Deciphering the role of wound healing genes in skin cutaneous melanoma: Insights into expression, methylation, mutations, and therapeutic implications.

Skin Cutaneous Melanoma (SKCM) is a form of cancer that originates in the pigment-producing cells, known as melanocytes, of the skin. Delay wound healing is often correlated with the occurrence of and progression of SKCM. In this comprehensive study, we investigated the intricate roles of two important wound healing genes in SKCM, including Matrix Metalloproteinase-2 (MMP2) and Matrix Metalloproteinase-9 (MMP9). Through a multi-faceted approach, we collected clinical samples, conducted molecular experiments, including RT-qPCR, bisulphite sequencing, cell culture, cell Counting Kit-8, colony formation, and wound healing assays. Beside this, we also used various other databases/tools/approaches for additional analysis including, UALCAN, GEPIA, HPA, MEXPRESS, cBioPortal, KM plotter, DrugBank, and molecular docking. Our results revealed a significant up-regulation of MMP2 and MMP9 in SKCM tissues compared to normal counterparts. Moreover, promoter methylation analysis suggested an epigenetic regulatory mechanism. Validations using TCGA datasets and immunohistochemistry emphasized the clinical relevance of MMP2 and MMP9 dysregulation. Functional assays demonstrated their synergistic impact on proliferation and migration in SKCM cells. Furthermore, we identified potential therapeutic candidates, Estradiol and Calcitriol, through drug prediction and molecular docking analyses. These compounds exhibited binding affinities, suggesting their potential as MMP2/MMP9 inhibitors. Overall, our study elucidates the diagnostic, prognostic, and therapeutic implications of MMP2 and MMP9 in SKCM, shedding light on their complex interplay in SKCM occurrence and progression.

Pericardioesophageal fistulae after left atrial ablation: a case series.

Pericardioesophageal fistula is an uncommon, yet serious complication that can occur after left atrial ablation for cardiac arrhythmias. Timing of this complication is variable; however, it has been reported to occur from a week to over a month post-ablation. The incidence of this complication after ablation is <0.05%; however with increasing rates of left atrial ablations, early recognition is imperative. Nonspecific symptoms, including chest pain, dysphagia, and fever, can indicate the presence of a fistula within the first month after ablation. Early drainage with subsequent definitive treatment is key to limiting morbidity. Here we report four cases of pericardioesophageal fistula all occurring ~1 month post-ablation, with two patients surviving after prompt diagnosis and surgical treatment. Successful treatment in these two cases was achieved with fistula takedown and intercostal muscle flap interposition and esophageal stenting.

Microlearning Environment of Orthodontic Postgraduate Training Programmes in Pakistan: A Multicentre Cross-Sectional Study.

OBJECTIVE: To explore the perception of residents regarding the microlearning environment of orthodontic postgraduate training programmes across Pakistan. STUDY DESIGN: Descriptive, cross-sectional, multicentre study. Place and Duration of the Study: Department of Orthodontics, Dental College, HITEC Institute of Medical Sciences, Taxila, from February to July 2022. METHODOLOGY: This questionnaire-based study was conducted using a pre-validated HEMLEM tool for data collection. QuestionPro survey tool was utilised for data collection and SPSS version 23 was used for data analysis. Independent t-test and one-way ANOVA were performed for comparison of different subgroups. RESULTS: A total of 204 residents participated in this study and collectively showed a mean score of 45.2. Male residents showed significantly higher level of satisfaction than females. Residents below the age of 25 years and those in the first year of training showed maximum level of satisfaction with their learning environments. In general, participants perceived the teaching quality and supervision as more satisfactory than the staff attitude and behaviour. CONCLUSION: Overall, a higher HEMLEM score was recorded, which suggested that Pakistani orthodontic residents felt satisfied with their microlearning environment. Clinical supervisors, curriculum designers, and programme directors could use the findings of this study to further improve the learning environment of their training programmes. KEY WORDS: Learning environment, Microlearning environment, Residents, Clinical training, Supervision, Staff support.

Gradual Analytics of Starch-Interacting Proteins Revealed the Involvement of Starch-Phosphorylating Enzymes during Synthesis of Storage Starch in Potato (Solanum tuberosum L.) Tubers.

The complete mechanism behind starch regulation has not been fully characterized. However, significant progress can be achieved through proteomic approaches. In this work, we aimed to characterize the starch-interacting proteins in potato (Solanum tuberosum L. cv. Desiree) tubers under variable circumstances. Starch-interacting proteins were extracted from developing tubers of wild type and transgenic lines containing antisense inhibition of glucan phosphorylases. Further, proteins were separated by SDS-PAGE and characterized through mass spectrometry. Additionally, starch-interacting proteins were analyzed in potato tubers stored at different temperatures. Most of the proteins strongly interacting with the potato starch granules corresponded to proteins involved in starch metabolism. GWD and PWD, two dikinases associated with starch degradation, were consistently found bound to the starch granules. This indicates that their activity is not only restricted to degradation but is also essential during storage starch synthesis. We confirmed the presence of protease inhibitors interacting with the potato starch surface as previously revealed by other authors. Starch interacting protein profiles of transgenic tubers appeared differently from wild type when tubers were stored under different temperatures, indicating a differential expression in response to changing environmental conditions.

Perioperative prophylactic corticosteroids for cardiac surgery in children: A systematic review and meta-analysis.

OBJECTIVE: Perioperative corticosteroids have been used for pediatric cardiac surgery for decades, but the underlying evidence is conflicting. We aimed to investigate the efficacy and safety of perioperative prophylactic corticosteroids in pediatric heart surgeries. METHODS: We searched electronic databases until March 2023 to retrieve all randomized controlled trials (RCTs) that administered perioperative prophylactic corticosteroids to children undergoing heart surgery. We used RevMan 5.4 to pool risk ratios (RRs) and mean differences (MDs). RESULTS: A total of 12 RCTs (2,209 patients) were included in our review. Corticosteroids administration was associated with a nonsignificant reduction in all-cause mortality (RR 0.62; 95% CI: 0.37-1.02, I2 = 0%; moderate certainty); however, it was associated with a lower duration of mechanical ventilation (MV) (MD -0.63 days; 95% CI: -1.16 to -0.09 days, I2 = 41%; high certainty). Corticosteroids did not affect the length of ICU and hospital stay but significantly reduced the incidence of postoperative low cardiac output syndrome (LCOS) (RR 0.76; 95% CI: 0.60-0.96, I2 = 0%; moderate certainty) and reoperation (RR 0.37; 95% CI: 0.19-0.74, I2 = 0%; moderate certainty). There was no increase in adverse events except a higher risk of hyperglycemia and postoperative insulin use. CONCLUSIONS: The use of perioperative corticosteroids in pediatric heart surgeries is associated with a trend toward reduced all-cause mortality without attaining statistical significance. Corticosteroids reduced MV duration, and probably decrease the incidence of LCOS, and reoperations. The choice of corticosteroid agent and dose is highly variable and further larger studies may help determine the ideal agent, dose, and patient population for this prophylactic therapy.

Toward Sustainable Healthcare Systems: A Low and Middle-Income Country's Case for Investing in Healthcare Reforms.

Pakistan, a low and middle-income country (LMIC), faces challenges in providing sustainable health care to its population due to inadequate financing, weak healthcare infrastructure, and insufficient health human resources. These challenges are not unique to Pakistan and are faced by many LMICs globally. In this paper, we aim to identify key strategies for achieving sustainable healthcare systems in Pakistan and to draw lessons for LMICs globally, keeping in view the healthcare reforms in Pakistan. We conducted a comprehensive literature review of existing policies and practices related to healthcare financing, service delivery, health information and communication technologies (ICTs), governance and leadership, and health human resources in Pakistan and other LMICs. We also reviewed relevant global policies and frameworks, including the Sustainable Development Goals (SDGs) and the World Health Organization's (WHO) health system strengthening guidelines. To achieve sustainable healthcare systems in Pakistan, we recommend comprehensive healthcare financing policies, including increasing budgetary allocations for health, social health protection through universal coverage, and supporting health and economic development processes. Service delivery can be improved through restructuring public health facilities, incorporating behavioral and social health determinants into primary health care, aligning healthcare delivery with the community, and promoting collaborative leadership between the public and private sectors. The use of ICT can be expanded by implementing e-health policies, disseminating authentic public health information, and enabling telemedicine services. Effective healthcare governance and leadership can be promoted through meritorious, transparent, and accountable reforms, stable healthcare structures at all community levels, and appropriate health policy and organizational frameworks. Finally, strengthening health human resources can be achieved through compliant policy implementation and revisions in laws and policies governing medical teaching institutions. Achieving sustainable healthcare systems in Pakistan and LMICs globally requires comprehensive strategies for healthcare financing, service delivery, health ICT, governance and leadership, and health human resources. By drawing on global policies and frameworks and lessons from other LMICs, Pakistan can overcome its healthcare challenges and contribute to the achievement of the SDGs.

Design of a facile, green and efficient graphene oxide-based electrochemical sensor for analysis of acetaminophen drug.

In this study an efficient and environment friendly electrochemical sensor has been designed for the analysis of acetaminophen (APAP) drug. Electrochemical impedance spectroscopy, differential pulse voltammetry and cyclic voltammetric techniques were used to demonstrate the fabricated erGO/GCE sensor performance. Voltammetric assessment of acetaminophen drug was done using bare GC electrode, drop-casted GO/GC electrode and erGO/GCE electrochemical sensor. Proposed sensor was precisely validated for APAP detection by differential pulse voltammetric technique. Subsequently LOD, LOQ, sensitivity and linearity were determined and found to be 7.23 nM, 21.909 nM, 20.14 µA nM-1 cm-2 and 0.0219-2.30 µM, respectively. The diffusion coefficient of APAP was determined by chronoamperometry, and it was found to be 2.24 × 10-5 cm2.s-1. The synthetic and analytical steps were assessed as per the Green Chemistry's 12 Principles giving a 66 score (acceptable) and 93 score (excellent) for the said steps, respectively. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02628-9.

Evaluating Gender-based Differences in Clinical Outcomes for Patients Undergoing Left Atrial Appendage Occlusion: A Single Centre Experience.

There is emerging recent data that has shown women to be more prone to in-hospital major adverse events after trans catheter left atrial appendage occlusion. Institutional LAAO registry at West Virginia University (WVU) was reviewed from January 2016 to October 2021 to identify 271 women and 293 men who underwent successful LAAO device implantation. Patients were evaluated for gender-based differences in baseline characteristics, CHA2DS2-VASc Score, HAS-BLED score, procedural data, in-hospital, and follow-up outcomes. Compared to men, women had lower baseline comorbidities including coronary artery disease (135 (49.6%) vs 172 (58.7%), P = 0.03), myocardial infarction (MI) (56 (20.5%) vs 85 (29%), P = 0.02) and coronary artery bypass surgery (10 (3.6%) vs 27 (9.2%), P = 0.008). Women were noted to have a higher CHA2DS2-VASc Score (5.3 ± 1.4 vs 4.4 ± 1.4, P < 0.001), and left ventricular ejection fraction (57.9 ± 7.7 vs 52.7 ± 12.4, P < 0.001). Women were noted to have a significantly higher rate of in-hospital composite adverse events (74 (27.2%) vs 58 (19.8%), P = 0.03); bleeding events (38 (10.2%) vs 19 (6.4%), P = 0.003) and associated blood transfusion (6 vs 0, P = 0.001) compared with men. No statistically significant differences were noted between both genders regarding the follow-up outcome. Our single center study shows women to have higher in-hospital composite adverse events as well as higher bleeding events during the index hospital admission.

The Era of Polypills in the Management of Cardiovascular Diseases: Are We There Yet?

Cardiovascular diseases (CVDs) are the leading cause of mortality globally. Wald and Law proposed the idea of a "polypill"; a fixed dose combination therapy (FDC) in the form of a single pill to curb the CVD epidemic. Such a drug would include the combination of a broad spectrum of drugs including cholesterol lowering drugs, antihypertensive drugs, antiplatelet drugs, anticoagulation drugs, and antiarrhythmic drugs, which are frequently integrated to combat specific CVDs. This "polypill" holds the potential to pose several advantages like increased compliance, improved quality of life, risk factor control, psychological relief, and cost effectiveness along with minimal side effects. Several trials (like TIPS, UMPIRE, PolyIran, etc.) have tested different treatment strategies to test the hypothesis of Wald and Law. Unlike the past, physicians are now highly aware of this new strategy. The future of polypill in the management of CVD lies in a strategy where polypills are treated supplementary to the already existing preventive care, which includes lifestyle modifications and efforts to reduce tobacco use.

Dual therapy with oral anticoagulation and single antiplatelet agent versus monotherapy with oral anticoagulation alone in patients with atrial fibrillation and stable ischemic heart disease: a systematic review and meta-analysis.

BACKGROUND: In patients with atrial fibrillation (AF) and stable ischemic heart disease, recent guidelines recommend oral anticoagulant (OAC) monotherapy in preference to OAC + single antiplatelet agent (SAPT) dual therapy. However, these data are based on the results of only two randomized controlled trials (RCTs) and a relatively small group of patients. Thus, the safety and efficacy of this approach may be underpowered to detect a significant difference. We hypothesized that OAC monotherapy will have a reduced risk of bleeding, but similar all-cause mortality and ischemic outcomes as compared to dual therapy (OAC + SAPT). METHODS: A systematic search of PubMed/MEDLINE, EMBASE, and Scopus was conducted. Safety outcomes included total bleeding, major bleeding, and others. Efficacy outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and major adverse cardiovascular events (MACE). RCTs and observational studies were pooled separately (study design stratified meta-analysis). Subgroup analyses were performed for vitamin K antagonists and direct oral anticoagulants (DOACs). Pooled risk ratios (RR) with corresponding 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method. RESULTS: Meta-analysis of 2 RCTs comprising a total of 2905 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant increase in major bleeding (RR 1.51; 95% CI [1.10, 2.06]). There was no significant reduction in MACE (RR 1.10; [0.71, 1.72]), stroke (RR 1.29; [0.85, 1.95]), myocardial infarction (RR 0.57; [0.28, 1.16]), cardiovascular mortality (RR 1.22; [0.63, 2.35]), or all-cause mortality (RR 1.18 [0.52, 2.68]). Meta-analysis of 20 observational studies comprising 47,451 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant higher total bleeding (RR 1.50; [1.20, 1.88]), major bleeding (RR = 1.49; [1.38, 1.61]), gastrointestinal bleeding (RR = 1.62; [1.15, 2.28]), and myocardial infarction (RR = 1.15; [1.05, 1.26]), without significantly lower MACE (RR 1.10; [0.97, 1.24]), stroke (RR 0.93; [0.73, 1.19]), cardiovascular mortality (RR 1.11; [0.95, 1.29]), or all-cause mortality (RR 0.93; [0.78, 1.11]). Subgroup analysis showed similar results for both vitamin K antagonists and DOACs, except a statistically significant higher intracranial bleeding with vitamin K antagonist + SAPT vs. vitamin K antagonist monotherapy (RR 1.89; [1.36-2.63]). CONCLUSIONS: In patients with AF and stable ischemic heart disease, OAC + SAPT as compared to OAC monotherapy is associated with a significant increase in bleeding events without a significant reduction in thrombotic events, cardiovascular mortality, and all-cause mortality.

A Serendipitous Outcome of COVID-19: Modifications to ICU Management.

Nosocomial infections are common in intensive care units (ICUs) and often cause increased morbidity and mortality rates in ICU patients. With the emergence of the highly infectious COVID-19, the high prevalence of hospital-acquired infections (HAIs) in ICU has caused much more concern because patients admitted to the ICU have a more severe and prolonged form of the disease. These patients are more likely to develop HAIs than non-ICU patients. Medical communities adopted several measures to make ICU management safer during the pandemic all over the world. In this study, we re-examined the challenges faced and the changes made in ICU management during the pandemic to speculate how these changes will be relevant post-pandemic and can be permanently incorporated into the ICU to improve safety, management, and critical care and make critical care better equipped for future disease breakouts.

Comparison of Phytochemical Constituents and Pharmacological Activities of Various Solvent Extracts Obtained from Millettia speciosa Stem Powder.

Millettia speciosa is a plant extensively used as an important component in Chinese herbal medicine and food-based medicines. The present study was carried out to determine the total flavonoid content (TFC), volatile phytoconstituents, and pharmacological activities, i.e., antityrosinase, sunscreen, and anticancer activity, of different fractions of M. speciosa stem. Different organic solvents of increasing polarity, i.e., petroleum ether (PE), ethyl acetate (EtOAc), and methanol (MeOH), were used for extraction. The highest total flavonoid content, i.e., 48.30 ± 0.90%, was reported for PE extract. Various important phytocomponents were revealed by gas chromatography-mass spectroscopy (GC-MS) analysis. Based on abundance, the major compounds were n-hexadecanoic acid (16.654%), n-hexadecanoic acid (14.808%), and beta-sitosterol (6.298%) for PE, EtOAc, and MeOH extract, respectively. The significant antityrosinase activity, i.e., 70.97 ± 0.66%, with an IC50 value of 4.58 mg/mL was noted for PE extract followed by EtOAc extract, i.e., 59.84 ± 0.67%, with IC50 value of 6.10 mg/mL. The maximum sunscreen activity was reported for PE extract exhibiting the maximum absorbance value (0.633 ± 0.06) in the ultraviolet (UV) region, i.e., UVC, while EtOAc extract showed the second highest level of absorbance in the UVB range, i.e., 0.632 ± 0.07. The strongest anticancer activity (49.73 ± 0.49% cell viability) towards MCF-7 breast cancer cell line was reported for PE extract with IC50 197.51 µg/mL. Our results confirmed the presence of potential therapeutic components for each extract with significant biological functions, showing the importance of the M. speciosa stem as a source of biomedicine. To our knowledge, this is the first report on M. speciosa stem extending comprehensive research about its phytochemical profile and various significant pharmacological activities.

Impact of Sociocultural Factors on Contraceptive Use: A Case Study of Pakistan.

Background: The use of birth control methods is influenced by complex and competing socioeconomic and demographic factors. Regardless of the complexity of the behavioral approach of women, the utility of contraceptive methods in providing the opportunity of choice is well paired. This study examined the factors driving the usage of contraception and the impact of contraceptive practices on population growth in Pakistan. We also perused the quantification of sociocultural contraceptive use. Methodology. The Pakistan Demographic and Health Survey (PDHS, 2017-18) dataset collected by the National Institute of Population Study (NIPS) was used for all analyses. We applied the frequentist logistic regression model and multinomial logistic regression model in assessing factors impacting contraceptive practices. Bayesian logistic and multinomial regression models were also implemented to compare estimates. The regions and provinces in Pakistan were considered as different clusters, thereby introducing hierarchical structures in the regression model. Results: The study revealed a distinctive highly significant negative effect on contraceptive use and women's age. The odds ratio (OR) for women aged 25-34, 35-44, and above 44 was 1.242, 1.155, and 0.638, respectively, which shows that the OR of contraceptive use decreases in women aged 25-44. Our study showed the superior performance of the Bayesian model in highlighting disparities among the various cultural streams existing in the country. Estimates of the Bayesian analysis of competing models indicated that the Bayesian models provide powerful estimates compared to the classical models. Conclusion: Our results indicated that contraceptive use is almost relevant to sociodemographic factors (education, age, language, partner, work, etc.). Women with no formal education living in rural areas were not aware of the use of contraception, thereby not using it. Contraceptive use and methods are most probably influenced by the age and the number of children of women. We recommend that high-quality education, counseling, and widespread access to contraceptives should be prioritized in family planning healthcare in all areas of the country, especially rural areas.

Recurrent appendicitis of vermiform appendix after a prior appendectomy: A case report and review of the literature.

Introduction: Acute appendicitis is one of the leading causes of acute abdominal pain and surgical emergency. Stump appendicitis is a known complication of appendectomy whereby a retained appendiceal tip serves as a nidus for recurrent bouts of inflammation. Nevertheless, full-blown appendicitis of the vermiform appendix after a prior appendectomy remains a diagnostic conundrum. Case presentation: A 45-year-old woman presented with a six-month history of right iliac fossa pain. Pertinently, she had undergone a prior open appendectomy twelve years ago. Further investigative workup revealed full-blown appendicitis, which was not attributable to a retained appendiceal stump. A subsequent laparoscopic appendectomy was performed, and the resultant specimen was sent for further evaluation, confirming the diagnosis of recurrent appendicitis. Clinical discussion: Acute appendicitis is one of the most common life-threatening abdominal surgical emergencies worldwide, with 300000 appendectomies performed annually in the United States alone. Stump and chronic appendicitis are two separate and exceedingly rare clinical entities that may present simultaneously and develop serious complications unless promptly recognized and appropriately managed. The present paper prompts the clinicians to distinguish amongst the two at the initial surgery in order to thwart further exacerbations. Conclusion: While stump appendicitis is a rare but well-characterized complication of a prior appendectomy, full-blown appendicitis of vermiform appendix remains elusive. It is therefore imperative to distinguish between a duplicated and a recurrent appendix at the initial operative procedure to facilitate optimal patient management.

Silencing of Curlin Protein via M13 Phagemid-Mediated Synthetic sRNA Expression Reduces Virulence in the Avian Pathogenic E. coli (APEC).

Curli fimbriae, a virulent factor of the Avian Pathogenic Escherichia coli (APEC), is responsible for adhesion, biofilm formation, and colonization of pathogen. Major curli fimbriae protein is encoded by csgA gene. APEC is one of the leading causes of colibacillosis in poultry flocks and due to excessive use of antibiotics and vaccines in poultry, the emergence of various multi-drug resistant (MDR) bacterial strainsare is frequently reported. The growing concern of MDR bacterial strains necessitate novel antibacterial approaches to combat colibacillosis in poultry. RNA-based gene silencing is a very specific and robust strategy to target specific bacterial factors involved in pathogenicity and virulence. In this study, a phagemid-mediated sRNA expression system to target a vital gene, csgA, is employed. This comprises an M13 phagemid harboring a sRNA expression cassette and a pre-designed GUIDE sequences for the csgA target gene. To target the csgA gene at the mRNA level, a GUIDE sequence was computationally designed for pre-designed sRNA expression cassette. Online web tools were used to predict the binding energy, secondary structure, and off-target binding potential of the sRNA to optimize its expression. Results showed that the designed sRNA has a binding energy of - 29.60 kcal/mol with zero off-targets. After expression of the sRNA in the APEC cells, Ì´ 45% reduction in the csgA level was observed via RT-PCR in the CS-APEC-O1 strains compared to the wt-APEC-O1. Similarly, the biofilm forming ability decreased by 40% in the CS-APEC-O1 strains. The swarming motility and hemagglutination efficiency were not affected by the sRNA expression. Future studies investigating the in vivo efficiency of M13 phagemid delivery are required to evaluate its candidacy in phage therapy.

Gastrointestinal pathophysiology of SARS-CoV2 - a literature review.

SARS-CoV2 is a novel coronavirus responsible for causing COVID-19, first identified in the city of Wuhan, China and officially declared a pandemic by the World Health Organization. SARS-CoV2 expresses high affinity to human ACE2 receptors, including within the gastrointestinal tract. Patients with COVID-19 exhibit a wide spectrum of GI symptoms including anorexia, nausea, vomiting, abdominal pain, and abnormal liver function tests. Pathogenesis behind gastrointestinal symptoms caused by SARS-CoV2 has been postulated to be multifactorial including disruption of the intestinal mechanical barrier integrity, alteration of the gut microbiome and systemic inflammatory response to the virus. SARS-CoV-2 RNA has also been found in stool samples of infected patients for a significantly longer period than in nasopharyngeal samples, though the implication of this finding is unclear at this time. Liver injury in patients with COVID-19 is usually mild, stemming from immune-mediated damage, drug induced hepatotoxicity, or ischemia from sepsis. Patients with pre-existing liver disease may be at a higher risk for hospitalization and mortality. Given the high degree of infectivity of this disease, healthcare providers will need to remain watchful for resurgence of this virus. Strict protocols should be implemented regarding hand hygiene, isolation, personal protective equipment, and appropriate disposal of waste. It is also imperative to identify patients with gastrointestinal symptoms at an early stage as these patients may have a prolonged course between symptom onset and viral clearance.

Not so Element-ary: A Copper Conundrum.

Copper is an essential micronutrient required for a number of enzymatic activities. Deficiency is relatively rare as only trace amounts are needed to maintain homeostasis. Deficiencies however do occur and are most commonly seen in malabsorptive states such as after bariatric surgeries. Herein, we present an interesting case of copper deficiency diagnosed in a 70-year-old male patient post duodenal switch procedure which persisted despite aggressive oral and intravenous copper supplementation. This lack of response to supplementation prompted further evaluation, leading to a diagnosis of underlying heterozygous Wilson's disease.

Jejunal-Ileal Bypass and its Complications: Case Report and Review of the Literature.

Herein, we describe an interesting case of a patient who underwent a jejunal-ileal bypass (JIB). She presented to the hospital with gastrointestinal bleeding after which her hospital course was complicated by electrolyte abnormalities. She was a 76-year-old Caucasian female with a past medical history of hypertension, type II diabetes, atrial fibrillation on warfarin, chronic obstructive pulmonary disease (COPD) treated with 3 liters of oxygen at home, obstructive sleep apnea, and morbid obesity, with history of an unknown type of bariatric procedure done in the 1970s. Her upper endoscopy showed a normal esophagus, stomach, and duodenum despite her history of bariatric surgery. Her colonoscopy revealed stenotic terminal ileum and an incidental colonic anastomosis at 35 cm from the anal verge with spot tattoo ink of unknown significance. Also noted were moderate internal hemorrhoids and large external hemorrhoids which were likely the source of her bleeding. Post endoscopy she had marked derangement in electrolytes, specifically hypocalcemia, hypomagnesemia, and hypo-phosphatemia.  JIB was first popularized in the 1960s for the treatment of obesity. There are two variations of the procedure, colloquially known as the Scott bypass and the Payne bypass. Our patient underwent the Scott JIB. The relatively longer intestinal tract combined with her ileal stenosis may explain her 50 years of relatively stable adaptation. It is imperative that treating physicians have a keen understanding of anatomy and physiology to adequately care for the long-term needs of these patients.

Extensively Drug-Resistant (XDR) Typhoid: Evolution, Prevention, and Its Management.

Typhoid fever is the result of a human host-restricted Salmonella enteric serotype typhi infection that causes enteric fever. Around 21 million people contract typhoid annually, with Pakistan's inhabitants at most risk amongst Asian countries where typhoid remains prevalent. Decades of indiscriminate antibiotic usage has driven the evolution of multidrug-resistant strains and more recently, extensively drug-resistant (XDR) strains of Salmonella enteric serotype typhi. Current reports of extensively drug-resistant typhoid fever outbreak in Pakistan are not only a major concern for Pakistan but also for health authorities worldwide: intercontinental transmission, spread, and replacement of native strains in neighboring countries and a major impediment to Pakistani health care management. The WHO records that there are 5274 cases of extensively drug-resistant (XDR) typhoid fever out of a total of 8188 total cases of typhoid fever reported in Pakistan. The last remaining feasible oral antibiotic that XDR typhoid remains susceptible to is azithromycin; this is a cause of major concern. Additionally, several cases of XDR typhoid fever have also been reported in patients travelling from Pakistan to the USA, UK, and Canada. This review article attempts to raise the issue of XDR typhoid with respect to its epidemiology, prevention, management, and future outlook and stresses a better understanding of antimicrobial stewardship and general surveillance of the disease. Although progress is being made to combat XDR typhoid locally, efficient, unified efforts on a national and international scale are required to contain the XDR outbreak before it is no longer manageable and leads us back to the preantibiotic era.