Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has posed a major public health concern worldwide. Patients with comorbid conditions are at risk of adverse outcomes following COVID-19. Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection. It could lead to higher rates of inpatient complications and mortality in this patient population. However, studies on COVID-19 outcomes in liver transplant (LT) recipients have yielded inconsistent findings. AIM: To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States. METHODS: We conducted a retrospective cohort study using the 2019-2020 National Inpatient Sample database. Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classification of Diseases, Tenth Revision coding system. The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic. Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients. RESULTS: A total of 15720 hospitalized LT recipients were included. Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection. In both cohorts, the median admission age was 57 years. The linear trends for LT hospitalizations did not differ significantly before and during the pandemic (P = 0.84). The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020. Compared to the pre-pandemic period, a higher association was noted between LT recipients and in-hospital mortality during the pandemic, with an odds ratio (OR) of 1.69 [95% confidence interval (CI): 1.55-1.84), P < 0.001]. The frequency of transplant rejections among hospitalized LT recipients increased from 0.2% to 3.6% between January 2019 and December 2020. LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic [OR: 1.53 (95%CI: 1.26-1.85), P < 0.001]. CONCLUSION: The hospitalization rates for LT recipients were comparable before and during the pandemic. Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.

Association between acute peripancreatic fluid collections and early readmission in acute pancreatitis: A propensity-matched analysis.

BACKGROUND: Patients with acute pancreatitis (AP) frequently experience hospital readmissions, posing a significant burden to healthcare systems. Acute peripancreatic fluid collection (APFC) may negatively impact the clinical course of AP. It could worsen symptoms and potentially lead to additional complications. However, clinical evidence regarding the specific association between APFC and early readmission in AP remains scarce. Understanding the link between APFC and readmission may help improve clinical care for AP patients and reduce healthcare costs. AIM: To evaluate the association between APFC and 30-day readmission in patients with AP. METHODS: This retrospective cohort study is based on the Nationwide Readmission Database for 2016-2019. Patients with a primary diagnosis of AP were identified. Participants were categorized into those with and without APFC. A 1:1 propensity score matching for age, gender, and Elixhauser comorbidities was performed. The primary outcome was early readmission rates. Secondary outcomes included the incidence of inpatient complications and healthcare utilization. Unadjusted analyses used Mann-Whitney U and χ 2 tests, while Cox regression models assessed 30-day readmission risks and reported them as adjusted hazard ratios (aHR). Kaplan-Meier curves and log-rank tests verified readmission risks. RESULTS: A total of 673059 patients with the principal diagnosis of AP were included. Of these, 5.1% had APFC on initial admission. After propensity score matching, each cohort consisted of 33914 patients. Those with APFC showed a higher incidence of inpatient complications, including septic shock (3.1% vs 1.3%, P < 0.001), portal venous thrombosis (4.4% vs 0.8%, P < 0.001), and mechanical ventilation (1.8% vs 0.9%, P < 0.001). The length of stay (LOS) was longer for APFC patients [4 (3-7) vs 3 (2-5) days, P < 0.001], as were hospital charges ($29451 vs $24418, P < 0.001). For 30-day readmissions, APFC patients had a higher rate (15.7% vs 6.5%, P < 0.001) and a longer median readmission LOS (4 vs 3 days, P < 0.001). The APFC group also had higher readmission charges ($28282 vs $22865, P < 0.001). The presence of APFC increased the risk of readmission twofold (aHR 2.52, 95% confidence interval: 2.40-2.65, P < 0.001). The independent risk factors for 30-day readmission included female gender, Elixhauser Comorbidity Index ≥ 3, chronic pulmonary diseases, chronic renal disease, protein-calorie malnutrition, substance use disorder, depression, portal and splenic venous thrombosis, and certain endoscopic procedures. CONCLUSION: Developing APFC during index hospitalization for AP is linked to higher readmission rates, more inpatient complications, longer LOS, and increased healthcare costs. Knowing predictors of readmission can help target high-risk patients, reducing healthcare burdens.

Predicting short-term thromboembolic risk following Roux-en-Y gastric bypass using supervised machine learning.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is a widely recognized bariatric procedure that is particularly beneficial for patients with class III obesity. It aids in significant weight loss and improves obesity-related medical conditions. Despite its effectiveness, postoperative care still has challenges. Clinical evidence shows that venous thromboembolism (VTE) is a leading cause of 30-d morbidity and mortality after RYGB. Therefore, a clear unmet need exists for a tailored risk assessment tool for VTE in RYGB candidates. AIM: To develop and internally validate a scoring system determining the individualized risk of 30-d VTE in patients undergoing RYGB. METHODS: Using the 2016-2021 Metabolic and Bariatric Surgery Accreditation Quality Improvement Program, data from 6526 patients (body mass index ≥ 40 kg/m2) who underwent RYGB were analyzed. A backward elimination multivariate analysis identified predictors of VTE characterized by pulmonary embolism and/or deep venous thrombosis within 30 d of RYGB. The resultant risk scores were derived from the coefficients of statistically significant variables. The performance of the model was evaluated using receiver operating curves through 5-fold cross-validation. RESULTS: Of the 26 initial variables, six predictors were identified. These included a history of chronic obstructive pulmonary disease with a regression coefficient (Coef) of 2.54 (P < 0.001), length of stay (Coef 0.08, P < 0.001), prior deep venous thrombosis (Coef 1.61, P < 0.001), hemoglobin A1c > 7% (Coef 1.19, P < 0.001), venous stasis history (Coef 1.43, P < 0.001), and preoperative anticoagulation use (Coef 1.24, P < 0.001). These variables were weighted according to their regression coefficients in an algorithm that was generated for the model predicting 30-d VTE risk post-RYGB. The risk model's area under the curve (AUC) was 0.79 [95% confidence interval (CI): 0.63-0.81], showing good discriminatory power, achieving a sensitivity of 0.60 and a specificity of 0.91. Without training, the same model performed satisfactorily in patients with laparoscopic sleeve gastrectomy with an AUC of 0.63 (95%CI: 0.62-0.64) and endoscopic sleeve gastroplasty with an AUC of 0.76 (95%CI: 0.75-0.78). CONCLUSION: This simple risk model uses only six variables to assist clinicians in the preoperative risk stratification of RYGB patients, offering insights into factors that heighten the risk of VTE events.

Predicting the risk of early intensive care unit admission for patients hospitalized with acute pancreatitis using supervised machine learning.

Background: Acute pancreatitis (AP) is a complex and life-threatening disease. Early recognition of factors predicting morbidity and mortality is crucial. We aimed to develop and validate a pragmatic model to predict the individualized risk of early intensive care unit (ICU) admission for patients with AP. Methods: The 2019 Nationwide Readmission Database was used to identify patients hospitalized with a primary diagnosis of AP without ICU admission. A matched comparison cohort of AP patients with ICU admission within 7 days of hospitalization was identified from the National Inpatient Sample after 1:N propensity score matching. The least absolute shrinkage and selection operator (LASSO) regression was used to select predictors and develop an ICU acute pancreatitis risk (IAPR) score validated by 10-fold cross-validation. Results: A total of 1513 patients hospitalized for AP were included. The median age was 50.0 years (interquartile range: 39.0-63.0). The three predictors that were selected included hypoxia (area under the curve [AUC] 0.78), acute kidney injury (AUC 0.72), and cardiac arrhythmia (AUC 0.61). These variables were used to develop a nomogram that displayed excellent discrimination (AUC 0.874) (bootstrap bias-corrected 95% confidence interval 0.824-0.876). There was no evidence of miscalibration (test statistic = 2.88; P = 0.09). For high-risk patients (total score >6 points), the sensitivity was 68.94% and the specificity was 92.66%. Conclusions: This supervised machine learning-based model can help recognize high-risk AP hospitalizations. Clinicians may use the IAPR score to identify patients with AP at high risk of ICU admission within the first week of hospitalization.

Efficacy and Safety of Different Dosing Regimens of Rivaroxaban in Patients With Atrial Fibrillation for Stroke Prevention: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) poses a substantial risk of stroke, necessitating effective anticoagulation therapy. This systematic review and meta-analysis (SRMA) evaluates the efficacy and safety of different dosing regimens of rivaroxaban in patients with AF. A comprehensive search of relevant databases, focusing on studies published from 2017 onward, was conducted. Inclusion criteria comprised randomized controlled trials (RCTs) and observational studies comparing standard and reduced dosing of rivaroxaban in AF. Data extraction and risk of bias (ROB) assessment were performed, and a meta-analysis was conducted for relevant outcomes. A total of 21 studies fulfilled the inclusion criteria. Standard dosing demonstrates a slightly lower risk of composite effectiveness outcomes and safety outcomes (HR: 0.79, 95% CI: 0.66-0.94, P=0.01) compared to reduced dosing (HR: 0.83, 95% CI: 0.71-0.97, P=0.02). Notable differences in major bleeding, gastrointestinal bleeding (GIB), and intracranial bleeding favored standard dosing. Hemorrhagic stroke and all-cause stroke rates differed significantly, with standard dosing showing a more favorable profile for ischemic stroke prevention. This study highlights the pivotal role of personalized anticoagulation therapy in AF. Standard dosing of rivaroxaban emerges as a preferred strategy for stroke prevention, balancing efficacy and safety. Clinical decision-making should consider individual patient characteristics and future research should delve into specific subpopulations and long-term outcomes to further refine treatment guidelines. The study bridges evidence from clinical trials to real-world practice, offering insights into the evolving landscape of AF management.

Association between alcohol-associated cirrhosis and inpatient complications among COVID-19 patients: A propensity-matched analysis from the United States.

BACKGROUND: Alcohol-associated cirrhosis (AC) contributes to significant liver-related mortality in the United States. It is known to cause immune dysfunction and coagulation abnormalities. Patients with comorbid conditions like AC are at risk of worse clinical outcomes from coronavirus disease 2019 (COVID-19). The specific association between AC and COVID-19 mortality remains inconclusive, given the lack of robust clinical evidence from prior studies. AIM: To study the predictors of mortality and the outcomes of AC in patients hospitalized with COVID-19 in the United States. METHODS: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) database 2020. Patients were identified with primary COVID-19 hospitalizations based on an underlying diagnosis of AC. A matched comparison cohort of COVID-19 patients without AC was identified after 1:N propensity score matching based on baseline sociodemographic characteristics and Elixhauser comorbidities. Primary outcomes included median length of stay, median inpatient charges, and in-hospital mortality. Secondary outcomes included a prevalence of systemic complications. RESULTS: A total of 1325 COVID-19 patients with AC were matched to 1135 patients without AC. There was no difference in median length of stay and hospital charges in COVID-19 patients with AC compared to non-AC (P > 0.05). There was an increased prevalence of septic shock (5.7% vs 4.1%), ventricular fibrillation/ventricular flutter (0.4% vs 0%), atrial fibrillation (13.2% vs 8.8%), atrial flutter (8.7% vs 4.4%), first-degree atrioventricular nodal block (0.8% vs 0%), upper extremity venous thromboembolism (1.5% vs 0%), and variceal bleeding (3.8% vs 0%) in the AC cohort compared to the non-AC cohort (P < 0.05). There was no difference in inpatient mortality in COVID-19 patients with non-AC compared to AC, with an odds ratio of 0.97 (95% confidence interval: 0.78-1.22, P = 0.85). Predictors of mortality included advanced age, cardiac arrhythmias, coagulopathy, protein-calorie malnutrition, fluid and electrolyte disorders, septic shock, and upper extremity venous thromboembolism. CONCLUSION: AC does not increase mortality in patients hospitalized with COVID-19. There is an increased association between inpatient complications among COVID-19 patients with AC compared to non-AC.

Operator-specific outcomes in endoscopic sleeve gastroplasty: a propensity-matched analysis of the US population using a multicenter database.

Background: Endoscopic sleeve gastroplasty (ESG) has emerged as an effective endoscopic bariatric procedure over the past decade. Data comparing short-term outcomes of ESG based on operator specialty is scarce. We aimed to assess the impact of operator specialization on patient outcomes using a large bariatric-specific database. Methods: We identified a retrospective cohort of patients who underwent ESG by gastroenterologists using the Metabolic and Bariatric Surgery Accreditation Quality Improvement Program database (2020-2021). A matched comparison cohort of patients who underwent ESG by surgeons was identified and underwent 1:1 propensity score matching based on age, race, gender, American Society of Anesthesiologists physical status classification, and preoperative body mass index. Results: After matching, 154 patients were included in the final analysis. Of these, 77 patients underwent ESG by surgeons and 77 by gastroenterologists. In the matched cohort, the median operation time was lower in ESG by surgeons compared to gastroenterologists (P < 0.001). The median percent body mass index decrease was higher in the gastroenterologist cohort compared to the surgeon cohort (4.9% vs 3.8%, P = 0.04). The median percent weight loss after ESG was 4.8% in the surgeon cohort and 5.9% in the gastroenterologist cohort (P = 0.09). There was no statistically significant difference in postoperative emergency department visits (P = 0.65), reoperations (P = 0.15), or reinterventions within 30 days (P = 0.87) between the cohorts. There was no difference in major adverse effects between the groups (0% each). Conclusions: Operator choice does not affect ESG-related adverse events or 30-day outcomes in patients undergoing ESG.

Association of nonalcoholic fatty liver disease with acute cholangitis: a nationwide propensity-matched analysis from the United States.

Background: Nonalcoholic fatty liver disease (NAFLD) has previously been linked to several disease states with an impact on patient outcomes. However, clinical evidence on the association between NAFLD and acute cholangitis (AC) remains scarce. We aimed to evaluate the potential association between NAFLD and AC. Methods: We conducted a retrospective cohort study using the US National Inpatient Sample database from 2016 to 2019 to analyze primary AC hospitalizations with NAFLD compared to non-NAFLD in a 1:1 propensity-matched population. Results: A total of 1550 AC patients with NAFLD were matched to 1550 AC patients without NAFLD. NAFLD had a higher association with AC when compared to patients without NAFLD, with an odds ratio of 2.33 (95% CI [1.81-3.0], P < 0.001). The length of stay was higher in NAFLD than in non-NAFLD (4 vs 3 days, P < 0.001). The median inpatient charges in NAFLD were also higher than in the non-NAFLD cohort ($36,182 vs $35,244, P < 0.001). Inpatient mortality was higher in NAFLD compared to non-NAFLD (1.6% vs 0%, P < 0.001). There was an increased prevalence of portal vein thrombosis (3.2% vs 0%), acute kidney injury (24.2% vs 17.7%), sepsis (3.2% vs 1.6%), mechanical ventilation (3.2% vs 0%), and percutaneous cholecystostomy tube insertion (3.2% vs 1.6%) in NAFLD compared to non-NAFLD (P < 0.05). NAFLD also had a higher association with acute cholecystitis, with an odds ratio of 3.70 (95% CI [3.19-4.29], P < 0.001). Conclusions: This study showed an association between NALFD and AC, resulting in increased length of stay, hospital charges, and inpatient mortality. Underlying NAFLD also increases acute complications of AC.

Trends in hospital admissions and mortality among inflammatory bowel disease patients with substance use disorder: a 10-year United States nationwide analysis.

Background: Patients with inflammatory bowel disease (IBD) and substance use disorder (SUD) may have worse clinical outcomes. However, data specific to the hospital admission and mortality rates among IBD patients with SUD are scarce. Our objective was to assess trends in admission, healthcare expenses, and mortality for IBD patients with SUD. Methods: We conducted a retrospective study using the National Inpatient Sample database to analyze SUD (alcohol, opioids, cocaine, and cannabis) among IBD hospitalizations from 2009 to 2019. Results: A total of 132,894 hospitalizations for IBD had a secondary diagnosis of SUD. Of these patients, 75,172 (57%) were men and 57,696 (43%) were women. The IBD-SUD cohort had a longer length of stay than the non-SUD cohort (P < 0.001). The mean inpatient charges for IBD hospitalizations with SUD increased from $48,699 ± $1374 in 2009 to $62,672 ± $1528 in 2019 (P < 0.001). We found a 159.5% increase in IBD hospitalizations with SUD. The hospitalization rate increased from 3492 per 100,000 IBD hospitalizations in 2009 to 9063 per 100,000 in 2019 (P < 0.001). In-hospital mortality for IBD hospitalizations with SUD increased by 129.6% (from 250 deaths per 100,000 IBD hospitalizations in 2009 to 574 deaths per 100,000 IBD hospitalizations in 2019) (P < 0.001). Conclusions: Over the last decade, there has been a rise in IBD hospitalizations with SUD. This has resulted in a longer length of stay, higher inpatient charges, and higher mortality rates. Identifying IBD patients potentially at risk for SUD by screening for anxiety, depression, pain, or other factors has become crucial.

Acute ischemic colitis associated with oral decongestant use: a systematic review.

Background and Aim: Acute ischemic colitis (IC) has been linked with the use of oral decongestants. However, clinical evidence on this association remains limited. We aim to evaluate the occurrence and clinical outcomes of acute IC following over-the-counter (OTC) use of pseudoephedrine and phenylephrine. Methods: We conducted a systematic review of the MEDLINE, Google Scholar, Scopus, and Embase databases between inception and July 20, 2022. Specific search terms were used. The inclusion criteria consisted of English-language articles describing acute IC secondary to pseudoephedrine or phenylephrine. Results: A total of 18 case reports (level of clinical evidence: IV) fulfilled our inclusion criteria. The mean age of patients was 51.6 ± 15.3 years, with 14 (77.8%) cases reported in women. The clinical presentation was mainly related to abdominal pain 16 (88.9%), hematochezia 15 (83.3%), and/or abdominal tenderness 10 (55.6%). The medical background showed that 5 (27.8%) patients were previously healthy. In the 13 (72.2%) patients with comorbidities, hypertension 6 (46.2%), a history of tobacco use 5 (38.5%), and psychiatric illnesses 4 (30.8%) were commonly reported. Leukocytosis was encountered in 13 (72.2%) patients. Diagnostic investigations included a combination of computed tomography scan and colonoscopy in 10 (55.6%), colonoscopy alone in 6 (33.3%), and flexible sigmoidoscopy in 1 (5.6%) patient. Colonoscopic biopsy was the mainstay of diagnosis in 15 (83.3%) patients. Treatment was based on supportive care in 18 (100%), concurrent antibiotic use in 2 (11.1%), and surgical intervention in 1 (5.6%) patient. Recurrent episodes of IC occurred in 4 (22.2%) patients. Conclusions: Acute IC secondary to oral decongestants remains a rare but important clinical phenomenon. Clinical suspicion and imaging findings are important for the early diagnosis. Relevance to Patients: In unexplained cases of IC, clinicians should specifically inquire about oral decongestants since they are OTC and patients commonly fail to reveal their usage. These drugs should be avoided for transient cold symptoms, especially in women.

Isolated Colonic Histoplasmosis in Patients Undergoing Immunomodulator Therapy: A Systematic Review.

Gastrointestinal histoplasmosis remains an inconspicuous clinicopathologic entity. It is predominantly considered a protean manifestation of disseminated disease. We hereby delineate a unique case of biopsy-proven isolated colonic histoplasmosis in a patient undergoing methotrexate therapy. Furthermore, we present the first systematic review of the MEDLINE, Google Scholar, Embase, and Scopus databases regarding isolated colonic histoplasmosis in adult patients receiving immunomodulator therapy (IMT). A total of 13 case reports (level of clinical evidence: IV) were identified. The mean age was 55.6 ± 11.1 years, with 9 (69.2%) cases reported in women. Patients with subclinical disease (5, 38.5%) were often incidentally diagnosed by screening colonoscopy. Symptomatic individuals predominantly presented with diarrhea (4, 30.8%), weight loss (3, 23.1%), and/or abdominal pain (3, 23.1%). IMT was mainly administered for liver transplant (4, 30.8%), renal transplant (4, 30.8%), and ulcerative colitis (2, 15.4%). Common colonoscopy features included colonic ulcerations (7, 53.8%), polyps or pseudopolyps (3, 23.1%), and/or mass-like lesions (3, 23.1%). Diagnosis was made by histology of colonic biopsy in 11 (84.6%) and resected specimens in 2 (15.4%) patients. Treatment consisted of a combination of amphotericin B with oral itraconazole in 6 (46.2%), oral itraconazole alone in 5 (38.5%), and amphotericin B alone in 2 (15.4%) patients. Complete clinical recovery was achieved in all patients. This article illustrates that isolated colonic involvement can be the only clinical presentation of histoplasmosis. It may masquerade as other bowel disorders, presenting diagnostic and therapeutic conundrums. Gastroenterologists should rule out colonic histoplasmosis in IMT recipients who develop unexplained colitis symptoms.

Organ Regeneration Through Stem Cells and Tissue Engineering.

Loss of organ and tissue due to injuries or diseases led to the development of regenerative therapies to decrease reliance on organ transplantations. It deals with employing the self-renewal ability of stem cells to differentiate into numerous lineages to assist in providing effective treatment for a range of various injuries and diseases. Regenerative engineering of organs or tissues represents an ever-expanding field that is aimed at developing biological replacements for dysfunctional organs or injured tissues. The critical issue, however, with the engineering of organs outside the human body is the insufficient availability of human cells, the absence of a suitable matrix with the same architecture and composition as the target tissue, and the maintenance of organ viability in the absence of the blood supply. The issue regarding the maintenance of the engineered organ viability can be solved using bioreactors consisting of mediums with defined chemical composition, i.e., nutrients, cofactors, and growth factors that can successively sustain the target cell's viability. Engineered extracellular matrices and stem cells to regenerate organs outside the human body are also being used. Clinically, various adult stem cell therapies are readily under practice. This review will focus on the regeneration of organs through various types of stem cells and tissue engineering techniques.

Colorectal carcinoma and chronic inflammatory demyelinating polyneuropathy: is there a possible paraneoplastic association?

A plethora of paraneoplastic syndromes have been reported as remote effects of colorectal carcinoma (CRC). However, there is a dearth of data pertaining to the association of this cancer with demyelinating neuropathies. Herein, we describe the case of a young woman diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). Treatment with intravenous immunoglobulins and prednisone did not improve her condition, and her neurological symptoms worsened. Subsequently, she was readmitted with exertional dyspnea, lightheadedness, malaise, and black stools. Colonoscopy revealed a necrotic mass in the ascending colon, which directly invaded the second part of the duodenum. Pathologic results confirmed the diagnosis of locally advanced CRC. Upon surgical resection of the cancer, her CIDP showed dramatic resolution without any additional therapy. Patients with CRC may develop CIDP as a type of paraneoplastic syndrome. Clinicians should remain cognizant of this potential association, as it is of paramount importance for the necessary holistic clinical management.

Acute pancreatitis secondary to tamoxifen-associated hypertriglyceridemia: A clinical update.

INTRODUCTION: Drug-induced pancreatitis has been increasingly recognized, but it is frequently encountered as an inconspicuous etiology. The underlying mechanisms of injury vary with different drugs. Tamoxifen is a frequently used anticancer drug that acts by selective modulation of the estrogen receptor in patients with breast cancer. Tamoxifen-induced hypertriglyceridemia is a relatively rare etiological factor for acute pancreatitis. However, acute pancreatitis secondary to this adverse effect remains an exceedingly important clinicopathologic entity. CASE REPORT: We hereby delineate a rare case of acute pancreatitis secondary to hypertriglyceridemia in a patient who was on tamoxifen treatment for the past 3 years. Her serum lipase and triglyceride levels were markedly elevated at 14,285 IU/L and 20,344 mg/dL, respectively. The diagnosis was considered based on the findings of a standard diagnostic workup and exclusion of alternative causes of acute pancreatitis. MANAGEMENT AND OUTCOME: The patient was instituted prompt treatment with intravenous insulin infusion and gemfibrozil. The clinical outcome was favorable with no complications. Tamoxifen was permanently discontinued and was replaced with letrozole. DISCUSSION: This article illustrates that acute pancreatitis should be considered in the differential diagnoses of abdominal pain and elevated pancreatic enzymes in patients undergoing tamoxifen treatment. It also underscores the importance of pre- and post-tamoxifen lipid screening, especially in patients with a history of dyslipidemia and diabetes mellitus. It will facilitate an expedient detection of hypertriglyceridemia, potentially saving patients from associated morbidity and mortality.

Association of Malnutrition With Weaning Practices Among Infants in Pakistan.

Background An appropriate diet is critical for the growth and development of infants, especially in the first two years of life. Despite considerable efforts made by government and local authorities to raise awareness, mothers still lack basic knowledge of weaning practices; as a result, infants face a growing number of health problems in their later years of life. This research aims to investigate the association between malnutrition and knowledge of different weaning practices among mothers and to study the factors influencing it. Methodology The current study was a cross-sectional study conducted at Mayo Hospital, Services Hospital, and Jinnah Hospital, Lahore, Pakistan between November 2019 and May 2020. A total of 200 infants of both genders aged between one and 12 months were included in the study. Knowledge and practices of complementary feeding by the mothers were assessed using a close-ended, pre-tested questionnaire. Results Mothers of 200 infants were interviewed and it was found that 79.5% of the infants were being breastfed while 24% never received breast milk. Among those who never received breast milk were given liquids (25%) and semi-solid foods (64.5%). Of the mothers, 8% started weaning at an early age (less than six months old) while the remaining started weaning at the age of six months or later and reported that their infants were either underweight or had reduced heights for that age. Based on the medical reports obtained from the hospital after getting parental consent, it was also found that the infants had distinct signs of deficiency of vitamins A and D, iron, and folate. Conclusions The majority of infants were breastfed, and, in most cases, weaning started at an age of less than six months. Most of the infants were fed semi-solid food as their first complementary food. Two-thirds of the infants were underweight for that age, and one-fifth had reduced heights. Based on deficiency statistics, mothers should be encouraged to start weaning at six months to have minimized malnourishment instances in infants.

Blastomycosis-Induced Acute Respiratory Distress Syndrome.

Blastomycosis is a systemic mycosis endemic to the Midwestern and South Central United States. Infection is caused by inhaling spores of Blastomyces dermatitidis (B. dermatitidis) that inhabit soil. Acute respiratory distress syndrome (ARDS) is a rare complication of pulmonary blastomycosis with a significantly high mortality rate. We present a case of blastomycosis associated with severe ARDS treated with traditional prone position ventilation (PPV) and neurally adjusted ventilator assist (NAVA) along with antifungal therapy, steroids, and supportive care in a rural setting with no access to extracorporeal membrane oxygenation (ECMO). This case demonstrates that traditional therapies such as prone position ventilation can help patients with blastomycosis-associated ARDS especially in rural settings where advanced therapies such as ECMO are lacking. The use of NAVA in blastomycosis-associated ARDS needs further research.

CRISPR/Cas9 Guided Mutagenesis of Grain Size 3 Confers Increased Rice (Oryza sativa L.) Grain Length by Regulating Cysteine Proteinase Inhibitor and Ubiquitin-Related Proteins.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas9)-mediated genome editing has become an important way for molecular breeding in crop plants. To promote rice breeding, we edited the Grain Size 3 (GS3) gene for obtaining valuable and stable long-grain rice mutants. Furthermore, isobaric tags for the relative and absolute quantitation (iTRAQ)-based proteomic method were applied to determine the proteome-wide changes in the GS3 mutants compared with wild type (WT). Two target sites were designed to construct the vector, and the Agrobacterium-mediated method was used for rice transformation. Specific mutations were successfully introduced, and the grain length (GL) and 1000-grain weight (GWT) of the mutants were increased by 31.39% and 27.15%, respectively, compared with WT. The iTRAQ-based proteomic analysis revealed that a total of 31 proteins were differentially expressed in the GS3 mutants, including 20 up-regulated and 11 down-regulated proteins. Results showed that differentially expressed proteins (DEPs) were mainly related to cysteine synthase, cysteine proteinase inhibitor, vacuolar protein sorting-associated, ubiquitin, and DNA ligase. Furthermore, functional analysis revealed that DEPs were mostly enriched in cellular process, metabolic process, binding, transmembrane, structural, and catalytic activities. Pathway enrichment analysis revealed that DEPs were mainly involved in lipid metabolism and oxylipin biosynthesis. The protein-to-protein interaction (PPI) network found that proteins related to DNA damage-binding, ubiquitin-40S ribosomal, and cysteine proteinase inhibitor showed a higher degree of interaction. The homozygous mutant lines featured by stable inheritance and long-grain phenotype were obtained using the CRISPR/Cas9 system. This study provides a convenient and effective way of improving grain yield, which could significantly accelerate the breeding process of long-grain japonica parents and promote the development of high-yielding rice.

Determinants of infant and young complementary feeding practices among children 6-23 months of age in urban Pakistan: a multicenter longitudinal study.

BACKGROUND: Suboptimal feeding practices have a negative impact on children's health and growth in the first 2 years of life and increase their risk of undernutrition, morbidity, and mortality. The aim of the study was to assess the factors that influence infant and young child feeding practices among urban mothers in a hospital setting at Karachi, Pakistan. METHODS: A longitudinal multi-center cohort study was conducted in four countries, MULTICENTER BODY COMPOSITION REFERENCE STUDY (MBCRS) to produce normal body composition reference data in healthy infants from 3 months to 24 months of age. Repeated anthropometric (weight, length and head circumference) and body composition measurements using "deuterium dilution method" along with 24-h dietary recall questionnaires were performed on 250 healthy term infants at 3, 6, 9, 12, 18, and 24 months of age. The 24-h dietary recall data from this study was used to assess the breastfeeding and complementary feeding practices in children aged 6-24 months. RESULTS: A total of 250 healthy infants were enrolled in the study. A majority of newborns (75.4%) were exclusively breastfed till 3 months of age; however, by 6 months of age, only 30.2% of infants were exclusively breastfed. Only 44.1% of children aged 6-24 months achieved minimum dietary diversity (MDD), 84.7% achieved minimum meal frequency (MMF), and 44.1% achieved a minimum acceptable diet (MAD). 71.4% achieved MDD and MAD and 100% achieved MMF at 24 months. The bivariate analysis found that breastfed children (OR 3.93, 95% CI 2.72-5.68), with employed mothers (OR 1.55, 95% CI 1.06-2.27) who had graduated from secondary school (OR 1.45, 95% CI 1.08-1.94) were more likely to meet minimum dietary diversity. The multivariable analysis showed that only the child's age was significantly associated with MDD (p value< 0.0001), with the likelihood of meeting MDD increasing as the children aged; 9 months (OR 18.96, 95% CI 6.63-54.19), 12 months (OR 40.25, 95% CI 14.14-114.58), 18 months (OR 90.02, 95% CI 30.84-262.77) and 24 months (OR 82.14, 95% CI 27.23-247.83). CONCLUSION: Our study revealed that Infant and young child feeding practices are significantly associated with maternal education, employment, and the child's age. Therefore, it is essential that investments be made towards protective breastfeeding and complementary feeding policies and legislations, emphasis on female education and ensuring the availability of affordable nutritious and diverse foods.

Precise Editing of the OsPYL9 Gene by RNA-Guided Cas9 Nuclease Confers Enhanced Drought Tolerance and Grain Yield in Rice (Oryza sativa L.) by Regulating Circadian Rhythm and Abiotic Stress Responsive Proteins.

Abscisic acid (ABA) is involved in regulating drought tolerance, and pyrabactin resistance-like (PYL) proteins are known as ABA receptors. To elucidate the role of one of the ABA receptors in rice, OsPYL9 was mutagenized through CRISPR/Cas9 in rice. Homozygous and heterozygous mutant plants lacking any off-targets and T-DNA were screened based on site-specific sequencing and used for morpho-physiological, molecular, and proteomic analysis. Mutant lines appear to accumulate higher ABA, antioxidant activities, chlorophyll content, leaf cuticular wax, and survival rate, whereas a lower malondialdehyde level, stomatal conductance, transpiration rate, and vascular bundles occur under stress conditions. Proteomic analysis found a total of 324 differentially expressed proteins (DEPs), out of which 184 and 140 were up and downregulated, respectively. The OsPYL9 mutants showed an increase in grain yield under both drought and well watered field conditions. Most of the DEPs related to circadian clock rhythm, drought response, and reactive oxygen species were upregulated in the mutant plants. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DEPs were only involved in circadian rhythm and Gene Ontology (GO) analysis showed that most of the DEPs were involved in response to abiotic stimulus, and abscisic acid-activated signaling pathways. Protein GIGANTEA, Adagio-like, and Pseudo-response regulator proteins showed higher interaction in protein-protein interaction (PPI) network. Thus, the overall results showed that CRISPR/Cas9-generated OsPYL9 mutants have potential to improve both drought tolerance and the yield of rice. Furthermore, global proteome analysis provides new potential biomarkers and understandings of the molecular mechanism of rice drought tolerance.

Development of Chromosome Segment Substitution Lines (CSSLs) Derived from Guangxi Wild Rice (Oryza rufipogon Griff.) under Rice (Oryza sativa L.) Background and the Identification of QTLs for Plant Architecture, Agronomic Traits and Cold Tolerance.

Common wild rice contains valuable resources of novel alleles for rice improvement. It is well known that genetic populations provide the basis for a wide range of genetic and genomic studies. In particular, chromosome segment substitution lines (CSSLs) ais a powerful tool for fine mapping of quantitative traits, new gene discovery and marker-assisted breeding. In this study, 132 CSSLs were developed from a cultivated rice (Oryza sativa) cultivar (93-11) and common wild rice (Oryza rufipogon Griff. DP30) by selfing-crossing, backcrossing and marker-assisted selection (MAS). Based on the high-throughput sequencing of the 93-11 and DP30, 285 pairs of Insertion-deletions (InDel) markers were selected with an average distance of 1.23 Mb. The length of this DP30-CSSLs library was 536.4 cM. The coverage rate of substitution lines cumulatively overlapping the whole genome of DP30 was about 91.55%. DP30-CSSLs were used to analyze the variation for 17 traits leading to the detection of 36 quantitative trait loci (QTLs) with significant phenotypic effects. A cold-tolerant line (RZ) was selected to construct a secondary mapping F2 population, which revealed that qCT2.1 is in the 1.7 Mb region of chromosome 2. These CSSLs may, therefore, provide powerful tools for genome wide large-scale gene discovery in wild rice. This research will also facilitate fine mapping and cloning of QTLs and genome-wide study of wild rice. Moreover, these CSSLs will provide a foundation for rice variety improvement.