Category: Nevin Manimala

Blood Adv. 2023 Nov 16:bloodadvances.2023011489. doi: 10.1182/bloodadvances.2023011489. Online ahead of print.

ABSTRACT

During the manufacturing period of autologous chimeric antigen receptor (CAR) T cell therapy, patients may experience a decline in their condition due to cancer progression. In this study, we investigated the impact of “bridging therapy” (BT) on the outcome of patients with relapsed/refractory large B cell lymphoma who received anti-lymphoma treatment between leukapheresis and axicabtagene ciloleucel (axi-cel) infusion. We conducted our analysis using data from the multicenter US Lymphoma CAR T Consortium, with a median follow-up of 33 months (range: 4.3-42.1). Out of the 298 patients who underwent leukapheresis, 275 patients received axi-cel. The 52% (n=143) of patients who received BT had a higher baseline risk profile compared to patients who did not receive BT and these patients as a group had inferior outcomes than those who did not have BT. However, after propensity score matching between the two groups, there was no statistically significant differences in ORR (77% vs 87%, p=0.13), CR rate (58% vs 70%, p=0.1), PFS (HR=1.25, p=0.23), and OS (HR=1.39, p=0.09) between BT group and no BT group respectively. Analyzing effects of BT in the whole leukapheresed cohort regardless of receiving axi-cel (intention to treat analysis) showed similar results. Bridging radiation therapy resulted in outcomes similar to those observed with non-radiation BT. Our findings suggest that BT may be safe without a significant impact on long-term survival in patients who require disease stabilization during the manufacturing period. Moreover, our results suggest that there is no clear advantage in using radiation-based BT over non-radiation-based BT.

PMID:38051550 | DOI:10.1182/bloodadvances.2023011489

JAMA Netw Open. 2023 Dec 1;6(12):e2346121. doi: 10.1001/jamanetworkopen.2023.46121.

ABSTRACT

IMPORTANCE: Trial protocols outline a trial’s objectives as well as the methods (design, conduct, and analysis) that will be used to meet those objectives, and transparent reporting of trial protocols ensures objectives are clear and facilitates appraisal regarding the suitability of study methods. Factorial trials, in which 2 or more interventions are assessed in the same set of participants, have unique methodological considerations. However, no extension of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement, which provides guidance on reporting of trial protocols, for factorial trials is available.

OBJECTIVE: To develop a consensus-based extension to the SPIRIT 2013 Statement for factorial trials.

EVIDENCE REVIEW: The SPIRIT extension for factorial trials was developed using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework. First, a list of reporting recommendations was generated using a scoping review of methodological articles identified using a MEDLINE search (inception to May 2019), which was supplemented with relevant articles from the personal collections of the authors. Second, a 3-round Delphi survey (January to June 2022, completed by 104 panelists from 14 countries) was conducted to assess the importance of items and identify additional recommendations. Third, a hybrid consensus meeting was held, attended by 15 panelists to finalize selection and wording of the checklist.

FINDINGS: This SPIRIT extension for factorial trials modified 9 of the 33 items in the SPIRIT 2013 checklist. Key reporting recommendations were that the rationale for using a factorial design should be provided, including whether an interaction is hypothesized; the treatment groups that will form the main comparisons should be identified; and statistical methods for each main comparison should be provided, including how interactions will be assessed.

CONCLUSIONS AND RELEVANCE: In this consensus statement, 9 factorial-specific items were provided that should be addressed in all protocols of factorial trials to increase the trial’s utility and transparency.

PMID:38051535 | DOI:10.1001/jamanetworkopen.2023.46121

JAMA Netw Open. 2023 Dec 1;6(12):e2346085. doi: 10.1001/jamanetworkopen.2023.46085.

ABSTRACT

IMPORTANCE: The association between sleep duration and all-cause mortality remains unclear among people with obstructive sleep apnea (OSA).

OBJECTIVE: To explore whether there is an association between sleep duration and all-cause mortality among people with OSA.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study investigated participants with OSA from the Sleep Heart Health Study (SHHS) in which participants were enrolled between 1995 and 1998 with questionnaires and polysomnography (PSG) assessment and followed up for a median of 11.8 years. SHHS was a multicenter community-based study; 2574 participants with OSA defined by apnea-hypopnea index (AHI) greater than or equal to 15 from SHHS were found; all of them had all-cause mortality data and were included in the study. Data were analyzed from November 2022 to October 2023.

EXPOSURES: Participants were divided into 4 groups with objective sleep duration of (1) at least 7 hours, (2) 6 to less than 7 hours, (3) 5 to less than 6 hours, and (4) less than 5 hours, which was determined by total sleep time on PSG at baseline.

MAIN OUTCOMES AND MEASURES: All-cause mortality was defined as deaths from any cause and its risk was compared among 4 OSA groups using Cox regression models.

RESULTS: A total of 2574 participants with OSA were included (1628 [63.2%] men and 946 [36.8%] women; mean [SD] age, 65.4 [10.7] years; 211 [8.2%] Black, 2230 [86.6%] White, 133 [5.2%] other race). Overall, 688 all-cause deaths were observed in participants. Compared with the group sleeping at least 7 hours, the groups sleeping 6 to less than 7 hours (hazard ratio [HR], 1.53 [95% CI, 1.13-2.07]), 5 to less than 6 hours (HR, 1.40 [95% CI, 1.03-1.90]), and less than 5 hours (HR, 1.64 [95% CI, 1.20-2.24]) had significantly higher risks of all-cause mortality independent of AHI. Sensitivity analyses were performed among participants with available data of positive airway pressure treatment during follow-up and the finding was mostly consistent, albeit the HR for the group of 5 to less than 6 hours was not statistically significant.

CONCLUSIONS AND RELEVANCE: In this cohort study of 2574 participants with OSA, those with shorter objective sleep duration had higher risk of all-cause mortality independent of AHI compared with those sleeping at least 7 hours. Further studies would be needed to investigate health benefits of extending sleep length among people with OSA with short sleep duration.

PMID:38051532 | DOI:10.1001/jamanetworkopen.2023.46085

JAMA Netw Open. 2023 Dec 1;6(12):e2346223. doi: 10.1001/jamanetworkopen.2023.46223.

ABSTRACT

IMPORTANCE: Patients with breast cancer and comorbid HIV experience higher mortality than other patients with breast cancer.

OBJECTIVE: To compare time to cancer treatment initiation and relative dose intensity (RDI) of neoadjuvant and adjuvant chemotherapy among patients with breast cancer with vs without HIV.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective, matched cohort study enrolled women who received a diagnosis of breast cancer from January 1, 2000, through December 31, 2018. The electronic medical records of 3 urban, academic cancer centers were searched for women with confirmed HIV infection prior to or simultaneous with diagnosis of stage I to III breast cancer. Tumor registry data were used to identify 2 control patients with breast cancer without HIV for each participant with HIV, matching for study site, stage, and year of cancer diagnosis. Statistical analysis was performed from December 2022 to October 2023.

EXPOSURE: HIV infection detected before or within 90 days of participants’ breast cancer diagnosis.

MAIN OUTCOMES AND MEASURES: The primary outcome was time to breast cancer treatment initiation, defined as the number of days between cancer diagnosis and first treatment. The secondary outcome was overall RDI for patients who received chemotherapy. These outcomes were compared by HIV status using Cox proportional hazards regression and linear regression modeling, respectively, adjusting for confounding demographic and clinical factors. Exploratory outcomes included instances of anemia, neutropenia, thrombocytopenia, and liver function test result abnormalities during chemotherapy, which were compared using Fisher exact tests.

RESULTS: The study enrolled 66 women with comorbid breast cancer and HIV (median age, 51.1 years [IQR, 45.7-58.2 years]) and 132 with breast cancer alone (median age, 53.9 years [IQR, 47.0-62.5 years]). The median time to first cancer treatment was not significantly higher among patients with HIV than those without (48.5 days [IQR, 32.0-67.0 days] vs 42.5 days [IQR, 25.0-59.0 days]; adjusted hazard ratio, 0.78, 95% CI, 0.55-1.12). Among the 36 women with HIV and 62 women without HIV who received chemotherapy, the median overall RDI was lower for those with HIV vs without HIV (0.87 [IQR, 0.74-0.97] vs 0.96 [IQR, 0.88-1.00]; adjusted P = .01). Grade 3 or higher neutropenia during chemotherapy occurred among more women with HIV than those without HIV (13 of 36 [36.1%] vs 5 of 58 [8.6%]).

CONCLUSIONS AND RELEVANCE: This matched cohort study suggests that patients with breast cancer and HIV may have experienced reduced adjuvant chemotherapy RDI, reflecting greater dose reductions, delays, or discontinuation. Strategies for supporting this vulnerable population during chemotherapy treatment are necessary.

PMID:38051529 | DOI:10.1001/jamanetworkopen.2023.46223

J Acoust Soc Am. 2023 Dec 1;154(6):3627-3643. doi: 10.1121/10.0022577.

ABSTRACT

Hearing aids show more benefit in traditional laboratory speech-in-noise tests than in real-world noisy environments. Real-world noise comprises a large range of acoustic properties that vary randomly and rapidly between and within environments, making quantifying real-world noise and using it in experiments and clinical tests challenging. One approach is to use acoustic features and statistics to quantify acoustic properties of real-world noise and control for them or measure their relationship to listening performance. In this study, the complexity of real-world noise from different environments was quantified using entropy in both the time- and frequency-domains. A distribution of noise segments from low to high entropy were extracted. Using a trial-by-trial design, listeners with normal hearing and hearing loss (in aided and unaided conditions) repeated back sentences embedded in these noise segments. Entropy significantly affected speech perception, with a larger effect of entropy in the time-domain than the frequency-domain, a larger effect for listeners with normal hearing than for listeners with hearing loss, and a larger effect for listeners with hearing loss in the aided than unaided condition. Speech perception also differed between most environment types. Combining entropy with the environment type improved predictions of speech perception above the environment type alone.

PMID:38051522 | DOI:10.1121/10.0022577

Ann Ital Chir. 2023;94:478-482.

ABSTRACT

BACKGROUND: The inguinal hernia is the protrusion of intra-abdominal contents through a defect of the abdominal wall. This content can be represented by omentum, most frequently intestine. Theoretically, any intraperitoneal organ can be located in the hernia sac.The inguinal hernia is distinguished by several features: it is the most common form of hernia, it can occur in any age category, the only treatment is the surgical treatment, in the absence of the treatment, severe complications can endanger the patient’s life.The treatment of hernias consists either in the use of a classical (“open”) surgical procedure or of a laparoscopic procedure. The objective of both procedures is to remove and treat the hernia sac and repair the defect that appeared in the posterior wall of the groin canal.

OBJECTIVES: The purpose of this study is to compare the effectiveness of the two surgery types, considering the immediate postoperative pain.

METHODS: This paper is a prospective study conducted between September 2019 and February 2020, including a number of 80 patients admitted in the Department of General Surgery I and II, Emergency Clinical County Hospital of Târgu Mureș. In the study were included patients with uncomplicated inguinal hernia for which a classical or laparoscopic procedure was performed. Patients with complicated inguinal hernia (strangulation, incarceration) and patients with associated comorbidities (neoplasms, autoimmune diseases, neurological disorders) were excluded. For the study group were taken into consideration: demographic data (age, gender), type of surgery and the pain assessment using the VAS scale.

RESULTS: Following the study, it was statistically confirmed the prevalence of elderly patients to the detriment of young patients in both classical and laparoscopic study group. As we age, the pain sensitivity decreases, an aspect highlighted in the classical study group, the statistics showing the presence of less pain in elderly patients on the second postoperative day compared to young patients. Regarding the pain in both postoperative days, it was statistically proved that the pain tends to decrease in intensity on the second postoperative day compared to the first postoperative day.

CONCLUSIONS: As seen from this paper, taking into consideration the pain aspect, the two surgeries are very similar. Regardless of the chosen type of procedure, a preponderance of elderly patients was observed. The “Open Tension Free” procedure is a modern and efficient technique due to the absence of the local tension that can generate recurrence. The laparoscopic procedure has the advantage of reducing surgical trauma and minimizing recurrences. In the end, the type of treatment should be chosen by the surgeon after taking into consideration the type of hernia, the age and the patient’s comorbidities and the economic considerations.

KEY WORDS: Classical procedure, Inguinal hernia, Laparoscopic procedure.

PMID:38051514

Ann Ital Chir. 2023;94:483-492.

ABSTRACT

INTRODUCTION: Laparoscopic approach for inguinal hernia offers considerable advantages. Several risk factors for postoperative pain have been investigated, but few articles can be found about learning curve and surgeon’s influence on postoperative pain after inguinal herniorrhaphy.

PATIENTS AND METHODS: A prospective study was conducted including 105 patients. Surgical procedures were performed by two general surgeons performing TAPP procedure. Follow up was realized at one and three months after surgery.

RESULTS: Majority of investigated data were without significant differences. In case of the Senior Surgeon we registered higher SEI (surgeon experience index), increased proportion of bilateral inguinal hernias (P = 0.0309) and higher percentage of longer surgical procedures (P = 0.0309). Meantime in case of the Junior Surgeon we recorded operations with intermediate duration (P = 0.0232) in a greater manner. During the follow up period, similar incidence of pain senzation was remarked among patients, without statistical significance.

CONCLUSION: With adequate learning program and supervision TAPP procedure can be a safe technique when performed by young specialist too, presenting similar postoperative results with those of experienced surgeons.

KEY WORDS: Inguinal hernia, TAPP, Selfgripping surgical mesh, Postoperative pain.

PMID:38051509

Ann Ital Chir. 2023;94:512-517.

ABSTRACT

INTRODUCTION: Hernia repair using prosthetic mesh materials has become the preferred method of repair, as the recurrence rates are much lower than with conventional repair techniques. The aim of this retrospective study was to compare open small- and medium-sized abdominal wall hernia repair with flat patch mesh versus three-dimensional mesh (plug) in terms of recurrence and complication rates.

METHODS: The medical records of 300 patients who underwent abdominal wall hernia repair using flat patch mesh versus three-dimensional mesh between January 2010 to December 2015 were reviewed. All patients were followed up after 1 month, 3 month and 1 year. The rate of recurrence, and short-term postoperative complications such as incidence of Surgical Site Infections (SSIs), hematoma and seroma were evaluated.

RESULTS: Short-term follow-up data were available for all patients. The first group was composed of 150 patients that were treated with a flat polypropylene mesh (68% presened umbilical hernia and 32% presented epigastric hernia). The second group was composed of 150 patients that were treated with a three-dimensional polypropylene mesh (60% presented umbilical hernia and 40% presented epigastric hernia). The majority of postoperative (1-month) complications were wound related, representing superficial SSI or seroma. Our results showed a statistically significant reduction of SSIs [3 (2%) vs 13 (8.6%); p = 0.038] and seroma [2 (1.3%) vs 12 (8%); p = 0.030] in the group of patients treated with plugs compared to flat-mesh group. There was no statistically significant difference in hernia recurrences.

DISCUSSION: Usage three-dimensional mesh for open small- and medium-sized umbilical or epigastric hernia repair represents a feasible and safe technique that significantly lowers the incidence of complications such as SSIs and seroma. Furthermore, compared to flat patch mesh, plugs displayed non-inferiority in terms recurrence. Further, well-designed clinical trials could be realized to investigate possible applications of plugs in treatment of small- and medium-sized umbilical and epigastric hernias.

KEY WORDS: Mesh, Umbilical Hernia.

PMID:38051502

Ann Ital Chir. 2023;94:506-511.

ABSTRACT

AIM: The aim of this retrospective study is to evaluate if antiplatelet therapy in elderly patients undergoing surgical excision of nasal non-melanoma skin cancer and contemporary reconstruction with full-thickness skin graft can be related to a better vitality of the graft and consequently improved aesthetic result.

MATERIALS AND METHODS: Patients affected by BCC or SCC of the nose that underwent surgical excision and contemporary reconstruction with full-thickness skin graft were divided into two groups according to antiplatelet therapy. Medications were performed 7 and 15 days after surgery. To asses engraftment, we clinically evaluated the percentage of vital flap recognizing 3 different results: less than 20%, between 20% and 80%, and more than 80% of vital surface. Finally, patients were asked to express a subjective evaluation of the aesthetic result using a numeric scale ranging from 1 to 10. Statistical analyses were performed with SPSS 15.0 for Windows.

RESULTS: Twenty-four of the 36 eligible patients took antiplatelet therapy (Group 1). Statistical analysis was very close to demonstrate a significant difference between the two groups after the first evaluation (X2= 3.6; p-value = 0.0578) and it showed a clear significant difference between the two groups after the second evaluation (X2 = 13.5692 e p-value = 0.0002). The average value of the subjective evaluation conducted only on 32 of 36 patients, was 9.12. Any significant difference was observed between the two groups (p-value >0.1).

CONCLUSIONS: Our preliminary results seem to suggest that antiplatelet therapy in elderly patients with non-melanoma skin cancer of the nose treated with surgical excision and contemporary reconstruction with fill-thickness skin graft could favor the graft vitality with low risk of bleeding. Further studies will be useful to determinate if antiplatelet drugs can be prescribed in the perioperative period to selected patients presenting risk factors for wound healing to increase the chances of engraftment.

KEY WORDS: Antiplatelet Therapy, Non Melanoma Skin Cancer, Skin Graft.

PMID:38051499

Sleep Breath. 2023 Dec 5. doi: 10.1007/s11325-023-02946-6. Online ahead of print.

ABSTRACT

PURPOSE: To assess changes in sleep-related symptoms in patients with breast cancer, endometrial cancer and melanoma previously examined for sleep-related symptoms and the presence of PSG (polysomnography)-determined OSA, ≥ 3 years post-treatment; and to evaluate how CPAP treatment affects sleep-related symptoms in patients previously diagnosed with OSA.

METHODS: Patients initially recruited from breast cancer, endometrial cancer, and melanoma follow-up clinics at Westmead Hospital (Sydney, Australia) participated in this questionnaire-based study. Demographic and change in cancer status data were collected at follow-up. Patients completed the Pittsburgh Sleep Quality Index [poor sleep quality, PSQI_TOTAL ≥ 5au], Insomnia Severity Index, Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire; with ΔPSQI_TOTAL ≥ 3au indicating a clinically meaningful change in sleep quality over follow-up. PSG-determined OSA was confirmed using the apnoea-hypopnoea index. CPAP compliance was determined via self-report (CPAP compliant, CPAP; not compliant, non-CPAP). Logistic regression models determined if changes in cancer status, AHI, cancer subgroup or CPAP treatment was predictive of ΔPSQI_TOTAL ≥ 3 au and p < 0.05 indicated statistical significance.

RESULTS: The 60 patients recruited had breast cancer (n = 22), endometrial cancer (n = 15), and melanoma (n = 23). Cancer subgroups were similarly aged, and all had median follow-up PSQI_TOTAL scores ≥ 5au; breast cancer patients scoring the highest (p < 0.05). The CPAP group had significantly reduced PSQI_TOTAL scores (p = 0.02) at follow-up, unlike the non-CPAP group. Cancer subgroups had similar median ISI_TOTAL, ESS_TOTAL and FOSQ-10_TOTAL scores at follow-up, regardless of CPAP treatment. There were no significant predictors of ΔPSQI_TOTAL ≥ 3 au at follow-up.

CONCLUSION: Sleep-related symptoms persist in patients with cancer ≥ 3 years after treatment, although these symptoms improve with CPAP. Future studies should evaluate how CPAP affects survival outcomes in cancer patients with comorbid OSA.

PMID:38051468 | DOI:10.1007/s11325-023-02946-6