Time Interval Between the End of Neoadjuvant Therapy and Elective Resection of Locally Advanced Rectal Cancer in the CRONOS Study.

Importance: The treatment for extraperitoneal locally advanced rectal cancer (LARC) is neoadjuvant therapy (NAT) followed by total mesorectal excision (TME). Robust evidence on the optimal time interval between NAT completion and surgery is lacking. Objective: To assess the association of time interval between NAT completion and TME with short- and long-term outcomes. It was hypothesized that longer intervals increase the pathologic complete response (pCR) rate without increasing perioperative morbidity. Design, Setting, and Participants: This cohort study included patients with LARC from 6 referral centers who completed NAT and underwent TME between January 2005 and December 2020. The cohort was divided into 3 groups depending on the time interval between NAT completion and surgery: short (≤8 weeks), intermediate (>8 and ≤12 weeks), and long (>12 weeks). The median follow-up duration was 33 months. Data analyses were conducted from May 1, 2021, to May 31, 2022. The inverse probability of treatment weighting method was used to homogenize the analysis groups. Exposure: Long-course chemoradiotherapy or short-course radiotherapy with delayed surgery. Main outcome and Measures: The primary outcome was pCR. Other histopathologic results, perioperative events, and survival outcomes constituted the secondary outcomes. Results: Among the 1506 patients, 908 were male (60.3%), and the median (IQR) age was 68.8 (59.4-76.5) years. The short-, intermediate-, and long-interval groups included 511 patients (33.9%), 797 patients (52.9%), and 198 patients (13.1%), respectively. The overall pCR was 17.2% (259 of 1506 patients; 95% CI, 15.4%-19.2%). When compared with the intermediate-interval group, no association was observed between time intervals and pCR in short-interval (odds ratio [OR], 0.74; 95% CI, 0.55-1.01) and long-interval (OR, 1.07; 95% CI, 0.73-1.61) groups. The long-interval group was significantly associated with lower risk of bad response (tumor regression grade [TRG] 2-3; OR, 0.47; 95% CI, 0.24-0.91), systemic recurrence (hazard ratio, 0.59; 95% CI, 0.36-0.96), higher conversion risk (OR, 3.14; 95% CI, 1.62-6.07), minor postoperative complications (OR, 1.43; 95% CI, 1.04-1.97), and incomplete mesorectum (OR, 1.89; 95% CI, 1.02-3.50) when compared with the intermediate-interval group. Conclusions and Relevance: Time intervals longer than 12 weeks were associated with improved TRG and systemic recurrence but may increase surgical complexity and minor morbidity.

Status of the management of hypertension and diabetes in rural Kenya: a multi-institutional joint intervention of cross-sectional surveys.

Introduction: the aim of this study was to analyze the status of the management of vascular risk factors (hypertension and diabetes) at hospital level (3, 4 and 5) in Murang'a County (Kenya) health system. Methods: between July and December 2018 we performed a joint intervention about the strategies for improving care management of hypertension and diabetic patients in Murang'a (Kenya). A survey based on the recommendations from WHO about management of diabetes and hypertension was completed for 9 health-care centers. The survey made use of a semi-structured questionnaire, while the units of analysis for the survey were households. Results: the number of patients recorded at medical registers with diabetes and hypertension registered in public hospitals in Murang'a County were 6628 (0.45%) and y 6694 (0.45%), respectively. In the surveyed health-care centers, no hospital use electrogram and only one had troponin test. No hospital stocked Isosorbide dinitrate and Glicerine trinitate to prevent chest pain in patients with a heart condition. Only 3 of the clinics performed visual acuity examination and no facility did neurologic examination for neuropathy complications. No public hospital had HbA1 and did microalbuminuria test available. Conclusion: it is necessary to improve to establish screening methods, diagnosis, treatment and follow-up of patients with hypertension and diabetes in Murang'a County at the various levels of health care.

Goiter surgery recommendations in sub-Saharan Africa in humanitarian cooperation.

Background: The standard treatment for endemic goiter is usually total thyroidectomy. In low- and middle-income countries, the management of thyroid disease, which is commonplace in fully developed countries, is not always possible. The purpose of this study is to establish a treatment algorithm to calculate the extent of thyroidectomy based on the risk factors of each patient. Methods: This is a retrospective observational study conducted during the period between 2017 and 2019. A total of 287 patients with thyroid pathology were treated in Maragua Hospital (Kenya). The results of surgical treatment were analyzed after the implementation of an individualized treatment protocol. Results: One hundred and sixty patients with different types of goiter underwent surgery: solitary nodule (54.4%), multi-nodular goiter (30.6%), diffuse goiter (10.6%), and intrathoracic goiter (3.8%). The techniques used were hemithyroidectomy (78.8%), Dunhill thyroidectomy (9.4%), bilateral subtotal thyroidectomy (6.9%), and total thyroidectomy (3.1%). There was no mortality. The surgical morbidity rate was 16% (only one major complication (3b)). Two cases of dysphonia were resolved in the first week. There were three cases of symptomatic hypocalcaemia, two of which resolved in the first week and the other of which was definitive. The follow-up at 6 months was 67%. The cancer rate found in the resection specimens was 5%. Discussion: The implementation of individualized surgical protocols for thyroid surgery in sub-Saharan Africa can improve outcomes. The cooperation projects can increase access to complex surgical treatment for patients with limited resources in low- and middle-income countries.

Humanitarian Surgical Missions in Times of COVID-19: Recommendations to Safely Return to a Sub-Saharan Africa Low-Resource Setting.

BACKGROUND: Since the declaration of the pandemic, humanitarian medicine has been discontinued. Until now, there have been no general recommendations on how humanitarian surgical missions should be organized. METHODS: Based on our experience in the field of humanitarian surgical missions to Sub-Saharan Africa, a panel of recommendations in times of COVID-19 was developed. The fields under study were as follows: (1) Planning of a multidisciplinary project; (2) Organization of the infrastructure; (3) Screening, management and treatment of SARS-COV-2; (4) Diagnostic tests for SARS-COV-2; (5) Surgical priorization and (6) Context of patients during health-care assistance. We applied a risk bias measurement to obtain a consensus among humanitarian health-care providers with experience in this field. RESULTS: A total of 94.36% of agreement were reached for the approval of the recommendations. Emergency surgery must be a priority, and elective surgery adapted. For emergency surgery, we established a priority level 1a (< 24 h) and 1b (< 72 h). For an elective procedure, according our American College of Surgeon adaptation score, process with more than 60 points should be reconsidered. Due to the low life expectancy in many African countries, we consider 45-50 years as age of risk. In case of SARS-COV-2 active infection or high clinical suspicion, the screening, management and treatment should be following the international guidelines adapted to duration of the stay, available infrastructure, size of the cooperation team and medical resources. CONCLUSIONS: Humanitarian surgical mission in times of COVID-19 is a challenge that must extrapolate the established recommendations to the local cooperation environment.

Heme oxygenase-1 induction improves ischemic renal failure: role of nitric oxide and peroxynitrite.

The present study evaluated the effects of heme oxygenase-1 (HO-1) induction on the changes in renal outer medullary nitric oxide (NO) and peroxynitrite levels during 45-min renal ischemia and 30-min reperfusion in anesthetized rats. Glomerular filtration rate (GFR), outer medullary blood flow (OMBF), HO and nitric oxide synthase (NOS) isoform expression, and renal low-molecular-weight thiols (-SH) were also determined. During ischemia significant increases in NO levels and peroxynitrite signal were observed (from 832.1 +/- 129.3 to 2,928.6 +/- 502.0 nM and from 3.8 +/- 0.7 to 9.0 +/- 1.6 nA before and during ischemia, respectively) that dropped to preischemic levels during reperfusion. OMBF and -SH significantly decreased after 30 min of reperfusion. Twenty-four hours later, an acute renal failure was observed (GFR 923.0 +/- 66.0 and 253.6 +/- 55.3 microl.min(-1).g kidney wt(-1) in sham-operated and ischemic kidneys, respectively; P < 0.05). The induction of HO-1 (CoCl(2) 60 mg/kg sc, 24 h before ischemia) decreased basal NO concentration (99.7 +/- 41.0 nM), although endothelial and neuronal NOS expression were slightly increased. CoCl(2) administration also blunted the ischemic increase in NO and peroxynitrite (maximum values of 1,315.6 +/- 445.6 nM and 6.3 +/- 0.5 nA, respectively; P < 0.05), preserving postischemic OMBF and GFR (686.4 +/- 45.2 microl.min(-1).g kidney wt(-1)). These beneficial effects of CoCl(2) on ischemic acute renal failure seem to be due to HO-1 induction, because they were abolished by stannous mesoporphyrin, a HO inhibitor. In conclusion, HO-1 induction has a protective effect on ischemic renal failure that seems to be partially mediated by decreasing the excessive production of NO with the subsequent reduction in peroxynitrite formation observed during ischemia.