Managing Sickle Cell Disease in Patients for Whom Blood Transfusion Is Not an Option.

Sickle Cell Disease (SCD) is a hereditary blood disorder affecting beta hemoglobin. This disorder causes sickle-shaped red blood cells with decreased oxygen-carrying capacity resulting in vaso-occlusive crises. These crises are often treated with analgesics, antibiotics, IV fluids, supplementary oxygen, and allogeneic blood transfusion. This treatment regimen becomes complicated when caring for SCD patients for whom blood transfusion is not an option. Blood transfusion may not be an option due to the patient's religious, personal, or medical concerns and in scenarios where blood is not available for transfusion. Some examples include the patient being a Jehovah's Witness, blood-borne pathogens concerns, or prior history of multiple alloantibodies and severe transfusion reactions. The number of patients in these categories is growing. The patients and their autonomy should be respected during treatment. This review focuses on the currently available modalities to best manage this subgroup of SCD patients without blood transfusion, including new professional guidelines and new therapies to reduce the severity of SCD as approved by the Food and Drug Administration since 2017.

A Systematic Review of the Long-Term Trajectory of Hemodynamics and Body Composition in Childhood Obesity.

Obesity has long been cited as a significant risk factor for high blood pressure, with long-term exposure linked with an increased incidence of carotid artery atherosclerosis. However, as obesity is becoming more common in young-aged children, it is important to recognize combinational factors like lifestyle, socioeconomic, and genetic factors as a cause. Increasing weight during childhood, on the other hand, is a clinically significant challenge for many physicians. It is critical to identify these risk factors since early prevention (primordial prevention) or treatment (primary prevention) to reverse the potential risks is much more likely to be effective. The objective of this review was to explore the relationship between lifestyle, anthropometric, and genetic factors and cardiometabolic risk factors. We are hopeful that our findings may aid in the primary prevention of hypertension in children and the prevention of any related cardiovascular complications that may arise later in life as a result of obesity. The synthesis of this systematic review includes a total of 15 studies using defined criteria, published up to October 2021. In addition, a total of 2,397 articles were found through an initial electronic database search and included a total of 38,182 participants. Studies explored included one or more of the following cardiovascular risk factors: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG). The findings of this study support the notion that childhood obesity may be a risk factor for a variety of adult cardiovascular disease risk factors. Several behavioral, genetic, and anthropometric factors are linked to the development of obesity during early ages, overall creating challenges in cardiovascular health during adulthood. As a result, addressing the risk factors for childhood hypertension would be advantageous for the primary prevention of its sequelae in adulthood.

Pericardiectomy for Constrictive Tuberculous Pericarditis: A Systematic Review and Meta-analysis on the Etiology, Patients' Characteristics, and the Outcomes.

Tuberculosis (TB) is the most common etiology of constrictive pericarditis in the developing world. In this study, we collected currently available data to evaluate the outcomes following pericardiectomy in patients with constrictive tuberculous pericarditis. We retrieved electrical databases, including PubMed and PubMed Central, from 1985 AD and onwards. We included articles that had more than 80% TB as the etiology and articles with mixed etiologies. Pooled analysis was done in Review Manager (RevMan) version 5.2 (The Nordic Cochrane Centre, Copenhagen). and Stata Statistical Software, Release 16 ( StataCorp LLC, College Station, TX). We compared the mortality in patients after pericardiectomy due to TB with other etiologies. In-hospital mortality versus one-year mortality was analyzed in studies with constrictive pericarditis of mixed etiologies. We also compared pre-operative New York Heart Association (NYHA) grade to post-operative NYHA grade one year after pericardiectomy. We calculated the pooled mean of postoperative hospital stay, postoperative intensive care unit (ICU) stay, and in-hospital mortality. A total of 12 articles and 859 patients were included in the final analysis. Pericardiectomy was performed mostly on middle-aged men with or without previous comorbidity. Total pericardiectomy was the preferred surgical procedure performed on a mean of 93% of patients. The pooled analysis shows a significant decrease in all-cause mortality in patients with TB as compared to other etiologies (pooled risk ratios (RR) 0.34 CI [0.12,1.01] I2 = 61%) and a lower but insignificant in-hospital mortality in comparison to one-year mortality in studies with mixed etiologies (RR 0.59 [0.11,3.11] I2= 61%). There was a significant improvement in the NYHA grade of the patients one year following pericardiectomy (RR 8.04, CI [5.20,12.45], I2= 0%). The mean postoperative hospital stay and the postoperative ICU stay were calculated and reported in terms of days. The mean postoperative hospital stays in studies with more than 80% of TB cases is 13.34 (10.21, 16.47) with a mean standard deviation of 4.46 (2.87, 6.05). The mean postoperative ICU stay is 1.93 (1.47, 2.39), with a mean standard deviation of 3.26 (2.51, 4.00), and the mean in-hospital mortality is 0.07 (0.02, 0.12). Similarly, the mean postoperative hospital stay in studies with mixed etiologies is 19.40 (11.93, 26.87) with a mean standard deviation of 8.26 (4.21, 12.52). The mean postoperative ICU stay is 3.52 (1.93, 5.10) with a mean standard deviation of 2.34 (1.36, 3.32). The mean in-hospital mortality is 0.06 (0.04, 0.08). There is significant heterogeneity along with a number of methodological concerns, and therefore, generalization of the data should be done with caution, and a randomized controlled trial in the future may be beneficial.

Vitamin D and Gastric Cancer: A Ray of Sunshine?

Gastric cancer (GC) is one of the most aggressive malignancies, currently ranking third among cancers leading to death worldwide. Despite the recent advancements in GC research, it is most often diagnosed during the terminal stages and with limited treatment modalities contributing to its poor prognosis and a lower survival rate. Much research has provided conflicting results between a vitamin D deficient status and the development of GC. Vitamin D is a well-known and essential hormone classically known to regulate calcium and phosphate absorption, enabling adequate mineralization of the skeletal system. However, the function of vitamin D is multidimensional. It possesses unique roles, including acting as antioxidants or immunomodulators while crossing the cell membrane, performing several intracellular functions, participating in gene regulation, and controlling the proliferation and invasion of cancer cells, including those of GC. In light of this, it is imperative to analyze the causes of GC, review the factors that can be used to enhance the effectiveness of treatments, and discover the tools to determine prognosis, reduce mortality, and prevent GC development. In this review, we have summarized recent investigations on multiple associations between vitamin D and GC, emphasizing genetic associations, vitamin D receptors, and the prevalence of hormone deficiency in those developing this aggressive malignancy.

A Deep Dive Into the Newest Avenues of Immunotherapy for Pediatric Osteosarcoma: A Systematic Review.

Osteosarcoma (OS) is the most common primary bone cancer affecting children and young adults, most often occurring at the metaphysis of long bones. At present, treatment with combinations of surgery and chemotherapy for the localized OS has only brought minuscule improvements in prognosis. In comparison, the advanced, metastatic, or recurrent forms of OS are often non-responsive to chemotherapy, adding to the dire need to develop new and efficient therapies. The question of interest investigated in this systematic review is whether immunotherapy can play a meaningful role in improving the clinical outcomes of children with OS. This article aims to summarize the preclinical and clinical research conducted thus far on potential therapeutic avenues for pediatric OS using immunotherapy, including methods like checkpoint inhibition, adoptive cellular therapy with T-cells, chimeric antigen receptor T (CAR-T), and natural killer (NK) cells. It also highlights the influence of the innate and adaptive immune system on the tumor microenvironment, allowing for OS progression and metastasis. This systematic review contains 27 articles and analyses of multiple clinical trials employing immunotherapeutic drugs to 785 osteosarcoma participants and over 243 pediatric patients. The articles were obtained through PubMed, PubMed Central, and ClinicalTrials.gov and individually assessed for quality using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist and the Cochrane risk-of-bias tool. The reviews reveal that immunotherapy's most significant impact on pediatric OS includes combining immune checkpoint blockers with traditional chemotherapy and surgery. However, due to the bimodal distribution of this aggressive malignancy, these studies cannot precisely estimate the overall effect and any potential life-threatening adverse events following therapy in children. Further research is required to fully assess the impact of these immunotherapies, including more extensive multinational clinical trials to focus on the pediatric population.

Pulmonary Rehabilitation in Management of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disorder that is linked with a significant loss in daily physical activity as well as psychological issues that contribute to the patient's impairment and poor health-related quality of life. Over the last two decades, however, the research and application of nonpharmacologic therapies such as lung rehabilitation have been expedited with increasing evidence of systemic events in COPD patient groups and their nugatory impact on their functioning pulmonary rehabilitation (PR). It is a key part of integrated treatment for COPD and other chronic breathing disorders and is helpful in supporting the recovery of patients following COPD hospitalization. In this paper, we summarize current evidence regarding the effectiveness of PR in the management of chronic COPD. A systematic review was carried out during June 2021, searching databases PubMed, Google Scholar, and EBSCO. The authors extracted qualitative data, and then the author's names, year, study type, methodology, and the result were reported. The search of the aforementioned databases returned a total of 127 studies that were included for title, abstract, and full-text screening, and nine studies were enrolled for final data extraction. PR alleviates tiredness and dyspnea, improves emotional function, and increases the ability to do daily activities. These benefits are relatively extensive and substantial clinically. Rehabilitation acts as an important component of COPD management and helps to improve the quality of life and training linked to health.

Exogenous glucagon-like peptide-2 improves outcomes of intestinal adaptation in a distal-intestinal resection neonatal piglet model of short bowel syndrome.

BACKGROUND: Endogenous glucagon-like peptide-2 (GLP-2) levels and intestinal adaptation are reduced in distal-intestinal resection animal models of short bowel syndrome (SBS) that lack remnant ileum. We hypothesized that exogenous GLP-2 would improve intestinal adaptation in a distal-intestinal resection neonatal piglet model of SBS. METHODS: In all, 35 piglets were randomized to 2 treatment and 3 surgical groups: control (sham), 75% mid-intestinal resection (JI), and 75% distal-intestinal resection (JC). Parenteral nutrition (PN) commenced on day 1 and was weaned as enteral nutrition (EN) advanced. IV GLP-2 (11 nmol/kg/d) or saline was initiated on day 2. Piglets were maintained for 14 d. Clinical, functional, morphological, and histological outcomes were obtained. RESULTS: JC-GLP-2 piglets had fewer days on PN (10.0 ± 0.6 vs. 13.8 ± 0.2), more days on EN (4.0 ± 0.6 vs. 0.2 ± 0.2), a higher percentage of EN at termination (92 ± 5 vs. 52 ± 10%), fewer days of diarrhea (8.0 ± 0.7 vs. 12.3 ± 0.4), increased intestinal length (19 ± 4 vs. -5 ± 3%), and deeper jejunal crypts (248 ± 21 vs. 172 ± 12 µm), compared with saline piglets. CONCLUSION: GLP-2 therapy improves clinical, morphological, and histological outcomes of intestinal adaptation in a distal-intestinal resection model of SBS. Since this anatomical subtype represents the majority of clinical cases of neonatal SBS, these results support a potential role for GLP-2 therapy in pediatric SBS.

Tragic knowledge: truth telling and the maintenance of hope in surgery.

Surgeons often are faced with the challenge of balancing truth telling and the maintenance of hope in the setting of a poor prognosis. This ethical dilemma is informed by conflicting appeals to principles of autonomy and nonmaleficence, where a patient's right to be told important medical information must be weighed against the potential harm that may result from the knowledge of an unfavourable diagnosis. Truth telling in surgery raises questions on the nature of truth itself, how much information ought to be shared, what information can be withheld, and how surgeons should share tragic knowledge with patients. This paper will address these questions and provide some insight on how surgeons may navigate the sharing of tragic knowledge.

The next step? Use of tissue fusion technology to perform the serial transverse enteroplasty--proof of principle.

BACKGROUND: Serial transverse enteroplasty (STEP) is an established procedure for intestinal lengthening and tapering. A gastrointestinal linear stapler is used to taper the bowel sequentially. We report preliminary experience with tissue fusion technology to perform STEP in a porcine model. METHODS: Four weaned male pigs (mean age, 4 ± 0 weeks; mean weight, 6.8 ± 0.1 kg) first underwent a 60-cm reversed intestinal segment followed by a STEP 4 to 6 weeks later. The LigaSure Impact (Covidien, Valleylab, Tyco Healthcare Group LP, Boulder, CO) was used to perform the procedure. Animals were fed on postoperative day 2 and terminated 1 week later. Morphometric data were collected, and intestinal tissue was obtained for histology. RESULTS: Mean bowel caliber of 5.1 ± 0.5 cm was tapered to 1.8 ± 0.3 cm post-STEP with a mean increase in the length of the dilated segment of 82% ± 20%. All animals tolerated enteral feeding, and all survived to termination on day 7. Histologic evaluation revealed the zone of tissue fusion to be 7.1 ± 1.5 mm. Masson trichrome, hematoxylin and eosin, and polarized picrosirius red stains demonstrated that the fusion zone was well healed with overlying granulation tissue. CONCLUSION: This is the first report of the successful application of radiofrequency energy to perform the STEP procedure in animals. Although further evaluation is required, tissue fusion devices may eventually provide an alternative to the linear stapler for the STEP procedure.

A comparison of circumumbilical and transverse abdominal incisions for neonatal abdominal surgery.

PURPOSE: Although neonatal bowel surgery traditionally involves a transverse abdominal incision, several authors have reported that the circumumbilical incision is effective and cosmetically appealing. We report the first study comparing the circumumbilical incision to the transverse abdominal incision for a variety of neonatal abdominal operations. METHODS: Retrospective cohort analysis comparing the circumumbilical incision to the transverse abdominal incision for neonates who underwent surgical repair of malrotation, duodenal atresia/web, or intestinal atresia/web was performed between 1999 and 2009. RESULTS: One hundred thirty-two patients underwent a laparotomy through a transverse abdominal incision (n = 106) or a circumumbilical incision (n = 26). Baseline characteristics between groups were similar. No differences were found when comparing operative time, postoperative days on a ventilator, narcotic infusion, time to full feeds, length of hospital stay, incidence of surgical site infection, and bowel obstruction. Although more incisional hernias occurred in the circumumbilical incision group (38%) than the transverse abdominal incision group (6%), all hernias in the circumumbilical group resolved without intervention, whereas 33% required surgical repair in the transverse abdominal group. CONCLUSIONS: Because of its cosmetic advantages and similar outcomes to the transverse abdominal incision, the circumumbilical incision should be considered as an alternative to the transverse abdominal approach in neonatal surgery.

Remission of steroid-resistant nephrotic syndrome due to focal and segmental glomerulosclerosis using rituximab.

BACKGROUND: Therapeutic options are limited in cases of focal and segmental glomerulosclerosis (FSGS) that fail to respond to steroids and calcineurin inhibitors. We describe a case in which steroid-resistant nephrotic syndrome (SRNS) secondary to FSGS did not respond to conventional treatment, but was successfully treated with rituximab. Unlike previous reports in which rituximab was used in conjunction with a calcineurin inhibitor, we present the first case where rituximab was used as the sole therapeutic agent. CASE REPORT: An 11-month-old boy presented with severe manifestations of primary nephrotic syndrome with a subsequent non-responsive steroid course. A renal biopsy confirmed FSGS, with normal staining for podocin and nephrin. Genetic studies for podocin were normal. The child developed ciclosporin-induced hemolytic uremic syndrome (HUS), and the response to plasma exchange, following ciclosporin withdrawal, was only temporary. A trial of a combination of mycophenolate and dexamethasone did not have any effect on proteinuria or fluid status. Four weekly rituximab infusions at 375 mg/m2/dose induced a complete remission without any adverse effects. CONCLUSIONS: This case suggests that rituximab may be used as the sole therapeutic agent in the treatment of SRNS secondary to FSGS, especially in cases where calcineurin inhibitors are contraindicated.