Early Treatment Outcome of Humeral Shaft Fracture Non-Union in Adults: Comparative Study of Plating versus Interlocking Nailing

Background: Fractures of humeral shaft in adults are common injuries. Humeral shafts non-union either from late presentation after initial treatment by traditional bone setters or failed non-operative orthodox care is a major problem in this part of the world. This non-union is a major treatment challenge with increased cost of care and morbidity in this part of the world. Humeral shaft non-union can be treated with locked intra-medullary nailing (LIMN) or dynamic compression plating (DCP). Study on comparison of these methods of fixation in this part of the world is scarce in literature search, hence the reason for this study. Objective: The objectives of this study are: (1) to compare early clinical outcome following fixation of humeral shaft fracture nonunion with DCP versus LIMN;(2) to compare the time of radiologic fracture union of DCP with LIMN;(3) to compare complications following fixation of humeral shaft fracture nonunion with DCP versus LIMN. Patients and Methods: This was a randomized control study done for 2 years in which fifty adult patients with humeral shaft non-union were recruited. The patients were grouped into 2 (P = DCP & N = LIMN). Forty five of the patients completed the follow up periods of the study and then analyzed. The P group had ORIF with DCP while the N group had ORIF with LIMN. Both groups had grafting with cancellous bones. Each patient was followed up for a period of 6 months at the time which radiographic union is expected. Any patient without clinical and/or radiographic evidence of union after six months of surgery was diagnosed as having recurrent non-union. The data generated was analyzed using SPSS Version 23. The results were presented in charts and tables. The paired t-test was used while considering p value Result: Forty five patients completed follow up. There was a male preponderance (4:1), right humerus predominated (3:2). Motor vehicular accidents were the commonest cause of the fractures (62%). Most non-union fractures occurred at the level of the middle 3rd of the humeral shaft (60%). Failed TBS treatment was the commonest indication for the osteosynthesis (71%). More patients had plating (53%) compared to 47% who had LIMN. Most patients (93.4%) had union between 3 to 6 months irrespective of fixation type with no significant statistical difference between the union rate of DCP and LIMN (p value 0.06) with similar functional outcome and complication rates irrespective of the type of fixation. Conclusion: This study showed that the success rates in term of fracture union, outcome functional grades and complication rates were not directly dependent on the types of the fixation: plating or locked intra-medullary nailing.

Hidden army within:Harnessing the microbiome to improve cancer treatment outcomes

The gut microbiome has emerged as a critical player in cancer pathogenesis and treatment response.Dysbiosis,an imbalance in the gut microbial community,impacts tumor initiation,progression,and therapy outcomes.Specific bacterial species have been associated with either promoting or inhibiting tumor growth,offering potential targets for therapeutic intervention.The gut microbiome in-fluences the efficacy and toxicity of conventional treatments and cutting-edge immunotherapies,highlighting its potential as a therapeutic target in cancer care.However,translating microbiome research into clinical practice requires addres-sing challenges such as standardizing methodologies,validating microbial bio-markers,and ensuring ethical considerations.Here,we provide a comprehensive overview of the gut microbiome's role in cancer highlighting the need for on-going research,collaboration,and innovation to harness its full potential for im-proving patient outcomes in oncology.The current editorial aims to explore these insights and emphasizes the need for standardized methodologies,validation of microbial biomarkers,and interdisciplinary collaboration to translate microbiome research into clinical applications.Furthermore,it underscores ethical consider-ations and regulatory challenges surrounding the use of microbiome-based the-rapies.Together,this article advocates for ongoing research,collaboration,and innovation to realize the full potential of microbiome-guided oncology in impro-ving patient care and outcomes.

Clinical Presentation and Treatment Outcomes of Pregnancy-Related Acute Kidney Injury among Pregnant Women Admitted at the Benjamin Mkapa Hospital in Tanzania

Background: Globally, PRAKI is among the leading causes of death in pregnant women. The prevalence, causes and outcome of this condition vary among countries due to differences in environmental, socioeconomic, and health delivery systems. The common causes that have been reported in several studies are PIH, Haemorrhages and Sepsis while the outcomes may be either complete renal recovery, progression to CKD and hence dialysis dependency or death. This study aimed at determining clinical presentation and treatment outcomes of Pregnancy-Related Acute Kidney Injury in Pregnant women admitted at the Benjamin Mkapa Hospital, Dodoma, Tanzania. Results: Out of 4007 pregnant women who were admitted to the maternity ward 51 pregnant women were found to have PRAKI. Of those with PRAKI, 74.5% were between 21 to 25 years. The leading causes of PRAKI were PPH 12 (23.53%), Eclampsia 12 (23.53%), and pre-eclampsia 12 (23.5%). Hemodialysis therapy was provided to 22 (43.1%) patients, 15 (29.4%) individuals recovered spontaneously with medical management and 14 (27.5%) missed haemodialysis therapy due to various reasons. The mortality due to PRAKI was 17 (33.3%). Conclusion and Recommendation: Pre-eclampsia/eclampsia and post-partum haemorrhage were found to be the main causes of PRAKI. The mortality related to PRAKI is high and Hemodialysis therapy is vital help to prevent deaths for pregnant women with PRAKI. Pregnant women who develop acute kidney injury should be followed closely and a nephrologist should be consulted early. Early referral should be done by the lower level facilities for all at-risk pregnant women to a specialized multidisciplinary health facility.

Pregnancy and Obstetrical Outcomes Following Treatment for Cervical Intra-Epithelial Neoplasia (CIN) in Two Hospitals of a Low-Resource Country

Objective: In Cameroon, more than 80% of women suffering from cervical intraepithelial neoplasia (CIN) are within the reproductive age. This study intended to analyze the pregnancy outcomes following cervical treatment in Cameroon. Methods: This was a cohort study with two years retrospective data collection involving 82 women who underwent cervical treatment for CIN in two Cameroonian hospitals from January 2015 to December 2017. Data were collected from CIN treatment to end of pregnancy where applicable. Data analysis was done using Epi Info software version 3.5.4. Results: We collected data from 82 patients aged 27 to 48 years, with a mean age of 36.5 (SD: 5.3) years. During the study period, 33 out of 82 participants became pregnant 40.2 [29.56 - 51.66]%. The factor associated with pregnancy occurrence after treatment was age less than 35 years (Odds ratio = 4.37 [1.7 - 11.2]. From the 33 pregnancies recorded, 17 (51.5%) ended in a delivery, amongst which 15 (88.2%) were vaginal. Conclusion: Pregnancy frequency over two years following cervical treatment for CIN was relatively good, and younger women (age 35 years) were significantly more like to have conceived compared to their older counterparts. Post-treatment delivery outcomes seem to be similar to those in the general population.

Presurgical structural imaging and clinical outcome in combined bed nucleus of the stria terminalis-nucleus accumbens deep brain stimulation for treatment-resistant depression

Background Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation(DBS).The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of DBS in treatment-resistant depression(TRD).Aims The primary aim is to identify preoperative imaging biomarkers that correlate with the efficacy of DBS in patients with TRD.Methods Preoperative imaging parameters were estimated and correlated with the 6-month clinical outcome of patients with TRD receiving combined bed nucleus of the stria terminalis(BNST)-nucleus accumbens(NAc)DBS.White matter(WM)properties were extracted and compared between the response/non-response and remission/non-remission groups.Structural connectome was constructed and analysed using graph theory.Distances of the volume of activated tissue(VAT)to the main modulating tracts were also estimated to evaluate the correlations.Results Differences in fibre bundle properties of tracts,including superior thalamic radiation and reticulospinal tract,were observed between the remission and nonremission groups.Distance of the centre of the VAT to tracts connecting the ventral tegmental area and the anterior limb of internal capsule on the left side varied between the remission and non-remission groups(p=0.010,t=3.07).The normalised clustering coefficient(γ)and the small-world property(σ)in graph analysis correlated with the symptom improvement after the correction of age.Conclusions Presurgical structural alterations in WM tracts connecting the frontal area with subcortical regions,as well as the distance of the VAT to the modulating tracts,may influence the clinical outcome of BNST-NAc DBS.These findings provide potential imaging biomarkers for the DBS treatment for patients with TRD.

Effects of L-carnitine on treatment outcomes of COVID-19 patients hospitalized in intensive care units:A double-blind randomized clinical trial

Objective:To assess the effects of L-carnitine on the outcomes of patients with moderate to severe coronavirus disease 2019(COVID-19)in intensive care unit(ICU).Methods:This double-blind clinical trial was carried out in 2022-2023.64 Patients with COVID-19 were selected from Amiralmomenin and Khansari hospitals in Arak,Iran.They were randomly assigned to the control and the L-carnitine treatment group via block randomization.Venous blood gases,disease severity,and levels of D-dimer,lactate dehydrogenase,ferritin,and C-reactive protein were daily assessed during the seven days of the intervention,and the length of ICU stay,the need for endotracheal intubation,and mortality rate were documented.Results:There were significant differences in length of ICU stay,the need for endotracheal intubation,and levels of D-dimer,lactate dehydrogenase,ferritin,APACHE栻score,and C-reactive protein between the two groups(P<0.05).However,the groups did not significantly differ in mortality rate and venous blood gas indexes(P>0.05).Conclusions:L-carnitine can improve outcomes of patients with COVID-19.Therefore,it can be used as an adjuvant therapy for these patients.

Treatment patterns and survival outcomes in patients with nonmetastatic early-onset pancreatic cancer

BACKGROUND The incidence of patients with early-onset pancreatic cancer(EOPC;age≤50 years at diagnosis)is on the rise,placing a heavy burden on individuals,families,and society.The role of combination therapy including surgery,radiotherapy,and chemotherapy in non-metastatic EOPC is not well-defined.AIM To investigate the treatment patterns and survival outcomes in patients with non-metastatic EOPC.METHODS A total of 277 patients with non-metastatic EOPC who were treated at our institution between 2017 and 2021 were investigated retrospectively.Overall survival(OS),disease-free survival,and progression-free survival were estimated using the Kaplan-Meier method.Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors.RESULTS With a median follow-up time of 34.6 months,the 1-year,2-year,and 3-year OS rates for the entire cohort were 84.3%,51.5%,and 27.6%,respectively.The median OS of patients with localized disease who received surgery alone and adjuvant therapy(AT)were 21.2 months and 28.8 months,respectively(P=0.007).The median OS of patients with locally advanced disease who received radiotherapy-based combination therapy(RCT),surgery after neoadjuvant therapy(NAT),and chemotherapy were 28.5 months,25.6 months,and 14.0 months,respectively(P=0.002).The median OS after regional recurrence were 16.0 months,13.4 months,and 8.9 months in the RCT,chemotherapy,and supportive therapy groups,respectively(P=0.035).Multivariate analysis demonstrated that carbohydrate antigen 19-9 level,pathological grade,T-stage,N-stage,and resection were independent prognostic factors for non-metastatic EOPC.CONCLUSION AT improves postoperative survival in localized patients.Surgery after NAT and RCT are the preferred therapeutic options for patients with locally advanced EOPC.

Impact of uterine artery embolization on ovarian function and pregnancy outcome after uterine-fibroids treatment:A prospective study

Uterine fibroids are benign tumors that originate from smooth muscle cells of the uterus.It is the most common gynecological disorder,affecting up to 80%of women of reproductive age.Uterine fibroids can cause various symptoms such as abnormal uterine bleeding,pelvic pain,infertility,and pregnancy complications.The treatment options for uterine fibroids include medical therapy,surgical intervention,and minimally invasive techniques.AIM To compare ovarian function of women with uterine fibroids who did or did not undergo uterine artery embolization(UAE).METHODS This prospective cohort study enrolled 87 women with symptomatic uterine fibroids who underwent UAE,and 87 women with the same symptoms who did not undergo UAE but received conservative management or other treatments.The two groups were matched for age,body mass index,parity,and baseline characteristics of uterine fibroids.The primary outcome was ovarian function that was evaluated by serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),and anti-Müllerian hormone(AMH),as well as ovarian reserve tests,such as antral follicle count(AFC)and ovarian volume(OV).The secondary outcome was fertility that was evaluated based on the menstrual cycle,ovulation,conception,pregnancy,and delivery.The participants were followed-up for 36 months and assessed at 1,3,6,12,24,and 36 months after treatment.RESULTS The study found that the most common minor complication of UAE was postembolization syndrome in 73.6% of women,resolving within a week.No significant differences were observed between the UAE group and the control group in serum levels of reproductive hormones(FSH,LH,E2,AMH)and ovarian reserve indicators(AFC,OV)at any point up to 36 months post-treatment.Additionally,there were no significant differences in conception,pregnancy,or delivery rates,with the average time to conception and gestational age at delivery being similar between the two groups.Birth weights were also comparable.Finally,there was no significant correlation between ovarian function,fertility indicators,and the type or amount of embolic agent used or the change in fibroids posttreatment.CONCLUSION UAE resulted in significantly positive pregnancy outcomes,no adverse events post-treatment,and is a safe and effective treatment for uterine fibroids that preserves ovarian function and fertility.

Adverse Pregnancy Outcomes Following Cryotherapy, Thermal Ablation and Loop Electrosurgical Excision Procedure for Cervical Intraepithelial Neoplasia Treatment: A Pilot Study among Zambian Women

Background: Cervical Intraepithelial neoplasia treatments have become essential interventions to manage cervical lesions. Majority of the recipients of these treatments are women within the reproductive age group, who according to literature may be at risk of adverse pregnancy outcomes. This pilot study is part of a study investigating adverse pregnancy outcomes among women who received Cryotherapy, Thermal ablation and Loop Electrosurgical Excision Procedure compared to the untreated women in Zambia. Materials and Methods: This descriptive study analyzed records of 886 (n = 443 treated and n = 443 untreated) women aged 15 - 49 years. The women were either screened with Visual Inspection with Acetic Acid or treated for Cervical Intraepithelial neoplasia at the Adult Infectious Disease Centre between January 2010 and December 2020. Women meeting the criteria were identified using the Visual Inspection with Acetic Acid screening records and telephone interviews to obtain the adverse pregnancy outcome experienced. Data were analysed using STATA version 16 to determine the prevalence and obtain frequency distribution of outcomes of interest. Univariate and multivariable binary logistic regression estimated odds of adverse pregnancy outcomes across the three treatments. Results: The respondents were aged 15 to 49 years. Adverse pregnancy outcomes were observed to be more prevalent in the treatment group (18.5%) compared to the untreated group (5.4%). Normal pregnancy outcomes were lower in the treated (46.3%;n = 443) than the untreated (53.7%;n = 443). The treated group accounted for the majority of abortions (85.2%), prolonged labour (85.7%) and low birth weight (80%), whereas, the untreated accounted for the majority of still births (72.7%). Women treated with cryotherapy (aOR = 2.43, 95% CI = 1.32 - 4.49, p = 0.004), thermal ablation (aOR = 6.37, 95% CI = 0.99 - 41.2, p = 0.052) and Loop Electrosurgical Excision Procedure (aOR = 9.67, 95% CI = 2.17 - 43.1, p = 0.003) had two-, six- and ten-times higher odds of adverse pregnancy outcomes respectively, relative to women who required no treatment. Conclusion: Adverse pregnancy outcomes are prevalent among women who have received treatment in Zambia. The findings indicate that treating Cervical Intraepithelial Neoplasia has been linked to higher chances of experiencing abortion, delivering low birth weight babies and enduring prolonged labor that may result in a caesarean section delivery. Cervical neoplasia treatments, particularly Loop Electrosurgical Excision Procedure, are associated with significantly increased odds of adverse pregnancy outcomes. It is essential to include information about prior Cervical Intraepithelial neoplasia treatment outcomes in obstetric care.

Adult minimal change disease:Clinicopathologic characteristics,treatment response and outcome at a single center in Pakistan

BACKGROUND Minimal change disease(MCD)is a significant cause of idiopathic nephrotic syndrome(INS)in adults,representing approximately 10%-15%of INS cases.The data is scanty on clinicopathological features,treatment responses,and long-term outcomes of MCD in adults.AIM To determine the clinicopathologic characteristics,treatment responses,and medium-term outcomes of adult patients with MCD in Pakistan.METHODS This retrospective cohort study included all adult patients with biopsy-proven MCD treated at the adult nephrology clinic,Sindh institute of urology and transplantation,between January 2010 and December 2020.The data was retrieved from the original renal biopsy request forms in the histopathology archives and the case files.Data on demographics,clinical presentation,laboratory findings,treatment regimens,and outcomes were collected and analyzed.Complete remission(CR),partial remission(PR),relapse,and steroid resistance were defined according to standard criteria.Statistical analyses were performed using statistical product and service solutions,Version 22.RESULTS The study cohort included 23 adults[15(65.2%males),mean age 26.34±10.28 years].Hypertension was found in 7(30.4%)and microscopic hematuria in 10(43.4%)of participants.Laboratory findings revealed a mean serum creatinine of 1.03±1.00 mg/dL,mean serum albumin of 1.94±0.90 g/dL and mean 24-hour urinary proteins of 4.53±2.43 g.The mean follow-up time was 38.09±22.3 months.Treatment with steroids was effective in 16/18(88.8%)of patients,with 10/16(62.5%)achieving CR and 6/16(37.5%)achieving PR.Two patients were resistant to steroids and required second-line immunosuppressive therapy.Relapse occurred in 4/20(19.04%)of patients,with a mean time to first relapse of 6.5±3.31 months.At the last follow-up,18/20(85.7%)of patients were in remission,and 16/20(76.1%)maintained normal renal function.No patients progressed to end-stage renal disease or died.CONCLUSION MCD in adults shows a favorable response to steroid therapy,with a majority achieving remission.However,relapses are common,necessitating second-line immunosuppressive treatments in some cases.The study highlights the need for standardized treatment guidelines for adult MCD to optimize outcomes.

Outcomes of treatment of male urethral stricture：a multivariate analysis

目的：分析外伤性和前列腺术后尿道狭窄各种治疗方法的优缺点及影响因素，为临床上合理选择治疗方式、减少狭窄复发提出有益建议。方法：对本科64例外伤性和59例前列腺术后的尿道狭窄初次治疗共123例进行回顾性多因素分析。结果：64例外伤性尿道狭窄患者中，尿扩22例，20例（90．9％）复发；尿道内切开21例，16例（76．2％）复发；尿道端端吻合21例，4例（19％）复发；59例前列腺术后尿道狭窄中，尿扩16例，15例（93．6％）复发；尿道内切开37例，5例（13．5％）复发；6例切开膀胱行膀胱颈疤痕切开切除膀胱颈整形术，3例（50％）复发。结论：①经尿道疤痕切开切除治疗外伤性尿道狭窄，其疗效与狭窄长度有关，狭窄长度〈2cm复发率低，〉2121／1则复发率高。②尿道疤痕切除端端吻合治疗外伤性尿道狭窄，其疗效与狭窄长度、狭窄部位、既往手术史无关，与手术本身有关，即术中如彻底切除狭窄疤痕及坏死组织、吻合无张力则复发率低，反之则高。⑧尿扩适用于尿道黏膜下狭窄，不适用于合并有尿道海绵体纤维化的尿道狭窄。④尿道内切开是治疗前列腺术后尿道狭窄的首选方法且疗效好。

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China

Objective Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.Methods A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients’ medical records. Multivariable logistic regression models were used to estimate the odds ratio(OR) and 95% confidence interval(95% CI) of the associations between comorbidities(cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19.Results Overall, 158(13.6%) patients were diagnosed with severe illness and 32(2.7%) had unfavorable outcomes. Hypertension(2.87, 1.30–6.32), type 2 diabetes(T2 DM)(3.57, 2.32–5.49),cardiovascular disease(CVD)(3.78, 1.81–7.89), fatty liver disease(7.53, 1.96–28.96), hyperlipidemia(2.15, 1.26–3.67), other lung diseases(6.00, 3.01–11.96), and electrolyte imbalance(10.40, 3.00–26.10)were independently linked to increased odds of being severely ill. T2 DM(6.07, 2.89–12.75), CVD(8.47,6.03–11.89), and electrolyte imbalance(19.44, 11.47–32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission(5.46,3.25–9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes(6.58, 1.46–29.64) within two weeks.Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

Reliability assessment and correlation analysis of evaluating orthodontic treatment outcome in Chinese patients

This study aimed to assess the reliability of experienced Chinese orthodontists in evaluating treatment outcome and to determine the correlations between three diagnostic information sources. Sixty-nine experienced Chinese orthodontic specialists each evaluated the outcome of orthodontic treatment of 108 Chinese patients. Three different information sources： study casts （SC）, lateral cephalometric X-ray images （LX） and facial photographs （PH） were generated at the end of treatment for 108 patients selected randomly from six orthodontic treatment centers throughout China. Six different assessments of treatment outcome were made by each orthodontist using data from the three information sources separately and in combination. Each assessment included both ranking and grading for each patient. The rankings of each of the 69 judges for the 108 patients were correlated with the rankings of each of the other judges yielding 13 873 Spearman rs values, ranging from -0.08 to ＋0.85. Of these, 90% were greater than 0.4, showing moderate-to-high consistency among the 69 orthodontists. In the combined evaluations, study casts were the most significant predictive component （R2=0.86, P〈0.000 1）, while the inclusion of lateral cephalometric films and facial photographs also contributed to a more comprehensive assessment （R2=0.96, P〈0.000 1）. Grading scores for SC＋LX and SC＋PH were highly significantly correlated with those for SC＋LX＋PH （r（SC＋LX）vs.（SC＋LX＋PH）=0.96, r（SC＋PH）vs.（SC＋LX＋PH）=0.97）, showing that either SC＋LX or SC＋PH is an excellent substitute for all three combined assessment,

Management of hilar cholangiocarcinoma in the North of England: Pathology, treatment, and outcome

AIM: To assess the management and outcome of hilar cholangiocarcinoma (Klatskin tumor) in a single tertiary referral center.METHODS: The notes of all patients with a diagnosis of hilar cholangiocarcinoma referred to our unit for over an 8-year period were identified and retrospectively reviewed. Presentation, management and outcome were assessed.RESULTS: Seventy-five patients were identified. The median age was 64 years (range 34-84 years). Male to female ratio was 1:1. Eighty-nine percent of patients presented with jaundice. Most patients referred were under Bismuth classification 3a, 3b or 4. Seventy patients required biliary drainage, 65 patients required 152percutaneous drainage procedures, and 25 had other complications. Forty-one patients had 51 endoscopic drainage procedures performed (15 failed). Of these,36 subsequently required percutaneous drainage. The median number of drainage procedures for all patients was three, 18 patients underwent resection (24%), nine had major complications and three died post-operatively.The 5-year survival rate was 4.2% for all patients, 21%for resected patients and 0% for those who did not undergo resection (P = 0.0021). The median number of admissions after diagnosis in resected patients was two and three in non-resected patients (P＜0.05).Twelve patients had external-beam radiotherapy, seven brachytherapy, and eight chemotherapy. There was no significant benefit in terms of survival (P = 0.46) or hospital admissions.CONCLUSION: Resection increases survival but carries the risk of significant morbidity and mortality.Percutaneous biliary drainage is almost always necessary and endoscopic drainage should be avoided if possible.

Heart valve disease in elderly Chinese population： effect of advanced age and comorbidities on treatment decision-making and outcomes

Background A considerable proportion of elderly patients with symptomatic severe heart valve disease are treated conservatively de- spite clear indications for surgical intervention. However, little is known about how advanced age and comorbidities affect treatment deci-sion-making and therapeutic outcomes. Methods Patients （n = 234, mean age： 78.5 ± 3.7 years） with symptomatic severe heart valve dis- ease hospitalized in our center were included. One hundred and fifty-one patients （65%） were treated surgically （surgical group） and 83 （35%） were treated conservatively （conservative group）. Factors that affected therapeutic decision-making and treatment outcomes were investi- gated and long-term survival was explored. Results Isolated aortic valve disease, female sex, chronic renal insufficiency, aged _〉 80 years, pneumonia, and emergent status were independent factors associated with therapeutic decision-making. In-hospital mortality for the surgical group was 5.3% （8/151）. Three patients （3.6%） in the conservative group died during initial hospitalization. Low cardiac output syndrome and chronic renal insufficiency were identified as predictors of in-hospital mortality in the surgical group. Conservative treatment was identi- fied as the single risk factor for late death in the entire study population. The surgical group had better 5-year （77.2% vs. 45.4%, P 〈 0.0001） and 10-year （34.5% vs. 8.9%, P 〈 0.0001） survival rates than the conservative group, even when adjusted by propensity score-matched analysis. Conclusions Advanced age and geriatric comorbidities profoundly affect treatment decision-making for severe heart valve disease. Valve surgery in the elderly was not only safe but was also associated with good long-term survival while conservative treatment was unfavorable for patients with symptomatic severe valve disease.

Treatment of central precocious puberty by GnRH analogs： long-term outcome in men

In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.

Patient-centric periodontal research:A pioneering application of patient-reported outcome measures

Conventional dentistry or periodontal research often ignores the human component in favor of clinical outcomes and biological causes.Clinical research is driven by the statistical significance of outcome parameters rather than the satisfaction level of the patient.In this context,patient-centric periodontal research(PCPR)is an approach that considers the patient´s feedback concerning their functional status,experience,clinical outcomes,and accessibility to their treatments.It is argued that data self-reported by the patient might have low reliability owing to the confounding effect of their personal belief,cultural background,and social and economic factors.However,literature has shown that the incorporation of“patient-centric outcome”components considerably enhances the validity and applicability of research findings.Variations in the results of different studies might be due to the use of different and non-standardized assessment tools.To overcome this problem,this editorial enlists various reliable tools available in the literature.In conclusion,we advocate that the focus of researchers should shift from mere periodontal research to PCPR so that the results can be effectively applied in clinical settings and the therapeutic strategy can also change from mere periodontal therapy to patient-centric periodontal therapy.

Low Doses of Rifampicin Used in New Tuberculosis Patients Correlated to Increased Frequency of Rifampicin-Resistance and Poorer Treatment Outcomes

The prognosis of patients with previously treated tuberculosis (TB) was suggested to be dependent on whether the initial treatment was in compliance with the established guidelines. The aim of this retrospective multicenter study was to determine the proportion of new TB patients who received standard doses of rifampicin in multiple provinces of China, and the relationship between low doses of rifampicin and frequency of rifampicin-resistance as well as treatment outcomes. A total of 713 new TB patients were treated with either once-daily dose of bulk anti-TB drugs (group I) or every other day combination blister packs of anti-TB drugs containing rifampicin (group II) at more than 30 TB treatment centers/hospitals in China. Treatment history, therapeutic doses of rifampicin, and information about patients were extracted from their medical records and analyzed, and rifampicin-resistance of isolates collected from patients following the treatment as well as treatment outcomes were compared between two treatment groups. Among 522 patients in treatment group I, 154 (29.5%) received standard and 363 (69.5%) received low doses of rifampicin;238 (45.6%) isolates were rifampicin-resistant, and 243 (46.6%) were successfully treated. Among 191 patients in treatment group II, 175 (91.6%) received standard and 15 (7.9%) received low doses of rifampicin;72 (37.7%) isolates were rifampicin-resistant, and 105 (55%) were successfully treated. When patients who received low doses of rifampicin were compared to others within the same treatment group, increased rates for rifampicin-resistance and treatment failure were observed. Results from this study showed that most new TB patients in treatment group I (69.5%) received low doses of rifampicin, and their treatment outcomes were worse than those in treatment group II, indicating that low doses of rifampicin used for the initial treatment of new TB patients were correlated to increased frequency of rifampicin-resistance and poorer treatment outcomes.

Treatment outcomes and adverse drug reactions among patients with drug-resistant tuberculosis receiving all-oral,long-term regimens:First record viewing report from Pakistan

Objective:To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis.Methods:This retrospective study was conducted at 10 Programmatic Management of Drug Resistant Tuberculosis sites in Punjab province of Pakistan.Patients receiving treatment for drug resistant tuberculosis from July 2019 to December 2020 with at least interim result i.e.6th month culture conversion or final outcomes(cured,complete,lost to follow-up,failure,death)available,were included in the study.Data was extracted from electronic data management system.For the reporting and management of adverse drug events,active tuberculosis drug safety monitoring and management was implemented across all sites.All the data was analyzed using SPSS version 22.Results:Out of 947 drug resistant tuberculosis patients included in this study,579(68%)of the patients had final outcomes available.Of these,384(67.9%)successfully completed their treatment.Out of 368(32%)patients who had their interim results available,all had their 6th month culture negative.Combining new medications was thought to result in serious adverse outcomes such as QT prolongation.However,this study did not record any severe adverse events among patients.Conclusions:All-oral regimens formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with traditional injectable treatment.

Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.