabilizer that has negative effects on cognitive memory as it inhibits cellular division and proliferation in the hippocampus. This study assessed the protective effects of fluvoxamine treatment versus the memory impairment, decreased hippocampal cellular proliferation, and weight loss produced by VPA treatment. The cognitive memory of 40 male Sprague-Dawley rats was assessed by the novel object location (NOL) test. Immunostaining by Ki67 and glutathione peroxidase 1 (GPX-1) was performed to quantify the number of dividing cells in the subgranular zone (SGZ) of the dentate gyrus and to assess the antioxidant activity of different treatments, respectively. Results showed that the VPA group had fewer Ki67-positive cells than the control group (p < 0.001), indicating reduced hippocampal proliferation. In contrast, the VPA and fluvoxamine combination group showed increased proliferation (p < 0.001) compared to VPA alone. Notably, fluvoxamine treatment significantly differed in cell counts compared to other groups (p < 0.001). Fluvoxamine also attenuated the weight loss caused by VPA (p < 0.0001). Our data suggested that fluvoxamine therapy attenuated the VPA-induced decrease in SGZ cellular proliferation, memory, and weight in rats.

Postoperative pancreatic fistula after pancreaticogastrostomy versus pancreatojejunostomy after pancreatic resection, a comparative systematic review and meta-analysis.

BACKGROUND: In patients undergoing pancreaticoduodenectomy (PD), there has been some evidence favoring pancreaticogastrostomy (PG) over pancreatojejunostomy (PJ) in the occurrence of postoperative pancreatic fistulas (POPF) and considering PG as a safer anastomotic technique. However, other publications revealed comparable incidences of POPF attributed to both techniques. The current work attempts to reach a more consolidated conclusion about such an issue. METHODS: This is a systematic review and meta-analysis that analyzed the studies comparing PG and PJ during PD in terms of the rate of POPF occurrence. Studies were obtained by searching the Scopus, PubMed Central, and Cochrane Central Register of Controlled Trials databases. RESULTS: 35 articles published between 1995 and 2022 presented data from 14,666 patients; 4547 underwent PG and 10,119 underwent PJ. Statistically significant lower rates of POPF (p = 0.044) and clinically relevant CR-POPF (p = 0.043) were shown in the PG group. The post-pancreatectomy hemorrhage (PPH) was significantly higher in the PG group, while no significant difference was found between the two groups in the clinically significant PPH. No statistically significant differences were found regarding the amount of intraoperative blood loss, length of hospital stay, DGE, overall morbidity rates, reoperation rates, or mortality rates. The percentage of male sex in the PG group and the percentage of soft pancreas in the PJ group seem to influence the odds ratio of CR-POPF (p = 0.076 and 0.074, respectively). CONCLUSION: The present study emphasizes the superiority of PG over PJ regarding CR-POPF rates. Higher rates of postoperative hemorrhage were associated with PG. Yet, the clinically significant hemorrhage rate was comparable between the two groups.

Long-term clinical outcomes of intravascular imaging-guided percutaneous coronary intervention versus angiography-guided percutaneous coronary intervention in complex coronary lesions: a systematic review and meta-analysis.

Background: In this study, we aim to discuss the long-term clinical outcomes of intravascular ultrasound imaging-guided percutaneous intervention (IVUS-PCI) versus angiography-guided percutaneous coronary intervention (PCI) in complex coronary lesions over a mean period of 2 years. Methods: A systematic search and meta-analysis were conducted to assess the efficacy of using intravascular ultrasound or optical coherence tomography guidance in coronary artery stenting compared to angiography. Results: A total of 11 randomized controlled trials with 6740 patients were included. For the primary outcome, a pooled analysis (3.2 vs 5.6%). For secondary outcomes, the risk was significantly low in image-guided percutaneous intervention compared with angiography. Conclusion: Intravascular imaging-guided PCI is significantly more effective than angiography-guided PCI in reducing the risk of target lesion revascularization, target vessel revascularization, cardiac death, major adverse cardiovascular events and stent thrombosis.

Need for Staging Investigations in Newly Diagnosed Breast Cancer: Establishing Local Guidelines for Radiological Staging in Bahrain.

Objective: Staging workup and detection of distant metastases is important in newly diagnosed breast cancer in order to make treatment decisions and establish the prognosis. There is wide variation in current recommendations for staging investigations in breast cancer. Routine staging is performed for all patients in Bahrain because of lack of consistent guidelines. Optimization of the criteria for staging is important for identification of metastases, while minimizing harm and costs. The aim of this study was to evaluate factors associated with distant metastases in newly diagnosed patients with breast cancer, in order to establish local guidelines for proper selection of patients for systemic staging. Materials and Methods: Patients with newly diagnosed breast cancer at Salmaniya Medical Complex in Bahrain who underwent staging investigations between January 2016 and December 2022 were identified from a pathology database. Patients with previous history of cancer, synchronous tumors, bilateral breast cancer and ductal carcinoma in situ were excluded. Clinical, radiological and pathological data were retrospectively analyzed. Results: A total of 593 patients underwent staging computed tomography and bone scans or a PET scan. Distant metastases were identified in 20.7% of cases. M1 disease was significantly associated with multifocality/multicentricity, high grade tumors, hormone receptor-negative cancers, high Ki67 index, advanced tumor stage, node-positive disease, triple-negative breast cancer, use of PET scans and those who underwent neoadjuvant chemotherapy. Age was not associated with identification of distant metastases. Conclusion: The prevalence of distant metastases in this population of newly diagnosed patients with breast cancer was higher than previously reported. Routine staging of all patients at presentation was not indicated, especially for asymptomatic patients with early breast cancer. This study identified certain groups of patients with a higher risk of distant metastasis, in whom metastatic workup should be performed. These findings may allow for the development of a local guideline that addresses the question of which breast cancer patients need staging investigations for distant metastases.

Predisposing deleterious variants in the cancer-associated human kinases in the global populations.

Human kinases play essential and diverse roles in the cellular activities of maintaining homeostasis and growth. Genetic mutations in the genes encoding the kinases (or phosphotransferases) have been linked with various types of cancers. In this study, we cataloged mutations in 500 kinases genes in >65,000 individuals of global populations from the Human Genetic Diversity Project (HGDP) and ExAC databases, and assessed their potentially deleterious impact by using the in silico tools SIFT, Polyphen2, and CADD. The analysis highlighted 35 deleterious non-synonymous SNVs in the ExAC and 5 SNVs in the HGDP project. Notably, a higher number of deleterious mutations was observed in the Non-Finnish Europeans (26 SNVs), followed by the Africans (14 SNVs), East Asians (13 SNVs), and South Asians (12 SNVs). The gene set enrichment analysis highlighted NTRK1 and FGFR3 being most significantly enriched among the kinases. The gene expression analysis revealed over-expression of NTRK1 in liver cancer, whereas, FGFR3 was found over-expressed in lung, breast, and liver cancers compared to their expression in the respective normal tissues. Also, 13 potential drugs were identified that target the NTRK1 protein, whereas 6 potential drugs for the FGFR3 target were identified. Taken together, the study provides a framework for exploring the predisposing germline mutations in kinases to suggest the underlying pathogenic mechanisms in cancers. The potential drugs are also suggested for personalized cancer management.

Association of Hyperparathyroidism with Depression and Anxiety Among Chronic Hemodialysis Patients in the Al Baha Region, Kingdom of Saudi Arabia.

Introduction Anxiety and depression are prevalent psychological issues among hemodialysis patients, adversely affecting their well-being and treatment response. The study aims to identify the relationship between these mental health concerns and hyperparathyroidism in chronic hemodialysis patients from the Al Baha Region, Kingdom of Saudi Arabia. Methods This retrospective study included 143 chronic hemodialysis patients aged 18-85 years. Monthly laboratory records for parathyroid hormone (PTH) levels and the Hospital Anxiety and Depression Scale (HADS) for mental health assessment were utilized. Demographic information and the primary causes of end-stage renal disease were obtained through patient interviews. Statistical analyses, including chi-square tests, odds ratio, and significance tests, were performed to assess associations. Results Elevated PTH levels were associated with increased anxiety and depression in hemodialysis patients. Patients with PTH levels >400 pg/ml exhibited higher rates of abnormal HADS scores for anxiety and depression than those with PTH levels <400 pg/ml. Gender differences were evident, with women showing a higher predisposition to anxiety disorders and men having depression. Additionally, patients with PTH levels <150 pg/ml had a significantly higher proportion of the "normal" depression score than those with PTH levels >800 pg/ml. Conclusion The study underscores the association between hyperparathyroidism and adverse mental health outcomes in chronic hemodialysis patients. Maintaining optimal PTH levels plays a crucial role in mitigating anxiety and depression. Gender differences in mental health outcomes highlight the need for tailored interventions. Routine mental health assessments, utilizing tools such as the HADS, are important in the comprehensive care of hemodialysis patients.

Rescue of cone and rod photoreceptor function in a CDHR1-model of age-related retinal degeneration.

Age-related macular degeneration (AMD) is the most common cause of untreatable blindness in the developed world. Recently, CDHR1 has been identified as the cause of a subset of AMD that has the appearance of the "dry" form, or geographic atrophy. Biallelic variants in CDHR1-a specialized protocadherin highly expressed in cone and rod photoreceptors-result in blindness from shortened photoreceptor outer segments and progressive photoreceptor cell death. Here we demonstrate long-term morphological, ultrastructural, functional, and behavioral rescue following CDHR1 gene therapy in a relevant murine model, sustained to 23-months after injection. This represents the first demonstration of rescue of a monogenic cadherinopathy in vivo. Moreover, the durability of CDHR1 gene therapy seems to be near complete-with morphological findings of the rescued retina not obviously different from wildtype throughout the lifespan of the mouse model. A follow-on clinical trial in patients with CDHR1-associated retinal degeneration is warranted. Hypomorphic CDHR1 variants may mimic advanced dry AMD. Accurate clinical classification is now critical, as their pathogenesis and treatment are distinct.

Exploring the modulation of MLH1 and MSH2 gene expression in hesperetin-treated breast cancer cells (BT-474).

The major mortality factor for women globally is breast cancer, and current treatments have several adverse effects. Hesperetin (HSP) is a flavone that occurs naturally with anti-tumor capabilities and has been investigated as a potential treatment for cancer. This study aimed to investigate the cytotoxic and anti-malignant potential of HSP on breast cancer cells (BT-474) and normal cells (MCF-10a). The results indicated that HSP has dose-dependent cytotoxicity in BT-474 and MCF-10a cells. The elevated concentration of HSP lowered cell viability and proliferation. The half-maximal inhibitory concentration (IC50) of HSP in BT-474 cancer cells after a 48-h exposure was 279.2 µM/ml, while the IC50 in normal cells was 855.4 µM/ml. The cytotoxicity of HSP was more significant in cancer cell lines than in normal cell lines and this aspect presents a favorable factor in utilizing the drug for the treatment of breast cancer. The apoptotic effect of HSP in BT-474 cells was investigated, and it was found that the higher the concentration of HSP more the cells underwent apoptosis. Furthermore, the highest concentration of HSP led to overexpression of the MLH1 and MSH2 genes in both breast cancer and normal cell lines. Overall, our study suggests that HSP has an anticancer effect on breast cancer cell lines, and the effect is concentration dependent.

The Counter Effect of Exercise on Cisplatin-Induced Cognitive and Proliferation Impairments.

Background Cisplatin, a widely used chemotherapeutic agent, offers therapeutic benefits for cancer treatment but often leads to adverse effects on neurogenesis and oxidative stress, causing cognitive impairment. Concurrent physical activity has been proposed as a potential strategy to counteract these side effects. This study aimed to investigate the impact of physical exercise on cisplatin-induced cognitive impairment in a mouse model. Methods Adult male mice (n=45) were divided into three groups: control, cisplatin-treated (2.3 mg/kg), and exercise/cisplatin. Cisplatin was administered intraperitoneally over one month, while the exercise/cisplatin group underwent moderate-intensity exercise alongside cisplatin treatment. Spatial memory was evaluated using the novel object recognition (NOR) task, and hippocampal proliferation and oxidative stress were examined using Ki-67 and glutathione peroxidase (GPx) immunohistochemistry (IHC) staining, respectively. Statistical analyses were performed using the GraphPad Prism 4.0 software (GraphPad Software, San Diego, CA). Results The cisplatin-treated mice exhibited significantly lower preference index (PI) scores in the NOR task compared to the control (p<0.001) and exercise/cisplatin (p<0.001) groups. IHC staining revealed impaired hippocampal proliferation and increased oxidative stress in the cisplatin-treated group relative to the control and exercise/cisplatin groups. The introduction of a moderate-intensity exercise protocol appeared to mitigate the decline in hippocampal proliferation and oxidative damage induced by cisplatin. Additionally, cisplatin-treated mice experienced weight loss, while exercise attenuated this effect. Conclusion Cisplatin treatment resulted in decreased memory, hippocampal proliferation, and weight loss in mice. Concurrent moderate-intensity exercise seemed to alleviate these effects, suggesting a potential role for physical activity in ameliorating cisplatin-induced cognitive decline. This study underscores the importance of incorporating exercise as a complementary strategy to enhance cognitive outcomes in cancer patients undergoing cisplatin treatment.

CRISPR Manipulation of Age-Related Macular Degeneration Haplotypes in the Complement System: Potential Future Therapeutic Applications/Avenues.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in the developed world. Whilst AMD is a multifactorial disease, the involvement of the complement system in its pathology is well documented, with single-nucleotide polymorphisms (SNPs) in different complement genes representing an increased risk factor. With several complement inhibitors explored in clinical trials showing limited success, patients with AMD are still without a reliable treatment option. This indicates that there is still a gap of knowledge in the functional implications and manipulation of the complement system in AMD, hindering the progress towards translational treatments. Since the discovery of the CRISPR/Cas system and its development into a powerful genome engineering tool, the field of molecular biology has been revolutionised. Genetic variants in the complement system have long been associated with an increased risk of AMD, and a variety of haplotypes have been identified to be predisposing/protective, with variation in complement genes believed to be the trigger for dysregulation of the cascade leading to inflammation. AMD-haplotypes (SNPs) alter specific aspects of the activation and regulation of the complement cascade, providing valuable insights into the pathogenic mechanisms of AMD with important diagnostic and therapeutic implications. The effect of targeting these AMD-related SNPs on the regulation of the complement cascade has been poorly explored, and the CRISPR/Cas system provides an ideal tool with which to explore this avenue. Current research concentrates on the association events of specific AMD-related SNPs in complement genes without looking into the effect of targeting these SNPs and therefore influencing the complement system in AMD pathogenesis. This review will explore the current understanding of manipulating the complement system in AMD pathogenesis utilising the genomic manipulation powers of the CRISPR/Cas systems. A number of AMD-related SNPs in different complement factor genes will be explored, with a particular emphasis on factor H (CFH), factor B (CFB), and complement C3 (C3).

Emerging novel sequence types of Staphylococcus aureus in Pakistan.

BACKGROUND: Despite an increasing incidence of Staphylococcus aureus infection and dissemination in Pakistan, the epidemiology of different Staphylococcus aureus research clones has been the subject of only a small number of investigations. By analyzing the collected data sequence, this study was designed to study the epidemiology of Staphylococcus aureus in the area using multilocus sequence typing (MLST). METHODS: A total of 1015 staphylococcus strains collected from the city's tertiary care facilities were biochemically screened, followed by antimicrobial susceptibility testing against a panel of 13 antibiotics. Analyzed methicillin-resistant Staphylococcus aureus (MRSA) was subjected to molecular characterization using multilocus sequence typing (MLST), clonal complex analysis, recombination testing, and phylogenetic analysis. RESULTS: Approximately 421 bacteria were verified as Staphylococcus aureus by biochemical analysis. 57% of the isolates exhibited multidrug resistance, of which 89% were found to be methicillin-resistant Staphylococcus aureus (MRSA). MLST results in a total of 39 sequence types (ST) and 5 clonal complexes (CC), out of which twenty-two STs were newly documented worldwide. The most common CC identified was CC8. The direct sequencing data also revealed significant shifts at MLST loci, with point mutations resulting in the aroE-343 and tpi-278 alleles. CONCLUSIONS: This study concludes that there is high diversity in the locally circulating clones of Staphylococcus aureus present in nature and that they are defined by their geographic epidemiology. These findings have practical implications for public health, including the need for tailored infection control strategies, antibiotic stewardship, global surveillance, and a deeper understanding of bacterial evolution.

The neuroprotective effects of Piracetam on cisplatin-induced cognitive decline.

AIM: This work explores the effect of Cisplatin-a chemotherapeutic agent known to cause deterioration in cognitive function in cancer patients, and spatial memory in mice. It also investigates the potential neuroprotective effects of Piracetam, which is a nootropic drug recognized for improving cognitive ability. MATERIALS AND METHODS: The study incorporates four groups of mice receiving varied medication regimens, with memory tested using the Novel Location Recognition (NLR) method. RESULTS: The findings from our study revealed that memory decline and a suppression of cellular proliferation were observed in adult male mice subjected to Cisplatin treatment; furthermore, a decline in antioxidant efficacy within the hippocampal dentate gyrus was evident. Moreover, analysis of treatment effects on the animals' weight revealed that the Cisplatin and Piracetam group exhibited the most significant weight loss during drug administration. Despite the significant weight loss, the simultaneous use of Cisplatin and Piracetam demonstrated a notable improvement in memory and an augmentation of hippocampal proliferation and antioxidant effect. LIMITATIONS: It is important to note that our study was hampered by budget limits, a lack of additional animals, and mice's low tolerance for protracted treatment. CONCLUSIONS: Should the outcomes of Piracetam observed in this investigation be applicable to patients, it might offer a relatively straightforward approach to mitigate the cognitive impacts endured by cancer survivors following exposure to chemotherapy. Future research will be needed to study Piracetam's effect on mice with brain cancer after Cisplatin treatment in order to extrapolate the results onto cancer patients.

Emulsion and liposome-based adjuvanted R21 vaccine formulations mediate protection against malaria through distinct immune mechanisms.

Adjuvanted protein vaccines offer high efficacy, yet most potent adjuvants remain proprietary. Several adjuvant compounds are being developed by the Vaccine Formulation Institute in Switzerland for global open access clinical use. In the context of the R21 malaria vaccine, in a mouse challenge model, we characterize the efficacy and mechanism of action of four Vaccine Formulation Institute adjuvants: two liposomal (LQ and LMQ) and two squalene emulsion-based adjuvants (SQ and SMQ), containing QS-21 saponin (Q) and optionally a synthetic TLR4 agonist (M). Two R21 vaccine formulations, R21/LMQ and R21/SQ, offer the highest protection (81%-100%), yet they trigger different innate sensing mechanisms in macrophages with LMQ, but not SQ, activating the NLRP3 inflammasome. The resulting in vivo adaptive responses have a different TH1/TH2 balance and engage divergent innate pathways while retaining high protective efficacy. We describe how modular changes in vaccine formulation allow for the dissection of the underlying immune pathways, enabling future mechanistically informed vaccine design.

Hemophagocytic Lymphohistiocytosis and Pancreatic Cancer: A Rare Association.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) or hemophagocytic syndrome (HPS) is a life-threatening and relatively rare condition that usually presents as a multisystem febrile illness. It is associated with excessive activation of the immune system and hypercytokinemia, leading to an unregulated aggregation of macrophages and lymphocytes. Here, we present the first likely case of HLH with metastatic pancreatic carcinoma being the underlying etiology. Case: A 44-year-old male with past medical history significant for heart transplant for which he was on tacrolimus, End-Stage Renal Disease (ESRD) on hemodialysis, recently treated CMV viremia, and necrotizing pancreatitis presented to the emergency with complaints of chills, decreased appetite, worsening non-bloody emesis, and dull left upper quadrant abdominal pain with radiation to the back for four days. No shortness of breath, fever, diarrhea, or blood in the stool was reported. Vitals on admission were blood pressure of 90/61 mmHg, a heart rate of 110 beats per minute, temperature of 98.1 °F, and respiratory rate of 18 per minute. Physical exam was significant for scleral icterus, decreased bibasilar breath sounds, moderate abdominal tenderness in the left flank and left upper abdominal quadrant without any palpable mass, and 1+ bilateral pedal edema. The remainder of the physical examination was benign. Electrocardiogram (EKG) showed sinus tachycardia without any ischemic changes, and chest x-ray showed mild pulmonary edema. Initial blood workup revealed WBC at 8.3 k/uL, hemoglobin of 10.2 g/dL, platelet count of 90 k/uL, and BUN/creatinine of 45/5.8 (baseline 40/5.0). Cardiac workup showed an elevated high sensitivity troponin level of 2479 pg/mL and brain natriuretic peptide (BNP) of 600 (0-100 pg/mL). The hepatobiliary profile showed an aspartate transaminase (AST) level of 2645 U/L, an alanine transaminase (ALT) of 2935 U/L, alkaline phosphatase (ALP) of 106 U/L, and lipase of 61 U/L, with total and conjugated bilirubin of 3.5 mg/dL and 2.1 mg/dL, respectively. Transthoracic echocardiogram (TTE) showed reduced left ventricular size with hyperdynamic systolic function. Computerized tomography (CT) scan of the abdomen (Fig. 1) revealed numerous new pulmonary nodules, ring-enhancing lesions within the liver, hyperenhancement of the pancreas with walled-off necrosis, and splenomegaly. Microbiological work-up was positive for cytomegalovirus (CMV) serologies (IgM and IgG) but absent viral load on Polymerase Chain Reaction (PCR). The initial diagnosis was systemic inflammatory respiratory syndrome (SIRS), likely septic versus distributive in the setting of pancreatitis, demand mediated non-ST segment elevation myocardial infarction (NSTEMI), and shock liver. Tacrolimus was held, and the patient was started on broad-spectrum antibiotics including vancomycin and cefepime for sepsis of unknown origin along with vasopressors for hypotension, requiring admission to the medical intensive care unit. Blood and urine cultures were collected on admission which remained negative throughout the course of hospital. CA19-9 levels were found elevated at 5587 U/mL. Liver biopsy was consistent with poorly differentiated adenocarcinoma of pancreatic origin. Both Infectious Disease and Hematology were consulted due to broad differential diagnoses. Due to the patient's continued hemodynamic instability and nonresponsiveness to the antibiotics, HLH was suspected with supporting labs as follows: ferritin 55,740 ng/mL (22-322 ng/mL), triglycerides 177 mg/dL (30-150 mg/dL), and fibrinogen 244 mg/dL (173-454 mg/dL), thus conferring 70-80% probability of HPS based on H-score. Soluble IL-2 R levels came out at 19,188 pg/mL (ref range 175-858 pg/mL). The patient couldn't be started on HLH treatment due to initial concerns of underlying infection and the delay in results of soluble IL-2 Receptor (IL-2 R) levels. The infection as a possible etiology was ruled out due to negative blood and urine cultures and HLH was attributed to pancreatic cancer. A marrow biopsy couldn't be pursued as the patient died within a week of hospitalization. An autopsy was not performed as per family's request. Conclusion: HLH can occur secondary to solid cell malignancies including those from the pancreas and should be kept high in the differential in critically ill cancer patients who are nonresponsive to antibiotics. H-score has been reported to be a more sensitive tool compared to the HLH protocol, especially if used earlier during the presentation. Further research is needed to compare diagnostic efficacy for HLH protocol verses H-score especially in critically ill patients as they might benefit from steroid trial.

The preparedness and knowledge of pharmacists and general practitioners in managing human monkeypox: a highly spreading infectious disease.

BACKGROUND: After the era of the COVID-19 pandemic, the role of pharmacists was emphasized in the battle against highly spreading and infectious diseases like human Monkeypox (hMPV). AIM: Assess the hMPV knowledge of the community, clinical pharmacists, and general practitioners (GPs) and raise their awareness about hMPV. METHODS: A web-based questionnaire was distributed randomly to Egyptian community pharmacists, clinical pharmacists, and GPs from all governorates. The questionnaire was divided into two sections: one for demographic information and the other for hMPV knowledge (nature of the disease, incubation period, transmission, symptoms, Prophylaxis, Prevention, and management). The evidence-based answers were provided after completing the submission. Data were descriptively analyzed using IBM SPSS software. RESULTS: From a total of 753 respondents, only 710 participants were included in the final data analysis. The % of respondents who presented good total knowledge scores about hMPV was comparable between study groups (P = 0.826). There were no differences between groups identifying different disease clinical characteristics (P = 0.689) and hMPV management (P = 0.324). Community pharmacists had better knowledge scores than GPs in the prevention and prophylaxis domain (P = 0.037). CONCLUSION: Pharmacists and GPs have good and similar knowledge levels of hMPV. However, a gap exists in recognizing the right hMPV incubation period, prophylaxis, and omitting antibiotics from hMPV management. Pharmacists and GPs are the frontline health care providers (HCPs), so they would require more knowledge enhancement about such contagious diseases to offer the best possible patient care.

Risk Factors Associated With Sentinel Lymph Node Metastasis in Clinically Node-Negative Breast Cancer.

Objective: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in clinically node negative breast cancer. If predictive factors for sentinel lymph node (SLN) metastasis could be identified, it would allow selection of candidates for SLNB and omit axillary surgery in those with the lowest risk of axillary lymph node involvement. The aim of this study was to determine risk factors associated with SLN metastasis in breast cancer patients in Bahrain. Materials and Methods: Patients with clinically node-negative breast cancer who underwent SLNB at a single institution between 2016 and 2022 were identified from the pathology database. Patients who had failure of localization of SLN, those with bilateral cancers and those treated for a local recurrence were excluded. Results: A total of 160 breast cancer patients were retrospectively analyzed. Of these, 64.4% had a negative SLNB and 21.9% of all cases underwent axillary dissection. The following parameters emerged as predictors of SLN metastasis in univariate analysis: age; tumour grade; ER status; presence of lymphovascular invasion (LVI) and tumor size. On multivariate analysis, age was not independently associated with the incidence of SLN metastasis. Conclusion: This study showed that high tumour grades, presence of LVI and large tumour size were all risk factors related to axillary metastasis after SLNB in breast cancer. In the elderly, the incidence of SLN metastasis appeared to be relatively low, providing an opportunity to de-escalate axillary surgery in these patients. These findings may allow for the development of a nomogram to estimate the risk of SLN metastasis.

Developmental Expression of the Cell Cycle Regulator p16INK4a in Retinal Glial Cells: A Novel Marker for Immature Ocular Astrocytes?

Retinal astrocytes are vital for neuronal homeostasis in the retina. Together with Müller glia, they provide retinal cells with neurotrophic factors, antioxidative support, and defense mechanisms such as the formation of the blood-retinal barrier. Substantial heterogeneity of astrocyte morphology and function represents a challenge for identification of distinct subtypes which may be potential targets for therapeutic purposes. Hence, identification of novel markers of astrocyte subpopulations is highly relevant to better understand the molecular mechanisms involved in retinal development, homeostasis, and pathology. In this study, we observed that the cell cycle regulator, p16INK4a, is expressed in immature astrocytes in the mouse retina. Immunohistochemical analysis showed p16INK4a expression in the optic nerve of wild-type mice from 3 days to 3 months of age and in the nerve fiber layer of the adult mouse retina. Colocalization of p16INK4a expression and glial fibrillary acidic protein (immature/mature astrocyte marker) tends to decrease with age. However, colocalization of p16INK4a expression and vimentin (immature astrocyte marker) remains high in the optic nerve from the early postnatal period to adulthood. The observations from this study provide a valuable tool for further investigations of ocular astrocytes in the developing retina as well as in degenerative retinopathies.

One Anastomosis Gastric Bypass (OAGB) with a 150-cm Biliopancreatic Limb (BPL) Versus a 200-cm BPL, a Systematic Review and Meta-analysis.

This is a systematic review and meta-analysis that assessed the impact of performing OAGB with a 150-cm BPL versus a 200-cm BPL concerning weight loss, comorbidities remission, and adverse nutritional effects. The analysis included studies that compared patients who underwent OAGB with a 150-cm BPL and 200-cm BPL. Eight studies were eligible for this review after searching in the EMBASE, PubMed central database, and Google scholar. The pooled analysis revealed favoring the 200-cm BPL limb length for weight loss, with a highly significant difference in the TWL% (p=0.009). Both groups showed comparable comorbidities remission. Significantly higher ferritin and folate deficiency rates were found in the 200-cm BPL group. Considering a 200-cm BPL when performing OAGB delivers a better weight loss outcome than a 150-cm BPL, which is at the expense of a more severe nutritional deficiency. No significant differences were found regarding the comorbidities' remission.