"Not even my husband knows that I have this [breast cancer]": survivors' experiences in accessing, navigating and coping with treatment.

PURPOSE: Nigeria has the highest burden of breast cancer (BC) in Africa. While the survival rates for BC are over 90% in many high-income countries; low-and middle-income countries like Nigeria have 40% BC survival rates. Prior studies show that the burden and poor BC survival rates are exacerbated by both health system and individual level factors, yet there is a paucity of literature on the experiences of BC survivors in Nigeria. Hence, this study explored the divergent and convergent experiences of BC survivors in accessing, navigating, and coping with treatment. METHODS: Participants (N = 24, aged 35 to 73 years) were recruited and engaged in focus group discussions (group 1, n = 11; group 2, n = 13 participants). Transcripts were transcribed verbatim and analyzed with inductive thematic analysis. RESULTS: Four themes were identified: "I am carrying this [breast cancer] alone," "Living my life," "'God' helped me," and "A very painful journey." Participants described how they concealed their BC diagnosis from family and significant others while accessing and navigating BC treatment. Also, they adopted spiritual beliefs as a coping mechanism while sticking to their treatment and acknowledging the burden of BC on their well-being. CONCLUSIONS: Our findings explored the emotional burden of BC diagnosis and treatment and the willingness of the BC survivors to find meaning in their diagnosis. Treatment for BC survivors should integrate supportive care and innovative BC access tools to reduce pain and mitigate the burdens of BC. IMPLICATIONS FOR CANCER SURVIVORS: The integration of innovative technologies for venous access and other treatment needs of BC is crucial and will improve survivorship. Non-disclosure of BC diagnosis is personal and complicated; hence, BC survivors need to be supported at various levels of care and treatment to make meaningful decisions. To improve survivorship, patient engagement is crucial in shared decision-making, collaboration, and active participation in care.

Advances in rectal cancer: Real-world evidence suggests limited gains in prognosis for elderly patients.

BACKGROUND: Rectal cancer treatment has improved considerably due to the introduction of total meso-rectal excision, radio-chemotherapy, and high-resolution imaging. The aim of this observational cohort study was to quantify the effectiveness of these advances using high-quality data from a representative cohort of patients. METHODS: 20 281 non-metastasized cases retrieved from the Munich Cancer Registry database were divided into three time periods corresponding to before (1988-1997), partial (1998-2007), and full implementation (2008-2019) of clinical advances. Early-onset (<50 yrs.), middle-aged, elderly patient subgroups (> 70 yrs.) were compared. The overall effectiveness of evidence-based guideline adherence was also examined. RESULTS: Median survival improved by 1.5 yrs. from the first to the last time period. Relative survival increased from 74.9% (5-yr 95%CI[73.3 - 76.6]) to 79.2% (95%CI[77.8 - 80.5]). The incidence of locoregional recurrences was reduced dramatically by more than half (5-yr 17.7% (95%CI[16.5 - 18.8]); 6.7% (95%CI[6.1 - 7.3])). Gains in 5-yr relative survival were limited to early-onset and middle-aged patients with no significant improvement seen in elderly patients (Female 68.6% [63.9 - 73.3] to 67.6% [64.0 - 71.2]; Male 71.7% [65.9 - 77.4] to 74.0% [70.8 - 77.2]). CONCLUSIONS: Real-world evidence suggests that recent treatment advances have lead to an increase in prognosis for rectal cancer patients. However, more effort should be made to improve the implementation of new developments in elderly patients. Especially considering, that these cases represent a growing majority of diagnosed patients.

A Community Health Worker-Based Intervention on Anthropometric Outcomes of Children Aged 3 to 21 Months in Urban Pakistan, 2019-2021.

Objectives. To evaluate the impact of a community health worker-based "in-home growth monitoring with counseling" (IHGMC) intervention on anthropometric outcomes in Pakistan, where 38% of children younger than 5 years are stunted. Methods. We used an individual, single-blind, step-wedge randomized controlled trial and a pure control group recruited at endline. We based the analysis on an intention-to-treat estimation using the coarsened exact matching (CEM) method for sample selection among treatments and the control. We conducted the baseline in July 2019 and completed endline in September-October 2021. We recruited 1639 households (treated: 1188; control: 451) with children aged 3 to 21 months who were residing in an urban informal settlement area. The CEM sample used for analysis numbered 1046 (treated: 636; control: 410). The intervention continued for 6 months. Results. Compared with the control group, the height-for-age z-score in the IHGMC group increased by 0.58 SD (95% confidence interval [CI] = 0.33, 0.83; P = .001) and the weight-for-age z-score by 0.43 SD (95% CI = 0.20, 0.67; P < .01), measured at endline. Conclusions. IHGMC substantially improved child anthropometric outcomes in disadvantaged localities, and this impact persisted during the COVID-19 pandemic. Trial Registration. AER-RCT registry (AEARCTR-0003248). (Am J Public Health. 2023;113(1):105-114. https://doi.org/10.2105/AJPH.2022.307111).

Global dynamics of SARS-CoV-2/malaria model with antibody immune response.

Coronavirus disease 2019 (COVID-19) is a new viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Malaria is a parasitic disease caused by Plasmodium parasites. In this paper, we explore a within-host model of SARS-CoV-2/malaria coinfection. This model consists of seven ordinary differential equations that study the interactions between uninfected red blood cells, infected red blood cells, free merozoites, uninfected epithelial cells, infected epithelial cells, free SARS-CoV-2 particles, and antibodies. We show that the model has bounded and nonnegative solutions. We compute all steady state points and derive their existence conditions. We use appropriate Lyapunov functions to confirm the global stability of all steady states. We enhance the reliability of the theoretical results by performing numerical simulations. The steady states reflect the monoinfection and coinfection with malaria and SARS-CoV-2. The shared immune response reduces the concentrations of malaria merozoites and SARS-CoV-2 particles in coinfected patients. This response reduces the severity of SARS-CoV-2 infection in this group of patients.

Burnout in diabetes and endocrinology specialist registrars across England, Scotland and Wales in the pre-COVID era.

BACKGROUND: Presence of either emotional exhaustion, depersonalization or lack of personal accomplishment define Burnout Syndrome which may lead to decreased workforce productivity, increased absenteeism, depression and medical errors as well as decreased patient satisfaction. OBJECTIVE: The aim of this study was to assess the frequency of burnout syndrome among Diabetes Specialist Registrars across England, Scotland and Wales and to identify any self-reported factors which may be contributory to burnout. METHODS: Over 430 Diabetes Specialist Registrars were invited to anonymously participate in an electronic survey which used Maslach Burnout Inventory and selfreporting questionnaire to identify burnout and contributory factors. RESULTS: In this pre-pandemic times study, Burnout was identified in 61 (57.5%; n = 106) respondents using Maslach burnout cut-off scores. 45.2% (48/106) participants had scored high in Emotional Exhaustion, while lack of personal accomplishment and depersonalization was seen in 24.5% (26/106) and 21.6% (23/106) of the respondents respectively. The commonest self-reported stressors by participants were "General Internal Medicine workload" 60.4% (64/106) followed by "Lack of specialty training" 36.8% (39/106) and "Lack of audit/research/Continuing Professional Development time" 10.8% (11/106) CONCLUSION: Burnout syndrome is frequent among the participating Diabetes Specialist Registrars and urgent steps may be required address this problem nationally to ensure that these physicians remain physically and mentally healthy, especially after the pandemic.

Serum OPG/TRAIL ratio predicts the presence of cardiovascular disease in people with type 2 diabetes mellitus.

AIMS: Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Epidemiological studies suggest serum Osteoprotegrin (OPG)/Tumour-necrosis-factor-related-apoptosis-inducing- ligand (TRAIL) ratio may be a useful marker of cardiovascular risk. This study aimed to compare serum levels of TRAIL, OPG and OPG/TRAIL ratio in people with T2DM, with and without a history of CVD, and controls; and to determine which of these indices, if any, predict cardiovascular risk. METHODS: In this single centre observational study of 133 participants, people with T2DM, with and without a history of a cardiovascular event in the last 5 years, were recruited along with a control cohort without T2DM or CVD. Demographic information and anthropometric measurements were recorded. Blood samples were taken and OPG and TRAIL were measured using ELISA. RESULTS: People with T2DM and CVD had higher OPG/TRAIL ratios compared to controls or those with a new diagnosis of T2DM. After adjustment for potential confounding factors, OPG/TRAIL ratio was significantly associated with the presence of CVD in people with T2DM and an OPG/TRAIL ratio cut-off > 38.6 predicted the presence of CVD in this cohort with a sensitivity of 80% and specificity of 82%. CONCLUSION: This study suggests that OPG/TRAIL ratio may have a role as a biomarker of CVD in people with T2DM.

Global analysis of within-host SARS-CoV-2/HIV coinfection model with latency.

The coronavirus disease 2019 (COVID-19) is a respiratory disease caused by a virus called the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, we analyze a within-host SARS-CoV-2/HIV coinfection model. The model is made up of eight ordinary differential equations. These equations describe the interactions between healthy epithelial cells, latently infected epithelial cells, productively infected epithelial cells, SARS-CoV-2 particles, healthy CD 4 + T cells, latently infected CD 4 + T cells, productively infected CD 4 + T cells, and HIV particles. We confirm that the solutions of the developed model are bounded and nonnegative. We calculate the different steady states of the model and derive their existence conditions. We choose appropriate Lyapunov functions to show the global stability of all steady states. We execute some numerical simulations to assist the theoretical contributions. Based on our results, weak CD 4 + T cell immunity in SARS-CoV-2/HIV coinfected patients causes an increase in the concentrations of productively infected epithelial cells and SARS-CoV-2 particles. This may lead to severe SARS-CoV-2 infection in HIV patients. This result agrees with many studies that discussed the high risk of severe infection and death in HIV patients when they get SARS-CoV-2 infection. On the other hand, increasing the death rate of infected epithelial cells during the latency period can reduce the severity of SARS-CoV-2 infection in HIV patients. More studies are needed to understand the dynamics of SARS-CoV-2/HIV coinfection and find better ways to treat this vulnerable group of patients.

A review of the antimicrobial activity of thermodynamically stable microemulsions.

Microemulsions are thermodynamically stable, transparent, isotropic mixtures of oil, water and surfactant (and sometimes a co-surfactant), which have shown potential for widespread application in disinfection and self-preservation. This is thought to be due to an innate antimicrobial effect. It is suggested that the antimicrobial nature of microemulsions is the result of a combination of their inherent kinetic energy and their containing surfactants, which are known to aid the disruption of bacterial membranes. This review examines the contemporary evidence in support of this theory.

Global dynamics of SARS-CoV-2/cancer model with immune responses.

The world is going through a critical period due to a new respiratory disease called coronavirus disease 2019 (COVID-19). This disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mathematical modeling is one of the most important tools that can speed up finding a drug or vaccine for COVID-19. COVID-19 can lead to death especially for patients having chronic diseases such as cancer, AIDS, etc. We construct a new within-host SARS-CoV-2/cancer model. The model describes the interactions between six compartments: nutrient, healthy epithelial cells, cancer cells, SARS-CoV-2 virus particles, cancer-specific CTLs, and SARS-CoV-2-specific antibodies. We verify the nonnegativity and boundedness of its solutions. We outline all possible equilibrium points of the proposed model. We prove the global stability of equilibria by constructing proper Lyapunov functions. We do some numerical simulations to visualize the obtained results. According to our model, lymphopenia in COVID-19 cancer patients may worsen the outcomes of the infection and lead to death. Understanding dysfunctions in immune responses during COVID-19 infection in cancer patients could have implications for the development of treatments for this high-risk group.

46, XX Male Disorder of Sexual Development.

Presentation A 47-year-old male was referred to endocrinology with a 9-year history of primary hypogonadism. Baseline testosterone was 4.3 nmol/L (RR 8-30) with an elevated follicle stimulating hormone (17.5 IU/L) and luteinizing hormone (15.2 mIU/ml). He had a short stature with bilateral small pre-pubertal testicles. Diagnosis Karyotyping showed 46 XX, making a diagnosis of 46, XX male disorder of sexual development. Fluorescence in situ hybridization analysis identified the presence of a translocated sex-determining region Y gene. Treatment Testosterone replacement therapy (testogel). Monitoring blood markers affected by testosterone therapy and metabolic risk factors. Conclusion Primary hypogonadism in males can be divided into congenital and acquired causes. 46, XX male disorder of sexual development is a rare congenital cause, with an incidence of approximately 1 in 20,000 newborn males. This case report highlights the value of karyotyping in the workup for primary hypogonadism.

Biopsy on progression in patients with EGFR mutation-positive advanced non-small-cell lung cancer-a Canadian experience.

Background: Epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are standard therapy for patients with advanced or metastatic non-small-cell lung cancer harbouring an EGFR mutation. Upon progression, 50%-60% develop a secondary T790M mutation. Recent trials demonstrated outcome improvement with osimertinib compared with standard platinum-based chemotherapy as second-line therapy for patients with secondary T790M mutation. To identify T790M, a biopsy of the tumour or, more recently, plasma is necessary. This retrospective study aimed to evaluate biopsy procedures and mutational analysis at 2 Canadian cancer centres. Methods: In a retrospective review of patients who were approached to enrol in the aura2, aura3, or astris studies, demographics, eligibility for rebiopsy upon progression after an egfr tki, rebiopsy methods and complications, number of rebiopsies, and incidence of the T790M mutation were collected. Results: Of 84 patients considered for trial enrolment, 80 signed a consent. In 78 patients who underwent rebiopsy, computed tomography or ultrasonography guidance were the most common methods used. The most common biopsy sites were lung and lymph nodes. The median number of rebiopsies performed to find a T790M mutation was 2. Only 9% of patients experienced complications. Of samples obtained, 74% were adequate for testing after initial rebiopsy. A T790M mutation was found in 47 patients, of whom 44 were enrolled on a trial. After multiple rebiopsies, only 5% of samples were inadequate for molecular analysis. Conclusions: In the Canadian setting, the acceptance of rebiopsy on progression was high. Multiple rebiopsies were clinically feasible and could increase the yield for T790M mutation. The incidence of complications was low despite the most common site for rebiopsy being lung.

Disease phenotype rather than treatment strategy impacts the long-term quality of life in patients with diverticular disease.

PURPOSE: To identify the impact of the severity of diverticular disease on long-term quality of life. METHODS: Consecutive patients, hospitalized between October 2009 and November 2015 due to uncomplicated (UD) and complicated diverticulitis (CD) of the left colon, were analyzed. Patients undergoing emergent surgery for perforated disease were excluded. Primary endpoint was health-related quality of life (HrQol), measured by the Short Form 36 questionnaire (SF-36). Physical (PCS) and mental (MCS) compository scores were calculated from SF-36 subscales. To overcome bias, one-to-one propensity score matching and multivariable logistic regression analysis were performed. RESULTS: Two hundred eighty of the overall 392 patients (Male 138, Female 142; mean age 60.5 years, range 27-91) answered the SF-36 questionnaire. The median follow-up period was 37.8 months (range 15-85). After propensity score matching, each group consisted of 51 patients. Results of the SF-36 questionnaires showed a statistically significant difference, favoring patients with CD in 5 of 8 domains. Also, PCS (56.3 vs. 52.9, p = 0.13) and MCS (53.3 vs. 46.7, p = 0.005) were higher in patients treated for CD. By a multivariate analysis, complicated disease was independently associated with a better scoring on 6 out of 8 SF-36 subscales and on MCS. Treatment strategy (surgery or conservative) did not have any impact on SF-36 subscales, MCS, or PCS on multivariate analysis. CONCLUSION: In contrast to complicated disease, the uncomplicated diverticular disease is associated with an impaired long-term quality of life especially in domains composing mental health scores independently of chosen treatment strategy. STUDY REGISTRATION: The study is registered with the Research Registry at June 19, 2019. Research registry UIN: researchregistry4959 .

[Preoperative imaging for colorectal cancer: surgeons' perspective]. / Bildgebung vor kolorektaler Chirurgie aus Sicht des Chirurgen.

Preoperative radiological diagnostics in patients with colorectal cancer has several objectives. The diagnostic localization of the colonic tumor is essential for planning the resection. The radiologically suspected infiltration of neighboring structures may lead to the decision for neoadjuvant treatment. In patients with rectal carcinomas, the T and N stages, the distance to the circumference resection margin (CRM), and the penetration of the tumor into the mesentery must be determined. This crucial to determine whether the patient should undergo neoadjuvant treatment. Prior to the planned relocation of an upstream stoma, radiological diagnostics may be added to clinical and endoscopic assessment but should not be routinely used.

Perforated Diverticulitis with Generalized Peritonitis: Low Stoma Rate Using a "Damage Control Strategy".

PURPOSE: Optimal surgical management of perforated diverticulitis of the sigmoid colon has yet to be clearly defined. The purpose of this study was to evaluate efficacy of a "Damage Control Strategy" (DCS). MATERIALS AND METHODS: Patients with perforated diverticulitis of the sigmoid colon complicated by generalized peritonitis (Hinchey III and IV) surgically treated according to a damage control strategy between May 2011 and February 2017 were enrolled in the present multicenter retrospective cohort study. Data were collected at three surgical centers. DCS comprises a two-stage concept: [1] limited resection of the perforated colon segment with oral and aboral blind closure during the emergency procedure and [2] definitive reconstruction at scheduled second laparotomy (anastomosis ∓ loop ileostomy or a Hartmann's procedure) after 24-48 h. RESULTS: Fifty-eight patients were included into the analysis [W:M 28:30, median age 70.1 years (30-92)]. Eleven patients (19%) initially presented with fecal peritonitis (Hinchey IV) and 47 patients with purulent peritonitis (Hinchey III). An anastomosis could be created during the second procedure in 48 patients (83%), 14 of those received an additional loop ileostomy. In the remaining ten patients (n = 17%), an end colostomy was created at second laparotomy. A fecal diversion was performed in five patients to treat anastomotic complications. Thus, altogether, 29 patients (50%) had stoma at the end of the hospital stay. The postoperative mortality was 9% (n = 5), and median postoperative hospital stay was 18.5 days (3-66). At the end of the follow-up, 44 of 53 surviving patients were stoma free (83%). CONCLUSION: The use of the Damage Control strategy leads to a comparatively low stoma rate in patients suffering from perforated diverticulitis with generalized peritonitis.

Damage control surgery in perforated diverticulitis: ongoing peritonitis at second surgery predicts a worse outcome.

PURPOSE: Damage control strategy (DCS) is a two-staged procedure for the treatment of perforated diverticular disease complicated by generalized peritonitis. The aim of this retrospective multicenter cohort study was to evaluate the prognostic impact of an ongoing peritonitis at the time of second surgery. METHODS: Consecutive patients who underwent DCS for perforated diverticular disease of the sigmoid colon with generalized peritonitis at four surgical centers were included. Damage control strategy is a two-stage emergency procedure: limited resection of the diseased colonic segment, closure of oral and aboral colon, and application of a negative pressure assisted abdominal closure system at the initial surgery followed by second laparotomy 48 h later. Therein, decision for definite reconstruction (anastomosis or Hartmann's procedure (HP)) is made. An ongoing peritonitis at second surgery was defined as presence of visible fibrinous, purulent, or fecal peritoneal fluid. Microbiologic findings from peritoneal smear at first surgery were collected and analyzed. RESULTS: Between 5/2011 and 7/2017, 74 patients underwent a DCS for perforated diverticular disease complicated by generalized peritonitis (female: 40, male: 34). At second surgery, 55% presented with ongoing peritonitis (OP). Patients with OP had higher rate of organ failure (32 vs. 9%, p = 0.024), higher Mannheim Peritonitis Index (25.2 vs. 18.9; p = 0.001), and increased operation time (105 vs. 84 min., p = 0.008) at first surgery. An anastomosis was constructed in all patients with no OP (nOP) at second surgery as opposed to 71% in the OP group (p < 0.001). Complication rate (44 vs. 24%, p = 0.092), mortality (12 vs. 0%, p = 0.061), overall number of surgeries (3.4 vs. 2.4, p = 0.017), enterostomy rate (76 vs. 36%, p = 0.001), and length of hospital stay (25 vs. 18.8 days, p = 0.03) were all increased in OP group. OP at second surgery occurred significantly more often in patients with Enterococcus infection (81 vs. 44%, p = 0.005) and with fungal infection (100 vs. 49%, p = 0.007). In a multivariate analysis, Enterococcus infection was associated with increased morbidity (67 vs. 21%, p < 0.001), enterostomy rate (81 vs. 48%, p = 0.017), and anastomotic leakage (29 vs. 6%, p = 0.042), whereas fungal peritonitis was associated with an increased mortality (43 vs. 4%, p = 0.014). CONCLUSION: Ongoing peritonitis after DCS is a predictor of a worse outcome in patients with perforated diverticulitis. Enterococcal and fungal infections have a negative impact on occurrence of OP and overall outcome.

Effect of salinity on gene expression, morphological and biochemical characteristics of stevia rebaudiana Bertoni under in vitro conditions.

Stevia rebaudiana Bertoni is a famous medicinal plant for its low calorific value compounds which are named steviol glycosides (SGs) and they are 150-300 times sweeter than sugar. Among various SGs, stevioside and rebaudioside A considered to be the main sweetening compounds.  Soil salinity is one of the most essential stress in the world. Salinity affects the survival and yield of crops. In current study the effects of salinity and osmotic stress caused by different concentration of NaCl (0, 20, 40, 60 and 80 mM) on morphological traits, genes expressionand amount of both stevioside and rebaudioside Aunder in vitro conditions has been investigated. The morphological traits such as bud numbers, root numbers, shoot length (after 15 and 30 days) were evaluated. With increasing salinity, the values of all studied morphological traits decreased. To investigation of UGT74G1 and UGT76G1 genes expression that are involved in the synthesis of SGs, RT-PCR was done and there were significant differences between all media. The highest expression of both genes was observed in plantlets grown on MS media (with NaCl-free). Also, the lowest amounts of gene expression of the both genes were seen in MS+ 60 mM NaCl. Based on HPLC results, the highest amount of both stevioside and rebaudioside A were observed in plantlets grown in MS media (with NaCl-free). Finally, it can be concluded that stevia can survive under salt stress, but it has the best performance in the lower salinity.